Special Issue "Pharmacology of Medicinal Plants"

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Natural and Bio-inspired Molecules".

Deadline for manuscript submissions: 10 November 2020.

Special Issue Editor

Prof. Dr. Raffaele Capasso
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Guest Editor

Special Issue Information

Dear Colleagues,

The end of the last century witnessed a vigorous resurgence in the interest in, and use of, medicinal plant products. Medicinal plants play an important role in the discovery of new drugs and innovative mechanisms of action.

Medicinal plants contain multiple compounds that, either individually or together, are responsible for the biological effects of these natural products. Although many plant-derived natural products have already been isolated and characterized, the molecular mechanisms underlying their therapeutic effects remain unexplored. This Special Issue aims to comprehensively cover the newest discoveries in herbal medicinal products with an emphasis on their molecular targets and pharmacological activity. Therefore, I cordially invite authors to contribute original articles, as well as reviews, covering the most recent advances in the use of medicinal plants.

Prof. Dr. Raffaele Capasso
Guest Editor

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Keywords

  • medicinal plants
  • biological activity
  • molecular mechanisms
  • medical use
  • plant side effects
  • pharmacological interactions

Published Papers (22 papers)

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Open AccessArticle
Phytochemical and Biological Screening of Oenothera Biennis L. Hydroalcoholic Extract
Biomolecules 2020, 10(6), 818; https://doi.org/10.3390/biom10060818 (registering DOI) - 26 May 2020
Abstract
Oenothera biennis L. (OB), also commonly known as evening primrose, belongs to the Onagraceae family and has the best studied biological activity of all the members in the family. In therapy, the most frequently used type of extracts are from the aerial part, [...] Read more.
Oenothera biennis L. (OB), also commonly known as evening primrose, belongs to the Onagraceae family and has the best studied biological activity of all the members in the family. In therapy, the most frequently used type of extracts are from the aerial part, which are the fatty oils obtained from the seeds and have a wide range of medicinal properties. The aim of this study was to evaluate the phytochemical composition and biological activity of OB hydroalcoholic extract and to provide directions for the antimicrobial effect, antiproliferative and pro-apoptotic potential against A375 melanoma cell line, and anti-angiogenic and anti-inflammatory capacity. The main polyphenols and flavonoids identified were gallic acid, caffeic acid, epicatechin, coumaric acid, ferulic acid, rutin and rosmarinic acid. The total phenolic content was 631.496 µgGAE/mL of extract and the antioxidant activity was 7258.67 μmolTrolox/g of extract. The tested extract had a mild bacteriostatic effect on the tested bacterial strains. It was bactericidal only against Candida spp. and S. aureus. In the set of experimental conditions, the OB extract only manifested significant antiproliferative and pro-apoptotic activity against the A375 human melanoma cell line at the highest tested concentration, namely 60 μg/mL. The migration potential of A375 cells was hampered by the OB extract in a concentration-dependent manner. Furthermore, at the highest tested concentration, the OB extract altered the mitochondrial function in vitro, while reducing the angiogenic reaction, hindering compact tumor formation in the chorioallantoic membrane assay. Moreover, the OB extract elicited an anti-inflammatory effect on the experimental animal model of ear inflammation. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
Open AccessArticle
Effects of Chronic Cannabidiol Treatment in the Rat Chronic Unpredictable Mild Stress Model of Depression
Biomolecules 2020, 10(5), 801; https://doi.org/10.3390/biom10050801 - 22 May 2020
Abstract
Several neuropharmacological actions of cannabidiol (CBD) due to the modulation of the endocannabinoid system as well as direct serotonergic and gamma-aminobutyric acidergic actions have recently been identified. The current study aimed to reveal the effect of a long-term CBD treatment in the chronic [...] Read more.
