International Journal of Molecular Sciences

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18 pages, 2958 KiB

Open AccessArticle

Antioxidant Activity, Stability in Aqueous Medium and Molecular Docking/Dynamics Study of 6-Amino- and N-Methyl-6-amino-L-ascorbic Acid

by Lara Saftić Martinović, Nada Birkic, Vedran Miletić, Roberto Antolović, Danijela Štanfel and Karlo Wittine

Int. J. Mol. Sci. 2023, 24(2), 1410; https://doi.org/10.3390/ijms24021410 - 11 Jan 2023

Cited by 4 | Viewed by 4306

Abstract

The antioxidant activity and chemical stability of 6-amino-6-deoxy-L-ascorbic acid (D1) and N-methyl-6-amino-6-deoxy-L-ascorbic acid (D2) were examined with ABTS and DPPH assays and compared with the reference L-ascorbic acid (AA). In addition, the optimal storing conditions, as well [...] Read more.

The antioxidant activity and chemical stability of 6-amino-6-deoxy-L-ascorbic acid (D1) and N-methyl-6-amino-6-deoxy-L-ascorbic acid (D2) were examined with ABTS and DPPH assays and compared with the reference L-ascorbic acid (AA). In addition, the optimal storing conditions, as well as the pH at which the amino derivatives maintain stability, were determined using mass spectrometry. Comparable antioxidant activities were observed for NH-bioisosteres and AA. Moreover, D1 showed higher stability in an acidic medium than the parent AA. In addition, AA, D1, and D2 share the same docking profile, with wild-type human peroxiredoxin as a model system. Their docking scores are similar to those of dithiothreitol (DTT). This suggests a similar binding affinity to the human peroxiredoxin binding site. Full article

(This article belongs to the Special Issue Comeback to Natural Therapeutics in Modern Age: Insights into Molecular Modes of Action of Natural Products)

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9 pages, 2104 KiB

Open AccessArticle

Inhibitory Mechanism of IL-6 Production by Orento in Oral Squamous Cell Carcinoma Cell Line CAL27 Stimulated by Pathogen-Associated Molecular Patterns from Periodontopathogenic Porphyromonas gingivalis

by Yasuhiro Imamura, Yoshimasa Makita, Kazuya Masuno and Hourei Oh

Int. J. Mol. Sci. 2023, 24(1), 697; https://doi.org/10.3390/ijms24010697 - 31 Dec 2022

Cited by 2 | Viewed by 1529

Abstract

Orento is a traditional Japanese medicinal kampo preparation that is also prescribed in oral care. In oral squamous cell carcinoma cell line CAL27, orento significantly inhibited periodontopathogenic bacterium Porphyromonas gingivalis lipopolysaccharide (LPS) and lipoproteins (PAMP)-stimulated production of interleukin (IL)-6. This suggests that orento [...] Read more.

Orento is a traditional Japanese medicinal kampo preparation that is also prescribed in oral care. In oral squamous cell carcinoma cell line CAL27, orento significantly inhibited periodontopathogenic bacterium Porphyromonas gingivalis lipopolysaccharide (LPS) and lipoproteins (PAMP)-stimulated production of interleukin (IL)-6. This suggests that orento negatively regulates PAMP-mediated toll-like receptor (TLR) signaling. Orento significantly suppressed PAMP-stimulated activation of the IL-6 promoter, indicating that orento may suppress the production of IL-6 by PAMP at the transcriptional level. Orento also suppressed TLR-mediated activation of transcription factor nuclear factor-kappa B (NF-kB) that was stimulated by PAMP. This finding indicates that orento may suppress the function and activation of factors involved in TLR signaling, thereby suppressing NF-kB-dependent expression of various genes. Orento suppressed IL-1 receptor-associated kinase (IRAK4), IRAK1, and c-Jun N-terminal kinase (JNK) phosphorylation in PAMP-stimulated CAL27 cells. This result indicates that orento is involved in the initiation of TLR signaling by PAMP and suppresses the downstream signaling pathways of myeloid differentiation primary response gene 88 (MyD88) such as mitogen-activated protein kinase (MAPK) and NF-kB cascades. These findings suggest that orento has an inhibitory effect on the production of inflammatory cytokines. Full article

