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Open AccessArticle

Sustainable Electropolymerization of Zingerone and Its C2 Symmetric Dimer for Amperometric Biosensor Films

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Myriam Caval

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Maria Antonietta Dettori

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Molecules 2023, 28(16), 6017; https://doi.org/10.3390/molecules28166017 - 11 Aug 2023

Viewed by 433

Abstract

Polymeric permselective films are frequently used for amperometric biosensors to prevent electroactive interference present in the target matrix. Phenylenediamines are the most commonly used for the deposition of shielding polymeric films against interfering species; however, even phenolic monomers have been utilized in the [...] Read more.

Polymeric permselective films are frequently used for amperometric biosensors to prevent electroactive interference present in the target matrix. Phenylenediamines are the most commonly used for the deposition of shielding polymeric films against interfering species; however, even phenolic monomers have been utilized in the creation of these films for microsensors and biosensors. The purpose of this paper is to evaluate the performances of electrosynthesized polymers, layered by means of constant potential amperometry (CPA), of naturally occurring compound zingerone (ZING) and its dimer dehydrozingerone (ZING DIM), which was obtained by straight oxidative coupling reaction. The polymers showed interesting shielding characteristics against the main interfering species, such as ascorbic acid (AA): actually, polyZING exhibited an AA shielding aptitude comprised between 77.6 and 99.6%, comparable to that obtained with PPD. Moreover, a marked capability of increased monitoring of hydrogen peroxide (HP), when data were compared with bare metal results, was observed. In particular, polyZING showed increases ranging between 55.6 and 85.6%. In the present work, the molecular structures of the obtained polymers have been theorized and docking analyses were performed to understand their peculiar characteristics better. The structures were docked using the Lamarckian genetic algorithm (LGA). Glutamate biosensors based on those polymers were built, and their performances were compared with biosensors based on PPD, which is the most widespread polymer for the construction of amperometric biosensors. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

A New HPLC-UV Method Using Hydrolyzation with Sodium Hydroxide for Quantitation of Trans-p-Hydroxycinnamic Acid and Total Trans-p-Hydroxycinnamic Acid Esters in the Leaves of Ligustrum robustum

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Molecules 2023, 28(14), 5309; https://doi.org/10.3390/molecules28145309 - 10 Jul 2023

Viewed by 414

Abstract

Trans-p-hydroxycinnamic acid and its esters in the leaves of Ligustrum robustum might be a new resource to prevent diabetes and its complications. In the present study, a new HPLC-UV method using hydrolyzation with sodium hydroxide for quantitation of trans- [...] Read more.

Trans-p-hydroxycinnamic acid and its esters in the leaves of Ligustrum robustum might be a new resource to prevent diabetes and its complications. In the present study, a new HPLC-UV method using hydrolyzation with sodium hydroxide for quantitation of trans-p-hydroxycinnamic acid and total trans-p-hydroxycinnamic acid esters in the leaves of L. robustum was developed, since it was difficult and troublesome to analyze no less than 34 trans-p-hydroxycinnamic acid esters by usual HPLC. The extract of L. robustum was hydrolyzed with sodium hydroxide at 80 °C for 2 h, and then, hydrochloride was added. HPLC analysis was performed in reverse phase mode using a C-18 column, eluting with methanol-0.1% acetic acid aqueous solution (40:60, v/v) in isocratic mode at a flow rate of 1.0 mL·min⁻¹ and detecting at 310 nm. The linear range for trans-p-hydroxycinnamic acid was 11.0–352.0 μg·mL⁻¹ (r² = 1.000). The limit of detection and limit of quantification were 2.00 and 6.07 μg·mL⁻¹, respectively. The relative standard deviations of intra-day and inter-day variabilities for trans-p-hydroxycinnamic acid were less than 2%. The percentage recovery of trans-p-hydroxycinnamic acid was 103.3% ± 1.1%. It is the first HPLC method using hydrolyzation for quantification of many carboxylic esters. Finally, the method was used successfully to determine trans-p-hydroxycinnamic acid and total trans-p-hydroxycinnamic acid esters in various extracts of the leaves of L. robustum. The 60–70% ethanol extracts of L. robustum showed the highest contents of free trans-p-hydroxycinnamic acid (3.96–3.99 mg·g⁻¹), and the 50–80% ethanol extracts of L. robustum displayed the highest contents of total trans-p-hydroxycinnamic acid esters (202.6–210.6 mg·g⁻¹). The method can be applied also to the quality control of the products of L. robustum. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

The Metschnikowia pulcherrima Clade as a Model for Assessing Inhibition of Candida spp. and the Toxicity of Its Metabolite, Pulcherrimin

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Dorota Kregiel

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Karolina H. Czarnecka-Chrebelska

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Hana Schusterová

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Renáta Vadkertiová

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Adriana Nowak

Molecules 2023, 28(13), 5064; https://doi.org/10.3390/molecules28135064 - 28 Jun 2023

Viewed by 494

Abstract

Candidiasis is one of the most frequent infections worldwide. In this study, the antimicrobial properties of six strains belonging to the Metschnikowia pulcherrima clade were evaluated against twenty Candida and Candida-related Filobasidiella neoformans var. bacillispora (syn. Cryptococcus neoformans) of different origins, [...] Read more.

Candidiasis is one of the most frequent infections worldwide. In this study, the antimicrobial properties of six strains belonging to the Metschnikowia pulcherrima clade were evaluated against twenty Candida and Candida-related Filobasidiella neoformans var. bacillispora (syn. Cryptococcus neoformans) of different origins, employing the agar cross method. The toxic effect of pulcherrimin, a red metabolite that is responsible for the antimicrobial activities of Metschnikowia spp., was evaluated in various experimental models. The results of agar tests showed that the selected M. pulcherrima strains inhibited the growth of the Candida and non-Candida strains. However, inhibition was dependent on the strain and the environment. The presence of peptone, sodium silicate, and a higher incubation temperature decreased the antifungal action of the M. pulcherrima strains. Pulcherrimin showed cytotoxic and antiproliferative activity, with oxidative stress in cells leading to apoptosis. More research is needed on the mechanism of action of pulcherrimin on somatic cells. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Do Ganoderma Species Represent Novel Sources of Phenolic Based Antimicrobial Agents?

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Aleksandra Petrović Fabijan

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Petar Knežević

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Maja Karaman

Molecules 2023, 28(7), 3264; https://doi.org/10.3390/molecules28073264 - 06 Apr 2023

Cited by 1 | Viewed by 1053

Abstract

Ganoderma species have been recognized as potential antimicrobial (AM) agents and have been used in traditional Chinese medicine (TCM) for a long time. The aim of this study is to examine the AM potential of autochthonous Ganoderma species (G. applanatum, G. [...] Read more.

Ganoderma species have been recognized as potential antimicrobial (AM) agents and have been used in traditional Chinese medicine (TCM) for a long time. The aim of this study is to examine the AM potential of autochthonous Ganoderma species (G. applanatum, G. lucidum, G. pfeifferi and G. resinaceum) from Serbia. The extraction of fungal material was prepared in different solvents (ethanol—EtOH, water—H₂O, chloroform—CHCl₃). Antibacterial activity (ABA) was determined using disk-diffusion, agar-well diffusion, and micro-dilution method, while for antifungal properties disk-diffusion and pour plate method were applied. Antiviral activity was tested on model DNA virus LK3 and determined by plaque assay. Statistical PCA analysis was applied for detection of correlation effects of phenolics and AM activities, while LC-MS/MS was performed for phenolics quantification. G. resinaceum CHCl₃ extract expressed the most potent ABA against P. aeruginosa (MIC = 6.25 mg/mL), probably due to presence of flavonoids and 2,5-dihydroxybenzoic acid. Among H₂O extracts, the highest ABA was determined for G. pfeifferi against both E. coli and S. aureus (21 and 19 mm, respectively). EtOH extracts of G. pfeifferi and G. resinaceum were the most effective against A. niger (23.8 and 20.15 mm, respectively), with special impact of phenolic acids and flavonoid isorhamnetin, while C. albicans showed the lowest susceptibility. The most potent antiviral inhibitor was G. lucidum (70.73% growth inhibition) due to the high amount of phenolic acids. To the best of our knowledge, this is the first report of a methodical AM profile of G. pfeifferi and G. resinaceum from the Balkan region including PCA analysis. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Soy Isoflavones Induce Cell Death by Copper-Mediated Mechanism: Understanding Its Anticancer Properties

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Molecules 2023, 28(7), 2925; https://doi.org/10.3390/molecules28072925 - 24 Mar 2023

Cited by 1 | Viewed by 1117

Abstract

Cancer incidence varies around the globe, implying a relationship between food and cancer risk. Plant polyphenols are a class of secondary metabolites that have recently attracted attention as possible anticancer agents. The subclass of polyphenols, known as isoflavones, includes genistein and daidzein, which [...] Read more.

Cancer incidence varies around the globe, implying a relationship between food and cancer risk. Plant polyphenols are a class of secondary metabolites that have recently attracted attention as possible anticancer agents. The subclass of polyphenols, known as isoflavones, includes genistein and daidzein, which are present in soybeans and are regarded as potent chemopreventive agents. According to epidemiological studies, those who eat soy have a lower risk of developing certain cancers. Several mechanisms for the anticancer effects of isoflavones have been proposed, but none are conclusive. We show that isoflavones suppress prostate cancer cell growth by mobilizing endogenous copper. The copper-specific chelator neocuproine decreases the apoptotic potential of isoflavones, whereas the iron and zinc chelators desferroxamine mesylate and histidine do not, confirming the role of copper. Reactive oxygen species (ROS) scavengers reduce isoflavone-induced apoptosis in these cells, implying that ROS are cell death effectors. Our research also clearly shows that isoflavones interfere with the expression of the two copper transporter genes, CTR1 and ATP7A, in cancerous cells. Copper levels are widely known to be significantly raised in all malignancies, and we confirm that isoflavones can target endogenous copper, causing prooxidant signaling and, eventually, cell death. These results highlight the importance of copper dynamics within cancer cells and provide new insight into the potential of isoflavones as cancer-fighting nutraceuticals. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Papaverinol-N-Oxide: A Microbial Biotransformation Product of Papaverine with Potential Antidiabetic and Antiobesity Activity Unveiled with In Silico Screening

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Gaber El-Saber Batiha

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Mohamed H. Mahmoud

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Michel De Waard

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Wagdy M. Eldehna

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Abdel-Rahim S. Ibrahim

Molecules 2023, 28(4), 1583; https://doi.org/10.3390/molecules28041583 - 07 Feb 2023

Viewed by 986

Abstract

Bioconversion of biosynthetic heterocyclic compounds has been utilized to produce new semisynthetic pharmaceuticals and study the metabolites of bioactive drugs used systemically. In this investigation, the biotransformation of natural heterocyclic alkaloid papaverine via filamentous fungi was explored. Molecular docking simulations, using protein tyrosine [...] Read more.

Bioconversion of biosynthetic heterocyclic compounds has been utilized to produce new semisynthetic pharmaceuticals and study the metabolites of bioactive drugs used systemically. In this investigation, the biotransformation of natural heterocyclic alkaloid papaverine via filamentous fungi was explored. Molecular docking simulations, using protein tyrosine phosphatase 1B (PTP1B), α-glucosidase and pancreatic lipase (PL) as target enzymes, were performed to investigate the antidiabetic potential of papaverine and its metabolites in silico. The metabolites were isolated from biotransformation of papaverine with Cunninghamella elegans NRRL 2310, Rhodotorula rubra NRRL y1592, Penicillium chrysogeneum ATCC 10002 and Cunninghamella blackesleeana NRRL 1369 via reduction, demethylation, N-oxidation, oxidation and hydroxylation reactions. Seven metabolites were isolated: namely, 3,4-dihydropapaverine (metabolite 1), papaveroline (metabolite 2), 7-demethyl papaverine (metabolite 3), 6,4′-didemethyl papaverine (metabolite 4), papaverine-3-ol (metabolite 5), papaverinol (metabolite 6) and papaverinol N-oxide (metabolite 7). The structural elucidation of the metabolites was investigated with 1D and 2D NMR and mass spectroscopy (EI and ESI). The molecular docking studies showed that metabolite 7 exhibited better binding interactions with the target enzymes PTP1B, α-glucosidase and PL than did papaverine. Furthermore, papaverinol-N-oxide (7) also displayed inhibition of α-glucosidase and lipase enzymes comparable to that of their ligands (acarbose and orlistat, respectively), as unveiled with an in silico ADMET profile, molecular docking and molecular dynamics studies. In conclusion, this study provides evidence for enhanced inhibition of PTP1B, α-glucosidase and PL via some papaverine fungal transformation products and, therefore, potentially better antidiabetic and antiobesity effects than those of papaverine and other known therapeutic agents. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Insect Antifeedant Benzofurans from Pericallis Species

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Azucena González-Coloma

Molecules 2023, 28(3), 975; https://doi.org/10.3390/molecules28030975 - 18 Jan 2023

Viewed by 922

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In this work, we have studied the benzofurans of Pericallis echinata (aerial parts and transformed roots), P. steetzii (aerial parts and transformed roots), P. lanata (aerial parts), and P. murrayi (aerial parts and roots). This work has permitted the isolation of the new benzofurans [...] Read more.