Several neuropharmacological actions of cannabidiol (CBD) due to the modulation of the endocannabinoid system as well as direct serotonergic and gamma-aminobutyric acidergic actions have recently been identified. The current study aimed to reveal the effect of a long-term CBD treatment in the chronic unpredictable mild stress (CUMS) model of depression. Adult male Wistar rats (n = 24) were exposed to various stressors on a daily basis in order to induce anhedonia and anxiety-like behaviors. CBD (10 mg/kg body weight) was administered by daily intraperitoneal injections for 28 days (n = 12). The effects of the treatment were assessed on body weight, sucrose preference, and exploratory and anxiety-related behavior in the open field (OF) and elevated plus maze (EPM) tests. Hair corticosterone was also assayed by liquid chromatography–mass spectrometry. At the end of the experiment, CBD-treated rats showed a higher rate of body weight gain (5.94% vs. 0.67%) and sucrose preference compared to controls. A significant increase in vertical exploration and a trend of increase in distance traveled in the OF test were observed in the CBD-treated group compared to the vehicle-treated group. The EPM test did not reveal any differences between the groups. Hair corticosterone levels increased in the CBD-treated group, while they decreased in controls compared to baseline (+36.01% vs. −45.91%). In conclusion, CBD exerted a prohedonic effect in rats subjected to CUMS, demonstrated by the increased sucrose preference after three weeks of treatment. The reversal of the effect of CUMS on hair corticosterone concentrations might also point toward an anxiolytic or antidepressant-like effect of CBD, but this needs further confirmation. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
Open AccessArticle
Antidepressant-Like Effect of Terpineol in an Inflammatory Model of Depression: Involvement of the Cannabinoid System and D2 Dopamine Receptor
Biomolecules 2020, 10(5), 792; https://doi.org/10.3390/biom10050792 - 20 May 2020
Abstract
Depression has a multifactorial etiology that arises from environmental, psychological, genetic, and biological factors. Environmental stress and genetic factors acting through immunological and endocrine responses generate structural and functional changes in the brain, inducing neurogenesis and neurotransmission dysfunction. Terpineol, monoterpenoid alcohol, has shown [...] Read more.
Depression has a multifactorial etiology that arises from environmental, psychological, genetic, and biological factors. Environmental stress and genetic factors acting through immunological and endocrine responses generate structural and functional changes in the brain, inducing neurogenesis and neurotransmission dysfunction. Terpineol, monoterpenoid alcohol, has shown immunomodulatory and neuroprotective effects, but there is no report about its antidepressant potential. Herein, we used a single lipopolysaccharide (LPS) injection to induce a depressive-like effect in the tail suspension test (TST) and the splash test (ST) for a preventive and therapeutic experimental schedule. Furthermore, we investigated the antidepressant-like mechanism of action of terpineol while using molecular and pharmacological approaches. Terpineol showed a coherent predicted binding mode mainly against CB1 and CB2 receptors and also against the D2 receptor during docking modeling analyses. The acute administration of terpineol produced the antidepressant-like effect, since it significantly reduced the immobility time in TST (100–200 mg/kg, p.o.) as compared to the control group. Moreover, terpineol showed an antidepressant-like effect in the preventive treatment that was blocked by a nonselective dopaminergic receptor antagonist (haloperidol), a selective dopamine D2 receptor antagonist (sulpiride), a selective CB1 cannabinoid receptor antagonist/inverse agonist (AM281), and a potent and selective CB2 cannabinoid receptor inverse agonist (AM630), but it was not blocked by a nonselective adenosine receptor antagonist (caffeine) or a β-adrenoceptor antagonist (propranolol). In summary, molecular docking suggests that CB1 and CB2 receptors are the most promising targets of terpineol action. Our data showed terpineol antidepressant-like modulation by CB1 and CB2 cannabinoid receptors and D2-dopaminergic receptors to further corroborate our molecular evidence. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessArticle
Ameliorative Effect of Gum Acacia on Hookah Smoke-Induced Testicular Impairment in Mice
Biomolecules 2020, 10(5), 762; https://doi.org/10.3390/biom10050762 - 13 May 2020
Abstract
We investigated some reproductive actions of hookah smoke (HS) exposure (30 min/day, for 30 days) in male mice, and the possible mitigative effect of the prebiotic agent gum acacia (GA) thereon. Control mice were air-exposed (AE). Twenty-four hours after the last exposure, the [...] Read more.
We investigated some reproductive actions of hookah smoke (HS) exposure (30 min/day, for 30 days) in male mice, and the possible mitigative effect of the prebiotic agent gum acacia (GA) thereon. Control mice were air-exposed (AE). Twenty-four hours after the last exposure, the levels of some plasma reproductive hormones, biochemical markers of inflammation, oxidative and nitrosative stress and testicular histopathology were assessed. The urinary level of cotinine, a major nicotine metabolite, was also measured. HS exposure induced significant decreases in testosterone, estradiol, luteinizing hormone, and androgen binding protein, as well as glutathione reductase activity and levels of nitrite and total nitrite. Plasma inhibin B, alkaline phosphatase, lipopolysaccharide binding protein, uric acid, lactate dehydrogenase, lipid peroxidation, 8-oxo-2’-deoxyguanosine, and cytochrome C were significantly increased following HS exposure. In testicular homogenate, nuclear factor-κB (NF-ĸB), nuclear factor erythroid 2–related factor 2 (Nrf2), interleukin- 6 (IL-6), interleukin-1β (IL-1β), transforming growth factor-β1(TGF- β1), and tumor necrosis factor-α (TNF- α) were all significantly elevated, and the steroidogenic acute regulatory protein (StAR) significantly decreased. Histopathologically, there was slight impairment and disorganization of spermatogenesis. Urinary cotinine concentration was elevated significantly in the HS-exposed group compared with the air-exposed group. GA co-administration mitigated the adverse actions of HS measured. In conclusion, daily exposure to HS at the above dose induced adverse actions on the reproductive system of male mice. GA co-administration significantly mitigated these effects by reducing the inflammation, oxidative and nitrosative stress, via a mechanism involving Nrf2, and reduction of StAR expression. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessArticle
Brazilian Red Propolis: Extracts Production, Physicochemical Characterization, and Cytotoxicity Profile for Antitumor Activity
Biomolecules 2020, 10(5), 726; https://doi.org/10.3390/biom10050726 - 06 May 2020
Abstract
Brazilian red propolis has been proposed as a new source of compounds with cytotoxic activity. Red propolis is a resinous material of vegetal origin, synthesized from the bees of the Appis mellifera family, with recognized biological properties. To obtain actives of low polarity [...] Read more.
Brazilian red propolis has been proposed as a new source of compounds with cytotoxic activity. Red propolis is a resinous material of vegetal origin, synthesized from the bees of the Appis mellifera family, with recognized biological properties. To obtain actives of low polarity and high cytotoxic profile from red propolis, in this work, we proposed a new solvent accelerated extraction method. A complete 23 factorial design was carried out to evaluate the influence of the independent variables or factors (e.g., temperature, number of cycles, and extraction time) on the dependent variable or response (i.e., yield of production). The extracts were analyzed by gas chromatography coupled with mass spectrometry for the identification of chemical compounds. Gas chromatography analysis revealed the presence of hydrocarbons, alcohols, ketones, ethers, and terpenes, such as lupeol, lupenone, and lupeol acetate, in most of the obtained extracts. To evaluate the cytotoxicity profile of the obtained bioactives, the 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide colorimetric assay was performed in different tumor cell lines (HCT116 and PC3). The results show that the extract obtained from 70 °C and one cycle of extraction of 10 min exhibited the highest cytotoxic activity against the tested cell lines. The highest yield, however, did not indicate the highest cytotoxic activity, but the optimal extraction conditions were indeed dependent on the temperature (i.e., 70 °C). Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessArticle
Machaerium hirtum (Vell.) Stellfeld Alleviates Acute Pain and Inflammation: Potential Mechanisms of Action
Biomolecules 2020, 10(4), 590; https://doi.org/10.3390/biom10040590 - 11 Apr 2020
Abstract
Machaerium hirtum (Vell.) Stellfeld (Fabaceae) known in Brazil as “jacaranda de espinho” or “espinheira santa nativa” is a medicinal plant commonly used in folk medicine to treat ulcers, cough and diarrhea. This study aimed to investigate the anti-inflammatory and antinociceptive effects of hydroalcoholic [...] Read more.
Machaerium hirtum (Vell.) Stellfeld (Fabaceae) known in Brazil as “jacaranda de espinho” or “espinheira santa nativa” is a medicinal plant commonly used in folk medicine to treat ulcers, cough and diarrhea. This study aimed to investigate the anti-inflammatory and antinociceptive effects of hydroalcoholic extracts from M. hirtum twig (HEMh) using in vivo experimental models of nociception through the involvement of transient receptor potential channels, acid-sensing ion channel (ASIC), nitrergic, opioidergic, glutamatergic, and supraspinal pathways. Our results revealed an antinociceptive effect of HEMh mediated by the opioidergic, l-arginine-nitric oxide and glutamate systems, as well as by interactions with TRPA1/ASIC channels. The anti-inflammatory effect of HEMh evaluated with a xylene-induced ear edema and by the involvement of arachidonic acid and prostaglandin E2 (PGE2) showed involvement of the COX pathway, based on observed decreases in PGE2 levels. A phytochemical investigation of the HEMh led to the isolation of α-amyrin, β-amyrin, allantoin, apigenin-7-methoxy-6-C-β-d-glucopyranoside, and apigenin-6-C-β-d-glucopyranosyl-8-C-β-d-xylopyranoside. In conclusion, the acute oral administration of HEMh inhibits the nociceptive behavioral response in animals through the nitrergic, opioid, glutamatergic pathways, and by inhibition of the TRPA1 and ASIC channels, without causing locomotor dysfunction. In addition, its anti-inflammatory effect is associated with the COX pathway and decreased PGE2 levels. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessArticle
Phytoestrogen Agathisflavone Ameliorates Neuroinflammation-Induced by LPS and IL-1β and Protects Neurons in Cocultures of Glia/Neurons
Biomolecules 2020, 10(4), 562; https://doi.org/10.3390/biom10040562 - 07 Apr 2020
Abstract
Inflammation and oxidative stress are common aspects of most neurodegenerative diseases in the central nervous system. In this context, microglia and astrocytes are central to mediating the balance between neuroprotective and neurodestructive mechanisms. Flavonoids have potent anti-inflammatory and antioxidant properties. Here, we have [...] Read more.
Inflammation and oxidative stress are common aspects of most neurodegenerative diseases in the central nervous system. In this context, microglia and astrocytes are central to mediating the balance between neuroprotective and neurodestructive mechanisms. Flavonoids have potent anti-inflammatory and antioxidant properties. Here, we have examined the anti-inflammatory and neuroprotective potential of the flavonoid agathisflavone (FAB), which is derived from the Brazilian plant Poincianella pyramidalis, in in vitro models of neuroinflammation. Cocultures of neurons/glial cells were exposed to lipopolysaccharide (LPS, 1 µg/mL) or interleukin (IL)-1β (10 ng/mL) for 24 h and treated with FAB (0.1 and 1 µM, 24 h). FAB displayed a significant neuroprotective effect, as measured by nitric oxide (NO) production, Fluoro-Jade B (FJ-B) staining, and immunocytochemistry (ICC) for the neuronal marker β-tubulin and the cell death marker caspase-3, preserving neuronal soma and increasing neurite outgrowth. FAB significantly decreased the LPS-induced microglial proliferation, identified by ICC for Iba-1/bromodeoxyuridine (BrdU) and CD68 (microglia M1 profile marker). In contrast, FAB had no apparent effect on astrocytes, as determined by ICC for glial fibrillary acidic protein (GFAP). Furthermore, FAB protected against the cytodestructive and proinflammatory effects of IL-1β, a key cytokine that is released by activated microglia and astrocytes, and ICC showed that combined treatment of FAB with α and β estrogen receptor antagonists did not affect NF-κB expression. In addition, qPCR analysis demonstrated that FAB decreased the expression of proinflammatory molecules TNF-α, IL-1β, and connexins CCL5 and CCL2, as well as increased the expression of the regulatory molecule IL-10. Together, these findings indicate that FAB has a significant neuroprotective and anti-inflammatory effect in vitro, which may be considered as an adjuvant for the treatment of neurodegenerative diseases. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessArticle
Intervention in Neuropsychiatric Disorders by Suppressing Inflammatory and Oxidative Stress Signal and Exploration of In Silico Studies for Potential Lead Compounds from Holigarna caustica (Dennst.) Oken leaves
Biomolecules 2020, 10(4), 561; https://doi.org/10.3390/biom10040561 - 06 Apr 2020
Abstract
Holigarna caustica (Dennst.), a popular plant used in folk medicine in Bangladesh, is often used by the local folk practitioner to treat a variety of chronic diseases. The present research is an attempt to find out an innovative therapeutic prospect for the management [...] Read more.
Holigarna caustica (Dennst.), a popular plant used in folk medicine in Bangladesh, is often used by the local folk practitioner to treat a variety of chronic diseases. The present research is an attempt to find out an innovative therapeutic prospect for the management of neuropsychiatric disorders. The methanol extract of H. caustica leaves (MEHC) were utilized on various behavioral tests for assessing anxiolytic, anti-depressant, and anti-inflammatory activities. The antioxidant potentials and quantitative phytochemicals were evaluated through spectrophotometric methods. Results revealed that treatment of MEHC (200 and 400 mg/kg) significantly reduced anxiety like behaviors in mice, particularly, 400 mg/kg efficiently improved % of entries and time spent (p < 0.05) in the open arms in elevated plus maze test, whereas, superior head dipping tendency (p < 0.05) was observed in hole-board test. In contrast, mice treated with 200 mg/kg revealed better anxiolytic effect in both open field and hole-cross tests. During antidepressant evaluation, mice administrated with MEHC exhibited active behaviors (swimming and struggling) in forced swimming and tail suspension tests. In parallel, MEHC manifested a noteworthy (p < 0.001) suppression of inflammatory response induced by histamine. The MEHC also showed strong antioxidant activities in 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) (IC50: 57.64 μg/mL) scavenging, H2O2 (IC50: 51.60 μg/mL) scavenging, and ferric reducing power assay. The levels of total phenol, flavonoid, flavonol, condensed tannin, and antioxidant were estimated as higher in MEHC. Moreover, 11 compounds were documented as bioactive, displayed good binding affinities to potassium channel receptor, human serotonin receptor, cyclooxygenase (COX-1 and 2), and xanthine oxidoreductase enzyme targets in molecular docking experiments. Furthermore, ADME/T and Prediction of Activity Spectra for Substances (PASS) analyses exposed their drug-likeness, nontoxic upon consumption, and likely pharmacological actions. Overall, the H. caustica is potentially bioactive as evident by in vivo, in vitro, and computational analysis. Our findings support the folkloric value of this plant, which may provide a potential source towards developing drug leads. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessArticle
Evaluation of Pharmacological and Phytochemical Profiles of Piptadeniastrum africanum (Hook.f.) Brenan Stem Bark Extracts
Biomolecules 2020, 10(4), 516; https://doi.org/10.3390/biom10040516 - 28 Mar 2020
Abstract
The stem bark (SB) of Piptadeniastrum africanum (PA) has been extensively used in African traditional medicinal systems. However, there is a dearth of scientific information regarding its possible activity in the management of type II diabetes, Alzheimer’s disease, and skin hyperpigmentation disorders. This [...] Read more.