(This article belongs to the Special Issue Comeback to Natural Therapeutics in Modern Age: Insights into Molecular Modes of Action of Natural Products)

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22 pages, 2677 KiB

Open AccessArticle

Effects of Piptoporus betulinus Ethanolic Extract on the Proliferation and Viability of Melanoma Cells and Models of Their Cell Membranes

by Justyna Bożek, Joanna Tomala, Sylwia Wójcik, Beata Kamińska, Izabella Brand, Ewa Pocheć and Elżbieta Szostak

Int. J. Mol. Sci. 2022, 23(22), 13907; https://doi.org/10.3390/ijms232213907 - 11 Nov 2022

Cited by 3 | Viewed by 2284

Abstract

Piptoporus betulinus is a fungus known for its medicinal properties. It possesses antimicrobial, anti-inflammatory, and anti-cancer activity. In this study, several tests were performed to evaluate the cytotoxic effect of the ethanolic extract of Piptoporus betulinus on two melanoma human cell lines, WM115 [...] Read more.

Piptoporus betulinus is a fungus known for its medicinal properties. It possesses antimicrobial, anti-inflammatory, and anti-cancer activity. In this study, several tests were performed to evaluate the cytotoxic effect of the ethanolic extract of Piptoporus betulinus on two melanoma human cell lines, WM115 primary and A375 metastatic cell lines, as well as Hs27 human skin fibroblasts. The extract proved to affect cancer cells in a dose-dependent manner, and at the same time showed a low cytotoxicity towards the normal cells. The total phenolic content (TPC) was determined spectrophotometrically by the Folin-Ciocalteu method (F-C), and the potential antioxidant activity was measured by ferric-reducing antioxidant power (FRAP) assay. One of the active compounds in the extract is betulin. It was isolated and then its cytotoxic activity was compared to the results obtained from the Piptoporus betulinus extract. To further understand the mechanism of action of the extract’s anticancer activity, tests on model cell membranes were conducted. A model membrane of a melanoma cell was designed and consisted of 1,2-dimyristoyl-sn-glycero-3-phosphocholine, disialoganglioside-GD_1a and cholesterol: DMPC:GD_1a:chol (5:2:3 mole ratio). Changes in a Langmuir monolayer were observed and described based on Π-A_mol isotherm and compressibility modulus changes. LB lipid bilayers were deposited on a hydrophilic gold substrate and analyzed by IR and X-ray photoelectron spectroscopy. Our study provides new data on the effect of Piptoporus betulinus extract on melanoma cells and its impact on the model of melanoma plasma membranes. Full article

(This article belongs to the Special Issue Comeback to Natural Therapeutics in Modern Age: Insights into Molecular Modes of Action of Natural Products)

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19 pages, 3286 KiB

Open AccessArticle

Antibiofilm Activity of Sundew Species against Multidrug-Resistant Escherichia coli Strains

by Sandy Gerschler, Sebastian Guenther and Christian Schulze

Int. J. Mol. Sci. 2022, 23(22), 13720; https://doi.org/10.3390/ijms232213720 - 8 Nov 2022

Cited by 7 | Viewed by 1526

Abstract

Species of the genus Drosera, known for carnivorous plants, such as sundew, have been traditionally used for centuries as medicinal plants. Efficacy-determining compounds are naphthoquinones and flavonoids. Flavonoids possess a broad spectrum of bioactive properties, including biofilm inhibitory activity. Biofilms render antibiotics [...] Read more.

Species of the genus Drosera, known for carnivorous plants, such as sundew, have been traditionally used for centuries as medicinal plants. Efficacy-determining compounds are naphthoquinones and flavonoids. Flavonoids possess a broad spectrum of bioactive properties, including biofilm inhibitory activity. Biofilms render antibiotics ineffective, contributing to the current rise in antimicrobial resistance. In this study, the biofilm inhibitory activity of two European sundew species (Drosera rotundifolia and Drosera intermedia) grown agriculturally in Germany and four commercial sundew products (declared as Drosera longifolia, Drosera sp. and Drosera planta trit.) against three multidrug-resistant Escherichia coli strains was tested. The aim of the study was to comparatively investigate the biofilm inhibitory potential of sundew species extracts grown locally in northern Germany and commercial sundew products. The minimum biofilm inhibitory concentration of the European sundew species was approx. 35 µg mL⁻¹. In comparison, commercial sundew products ranged in concentration from 75 to 140 µg mL⁻¹. Additionally, individual compounds isolated from European sundew were tested. Among these compounds, biofilm inhibitory activity was determined for four of the eight substances, with 2″-O-galloyl hyperoside standing out for its activity (38 µg mL⁻¹). The whole plant extracts of Drosera rotundifolia and Drosera intermedia proved to be more effective than the commercial products and the single compounds in its biofilm inhibition activity against Escherichia coli strains. Sundew extracts may serve as a potential therapeutic approach for targeting biofilm production. Full article