In this work, we have studied the benzofurans of Pericallis echinata (aerial parts and transformed roots), P. steetzii (aerial parts and transformed roots), P. lanata (aerial parts), and P. murrayi (aerial parts and roots). This work has permitted the isolation of the new benzofurans 10-ethoxy-11-hydroxy-10,11-dihydroeuparin (10), (-)-eupachinin A ethyl ether (12), 11,15-didehydro-eupachinin A (13), 10,12-dihydroxy-11-angelyloxy-10,11-dihydroeuparin (14), 2,4-dihydroxy-5-formyl-acetophenone (15) isolated for the first time as a natural product, 11-angelyloxy-10,11-dihydroeuparin (16), and 12-angelyloxyeuparone (17), along with several known ones (1–9, 11). In addition, the incubation of the abundant component, 6-hydroxytremetone (1), with the fungus Mucor plumbeus has been studied. Benzofurans in the tremetone series (1, 1a, 2–5, 18, 18a), the euparin series (6, 7, 7a, 8–10, 14, 16), and the eupachinin-type (11, 12) were tested for antifeedant effects against the insect Spodoptera littoralis. The antifeedant compounds (1, 4, 6, 11, 12) were further tested for postingestive effects on S. littoralis larvae. The most antifeedant compounds were among the tremetone series, with 3-ethoxy-hydroxy-tremetone (4) being the strongest antifeedant. Glucosylation of 1 by its biotransformation with Mucor plumbeus gave inactive products. Among the euparin series, the dihydroxyangelate 14 was the most active, followed by euparin (6). The eupachinin-type compounds (11, 12) were both antifeedants. Compounds 4, 11, and 12 showed antifeedant effects without postingestive toxicity to orally dosed S. littoralis larvae. Euparin (6) had postingestive toxicity that was enhanced by the synergist piperonyl butoxide. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Hesperidin Methyl Chalcone Reduces the Arthritis Caused by TiO₂ in Mice: Targeting Inflammation, Oxidative Stress, Cytokine Production, and Nociceptor Sensory Neuron Activation

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Molecules 2023, 28(2), 872; https://doi.org/10.3390/molecules28020872 - 15 Jan 2023

Viewed by 1312

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Arthroplasty is an orthopedic surgical procedure that replaces a dysfunctional joint by an orthopedic prosthesis, thereby restoring joint function. Upon the use of the joint prosthesis, a wearing process begins, which releases components such as titanium dioxide (TiO₂) that trigger an [...] Read more.

Arthroplasty is an orthopedic surgical procedure that replaces a dysfunctional joint by an orthopedic prosthesis, thereby restoring joint function. Upon the use of the joint prosthesis, a wearing process begins, which releases components such as titanium dioxide (TiO₂) that trigger an immune response in the periprosthetic tissue, leading to arthritis, arthroplasty failure, and the need for revision. Flavonoids belong to a class of natural polyphenolic compounds that possess antioxidant and anti-inflammatory activities. Hesperidin methyl chalcone’s (HMC) analgesic, anti-inflammatory, and antioxidant effects have been investigated in some models, but its activity against the arthritis caused by prosthesis-wearing molecules, such as TiO₂, has not been investigated. Mice were treated with HMC (100 mg/kg, intraperitoneally (i.p.)) 24 h after intra-articular injection of 3 mg/joint of TiO₂, which was used to induce chronic arthritis. HMC inhibited mechanical hyperalgesia, thermal hyperalgesia, joint edema, leukocyte recruitment, and oxidative stress in the knee joint (alterations in gp91^phox, GSH, superoxide anion, and lipid peroxidation) and in recruited leukocytes (total reactive oxygen species and GSH); reduced patellar proteoglycan degradation; and decreased pro-inflammatory cytokine production. HMC also reduced the activation of nociceptor-sensory TRPV1⁺ and TRPA1⁺ neurons. These effects occurred without renal, hepatic, or gastric damage. Thus, HMC reduces arthritis triggered by TiO₂, a component released upon wearing of prosthesis. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Effects of Fermented Citrus Peel on Ameliorating Obesity in Rats Fed with High-Fat Diet

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Molecules 2022, 27(24), 8966; https://doi.org/10.3390/molecules27248966 - 16 Dec 2022

Cited by 1 | Viewed by 1268

Abstract

Although citrus peel is a waste material, it contains a variety of bioactive components. As our preliminary findings showed that citrus peels fermented with Saccharomyces cerevisiae T1 contained increased levels of anti-obesity flavonoids, the objective of this study was to prepare fermented citrus [...] Read more.

Although citrus peel is a waste material, it contains a variety of bioactive components. As our preliminary findings showed that citrus peels fermented with Saccharomyces cerevisiae T1 contained increased levels of anti-obesity flavonoids, the objective of this study was to prepare fermented citrus peel and to investigate its effect on ameliorating obesity in Sprague Dawley (SD) rats fed with a high-fat diet (HFD). After fermentation, the amounts of limonene, nobiletin and 3-methoxynobiletin in citrus peel were markedly increased. SD rats were fed with an HFD for 10 weeks, followed by fermented citrus peel-containing HFD (0.3% or 0.9% w/w) for 6 weeks. Compared with those fed with an HFD alone, lower levels of body weight, visceral fat, body fat percentage, blood triglyceride, total cholesterol, low-density lipoprotein, malondialdehyde and hepatic adipose accumulation were observed in rats fed with fermented citrus peel. In parallel, hepatic levels of acetyl-CoA carboxylase and fatty acid synthase were diminished, and the level of hormone sensitivity lipase in visceral fat was elevated. These results reveal fermented citrus peel is a promising natural product with beneficial effects of alleviating HFD-induced obesity. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

A Green Blue LED-Driven Two-Liquid-Phase One-Pot Procedure for the Synthesis of Estrogen-Related Quinol Prodrugs

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Elisa De Marchi

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Lorenzo Botta

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Bruno Mattia Bizzarri

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Raffaele Saladino

Molecules 2022, 27(24), 8961; https://doi.org/10.3390/molecules27248961 - 16 Dec 2022

Cited by 1 | Viewed by 995

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Quinol derivatives of estrogens are effective pro-drugs in steroid replacement therapy. Here, we report that these compounds can be synthesized in one-pot conditions and high yield by blue LED-driven photo-oxygenation of parent estrogens. The oxidation was performed in buffer and eco-certified 2-methyltetrahydrofuran as [...] Read more.

Quinol derivatives of estrogens are effective pro-drugs in steroid replacement therapy. Here, we report that these compounds can be synthesized in one-pot conditions and high yield by blue LED-driven photo-oxygenation of parent estrogens. The oxidation was performed in buffer and eco-certified 2-methyltetrahydrofuran as the two-liquid-phase reaction solvent, and in the presence of meso-tetraphenyl porphyrin as the photosensitizer. Two steroidal prodrugs 10β, 17β-dihydroxyestra-1,4-dien-3-one (DHED) and 10β-Hydroxyestra-1,4-diene-3,17-dione (HEDD) were obtained with high yield and selectivity. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Medicinal Properties of Anchusa strigosa and Its Active Compounds

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Molecules 2022, 27(23), 8239; https://doi.org/10.3390/molecules27238239 - 25 Nov 2022

Cited by 1 | Viewed by 879

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Anchusa strigosa is a widespread weed in Greece, Syria, Turkey, Lebanon, Israel, Jordan, and Iran. The purpose of this study was to identify the phytochemicals of Anchusa strigose and estimate the pro-wound healing (pro-WH) and antimicrobial activities of its active compounds. An identification [...] Read more.

Anchusa strigosa is a widespread weed in Greece, Syria, Turkey, Lebanon, Israel, Jordan, and Iran. The purpose of this study was to identify the phytochemicals of Anchusa strigose and estimate the pro-wound healing (pro-WH) and antimicrobial activities of its active compounds. An identification of volatile compounds was performed by GC/MS analysis; HPLC, LC-ESI-MS, and MALDI-TOF-MS were also applied. Our results demonstrate that two specific combinations of compounds from A. strigosa extract significantly enhanced WH (p < 0.001). Several flavonoids of the plant extract, including quercetin 3-O-rutinoside, kaempferol, kaempferol 3-O-β-rhamnopyranosyl(1→6)-β-glucopyranoside, and kaempferol 3-O-α-rhamnopyranosyl(1→6)-β-galactopyranoside, were effective against drug-resistant microorganisms. In addition, all the above-mentioned compounds had antibiofilm activity against Escherichia coli and Salmonella enteritidis. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and Melanogenesis

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Molecules 2022, 27(22), 7942; https://doi.org/10.3390/molecules27227942 - 16 Nov 2022

Cited by 1 | Viewed by 1295

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Tyrosinase is a well-known copper-containing metalloenzyme typically involved in the synthesis of melanin. Recently, curcumin and several synthetic derivatives have been recognized as tyrosinase inhibitors with interesting anti-melanogenic therapeutic activity. In this study, three curcumin-inspired compounds 1, 6 and 7 were prepared [...] Read more.

Tyrosinase is a well-known copper-containing metalloenzyme typically involved in the synthesis of melanin. Recently, curcumin and several synthetic derivatives have been recognized as tyrosinase inhibitors with interesting anti-melanogenic therapeutic activity. In this study, three curcumin-inspired compounds 1, 6 and 7 were prepared in yields ranging from 60 to 88 % and spectrophotometric, electrochemical, in vitro and in silico analyses were carried out. The viability of PC12 cells, a rat pheochromocytoma derived-cell line, with compounds 1, 6 and 7, showed values around 80% at 5 µM concentration. In cell proliferation assays, compounds 1, 6 and 7 did not show significant toxicity on fibroblasts nor melanoma cells up to 10 µM with viability values over 90%. The inhibition of tyrosinase activity was evaluated both by a UV-Vis spectroscopic method at two different concentrations, 0.2 and 2.0 µM, and by amperometric assay with IC₅₀ for compounds 1, 6 and 7 ranging from 11 to 24 nM. Melanin content assays on human melanoma cells were performed to test the capability of compounds to inhibit melanin biosynthesis. All compounds exerted a decrease in melanin content, with compound 7 being the most effective by showing a melanogenesis inhibition up to four times greater than arbutin at 100 µM. Moreover, the antioxidant activity of the selected inhibitors was evaluated against H₂O₂ in amperometric experiments, whereby compound 7 was about three times more effective compared to compounds 1 and 6. The tyrosinase X-ray structure of Bacterium megaterium crystal was used to carry out molecular docking studies in the presence of compounds 1, 6 and 7 in comparison with that of kojic acid and arbutin, two conventional tyrosinase inhibitors. Molecular docking of compounds 6 and 7 confirmed the high affinity of these compounds to tyrosinase protein. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Characterization of Polyhydroxybutyrate, PHB, Synthesized by Newly Isolated Haloarchaea Halolamina spp.

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Rosa María Martínez-Espinosa

Molecules 2022, 27(21), 7366; https://doi.org/10.3390/molecules27217366 - 29 Oct 2022

Cited by 3 | Viewed by 1490

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This work aims to characterize the haloarchaeal diversity of unexplored environmental salty samples from a hypersaline environment on the southern coast of Jeddah, Saudi Arabia, looking for new isolates able to produce polyhydroxyalkanoates (PHAs). Thus, the list of PHA producers has been extended [...] Read more.

This work aims to characterize the haloarchaeal diversity of unexplored environmental salty samples from a hypersaline environment on the southern coast of Jeddah, Saudi Arabia, looking for new isolates able to produce polyhydroxyalkanoates (PHAs). Thus, the list of PHA producers has been extended by describing two species of Halolamina; Halolamina sediminis sp. strain NRS_35 and unclassified Halolamina sp. strain NRS_38. The growth and PHA-production were investigated in the presence of different carbon sources, (glucose, sucrose, starch, carboxymethyl cellulose (CMC), and glycerol), pH values, (5–9), temperature ranges (4–65 °C), and NaCl concentrations (100–350 g L⁻¹). Fourier-transform infra-red analysis (FT-IR) and Liquid chromatography–mass spectrometry (LC-MS) were used for qualitative identification of the biopolymer. The highest yield of PHB was 33.4% and 27.29% by NRS_35 and NRS_38, respectively, using starch as a carbon source at 37 °C, pH 7, and 25% NaCl (w/v). The FT-IR pattern indicated sharp peaks formed around 1628.98 and 1629.28 cm⁻¹, which confirmed the presence of the carbonyl group (C=O) on amides and related to proteins, which is typical of PHB. LC-MS/MS analysis displayed peaks at retention times of 5.2, 7.3, and 8.1. This peak range indicates the occurrence of PHB and its synthetic products: Acetoacetyl-CoA and PHB synthase (PhaC). In summary, the two newly isolated Halolamina species showed a high capacity to produce PHB using different sources of carbon. Further research using other low-cost feedstocks is needed to improve both the quality and quantity of PHB production. With these results, the use of haloarchaea as cell factories to produce PHAs is reinforced, and light is shed on the global concern about replacing plastics with biodegradable polymers. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Effects of Salicylic Acid Concentration and Post-Treatment Time on the Direct and Systemic Chemical Defense Responses in Maize (Zea mays L.) Following Exogenous Foliar Application

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Molecules 2022, 27(20), 6917; https://doi.org/10.3390/molecules27206917 - 15 Oct 2022

Cited by 3 | Viewed by 1110

Abstract

Salicylic acid (SA) plays a critical role in allergic reactions of plants to pathogens and acquired systemic resistance. Thus far, although some research has been conducted on the direct effects of different concentrations of SA on the chemical defense response of treated plant [...] Read more.

Salicylic acid (SA) plays a critical role in allergic reactions of plants to pathogens and acquired systemic resistance. Thus far, although some research has been conducted on the direct effects of different concentrations of SA on the chemical defense response of treated plant parts (leaves) after at multiple post-treatments times, few research has reported on the systematic effects of non-treated parts (roots). Therefore, we examined direct and systemic effects of SA concentration and time following foliar application on chemical defense responses in maize variety 5422 with two fully expanded leaves. In the experiments, maize leaves were treated with different SA concentrations of 0.1, 0.5, 1.0, 2.5, 5.0 mM, and then, the presence of defense chemicals and enzymes in treated leaves and non-treated roots was measured at different time points of 3, 12, 24, 48, 72 h following SA foliar application. The results showed that direct and systemic effects of SA treatment to the leaf on chemical defense responses were related to SA concentration and time of measurement after spraying SA. In treated leaves, total phenolics content increased directly by 28.65% at the time point of 12 h following foliar application of 0.5 mM SA. DIMBOA (2,4-dihydroxy-7-methoxy-2H, 1, 4-benzoxazin-3 (4H)-one) content was directly enhanced by 80.56~551.05% after 3~72 h following 0.5~5.0 mM SA treatments. Polyphenol oxidase and superoxide dismutase activities were directly enhanced after 12~72 h following 0.5~5.0 mM SA treatments, whereas peroxidase and catalase activities were increased after 3~24 h following application of 1.0~5.0 mM SA. In non-treated roots, DIMBOA content and polyphenol oxidase activity were enhanced systematically after 3~48 h following 1.0~5.0 mM SA foliar treatments. Superoxide dismutase activities were enhanced after 3~24 h following 0.5~2.5 mM SA applications, but total phenolics content, peroxidase and catalase activity decreased in some particular concentrations or at the different times of measurement in the SA treatment. It can be concluded that SA foliar application at 1.0 and 2.5 mM produces strong chemical defense responses in maize, with the optimal induction time being 24 h following the foliar application. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Dihydroxyquingdainone Induces Apoptosis in Leukaemia and Lymphoma Cells via the Mitochondrial Pathway in a Bcl-2- and Caspase-3-Dependent Manner and Overcomes Resistance to Cytostatic Drugs In Vitro

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Molecules 2022, 27(15), 5038; https://doi.org/10.3390/molecules27155038 - 08 Aug 2022

Cited by 1 | Viewed by 1668

Abstract

Isatis tinctoria and its indigo dyes have already provided highly active anti-leukaemic lead compounds, with the focus mainly being on indirubin, whereas indigo itself is inactive. There are many more indigoids to find in this plant extract, for example, quingdainone, an indigoid derived [...] Read more.

Isatis tinctoria and its indigo dyes have already provided highly active anti-leukaemic lead compounds, with the focus mainly being on indirubin, whereas indigo itself is inactive. There are many more indigoids to find in this plant extract, for example, quingdainone, an indigoid derived from tryptanthrin. We present here a new synthesis of hitherto neglected substituted quingdainones, which is very necessary due to their poor solubility behaviour, and a structure-dependent anti-leukaemic activity study of a number of compounds. Substituted α-phenylaminoacrylic acid was synthesised by hydrogen sulfide extrusion from an analogue mercaptoacetic acid, available from the condensation of rhodanin and a substituted tryptanthrin. It is shown that just improving water solubility does not increase anti-leukaemic activity, since a quingdainone carboxylic acid is inactive compared to dihydroxyquingdainone. The most effective compound, dihydroxyquingdainone with an AC₅₀ of 7.5 µmole, is further characterised, revealing its ability to overcome multidrug resistance in leukaemia cells (Nalm-6/BeKa) with p-glycoprotein expression. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Anti-Inflammatory Effects of Auranamide and Patriscabratine—Mechanisms and In Silico Studies

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Kit-Kay Mak

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Zhang Shiming

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Jun Sheng Low

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Madhu Katyayani Balijepalli

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Raghavendra Sakirolla

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Albena T. Dinkova-Kostova

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Ola Epemolu

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Zulkefeli Mohd

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Mallikarjuna Rao Pichika

Molecules 2022, 27(15), 4992; https://doi.org/10.3390/molecules27154992 - 05 Aug 2022

Cited by 1 | Viewed by 1878

Abstract

Auranamide and patriscabratine are amides from Melastoma malabathricum (L.) Smith. Their anti-inflammatory activity and nuclear factor erythroid 2-related factor 2 (NRF2) activation ability were evaluated using Escherichia coli lipopolysaccharide (LPSEc)-stimulated murine macrophages (RAW264.7) and murine hepatoma (Hepa-1c1c7) cells, respectively. The cytotoxicity [...] Read more.

Auranamide and patriscabratine are amides from Melastoma malabathricum (L.) Smith. Their anti-inflammatory activity and nuclear factor erythroid 2-related factor 2 (NRF2) activation ability were evaluated using Escherichia coli lipopolysaccharide (LPSEc)-stimulated murine macrophages (RAW264.7) and murine hepatoma (Hepa-1c1c7) cells, respectively. The cytotoxicity of the compounds was assessed using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The anti-inflammatory activity was determined by measuring the nitric oxide (NO) production and pro-inflammatory cytokines (Interleukin (IL)-1β, Interferon (IFN)-γ, tumour necrosis factor (TNF)-α, and IL-6) and mediators (NF-κB and COX-2). NRF2 activation was determined by measuring the nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) quinone oxidoreductase 1 (NQO1), nuclear NRF2 and hemeoxygenase (HO)-1. In vitro metabolic stability was assessed using the mouse, rat, and human liver microsomes. The compounds were non-toxic to the cells at 10 μM. Both compounds showed dose-dependent effects in downregulating NO production and pro-inflammatory cytokines and mediators. The compounds also showed upregulation of NQO1 activity and nuclear NRF2 and HO-1 levels. The compounds were metabolically stable in mouse, rat and human liver microsomes. The possible molecular targets of NRF2 activation by these two compounds were predicted using molecular docking studies and it was found that the compounds might inhibit the Kelch domain of KEAP1 and GSK-3β activity. The physicochemical and drug-like properties of the test compounds were predicted using Schrodinger small molecule drug discovery suite (v.2022-2). Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Pro-Apoptotic and Pro-Autophagic Properties of Cardenolides from Aerial Parts of Pergularia tomentosa

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Stefania Martucciello

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Gaetana Paolella

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Antonio Massimiliano Romanelli

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Molecules 2022, 27(15), 4874; https://doi.org/10.3390/molecules27154874 - 29 Jul 2022

Cited by 4 | Viewed by 999

Abstract

Pergularia tomentosa L., a milkweed tropical plant belonging to the family Asclepiadaceae, is a rich source of unusual cardiac glycosides, characterised by transfused A/B rings and a sugar moiety linked by a double link, generating a dioxanoid structure. In the present report, five [...] Read more.

Pergularia tomentosa L., a milkweed tropical plant belonging to the family Asclepiadaceae, is a rich source of unusual cardiac glycosides, characterised by transfused A/B rings and a sugar moiety linked by a double link, generating a dioxanoid structure. In the present report, five cardenolides isolated from the aerial parts of the plant (calactin, calotropin, 12β-hydroxycalactin, 12β,6′-dihydroxycalotropin, and 16α-hydroxycalotropin) were investigated for their biological effects on a human hepatocarcinoma cell line. Cell viability was monitored by an MTT assay. The occurrence of apoptosis was evaluated by detecting caspase-3 activation and chromatin fragmentation. The ability of these compounds to induce autophagy was analysed by monitoring two markers of the autophagic process, LC3 and p62. Our results indicated that all cardenolides had cytotoxic effects, with IC₅₀ ranging from 0.127 to 6.285 μM. All compounds were able to induce apoptosis and autophagy, calactin being the most active one. Some of them also caused a reduction in cell migration and a partial block of the cell cycle into the S-phase. The present study suggests that selected cardenolides from aerial parts of P. tomentosa, particularly calactin, possess potentially desirable properties for further investigation as anticancer agents. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Insecticidal Activity of Organic Extracts of Solidago graminifolia and Its Main Metabolites (Quercetin and Chlorogenic Acid) against Spodoptera frugiperda: An In Vitro and In Silico Approach

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Verónica Herrera-Mayorga

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José Alfredo Guerrero-Sánchez

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Domingo Méndez-Álvarez

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Francisco A. Paredes-Sánchez

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Luis Víctor Rodríguez-Duran

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Nohemí Niño-García

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Alma D. Paz-González

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Gildardo Rivera

Molecules 2022, 27(10), 3325; https://doi.org/10.3390/molecules27103325 - 22 May 2022

Cited by 4 | Viewed by 1676

Abstract

Spodoptera frugiperda (S. frugiperda) remains a global primary pest of maize. Therefore, new options to combat this pest are necessary. In this study, the insecticidal activity of three crude foliar extracts (ethanol, dichloromethane, and hexane) and their main secondary metabolites (quercetin [...] Read more.

Spodoptera frugiperda (S. frugiperda) remains a global primary pest of maize. Therefore, new options to combat this pest are necessary. In this study, the insecticidal activity of three crude foliar extracts (ethanol, dichloromethane, and hexane) and their main secondary metabolites (quercetin and chlorogenic acid) of the species Solidago graminifolia (S. graminifolia) by ingestion bioassays against S. frugiperda larvae was analyzed. Additionally, the extracts were phytochemically elucidated by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) analysis. Finally, an in silico study of the potential interaction of quercetin on S. frugiperda acetylcholinesterase was performed. Organic extracts were obtained in the range from 5 to 33%. The ethanolic extract caused higher mortality (81%) with a half-maximal lethal concentration (LC₅₀) of 0.496 mg/mL. Flavonoid secondary metabolites such as hyperoside, quercetin, isoquercetin, kaempferol, and avicularin and some phenolic acids such as chlorogenic acid, solidagoic acid, gallic acid, hexoside, and rosmarinic acid were identified. In particular, quercetin had an LC₅₀ of 0.157 mg/mL, and chlorogenic acid did not have insecticidal activity but showed an antagonistic effect on quercetin. The molecular docking analysis of quercetin on the active site of S. frugiperda acetylcholinesterase showed a −5.4 kcal/mol binding energy value, lower than acetylcholine and chlorpyrifos (−4.45 and −4.46 kcal/mol, respectively). Additionally, the interactions profile showed that quercetin had π–π interactions with amino acids W198, Y235, and H553 on the active site. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Evaluation of Immunotropic Activity of Iridoid-Anthocyanin Extract of Honeysuckle Berries (Lonicera caerulea L.) in the Course of Experimental Trichinellosis in Mice

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Molecules 2022, 27(6), 1949; https://doi.org/10.3390/molecules27061949 - 17 Mar 2022

Cited by 2 | Viewed by 1279

Abstract

Our experiment determined the immunotropic activity of a natural, iridoid-anthocyanin extract from honeysuckle berry (Lonicera caerulea L.) (LC). The extract was administered to mice infected with Trichinella spiralis, orally at a dose of 2 g/kg bw, six times at 24 h [...] Read more.

Our experiment determined the immunotropic activity of a natural, iridoid-anthocyanin extract from honeysuckle berry (Lonicera caerulea L.) (LC). The extract was administered to mice infected with Trichinella spiralis, orally at a dose of 2 g/kg bw, six times at 24 h intervals (from day 3 prior to the infection to day 3 post-infection (dpi) with T. spiralis. At 5, 7, 14, and 21 dpi, samples of blood, spleen, and mesenteric lymph nodes (MLN) were collected, and isolated lymphocytes were analyzed by flow cytometry. The splenocyte proliferation was estimated with MTT testing, and the intensity of intestinal and muscle infection was also studied. LC stimulated the local immune system by inducing lymphocyte proliferation in the spleen 7 dpi and altered the percentage and absolute count of B (CD19⁺) and T (CD3⁺, CD8⁺) cells 7, 14, and 21 dpi in the peripheral blood. LC extract affected the dynamics of expulsion of adult Trichinella from the intestines and prolonged the intestinal phase of the infection but did not change the number of larvae in the muscles. These results suggest that Lonicera caerulea L. fruit extract modulates murine cellular immune response during intestinal phase of T. spiralis infection but shows no antiparasitic activity. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

Open AccessArticle

Efficient Extraction of Total Polyphenols from Apple and Investigation of Its SPF Properties

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Aliona Ghendov-Mosanu

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Paula Podea

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Rodica Sturza

Molecules 2022, 27(5), 1679; https://doi.org/10.3390/molecules27051679 - 03 Mar 2022

Cited by 5 | Viewed by 1663

Abstract

The purpose of this study was to evaluate the sun protection factor (SPF) of cosmetic emulsions with the addition of hydroalcoholic apple extract. First, the total polyphenolic content, the antioxidant activity and SPF properties of the extracts obtained by sonication and refluxing were [...] Read more.