(This article belongs to the Special Issue Comeback to Natural Therapeutics in Modern Age: Insights into Molecular Modes of Action of Natural Products)

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8 pages, 1028 KiB

Open AccessArticle

Spermine Suppresses Adipocyte Differentiation and Exerts Anti-Obesity Effects In Vitro and In Vivo

by Sachie Nakatani, Yasuhiro Horimoto, Natsumi Nakabayashi, Mayumi Karasawa, Masahiro Wada and Kenji Kobata

Int. J. Mol. Sci. 2022, 23(19), 11818; https://doi.org/10.3390/ijms231911818 - 5 Oct 2022

Cited by 6 | Viewed by 1436

Abstract

Endogenous polyamines such as putrescine (Put), spermidine (Spd), and spermine (Spm) affect adipocyte differentiation. In this study, we investigated the effect of exogenously supplemented polyamines on mouse adipocyte differentiation and anti-obesity actions in vitro and in vivo. The preadipocyte cell line, 3T3-L1, was [...] Read more.

Endogenous polyamines such as putrescine (Put), spermidine (Spd), and spermine (Spm) affect adipocyte differentiation. In this study, we investigated the effect of exogenously supplemented polyamines on mouse adipocyte differentiation and anti-obesity actions in vitro and in vivo. The preadipocyte cell line, 3T3-L1, was cultured with Put, Spd, or Spm, and lipid accumulation in the cells was measured by Oil Red O staining. Lipid accumulation was significantly suppressed by Spm. Suppression of CCAAT/enhancer binding protein α mRNA by Spm suggested that the decreased lipid accumulation was due to delaying the cell differentiation. The body weight and fat of obese mice induced with a high-fat diet were reduced by oral ingestion of Spm. In conclusion, oral supplementation of Spm has the ability to prevent obesity through inhibition of adipocyte differentiation. Full article

(This article belongs to the Special Issue Comeback to Natural Therapeutics in Modern Age: Insights into Molecular Modes of Action of Natural Products)

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30 pages, 4723 KiB

Open AccessArticle

The Activity of Chelidonium majus L. Latex and Its Components on HPV Reveal Insights into the Antiviral Molecular Mechanism

by Oskar Musidlak, Alicja Warowicka, Justyna Broniarczyk, Damian Adamczyk, Anna Goździcka-Józefiak and Robert Nawrot

Int. J. Mol. Sci. 2022, 23(16), 9241; https://doi.org/10.3390/ijms23169241 - 17 Aug 2022

Cited by 4 | Viewed by 2757

Abstract

Yellow-orange latex of Chelidonium majus L. has been used in folk medicine as a therapeutic agent against warts and other visible symptoms of human papillomavirus (HPV) infections for centuries. The observed antiviral and antitumor properties of C. majus latex are often attributed to [...] Read more.

Yellow-orange latex of Chelidonium majus L. has been used in folk medicine as a therapeutic agent against warts and other visible symptoms of human papillomavirus (HPV) infections for centuries. The observed antiviral and antitumor properties of C. majus latex are often attributed to alkaloids contained therein, but recent studies indicate that latex proteins may also play an important role in its pharmacological activities. Therefore, the aim of the study was to investigate the effect of the crude C. majus latex and its protein and alkaloid-rich fractions on different stages of the HPV replication cycle. The results showed that the latex components, such as alkaloids and proteins, decrease HPV infectivity and inhibit the expression of viral oncogenes (E6, E7) on mRNA and protein levels. However, the crude latex and its fractions do not affect the stability of structural proteins in HPV pseudovirions and they do not inhibit the virus from attaching to the cell surface. In addition, the protein fraction causes increased TNFα secretion, which may indicate the induction of an inflammatory response. These findings indicate that the antiviral properties of C. majus latex arise both from alkaloids and proteins contained therein, acting on different stages of the viral replication cycle. Full article