The purpose of this study was to evaluate the sun protection factor (SPF) of cosmetic emulsions with the addition of hydroalcoholic apple extract. First, the total polyphenolic content, the antioxidant activity and SPF properties of the extracts obtained by sonication and refluxing were evaluated. The two extraction methods were improved using the central composite design. For cosmetic emulsion that contained a different concentration of apple extract (10–40%), a SPF value between 0.51 and 0.90 was obtained. The most efficient apple extract was obtained by reflux using 50% ethanol and a 60 min extraction time. The concentrated extract was incorporated in a cosmetic emulsion whose SPF maximum was 0.90. Accordingly, due to photoprotective properties, the apple extract can be a candidate for use in cosmetic formulations. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Isolation, Structural Characterization and Macrophage Activation Activity of an Acidic Polysaccharide from Raspberry Pulp

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Molecules 2022, 27(5), 1674; https://doi.org/10.3390/molecules27051674 - 03 Mar 2022

Cited by 5 | Viewed by 1554

Abstract

The discovery of safe and effective plant polysaccharides with immunomodulatory effects has become a research hotspot. Raspberry is an essential commercial fruit and is widely distributed, cultivated, and consumed worldwide. In the present study, a homogeneous acidic polysaccharide (RPP-2a), with a weight-average molecular [...] Read more.

The discovery of safe and effective plant polysaccharides with immunomodulatory effects has become a research hotspot. Raspberry is an essential commercial fruit and is widely distributed, cultivated, and consumed worldwide. In the present study, a homogeneous acidic polysaccharide (RPP-2a), with a weight-average molecular weight (Mw) of 55582 Da, was isolated from the pulp of raspberries through DEAE-Sepharose Fast Flow and Sephadex G-200 chromatography. RPP-2a consisted of rhamnose, arabinose, galactose, glucose, xylose, galacturonic acid and glucuronic acid, with a molar ratio of 15.4:9.6:7.6:3.2:9.1:54.3:0.8. The results of Fourier transform infrared spectroscopy (FT-IR), gas chromatography-mass spectrometer (GC-MS), 1D-, and 2D-nuclear magnetic resonance (NMR) analyses suggested that the backbone of RPP-2a was primarily composed of →2)-α-L-Rhap-(1→, →2,4)-α-L-Rhap-(1→, →4)-α-D-GalAp-(1→, and →3,4)-α-D-Glcp-(1→ sugar moieties, with side chains of α-L-Araf-(1→, α-L-Arap-(1→, and β-D-Galp-(1→3)-β-D-Galp-(1→ residues linked to the O-4 band of rhamnose and O-3 band of glucose residues. Furthermore, RPP-2a exhibited significant macrophage activation activity by increasing the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and the expression of inducible nitric oxide synthase (iNOS) and cytokines at the transcriptional level in RAW264.7 cells. Overall, the results indicate that RPP-2a can be utilized as a potential natural immune-enhancing agent. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Antiproliferation- and Apoptosis-Inducible Effects of a Novel Nitrated [6,6,6]Tricycle Derivative (SK2) on Oral Cancer Cells

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Molecules 2022, 27(5), 1576; https://doi.org/10.3390/molecules27051576 - 27 Feb 2022

Cited by 3 | Viewed by 1314

Abstract

The benzo-fused dioxabicyclo[3.3.1]nonane core is the central framework in several natural products. Using this core, we had developed a novel nitrated [6,6,6]tricycle-derived compound containing an n-butyloxy group, namely, SK2. The anticancer potential of SK2 was not assessed. This study aimed to determine [...] Read more.

The benzo-fused dioxabicyclo[3.3.1]nonane core is the central framework in several natural products. Using this core, we had developed a novel nitrated [6,6,6]tricycle-derived compound containing an n-butyloxy group, namely, SK2. The anticancer potential of SK2 was not assessed. This study aimed to determine the antiproliferative function and investigated possible mechanisms of SK2 acting on oral cancer cells. SK2 preferentially killed oral cancer cells but caused no harmful effect on non-malignant oral cells. After the SK2 exposure of oral cancer cells, cells in the sub-G1 phase accumulated. This apoptosis-like outcome of SK2 treatment was validated to be apoptosis via observing an increasing annexin V population. Mechanistically, apoptosis signalers such as pancaspase, caspases 8, caspase 9, and caspase 3 were activated by SK2 in oral cancer cells. SK2 induced oxidative-stress-associated changes. Furthermore, SK2 caused DNA damage (γH2AX and 8-hydroxy-2′-deoxyguanosine). In conclusion, a novel nitrated [6,6,6]tricycle-derived compound, SK2, exhibits a preferential antiproliferative effect on oral cancer cells, accompanied by apoptosis, oxidative stress, and DNA damage. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Fraxinol Stimulates Melanogenesis in B16F10 Mouse Melanoma Cells through CREB/MITF Signaling

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Molecules 2022, 27(5), 1549; https://doi.org/10.3390/molecules27051549 - 25 Feb 2022

Cited by 3 | Viewed by 1752

Abstract

Melanin pigment produced in melanocytes plays a protective role against ultraviolet radiation. Selective destruction of melanocytes causes chronic depigmentation conditions such as vitiligo, for which there are very few specific medical treatments. Here, we found that fraxinol, a natural coumarin from Fraxinus plants, [...] Read more.

Melanin pigment produced in melanocytes plays a protective role against ultraviolet radiation. Selective destruction of melanocytes causes chronic depigmentation conditions such as vitiligo, for which there are very few specific medical treatments. Here, we found that fraxinol, a natural coumarin from Fraxinus plants, effectively stimulated melanogenesis. Treatment of B16-F10 cells with fraxinol increased the melanin content and tyrosinase activity in a concentration-dependent manner without causing cytotoxicity. Additionally, fraxinol enhanced the mRNA expression of melanogenic enzymes such as tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2. Fraxinol also increased the expression of microphthalmia-associated transcription factor at both mRNA and protein levels. Fraxinol upregulated the phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB). Furthermore, H89, a cAMP–dependent protein kinase A inhibitor, decreased fraxinol-induced CREB phosphorylation and microphthalmia-associated transcription factor expression and significantly attenuated the fraxinol-induced melanin content and intracellular tyrosinase activity. These results suggest that fraxinol enhances melanogenesis via a protein kinase A-mediated mechanism, which may be useful for developing potent melanogenesis stimulators. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

A Simple LC-MS/MS Method for the Quantification of PDA-66 in Human Plasma

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Rico Schwarz

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Elisabeth R. D. Seiler

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Molecules 2022, 27(3), 974; https://doi.org/10.3390/molecules27030974 - 01 Feb 2022

Cited by 1 | Viewed by 1467

Abstract

The treatment of cancer is one of the most important pharmacotherapeutic challenges. To this end, chemotherapy has for some time been complemented by targeted therapies against specific structures. PDA-66, a structural analogue of the inhibitor of serine–threonine kinase glycogen synthase kinase 3β SB216763, [...] Read more.

The treatment of cancer is one of the most important pharmacotherapeutic challenges. To this end, chemotherapy has for some time been complemented by targeted therapies against specific structures. PDA-66, a structural analogue of the inhibitor of serine–threonine kinase glycogen synthase kinase 3β SB216763, has shown preclinical antitumour effects in various cell lines, with the key pathways of its anticancer activity being cell cycle modulation, DNA replication and p53 signalling. For the monitoring of anticancer drug treatment in the context of therapeutic drug monitoring, the determination of plasma concentrations is essential, for which an LC-MS/MS method is particularly suitable. In the present study, a sensitive LC-MS/MS method for the quantification of the potential anticancer drug PDA-66 in human plasma with a lower limit of quantification of 2.5 nM is presented. The method was successfully validated and tested for the determination of PDA-66 in mouse plasma and sera. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Phytochemical Characterization, Antioxidant Activity, and Cytotoxicity of Methanolic Leaf Extract of Chlorophytum Comosum (Green Type) (Thunb.) Jacq

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Igor V. Rzhepakovsky

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David A. Areshidze

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Svetlana S. Avanesyan

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Wolf D. Grimm

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Natalya V. Filatova

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Aleksander V. Kalinin

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Stanislav G. Kochergin

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Maria A. Kozlova

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Vladimir P. Kurchenko

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Marina N. Sizonenko

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Alexei A. Terentiev

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Lyudmila D. Timchenko

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Maria M. Trigub

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Andrey A. Nagdalian

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Sergei I. Piskov

Molecules 2022, 27(3), 762; https://doi.org/10.3390/molecules27030762 - 24 Jan 2022

Cited by 23 | Viewed by 3408

Abstract

Chlorophytum genus has been extensively studied due to its diverse biological activities. We evaluated the methanolic extract of leaves of Chlorophytum comosum (Green type) (Thunb.) Jacques, the species that is less studied compared to C. borivilianum. The aim was to identify phytoconstituents [...] Read more.

Chlorophytum genus has been extensively studied due to its diverse biological activities. We evaluated the methanolic extract of leaves of Chlorophytum comosum (Green type) (Thunb.) Jacques, the species that is less studied compared to C. borivilianum. The aim was to identify phytoconstituents of the methanolic extract of leaves of C. comosum and biological properties of its different fractions. Water fraction was analyzed with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Nineteen compounds belonging to different chemical classes were identified in the methanolic extract of leaves of C. comosum (Green type) (Thunb.) Jacques. In addition to several fatty acids, isoprenoid and steroid compounds were found among the most abundant constituents. One of the identified compounds, 4′-methylphenyl-1C-sulfonyl-β-d-galactoside, was not detected earlier in Chlorophytum extracts. The water fraction was toxic to HeLa cells but not to Vero cells. Our data demonstrate that methanolic extract of leaves of C. comosum can be a valuable source of bioactive constituents. The water fraction of the extract exhibited promising antitumor potential based on a high ratio of HeLa vs. Vero cytotoxicity. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Preparation of Hop Estrogen-Active Material for Production of Food Supplements

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Molecules 2021, 26(19), 6065; https://doi.org/10.3390/molecules26196065 - 07 Oct 2021

Cited by 3 | Viewed by 1808

Abstract

In recent years, the interest in the health-promoting effects of hop prenylflavonoids, especially its estrogenic effects, has grown. Unfortunately, one of the most potent phytoestrogens identified so far, 8-prenylnaringenin, is only a minor component of hops, so its isolation from hop materials for [...] Read more.

In recent years, the interest in the health-promoting effects of hop prenylflavonoids, especially its estrogenic effects, has grown. Unfortunately, one of the most potent phytoestrogens identified so far, 8-prenylnaringenin, is only a minor component of hops, so its isolation from hop materials for the production of estrogenically active food supplements has proved to be problematic. The aim of this study was to optimize the conditions (e.g., temperature, the length of the process and the amount of the catalyst) to produce 8-prenylnaringenin-rich material by the magnesium oxide-catalyzed thermal isomerization of desmethylxanthohumol. Under these optimized conditions, the yield of 8-prenylnaringenin was 29 mg per 100 gDW of product, corresponding to a >70% increase in its content relative to the starting material. This process may be applied in the production of functional foods or food supplements rich in 8-prenylnaringenin, which may then be utilized in therapeutic agents to help alleviate the symptoms of menopausal disorders. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Isolation, Characterization, Complete Structural Assignment, and Anticancer Activities of the Methoxylated Flavonoids from Rhamnus disperma Roots

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Hamdoon A. Mohammed

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Mohammed F. Abd El-Wahab

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Usama Shaheen

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Abd El-Salam I. Mohammed

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Ashraf N. Abdalla

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Ehab A. Ragab

Molecules 2021, 26(19), 5827; https://doi.org/10.3390/molecules26195827 - 26 Sep 2021

Cited by 8 | Viewed by 1859

Abstract

Different chromatographic methods including reversed-phase HPLC led to the isolation and purification of three O-methylated flavonoids; 5,4’-dihydroxy-3,6,7-tri-O-methyl flavone (penduletin) (1), 5,3’-dihydroxy-3,6,7,4’,5’-penta-O-methyl flavone (2), and 5-hydroxy-3,6,7,3’,4’,5’-hexa-O-methyl flavone (3) from Rhamnus disperma [...] Read more.

Different chromatographic methods including reversed-phase HPLC led to the isolation and purification of three O-methylated flavonoids; 5,4’-dihydroxy-3,6,7-tri-O-methyl flavone (penduletin) (1), 5,3’-dihydroxy-3,6,7,4’,5’-penta-O-methyl flavone (2), and 5-hydroxy-3,6,7,3’,4’,5’-hexa-O-methyl flavone (3) from Rhamnus disperma roots. Additionlly, four flavonoid glycosides; kampferol 7-O-α-L-rhamnopyranoside (4), isorhamnetin-3-O-β-D-glucopyranoside (5), quercetin 7-O-α-L-rhamnopyranoside (6), and kampferol 3, 7-di-O-α-L-rhamnopyranoside (7) along with benzyl-O-β-D-glucopyranoside (8) were successfully isolated. Complete structure characterization of these compounds was assigned based on NMR spectroscopic data, MS analyses, and comparison with the literature. The O-methyl protons and carbons of the three O-methylated flavonoids (1–3) were unambiguously assigned based on 2D NMR data. The occurrence of compounds 1, 4, 5, and 8 in Rhamnus disperma is was reported here for the first time. Compound 3 was acetylated at 5-OH position to give 5-O-acetyl-3,6,7,3’,4’,5’-hexa-O-methyl flavone (9). Compound 1 exhibited the highest cytotoxic activity against MCF 7, A2780, and HT29 cancer cell lines with IC₅₀ values at 2.17 µM, 0.53 µM, and 2.16 µM, respectively, and was 2–9 folds more selective against tested cancer cell lines compared to the normal human fetal lung fibroblasts (MRC5). It also doubled MCF 7 apoptotic populations and caused G₁ cell cycle arrest. The acetylated compound 9 exhibited cytotoxic activity against MCF 7 and HT29 cancer cell lines with IC₅₀ values at 2.19 µM and 3.18 µM, respectively, and was 6–8 folds more cytotoxic to tested cancer cell lines compared to the MRC5 cells. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

(+)-Usnic Acid as a Promising Candidate for a Safe and Stable Topical Photoprotective Agent

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Agnieszka Galanty

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Justyna Popiół

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Magdalena Paczkowska-Walendowska

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Elżbieta Studzińska-Sroka

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Paweł Paśko

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Judyta Cielecka-Piontek

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Elżbieta Pękala

and

Irma Podolak

Molecules 2021, 26(17), 5224; https://doi.org/10.3390/molecules26175224 - 28 Aug 2021

Cited by 7 | Viewed by 1888

Abstract

The study aimed to examine whether usnic acid—a lichen compound with UV-absorbing properties—can be considered as a prospective photoprotective agent in cosmetic products. Moreover, a comparison of two usnic acid enantiomers was performed to preselect the more effective compound. To meet this aim, [...] Read more.

The study aimed to examine whether usnic acid—a lichen compound with UV-absorbing properties—can be considered as a prospective photoprotective agent in cosmetic products. Moreover, a comparison of two usnic acid enantiomers was performed to preselect the more effective compound. To meet this aim, an in vitro model was created, comprising the determination of skin-penetrating properties via skin-PAMPA assay, safety assessment to normal human skin cells (keratinocytes, melanocytes, fibroblasts), and examination of photostability and photoprotective properties. Both enantiomers revealed comparable good skin-penetrating properties. Left-handed usnic acid was slightly more toxic to keratinocytes (IC₅₀ 80.82 and 40.12 µg/mL, after 48 and 72 h, respectively) than its right-handed counterpart. The latter enantiomer, in a cosmetic formulation, was characterized by good photoprotective properties and photostability, comparable to the UV filter octocrylene. Perhaps most interestingly, (+)-usnic acid combined with octocrylene in one formulation revealed enhanced photoprotection and photostability. Thus, the strategy can be considered for the potential use of (+)-usnic acid as a UV filter in cosmetic products. Moreover, the proposed model may be useful for the evaluation of candidates for UV filters. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Chemical Profile, Antioxidant Properties and Antimicrobial Activities of Malaysian Heterotrigona itama Bee Bread

by

Joseph Bagi Suleiman

,

Mahaneem Mohamed

,

Ainul Bahiyah Abu Bakar

,

Victor Udo Nna

,

Zaida Zakaria

,

Zaidatul Akmal Othman

and

Abdulqudus Bola Aroyehun

Molecules 2021, 26(16), 4943; https://doi.org/10.3390/molecules26164943 - 15 Aug 2021

Cited by 8 | Viewed by 2570

Abstract

The aim of the study was to determine the chemical profile, antioxidant properties and antimicrobial activities of Heterotrigona itama bee bread from Malaysia. The pH, presence of phytochemicals, antioxidant properties, total phenolic content (TPC) and total flavonoid content (TFC), as well as antimicrobial [...] Read more.

The aim of the study was to determine the chemical profile, antioxidant properties and antimicrobial activities of Heterotrigona itama bee bread from Malaysia. The pH, presence of phytochemicals, antioxidant properties, total phenolic content (TPC) and total flavonoid content (TFC), as well as antimicrobial activities, were assessed. Results revealed a decrease in the pH of bee bread water extract (BBW) relative to bee bread ethanolic extract (BBE) and bee bread hot water extract (BBH). Further, alkaloids, flavonoids, phenols, tannins, saponins, terpenoids, resins, glycosides and xanthoproteins were detected in BBW, BBH and BBE. Also, significant decreases in TPC, TFC, DPPH activity and FRAP were detected in BBW relative to BBH and BBE. We detected phenolic acids such as gallic acid, caffeic acid, trans-ferulic acid, trans 3-hydroxycinnamic acid and 2-hydroxycinnamic acid, and flavonoids such as quercetin, kaempferol, apigenin and mangiferin in BBE using high-performance liquid chromatography analysis. The strongest antimicrobial activity was observed in Klebsilla pneumonia (MIC₅₀ 1.914 µg/mL), followed by E. coli (MIC₅₀ 1.923 µg/mL), Shigella (MIC₅₀ 1.813 µg/mL) and Salmonella typhi (MIC₅₀ 1.617 µg/mL). Bee bread samples possess antioxidant and antimicrobial properties. Bee bread contains phenolic acids and flavonoids, and could be beneficial in the management and treatment of metabolic diseases. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

The Inhibitory Effect of Sulforaphane on Bladder Cancer Cell Depends on GSH Depletion-Induced by Nrf2 Translocation

by

Canxia He

,

Luigina P. Buongiorno

,

Wei Wang

,

Jonathan C. Y. Tang

,

Natalizia Miceli

,

Maria Fernanda Taviano

,

Yujuan Shan

and

Yongping Bao

Molecules 2021, 26(16), 4919; https://doi.org/10.3390/molecules26164919 - 13 Aug 2021

Cited by 4 | Viewed by 1788

Abstract

Sulforaphane (SFN), an isothiocyanate (ITCs) derived from glucosinolate that is found in cruciferous vegetables, has been reported to exert a promising anticancer effect in a substantial amount of scientific research. However, epidemical studies showed inconsistencies between cruciferous vegetable intake and bladder cancer risk. [...] Read more.

Sulforaphane (SFN), an isothiocyanate (ITCs) derived from glucosinolate that is found in cruciferous vegetables, has been reported to exert a promising anticancer effect in a substantial amount of scientific research. However, epidemical studies showed inconsistencies between cruciferous vegetable intake and bladder cancer risk. In this study, human bladder cancer T24 cells were used as in vitro model for revealing the inhibitory effect and its potential mechanism of SFN on cell growth. Here, a low dose of SFN (2.5 µM) was shown to promote cell proliferation (5.18–11.84%) and migration in T24 cells, whilst high doses of SFN (>10 µM) inhibited cell growth significantly. The induction effect of SFN on nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression at both low (2.5 µM) and high dose (10 µM) was characterized by a bell-shaped curve. Nrf2 and glutathione (GSH) might be the underlying mechanism in the effect of SFN on T24 cell growth since Nrf2 siRNA and GSH-depleting agent L-Buthionine-sulfoximine abolished the effect of SFN on cell proliferation. In summary, the inhibitory effect of SFN on bladder cancer cell growth and migration is highly dependent on Nrf2-mediated GSH depletion and following production. These findings suggested that a higher dose of SFN is required for the prevention and treatment of bladder cancer. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Analysis of Antioxidant Capacity and Antimicrobial Properties of Selected Polish Grape Vinegars Obtained by Spontaneous Fermentation

by

Justyna Antoniewicz

,

Karolina Jakubczyk

,

Paweł Kwiatkowski

,

Dominika Maciejewska-Markiewicz

,

Joanna Kochman

,

Ewa Rębacz-Maron

and

Katarzyna Janda-Milczarek

Molecules 2021, 26(16), 4727; https://doi.org/10.3390/molecules26164727 - 04 Aug 2021

Cited by 5 | Viewed by 2047

Abstract

Nowadays, products of natural origin with health-promoting properties are increasingly more common. Research shows that fruit vinegars can be a source of compounds with antioxidant activity. Research on the total antioxidant capacity, total phenolic content, and antimicrobial properties against Staphylococcus aureus, Escherichia [...] Read more.

Nowadays, products of natural origin with health-promoting properties are increasingly more common. Research shows that fruit vinegars can be a source of compounds with antioxidant activity. Research on the total antioxidant capacity, total phenolic content, and antimicrobial properties against Staphylococcus aureus, Escherichia coli, and Candida albicans of grape vinegars were conducted. Moreover, gas chromatography was used to measure acetic acid content in the vinegars. The research material consisted of vinegars produced from five different grape varieties. For each variety, two variants were prepared: with and without the addition of sugar in the fermentation process. The highest antimicrobial activity against all micro-organisms was observed in vinegar produced from Solaris grapes with added sugar. The highest polyphenol content was observed in vinegar produced from the Prior grape variety with added sugar and the highest total antioxidant capacity is the Johanniter grape variety with added sugar. The vinegars examined in this study differed, depending on grape variety, in terms of antimicrobial properties, antioxidant capacity, total phenolic content, as well as acetic acid content. Sugar addition caused significant differences in the antioxidant capacity of vinegar samples. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

Open AccessArticle

Inhibitory Effects of Cucurbitane-Type Triterpenoids from Momordica charantia Fruit on Lipopolysaccharide-Stimulated Pro-Inflammatory Cytokine Production in Bone Marrow-Derived Dendritic Cells

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Molecules 2021, 26(15), 4444; https://doi.org/10.3390/molecules26154444 - 23 Jul 2021

Cited by 10 | Viewed by 1927

Abstract

The bitter melon, Momordica charantia L., was once an important food and medicinal herb. Various studies have focused on the potential treatment of stomach disease with M. charantia and on its anti-diabetic properties. However, very little is known about the specific compounds [...] Read more.

The bitter melon, Momordica charantia L., was once an important food and medicinal herb. Various studies have focused on the potential treatment of stomach disease with M. charantia and on its anti-diabetic properties. However, very little is known about the specific compounds responsible for its anti-inflammatory activities. In addition, the in vitro inhibitory effect of M. charantia on pro-inflammatory cytokine production by lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) has not been reported. Phytochemical investigation of M. charantia fruit led to the isolation of 15 compounds (1−15). Their chemical structures were elucidated spectroscopically (one- and two-dimensional nuclear magnetic resonance) and with electrospray ionization mass spectrometry. The anti-inflammatory effects of the isolated compounds were evaluated by measuring the production of the pro-inflammatory cytokines interleukin IL-6, IL-12 p40, and tumor necrosis factor α (TNF-α) in LPS-stimulated BMDCs. The cucurbitanes were potent inhibitors of the cytokines TNF-α, IL-6, and IL-12 p40, indicating promising anti-inflammatory effects. Based on these studies and in silico simulations, we determined that the ligand likely docked in the receptors. These results suggest that cucurbitanes from M. charantia are potential candidates for treating inflammatory diseases. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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IgE-Induced Mast Cell Activation Is Suppressed by Dihydromyricetin through the Inhibition of NF-κB Signaling Pathway

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Molecules 2021, 26(13), 3877; https://doi.org/10.3390/molecules26133877 - 25 Jun 2021

Cited by 4 | Viewed by 2310

Abstract

Mast cells play a crucial role in the pathogenesis of type 1 allergic reactions by binding to IgE and allergen complexes and initiating the degranulation process, releasing pro-inflammatory mediators. Recently, research has focused on finding a stable and effective anti-allergy compound to prevent [...] Read more.

Mast cells play a crucial role in the pathogenesis of type 1 allergic reactions by binding to IgE and allergen complexes and initiating the degranulation process, releasing pro-inflammatory mediators. Recently, research has focused on finding a stable and effective anti-allergy compound to prevent or treat anaphylaxis. Dihydromyricetin (DHM) is a flavonoid compound with several pharmacological properties, including free radical scavenging, antithrombotic, anticancer, and anti-inflammatory activities. In this study, we investigated the anti-allergic inflammatory effects and the underlying molecular mechanism of DHM in the DNP-IgE-sensitized human mast cell line, KU812. The cytokine levels and mast cell degranulation assays were determined by enzyme-linked immunosorbent assay (ELISA). The possible mechanism of the DHM-mediated anti-allergic signaling pathway was analyzed by western blotting. It was found that treatment with DHM suppressed the levels of inflammatory cytokines TNF-α and IL-6 in DNP-IgE-sensitized KU812 cells. The anti-allergic inflammatory properties of DHM were mediated by inhibition of NF-κB activation. In addition, DHM suppressed the phosphorylation of signal transducer and activator of transcription 5 (STAT5) and mast cell-derived tryptase production. Our study shows that DHM could mitigate mast cell activation in allergic diseases. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Conventional and Organic Honeys as a Source of Water- and Ethanol-Soluble Molecules with Nutritional and Antioxidant Characteristics

by

Magdalena Polak-Śliwińska

and

Małgorzata Tańska

Molecules 2021, 26(12), 3746; https://doi.org/10.3390/molecules26123746 - 19 Jun 2021

Cited by 1 | Viewed by 2089

Abstract

The benefits of natural honeybee products (e.g., honey, royal jelly, beeswax, propolis, beevenom and pollen) to the immune system are remarkable, and many of them are involved in the induction of antibody production, maturation of immune cells and stimulation of the immune system. [...] Read more.