(This article belongs to the Special Issue Comeback to Natural Therapeutics in Modern Age: Insights into Molecular Modes of Action of Natural Products)

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Review

Jump to: Research

42 pages, 870 KiB

Open AccessReview

Natural Taxanes: From Plant Composition to Human Pharmacology and Toxicity

by Ľuboš Nižnanský, Denisa Osinová, Roman Kuruc, Alexandra Hengerics Szabó, Andrea Szórádová, Marián Masár and Žofia Nižnanská

Int. J. Mol. Sci. 2022, 23(24), 15619; https://doi.org/10.3390/ijms232415619 - 9 Dec 2022

Cited by 14 | Viewed by 2300

Abstract

Biologically active taxanes, present in small- to medium-sized evergreen conifers of various Taxus species, are widely used for their antioxidant, antimicrobial and anti-inflammatory effects, but mostly for their antitumour effects used in the treatment of solid tumours of the breast, ovary, lung, bladder, [...] Read more.

Biologically active taxanes, present in small- to medium-sized evergreen conifers of various Taxus species, are widely used for their antioxidant, antimicrobial and anti-inflammatory effects, but mostly for their antitumour effects used in the treatment of solid tumours of the breast, ovary, lung, bladder, prostate, oesophagus and melanoma. More of the substances found in Taxus plant extracts have medical potential. Therefore, at the beginning of this review, we describe the methods of isolation, identification and determination of taxanes in different plant parts. One of the most important taxanes is paclitaxel, for which we summarize the pharmacokinetic parameters of its different formulations. We also describe toxicological risks during clinical therapy such as hypersensitivity, neurotoxicity, gastrointestinal, cardiovascular, haematological, skin and renal toxicity and toxicity to the respiratory system. Since the effect of the drug-form PTX is enhanced by various Taxus spp. extracts, we summarize published clinical intoxications and all fatal poisonings for the Taxus baccata plant. This showed that, despite their significant use in anticancer treatment, attention should also be focused on the risk of fatal intoxication due to ingestion of extracts from these plants, which are commonly found in our surroundings. Full article

(This article belongs to the Special Issue Comeback to Natural Therapeutics in Modern Age: Insights into Molecular Modes of Action of Natural Products)

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22 pages, 2936 KiB

Open AccessReview

Probiotics and Commensal Gut Microbiota as the Effective Alternative Therapy for Multiple Sclerosis Patients Treatment

by Angela Dziedzic and Joanna Saluk

Int. J. Mol. Sci. 2022, 23(22), 14478; https://doi.org/10.3390/ijms232214478 - 21 Nov 2022

Cited by 8 | Viewed by 3454

Abstract

The gut-brain axis (GBA) refers to the multifactorial interactions between the intestine microflora and the nervous, immune, and endocrine systems, connecting brain activity and gut functions. Alterations of the GBA have been revealed in people with multiple sclerosis (MS), suggesting a potential role [...] Read more.

The gut-brain axis (GBA) refers to the multifactorial interactions between the intestine microflora and the nervous, immune, and endocrine systems, connecting brain activity and gut functions. Alterations of the GBA have been revealed in people with multiple sclerosis (MS), suggesting a potential role in disease pathogenesis and making it a promising therapeutic target. Whilst research in this field is still in its infancy, a number of studies revealed that MS patients are more likely to exhibit modified microbiota, altered levels of short-chain fatty acids, and enhanced intestinal permeability. Both clinical and preclinical trials in patients with MS and animal models revealed that the administration of probiotic bacteria might improve cognitive, motor, and mental behaviors by modulation of GBA molecular pathways. According to the newest data, supplementation with probiotics may be associated with slower disability progression, reduced depressive symptoms, and improvements in general health in patients with MS. Herein, we give an overview of how probiotics supplementation may have a beneficial effect on the course of MS and its animal model. Hence, interference with the composition of the MS patient’s intestinal microbiota may, in the future, be a grip point for the development of diagnostic tools and personalized microbiota-based adjuvant therapy. Full article

(This article belongs to the Special Issue Comeback to Natural Therapeutics in Modern Age: Insights into Molecular Modes of Action of Natural Products)

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