The benefits of natural honeybee products (e.g., honey, royal jelly, beeswax, propolis, beevenom and pollen) to the immune system are remarkable, and many of them are involved in the induction of antibody production, maturation of immune cells and stimulation of the immune system. The type of plants in the geographical area, climatic conditions and production method have a significantly influence on the nutritional quality of honey. However, this variability can influence consumer liking by the sensory attributes of the product. The aim of this work was to compare the most popular honeys from Poland in terms of nutritional value, organoleptic properties and antioxidant activity. In the study, five varieties of honey (honeydew, forest, buckwheat, linden and dandelion) from conventional and organic production methods were tested. The nutritional characteristics of honey samples included acidity, content of water, sugars, vitamin C, HMF and phenolics (total and flavonoids), while honey color, taste, aroma and consistency were investigated in the organoleptic characteristics. The antioxidant activity was determined in water- and ethanol-soluble honey extracts using DPPH and ORAC tests. The results showed that organoleptic and nutritional characteristics of popular Polish honeys differ significantly in relation to plant source and production method. The significant effect of honey variety on the content of HMF, saccharose and phenolics, as well as acidity and antioxidant capacity were noted. The impact of variety and variety × production method interaction was significant in the case of the content of vitamin C, glucose and fructose. A visible difference of buckwheat and forest honeys from other samples was observed. The highest content of total phenolics with antioxidant activity based on the SET mechanism was found in buckwheat honeys, while forest honeys were richer in flavonoids. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Impact of Harvest Conditions and Host Tree Species on Chemical Composition and Antioxidant Activity of Extracts from Viscum album L.

by

Wioleta Pietrzak

and

Renata Nowak

Molecules 2021, 26(12), 3741; https://doi.org/10.3390/molecules26123741 - 19 Jun 2021

Cited by 24 | Viewed by 1836

Abstract

The content of plant secondary metabolites is not stable, and factors such as the region/location effect and seasonal variations have an impact on their chemical composition, especially in parasitic plants. Research in this area is an important step in the development of quality [...] Read more.

The content of plant secondary metabolites is not stable, and factors such as the region/location effect and seasonal variations have an impact on their chemical composition, especially in parasitic plants. Research in this area is an important step in the development of quality parameter standards of medicinal plants and their finished products. The effects of the time and place of harvest and the host tree species on the chemical composition and antioxidant activity of mistletoe extracts were investigated. Statistical tools were used to evaluate the results of the spectrophotometric and LC-ESI-MS/MS studies of the phenolic composition and antioxidant activity. The investigations indicate that the qualitative and quantitative composition, influencing the biological activity of mistletoe extracts, largely depends on the origin of the plant. The mistletoe extracts exhibited a rich phenol profile and high antioxidant activity. The chemometric analysis indicated that mistletoe collected from conifers (Viscum abietis and Viscum austriacum) had the most advantageous chemical composition and antioxidant activity. Moreover, the chemical profile and biological activity of the plant material were closely related to the climatic conditions and location of the harvested plant. Higher levels of phenolic compounds and high antioxidant activity were found in extracts obtained from plant material collected in cold weather with the presence of snow and less sunshine (autumn–winter period). Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Interaction of Natural Compounds in Licorice and Turmeric with HIV-NCp7 Zinc Finger Domain: Potential Relevance to the Mechanism of Antiviral Activity

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Molecules 2021, 26(12), 3563; https://doi.org/10.3390/molecules26123563 - 10 Jun 2021

Cited by 3 | Viewed by 2004

Abstract

Nucleocapsid proteins (NCp) are zinc finger (ZF) proteins, and they play a central role in HIV virus replication, mainly by interacting with nucleic acids. Therefore, they are potential targets for anti-HIV therapy. Natural products have been shown to be able to inhibit HIV, [...] Read more.

Nucleocapsid proteins (NCp) are zinc finger (ZF) proteins, and they play a central role in HIV virus replication, mainly by interacting with nucleic acids. Therefore, they are potential targets for anti-HIV therapy. Natural products have been shown to be able to inhibit HIV, such as turmeric and licorice, which is widely used in traditional Chinese medicine. Liquiritin (LQ), isoliquiritin (ILQ), glycyrrhizic acid (GL), glycyrrhetinic acid (GA) and curcumin (CUR), which were the major active components, were herein chosen to study their interactions with HIV-NCp7 C-terminal zinc finger, aiming to find the potential active compounds and reveal the mechanism involved. The stacking interaction between NCp7 tryptophan and natural compounds was evaluated by fluorescence. To elucidate the binding mode, mass spectrometry was used to characterize the reaction mixture between zinc finger proteins and active compounds. Subsequently, circular dichroism (CD) spectroscopy and molecular docking were used to validate and reveal the binding mode from a structural perspective. The results showed that ILQ has the strongest binding ability among the tested compounds, followed by curcumin, and the interaction between ILQ and the NCp7 zinc finger peptide was mediated by a noncovalent interaction. This study provided a scientific basis for the antiviral activity of turmeric and licorice. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Malaysian Propolis and Metformin Synergistically Mitigate Kidney Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Rats

by

Victor Udo Nna

,

Ainul Bahiyah Abu Bakar

,

Zaida Zakaria

,

Zaidatul Akmal Othman

,

Nur Asyilla Che Jalil

and

Mahaneem Mohamed

Molecules 2021, 26(11), 3441; https://doi.org/10.3390/molecules26113441 - 05 Jun 2021

Cited by 6 | Viewed by 2940

Abstract

Diabetic nephropathy is reported to occur as a result of the interactions between several pathophysiological disturbances, as well as renal oxidative stress and inflammation. We examined the effect of Malaysian propolis (MP), which has anti-hyperglycemic, antioxidant and anti-inflammatory properties, on diabetes-induced nephropathy. Diabetic [...] Read more.

Diabetic nephropathy is reported to occur as a result of the interactions between several pathophysiological disturbances, as well as renal oxidative stress and inflammation. We examined the effect of Malaysian propolis (MP), which has anti-hyperglycemic, antioxidant and anti-inflammatory properties, on diabetes-induced nephropathy. Diabetic rats were either treated with distilled water (diabetic control (DC) group), MP (300 mg/kg b.w./day), metformin (300 mg/kg b.w./day) or MP + metformin for four weeks. We found significant increases in serum creatinine, urea and uric acid levels, decreases in serum sodium and chloride levels, and increase in kidney lactate dehydrogenase activity in DC group. Furthermore, malondialdehyde level increased significantly, while kidney antioxidant enzymes activities, glutathione level and total antioxidant capacity decreased significantly in DC group. Similarly, kidney immunoexpression of nuclear factor kappa B, tumor necrosis factor-α, interleukin (IL)-1β and caspase-3 increased significantly, while IL-10 immunoexpression decreased significantly in DC group relative to normal control group. Histopathological observations for DC group corroborated the biochemical data. Intervention with MP, metformin or both significantly mitigated these effects and improved renal function, with the best outcome following the combined therapy. MP attenuates diabetic nephropathy and exhibits combined beneficial effect with metformin. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Identification of the Active Principle Conferring Anti-Inflammatory and Antinociceptive Properties in Bamboo Plant

by

Bruna Araujo Sousa

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Osmar Nascimento Silva

,

William Farias Porto

,

Thales Lima Rocha

,

Luciano Paulino Silva

,

Ana Paula Ferreira Leal

,

Danieli Fernanda Buccini

,

James Oluwagbamigbe Fajemiroye

,

Ruy de Araujo Caldas

,

Octávio Luiz Franco

,

Maria Fátima Grossi-de-Sá

,

Cesar de la Fuente Nunez

and

Susana Elisa Moreno

Molecules 2021, 26(10), 3054; https://doi.org/10.3390/molecules26103054 - 20 May 2021

Viewed by 2209

Abstract

Early plants began colonizing earth about 450 million years ago. During the process of coevolution, their metabolic cellular pathways produced a myriad of natural chemicals, many of which remain uncharacterized biologically. Popular preparations containing some of these molecules have been used medicinally for [...] Read more.

Early plants began colonizing earth about 450 million years ago. During the process of coevolution, their metabolic cellular pathways produced a myriad of natural chemicals, many of which remain uncharacterized biologically. Popular preparations containing some of these molecules have been used medicinally for thousands of years. In Brazilian folk medicine, plant extracts from the bamboo plant Guadua paniculata Munro have been used for the treatment of infections and pain. However, the chemical basis of these therapeutic effects has not yet been identified. Here, we performed protein biochemistry and downstream pharmacological assays to determine the mechanisms underlying the anti-inflammatory and antinociceptive effects of an aqueous extract of the G. paniculata rhizome, which we termed AqGP. The anti-inflammatory and antinociceptive effects of AqGP were assessed in mice. We identified and purified a protein (AgGP), with an amino acid sequence similar to that of thaumatins (~20 kDa), capable of repressing inflammation through downregulation of neutrophil recruitment and of decreasing hyperalgesia in mice. In conclusion, we have identified the molecule and the molecular mechanism responsible for the anti-inflammatory and antinociceptive properties of a plant commonly used in Brazilian folk medicine. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Occurrence and Determination of Carotenoids and Polyphenols in Different Paprika Powders from Organic and Conventional Production

by

Alicja Ponder

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Klaudia Kulik

and

Ewelina Hallmann

Molecules 2021, 26(10), 2980; https://doi.org/10.3390/molecules26102980 - 17 May 2021

Cited by 10 | Viewed by 2182

Abstract

Paprika powder is a good source of different carotenoids and polyphenols, which play a key role in preventing certain diseases (some kinds of cancer and cardiovascular diseases). They can also be used as natural food colorants. Organic production is characterized by strict rules, [...] Read more.

Paprika powder is a good source of different carotenoids and polyphenols, which play a key role in preventing certain diseases (some kinds of cancer and cardiovascular diseases). They can also be used as natural food colorants. Organic production is characterized by strict rules, but products obtained in this way contain more bioactive compounds, such as carotenoids and polyphenols. The aim of this study was to measure and identify carotenoids and polyphenols in different paprika samples (sweet, hot, smoked, and chili) obtained by organic and conventional production. Quantitative and qualitative carotenoid and polyphenols analysis showed that the experimental samples contained different concentrations of these compounds. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Evaluation of Quality, Antioxidant Capacity, and Digestibility of Chickpea (Cicer arietinum L. cv Blanoro) Stored under N₂ and CO₂ Atmospheres

by

Liliana Maribel Perez-Perez

,

José Ángel Huerta-Ocampo

,

Saúl Ruiz-Cruz

,

Francisco Javier Cinco-Moroyoqui

,

Francisco Javier Wong-Corral

,

Luisa Alondra Rascón-Valenzuela

,

Miguel Angel Robles-García

,

Ricardo Iván González-Vega

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Ema Carina Rosas-Burgos

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María Alba Guadalupe Corella-Madueño

and

Carmen Lizette Del-Toro-Sánchez

Molecules 2021, 26(9), 2773; https://doi.org/10.3390/molecules26092773 - 08 May 2021

Cited by 12 | Viewed by 2407

Abstract

The aim of this work was to monitor the quality, antioxidant capacity and digestibility of chickpea exposed to different modified atmospheres. Chickpea quality (proximal analysis, color, texture, and water absorption) and the antioxidant capacity of free, conjugated, and bound phenol fractions obtained from [...] Read more.

The aim of this work was to monitor the quality, antioxidant capacity and digestibility of chickpea exposed to different modified atmospheres. Chickpea quality (proximal analysis, color, texture, and water absorption) and the antioxidant capacity of free, conjugated, and bound phenol fractions obtained from raw and cooked chickpea, were determined. Cooked chickpea was exposed to N₂ and CO₂ atmospheres for 0, 25, and 50 days, and the antioxidant capacity was analyzed by DPPH (2,2′-diphenyl-1-picrylhydrazyl), ABTS (2,2′-azino-bis-[3ethylbenzothiazoline-6-sulfonic acid]), and total phenols. After in vitro digestion, the antioxidant capacity was measured by DPPH, ABTS, FRAP (ferric reducing antioxidant power), and AAPH (2,2′-Azobis [2-methylpropionamidine]). Additionally, quantification of total phenols, and UPLC-MS profile were determined. The results indicated that this grain contain high quality and high protein (18.38%). Bound phenolic compounds showed the highest amount (105.6 mg GAE/100 g) and the highest antioxidant capacity in all techniques. Cooked chickpeas maintained their quality and antioxidant capacity during 50 days of storage at 4 and −20 °C under a nitrogen atmosphere. Free and conjugated phenolic compounds could be hydrolyzed by digestive enzymes, increasing their bioaccessibility and their antioxidant capacity during each step of digestion. The majority compound in all samples was enterodiol, prevailing the flavonoid type in the rest of the identified compounds. Chickpea contains biological interest compounds with antioxidant potential suggesting that this legume can be exploited for various technologies. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Comparison of the Effects of Conching Parameters on the Contents of Three Dominant Flavan3-ols, Rheological Properties and Sensory Quality in Chocolate Milk Mass Based on Liquor from Unroasted Cocoa Beans

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Molecules 2021, 26(9), 2502; https://doi.org/10.3390/molecules26092502 - 25 Apr 2021

Cited by 8 | Viewed by 3315

Abstract

The content of polyphenols in chocolate depends on many factors related to the properties of raw material and manufacturing parameters. The trend toward developing chocolates made from unroasted cocoa beans encourages research in this area. In addition, modern customers attach great importance to [...] Read more.

The content of polyphenols in chocolate depends on many factors related to the properties of raw material and manufacturing parameters. The trend toward developing chocolates made from unroasted cocoa beans encourages research in this area. In addition, modern customers attach great importance to how the food they consume benefits their bodies. One such benefit that consumers value is the preservation of natural antioxidant compounds in food products (e.g., polyphenols). Therefore, in our study we attempted to determine the relationship between variable parameters at the conching stage (i.e., temperature and time of) and the content of dominant polyphenols (i.e.,catechins, epicatechins, and procyanidin B2) in chocolate milk mass (CMM) obtained from unroasted cocoa beans. Increasing the conching temperature from 50 to 60 °C decreased the content of three basic flavan-3-ols. The highest number of these compounds was determined when the process was carried out at 50 °C. However, the time that caused the least degradation of these compounds differed. For catechin, it was 2 h; for epicatechin it was 1 h; and for procyanidin it was 3 h. The influence of both the temperature and conching time on the rheological properties of chocolate milk mass was demonstrated. At 50 °C, the viscosity and the yield stress of the conched mass showed its highest value. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Zinc Oxide Nanoparticles and Zinc Sulfate Impact Physiological Parameters and Boosts Lipid Peroxidation in Soil Grown Coriander Plants (Coriandrum sativum)

by

Norma Ruiz-Torres

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Antonio Flores-Naveda

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Enrique Díaz Barriga-Castro

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Neymar Camposeco-Montejo

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Sonia Ramírez-Barrón

,

Fernando Borrego-Escalante

,

Guillermo Niño-Medina

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Agustín Hernández-Juárez

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Carlos Garza-Alonso

,

Pablo Rodríguez-Salinas

and

Josué I. García-López

Molecules 2021, 26(7), 1998; https://doi.org/10.3390/molecules26071998 - 01 Apr 2021

Cited by 12 | Viewed by 2424

Abstract

The objective of this study was to determine the oxidative stress and the physiological and antioxidant responses of coriander plants (Coriandrum sativum) grown for 58 days in soil with zinc oxide nanoparticles (ZnO NPs) and zinc sulfate (ZnSO₄) at [...] Read more.

The objective of this study was to determine the oxidative stress and the physiological and antioxidant responses of coriander plants (Coriandrum sativum) grown for 58 days in soil with zinc oxide nanoparticles (ZnO NPs) and zinc sulfate (ZnSO₄) at concentrations of 0, 100, 200, 300, and 400 mg of Zn/kg of soil. The results revealed that all Zn compounds increased the total chlorophyll content (CHLt) by at least 45%, compared to the control group; however, with 400 mg/kg of ZnSO₄, chlorophyll accumulation decreased by 34.6%. Zn determination by induction-plasma-coupled atomic emission spectrometry (ICP–AES) showed that Zn absorption in roots and shoots occurred in plants exposed to ZnSO₄ at all concentrations, which resulted in high levels of hydrogen peroxide (H₂O₂) and malondialdehyde (MDA). Only at 400 mg/kg of ZnSO₄, a 78.6% decrease in the MDA levels was observed. According to the results, the ZnSO₄ treatments were more effective than the ZnO NPs to increase the antioxidant activity of catalase (CAT), ascorbate peroxidase (APX), and peroxidases (POD). The results corroborate that phytotoxicity was higher in plants subjected to ZnSO₄ compared to treatments with ZnO NPs, which suggests that the toxicity was due to Zn accumulation in the tissues by absorbing dissolved Zn⁺⁺ ions. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Insight into Gentisic Acid Antidiabetic Potential Using In Vitro and In Silico Approaches

by

Hamza Mechchate

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Imane Es-safi

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Omkulthom Mohamed Al kamaly

and

Dalila Bousta

Molecules 2021, 26(7), 1932; https://doi.org/10.3390/molecules26071932 - 30 Mar 2021

Cited by 16 | Viewed by 2604

Abstract

Numerous scientific studies have confirmed the beneficial therapeutic effects of phenolic acids. Among them gentisic acid (GA), a phenolic acid extensively found in many fruit and vegetables has been associated with an enormous confirmed health benefit. The present study aims to evaluate the [...] Read more.

Numerous scientific studies have confirmed the beneficial therapeutic effects of phenolic acids. Among them gentisic acid (GA), a phenolic acid extensively found in many fruit and vegetables has been associated with an enormous confirmed health benefit. The present study aims to evaluate the antidiabetic potential of gentisic acid and highlight its mechanisms of action following in silico and in vitro approaches. The in silico study was intended to predict the interaction of GA with eight different receptors highly involved in the management and complications of diabetes (dipeptidyl-peptidase 4 (DPP4), protein tyrosine phosphatase 1B (PTP1B), free fatty acid receptor 1 (FFAR1), aldose reductase (AldR), glycogen phosphorylase (GP), α-amylase, peroxisome proliferator-activated receptor gamma (PPAR-γ) and α-glucosidase), while the in vitro study studied the potential inhibitory effect of GA against α-amylase and α-glucosidase. The results indicate that GA interacted moderately with most of the receptors and had a moderate inhibitory activity during the in vitro tests. The study therefore encourages further in vivo studies to confirm the given results. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessFeature PaperArticle

Antioxidant and Antibacterial Activity of Essential Oils and Hydroethanolic Extracts of Greek Oregano (O. vulgare L. subsp. hirtum (Link) Ietswaart) and Common Oregano (O. vulgare L. subsp. vulgare)

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Olga Kosakowska

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Zenon Węglarz

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Ewelina Pióro-Jabrucka

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Molecules 2021, 26(4), 988; https://doi.org/10.3390/molecules26040988 - 13 Feb 2021

Cited by 31 | Viewed by 3062

Abstract

Greek oregano and common oregano were compared in respect of the antioxidant and antibacterial activity of the corresponding essential oils and hydroethanolic extracts in relation with their chemical profile. The chemical composition of essential oils was determined by GC-MS and GC-FID, while extracts [...] Read more.

Greek oregano and common oregano were compared in respect of the antioxidant and antibacterial activity of the corresponding essential oils and hydroethanolic extracts in relation with their chemical profile. The chemical composition of essential oils was determined by GC-MS and GC-FID, while extracts (phenolic acids and flavonoids fractions) were analyzed by HPLC-DAD. Based on given volatiles, the investigated subspecies represented two chemotypes: a carvacrol/γ-terpinene/p-cymene type in the case of Greek oregano and a sabinyl/cymyl type rich in terpinen-4-ol in common oregano. Within non-volatile phenolic compounds, rosmarinic acid appeared to dominate in both subspecies. Lithospermic acid B, chlorogenic acid and isovitexin were present only in Greek oregano extracts. However, the total content of flavonoids was higher in common oregano extracts. The essential oil and extract of Greek oregano revealed visibly stronger antibacterial activity (expressed as MIC and MBC) than common oregano, whereas the antioxidant potential (determined by DPPH, ABTS and FRAP) of these extracts was almost equal for both subspecies. In the case of Origanum plants, the potential application of essential oils and extracts as antiseptic and antioxidant agents in the food industry should be preceded by subspecies identification followed by recognition of their chemotype concerning both terpene and phenolics composition. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

Open AccessArticle

Crataegus laevigata Suppresses LPS-Induced Oxidative Stress during Inflammatory Response in Human Keratinocytes by Regulating the MAPKs/AP-1, NFκB, and NFAT Signaling Pathways

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Molecules 2021, 26(4), 869; https://doi.org/10.3390/molecules26040869 - 06 Feb 2021

Cited by 5 | Viewed by 2562

Abstract

Crataegus laevigata belongs to the family Rosaceae, which has been widely investigated for pharmacological effects on the circulatory and digestive systems. However, there is limited understanding about its anti-oxidative stress and anti-inflammatory effects on skin. In this study, 70% ethanol C. laevigata berry [...] Read more.

Crataegus laevigata belongs to the family Rosaceae, which has been widely investigated for pharmacological effects on the circulatory and digestive systems. However, there is limited understanding about its anti-oxidative stress and anti-inflammatory effects on skin. In this study, 70% ethanol C. laevigata berry extract (CLE) was investigated on lipopolysaccharide (LPS)-stimulated keratinocytes. The LPS-induced overproduction of reactive oxygen species (ROS) was suppressed by the treatment with CLE. In response to ROS induction, the overexpression of inflammatory regulating signaling molecules including mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB), and nuclear factor of activated T-cells (NFAT) were reduced in CLE-treated human keratinocytes. Consequently, CLE significantly suppressed the mRNA levels of pro-inflammatory chemokines and interleukins in LPS-stimulated cells. Our results indicated that CLE has protective effects against LPS-induced injury in an in vitro model and is a potential alternative agent for inflammatory treatment. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Molecular Structure, In Vitro Anticancer Study and Molecular Docking of New Phosphate Derivatives of Betulin

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Elwira Chrobak

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Maria Jastrzębska

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Ewa Bębenek

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Monika Kadela-Tomanek

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Molecules 2021, 26(3), 737; https://doi.org/10.3390/molecules26030737 - 31 Jan 2021

Cited by 11 | Viewed by 2688

Abstract

A series of 30-diethylphosphate derivatives of betulin were synthesized and evaluated for their in vitro cytotoxic activity against human cancer cell lines, such as amelanotic melanoma (C-32), glioblastoma (SNB-19), and two lines of breast cancer (T47D, MDA-MB-231). The molecular structure and activities of [...] Read more.

A series of 30-diethylphosphate derivatives of betulin were synthesized and evaluated for their in vitro cytotoxic activity against human cancer cell lines, such as amelanotic melanoma (C-32), glioblastoma (SNB-19), and two lines of breast cancer (T47D, MDA-MB-231). The molecular structure and activities of the new compounds were also compared with their 29-phosphonate analogs. Compounds 7a and 7b showed the highest activity against C-32 and SNB-19 cell lines. The IC₅₀ values for 7a were 2.15 and 0.91 μM, and, for 7b, they were 0.76 and 0.8 μM for the C-32 and SNB-19 lines, respectively. The most potent compounds, 7a and 7b, were tested for their effects on markers of apoptosis, such as H3, TP53, BAX, and BCL-2. For the whole series of phosphate derivatives, a lipophilicity study was performed, and the ADME parameters were calculated. The most active products were docked to the active site of the EGFR protein. The relative binding affinity of selected phosphate betulin derivatives toward EGFR was compared with standard erlotinib on the basis of ChemScore and K_DEEP score. Positively, all derivatives docked inside the cavity and showed significant interactions. Moreover, a molecular dynamics study also reveals that ligands 7a,b form stable complexes and the plateau phase started after 7 ns. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Anticancer Potential of Sutherlandia frutescens and Xysmalobium undulatum in LS180 Colorectal Cancer Mini-Tumors

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Molecules 2021, 26(3), 605; https://doi.org/10.3390/molecules26030605 - 25 Jan 2021

Cited by 9 | Viewed by 3167

Abstract

Colorectal cancer remains to be one of the leading causes of death worldwide, with millions of patients diagnosed each year. Although chemotherapeutic drugs are routinely used to treat cancer, these treatments have severe side effects. As a result, the use of herbal medicines [...] Read more.

Colorectal cancer remains to be one of the leading causes of death worldwide, with millions of patients diagnosed each year. Although chemotherapeutic drugs are routinely used to treat cancer, these treatments have severe side effects. As a result, the use of herbal medicines has gained increasing popularity as a treatment for cancer. In this study, two South African medicinal plants widely used to treat various diseases, Sutherlandia frutescens and Xysmalobium undulatum, were evaluated for potential activity against colorectal cancer. This potential activity for the treatment of colorectal cancer was assessed relative to the known chemotherapeutic drug, paclitaxel. The cytotoxic activity was considered in an advanced three-dimensional (3D) sodium alginate encapsulated LS180 colorectal cancer functional spheroid model, cultured in clinostat-based rotating bioreactors. The LS180 cell mini-tumors were treated for 96 h with two concentrations of each of the crude aqueous extracts or paclitaxel. S. frutescens extract markedly decreased the soluble protein content, while decreasing ATP and AK per protein content to below detectable limits after only 24 h exposure. X. undulatum extract also decreased the soluble protein content, cell viability, and glucose consumption. The results suggested that the two phytomedicines have potential to become a source of new treatments against colorectal cancer. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Caffeoylquinic Acid Derivatives of Purple Sweet Potato as Modulators of Mitochondrial Function in Mouse Primary Hepatocytes

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Andrea Torres

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Lilia G. Noriega

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Claudia Delgadillo-Puga

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Armando R. Tovar

and

Arturo Navarro-Ocaña

Molecules 2021, 26(2), 319; https://doi.org/10.3390/molecules26020319 - 09 Jan 2021

Cited by 10 | Viewed by 2908

Abstract

Owing to their antioxidant properties, caffeoylquinic acid (CQA)-derivatives could potentially improve the impaired metabolism in hepatic cells, however, their effect on mitochondrial function has not been demonstrated yet. Here, we evaluated the impact of three CQA-derivatives extracted from purple sweet potato, namely 5-CQA, [...] Read more.

Owing to their antioxidant properties, caffeoylquinic acid (CQA)-derivatives could potentially improve the impaired metabolism in hepatic cells, however, their effect on mitochondrial function has not been demonstrated yet. Here, we evaluated the impact of three CQA-derivatives extracted from purple sweet potato, namely 5-CQA, 3,4- and 4,5-diCQA, on mitochondrial activity in primary hepatocytes using an extracellular flux analyzer. Notably, an increase of maximal respiration and spare respiratory capacity were observed when 5-CQA and 3,4-diCQA were added to the system indicating the improved mitochondrial function. Moreover, 3,4-diCQA was shown to considerably increase glycolytic reserve which is a measure of cell capability to respond to an energy demand through glycolysis. Conversely, 4,5-diCQA did not modify mitochondrial activity but increased glycolysis at low concentration in primary hepatocytes. All compounds tested improved cellular capacity to oxidize fatty acids. Overall, our results demonstrated the potential of test CQA-derivatives to modify mitochondrial function in hepatic cells. It is especially relevant in case of dysfunctional mitochondria in hepatocytes linked to hepatic steatosis during obesity, diabetes, and metabolic syndrome. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Curcumin Analogue L48H37 Suppresses Human Osteosarcoma U2OS and MG-63 Cells’ Migration and Invasion in Culture by Inhibition of uPA via the JAK/STAT Signaling Pathway

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Molecules 2021, 26(1), 30; https://doi.org/10.3390/molecules26010030 - 23 Dec 2020

Cited by 22 | Viewed by 2372

Abstract

Osteosarcoma, the most prevalent malignant bone tumor in the pediatric age group, is responsible for the great majority of cancer-associated deaths owing to its highly metastatic potential. The anti-metastatic effects of the new curcumin analogue L48H37 in human osteosarcoma are still unknown; hence, [...] Read more.

Osteosarcoma, the most prevalent malignant bone tumor in the pediatric age group, is responsible for the great majority of cancer-associated deaths owing to its highly metastatic potential. The anti-metastatic effects of the new curcumin analogue L48H37 in human osteosarcoma are still unknown; hence, we investigated whether L48H37 represses human osteosarcoma cells’ biological behavior of migratory potential and invasive activities and attempted to delve into its underlying mechanisms. L48H37 up to 5 μM inhibited, without cytotoxicity, the motility, migration, and invasion of human osteosarcoma U2OS and MG-63 cells. In U2OS cells, the human protease array revealed an obvious decrease in urokinase plasminogen activator (uPA) expression after L48H37 treatment, and L48H37 actually reduced the level, protein and mRNA expression, and promoter activity of uPA dose-dependently. L48H37 decreased the phosphorylation of STAT3, JAK1, JAK2, and JAK3 in U2OS cells, but did not affect the phosphorylation of ERK, JNK, p38, and Akt. Using colivelin, an activator of STAT3, the L48H37-induced decrease in uPA and migratory potential could be countered as expected. Collectively, L48H37 represses the invasion and migration capabilities of U2OS and MG-63 cells by the suppression of uPA expression and the inhibition of JAK/STAT signaling. These results suggest that L48H37 may be a potential candidate for anti-metastatic treatment of human osteosarcoma. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Morusin Suppresses Cancer Cell Invasion and MMP-2 Expression through ERK Signaling in Human Nasopharyngeal Carcinoma

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Molecules 2020, 25(20), 4851; https://doi.org/10.3390/molecules25204851 - 21 Oct 2020

Cited by 5 | Viewed by 1731

Abstract

The most important cause of treatment failure of nasopharyngeal carcinoma (NPC) patients is metastasis, including regional lymph nodes or distant metastasis, resulting in a poor prognosis and challenges for treatment. In the present study, we investigated the in vitro anti- tumoral properties of [...] Read more.

The most important cause of treatment failure of nasopharyngeal carcinoma (NPC) patients is metastasis, including regional lymph nodes or distant metastasis, resulting in a poor prognosis and challenges for treatment. In the present study, we investigated the in vitro anti- tumoral properties of morusin on human nasopharyngeal carcinoma HONE-1, NPC-39, and NPC-BM cells. Our study revealed that morusin suppressed the migration and invasion abilities of the three NPC cells. Gelatin zymography assay and Western blotting demonstrated that the enzyme activity and the level of matrix metalloproteinases-2 (MMP-2) protein were downregulated by the treatment of morusin. Mitogen-activated protein kinase proteins were examined to identify the signaling pathway, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of morusin. In summary, our data showed that morusin inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by downregulating the ERK1/2 signaling pathway, suggesting that morusin may be a potential candidate for chemoprevention or adjuvant therapy of NPC. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Pimpinella anisum Essential Oil Nanoemulsion Toxicity against Tribolium castaneum? Shedding Light on Its Interactions with Aspartate Aminotransferase and Alanine Aminotransferase by Molecular Docking

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Ahmed S. Hashem

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Marwa M. Ramadan

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Amira A. A. Abdel-Hady

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Stefania Sut

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Filippo Maggi

and

Stefano Dall’Acqua

Molecules 2020, 25(20), 4841; https://doi.org/10.3390/molecules25204841 - 20 Oct 2020

Cited by 12 | Viewed by 3601

Abstract

The insecticidal activity is the result of a series of complex interactions between toxic substances as ligands and insect’s enzymes as targets. Actually, synthetic insecticides used in pest control programs are harmful to the environment and may affect non-target organisms; thus, the use [...] Read more.

The insecticidal activity is the result of a series of complex interactions between toxic substances as ligands and insect’s enzymes as targets. Actually, synthetic insecticides used in pest control programs are harmful to the environment and may affect non-target organisms; thus, the use of natural products as pest control agents can be very attractive. In the present work, the toxic effect of aniseed (Pimpinella anisum L.) essential oil (EO) and its nanoemulsion (NE) against the red flour beetle Tribolium castaneum, has been evaluated. To assess the EO mode of action, the impact of sub-lethal concentrations of aniseed EO and NE was evaluated on enzymatic and macromolecular parameters of the beetles, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, total lipids and glucose. Finally, a molecular docking study was conducted to predict the mode of action of the major EO and NE components namely E-anethole, Limonene, alpha-himalachalene, trans-Verbenol and Linalool at binding site of the enzymes AST and ALT. Herein, the binding location of the main compounds in both proteins are discussed suggesting the possible interactions between the considered enzymes and ligands. The obtained results open new horizons to understand the evolution and response of insect-plant compounds interactions and their effect predicted at the molecular levels and side effects of both animal and human. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Cannabinoid Combination Induces Cytoplasmic Vacuolation in MCF-7 Breast Cancer Cells

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Recardia Schoeman

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Natasha Beukes

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Carminita Frost

Molecules 2020, 25(20), 4682; https://doi.org/10.3390/molecules25204682 - 14 Oct 2020

Cited by 25 | Viewed by 4047

Abstract

This study evaluated the synergistic anti-cancer potential of cannabinoid combinations across the MDA-MB-231 and MCF-7 human breast cancer cell lines. Cannabinoids were combined and their synergistic interactions were evaluated using median effect analysis. The most promising cannabinoid combination (C6) consisted of tetrahydrocannabinol, cannabigerol [...] Read more.

This study evaluated the synergistic anti-cancer potential of cannabinoid combinations across the MDA-MB-231 and MCF-7 human breast cancer cell lines. Cannabinoids were combined and their synergistic interactions were evaluated using median effect analysis. The most promising cannabinoid combination (C6) consisted of tetrahydrocannabinol, cannabigerol (CBG), cannabinol (CBN), and cannabidiol (CBD), and displayed favorable dose reduction indices and limited cytotoxicity against the non-cancerous breast cell line, MCF-10A. C6 exerted its effects in the MCF-7 cell line by inducing cell cycle arrest in the G₂ phase, followed by the induction of apoptosis. Morphological observations indicated the induction of cytoplasmic vacuolation, with further investigation suggesting that the vacuole membrane was derived from the endoplasmic reticulum. In addition, lipid accumulation, increased lysosome size, and significant increases in the endoplasmic reticulum chaperone protein glucose-regulated protein 78 (GRP78) expression were also observed. The selectivity and ability of cannabinoids to halt cancer cell proliferation via pathways resembling apoptosis, autophagy, and paraptosis shows promise for cannabinoid use in standardized breast cancer treatment. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Expanding the Scope of Orthogonal Translation with Pyrrolysyl-tRNA Synthetases Dedicated to Aromatic Amino Acids

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Molecules 2020, 25(19), 4418; https://doi.org/10.3390/molecules25194418 - 25 Sep 2020

Cited by 9 | Viewed by 3828

Abstract

In protein engineering and synthetic biology, Methanosarcina mazei pyrrolysyl-tRNA synthetase (MmPylRS), with its cognate tRNA^Pyl, is one of the most popular tools for site-specific incorporation of non-canonical amino acids (ncAAs). Numerous orthogonal pairs based on engineered MmPylRS variants [...] Read more.

In protein engineering and synthetic biology, Methanosarcina mazei pyrrolysyl-tRNA synthetase (MmPylRS), with its cognate tRNA^Pyl, is one of the most popular tools for site-specific incorporation of non-canonical amino acids (ncAAs). Numerous orthogonal pairs based on engineered MmPylRS variants have been developed during the last decade, enabling a substantial genetic code expansion, mainly with aliphatic pyrrolysine analogs. However, comparatively less progress has been made to expand the substrate range of MmPylRS towards aromatic amino acid residues. Therefore, we set to further expand the substrate scope of orthogonal translation by a semi-rational approach; redesigning the MmPylRS efficiency. Based on the randomization of residues from the binding pocket and tRNA binding domain, we identify three positions (V401, W417 and S193) crucial for ncAA specificity and enzyme activity. Their systematic mutagenesis enabled us to generate MmPylRS variants dedicated to tryptophan (such as β-(1-Azulenyl)-l-alanine or 1-methyl-l-tryptophan) and tyrosine (mainly halogenated) analogs. Moreover, our strategy also significantly improves the orthogonal translation efficiency with the previously activated analog 3-benzothienyl-l-alanine. Our study revealed the engineering of both first shell and distant residues to modify substrate specificity as an important strategy to further expand our ability to discover and recruit new ncAAs for orthogonal translation Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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Open AccessArticle

Novel Harmicines with Improved Potency against Plasmodium

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Lais Pessanha de Carvalho

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Molecules 2020, 25(19), 4376; https://doi.org/10.3390/molecules25194376 - 23 Sep 2020

Cited by 13 | Viewed by 2741

Abstract

Harmicines represent hybrid compounds composed of β-carboline alkaloid harmine and cinnamic acid derivatives (CADs). In this paper we report the synthesis of amide-type harmicines and the evaluation of their biological activity. N-harmicines 5a–f and O-harmicines 6a–h were [...] Read more.

Harmicines represent hybrid compounds composed of β-carboline alkaloid harmine and cinnamic acid derivatives (CADs). In this paper we report the synthesis of amide-type harmicines and the evaluation of their biological activity. N-harmicines 5a–f and O-harmicines 6a–h were prepared by a straightforward synthetic procedure, from harmine-based amines and CADs using standard coupling conditions, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo [4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) and N,N-diisopropylethylamine (DIEA). Amide-type harmicines exerted remarkable activity against the erythrocytic stage of P. falciparum, in low submicromolar concentrations, which was significantly more pronounced compared to their antiplasmodial activity against the hepatic stages of P. berghei. Furthermore, a cytotoxicity assay against the human liver hepatocellular carcinoma cell line (HepG2) revealed favorable selectivity indices of the most active harmicines. Molecular dynamics simulations demonstrated the binding of ligands within the ATP binding site of PfHsp90, while the calculated binding free energies confirmed higher activity of N-harmicines 5 over their O-substituted analogues 6. Amino acids predominantly affecting the binding were identified, which provided guidelines for the further derivatization of the harmine framework towards more efficient agents. Full article

(This article belongs to the Special Issue Natural Product-Inspired Molecules: From Weed to Remedy)

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