The stem bark (SB) of Piptadeniastrum africanum (PA) has been extensively used in African traditional medicinal systems. However, there is a dearth of scientific information regarding its possible activity in the management of type II diabetes, Alzheimer’s disease, and skin hyperpigmentation disorders. This study therefore attempted to elucidate the in vitro inhibitory action of ethyl acetate, methanol, and water extracts of P. africanum stem bark (PA-SB) on α-amylase, α-glucosidase, acetylcholinesterase, butyrylcholinesterase, and tyrosinase. Cell viability, catecholamine, and 3-hydroxykynurenine levels of hypothalamic HypoE22 cells exposed to PA-SB extracts were also investigated. The phytochemical profiles of the extracts were determined by high performance liquid chromatography (HPLC) and antioxidant properties were investigated. Saponin (867.42 mg quillaja equivalent/g) and tannin (33.81 mg catechin equivalent/g) contents were higher in the methanol extract. Multiple dihydroxy-trimethoxy(iso)flavone isomers, loliolide, eriodictyol, naringenin, luteolin, chrysoeriol, apigenin, and liquiritigenin, were characterized from PA-SB extracts using HPLC. The methanol extract of PA-SB showed highest inhibitory activity against acetylcholinesterase (4.88 mg galantamine equivalent (GALAE)/g extract), butyrylcholinesterase (5.37 mg GALAE/g extract), and tyrosinase (154.86 mg kojic acid equivalent/g extract) while α-glucosidase was effectively inhibited by the ethyl acetate extract (15.22 mmol acarbose equivalent/g extract). The methanol extract of PA-SB also showed potent antioxidant properties (493.87, 818.12, 953.07, and 732.19 mg Trolox equivalent/g extract, for 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS), cupric reducing antioxidant capacity (CUPRAC), and ferric reducing antioxidant power (FRAP) assays, respectively). PA-SB extracts exhibited antioxidant activity and promising inhibition against key enzymes related to type II diabetes, Alzheimer’s disease, and skin hyperpigmentation disorders. Additionally, all extracts were able to contrast hydrogen peroxide-induced oxidative stress, in HypoE22 cells, thus restoring basal catecholamine and 3-hydroxykinurenine levels, whereas only methanol and water extracts stimulated basal dopamine release. Overall, data from the present study contribute to the biological assessment of P. africanum that appears to be a promising source of natural compounds with protective and neuromodulatory effects. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessArticle
Origanum majorana Essential Oil Triggers p38 MAPK-Mediated Protective Autophagy, Apoptosis, and Caspase-Dependent Cleavage of P70S6K in Colorectal Cancer Cells
Biomolecules 2020, 10(3), 412; https://doi.org/10.3390/biom10030412 - 06 Mar 2020
Abstract
Colorectal cancer (CRC) is the third most common type of cancer in terms of incidence and mortality worldwide. Here we have investigated the anti-colon cancer potential of Origanum majorana essential oil (OMEO) and its underlying mechanisms of action. We showed that OMEO significantly [...] Read more.
Colorectal cancer (CRC) is the third most common type of cancer in terms of incidence and mortality worldwide. Here we have investigated the anti-colon cancer potential of Origanum majorana essential oil (OMEO) and its underlying mechanisms of action. We showed that OMEO significantly inhibited the cellular viability and colony growth of human HT-29 colorectal cancer cells. OMEO induced protective autophagy, associated with downregulation of the mTOR/p70S6K pathway, and activated caspase-8 and caspase-9-dependent apoptosis. Blockade of autophagy with 3-methyladenine (3-MA) and chloroquine (CQ), two autophagy inhibitors, potentiated the OMEO-induced apoptotic cell death. Inversely, inhibition of apoptosis with the pan-caspase inhibitor, Z-VAD-FMK, significantly reduced cell death, suggesting that apoptosis represents the main mechanism of OMEO-induced cell death. Mechanistically, we found that OMEO induces protective autophagy and apoptotic cells death via the activation of the p38 MAPK signaling pathway. Pharmacological inhibition of p38 MAPK by the p38 inhibitors SB 202190 and SB 203580 not only significantly decreased apoptotic cell death, but also reduced the autophagy level in OMEO treated HT-29 cells. Strikingly, we found that OMEO also induces p38 MAPK-mediated caspase-dependent cleavage of p70S6K, a protein reported to be overexpressed in colon cancer and associated with drug resistance. Our findings suggest that OMEO inhibits colon cancer through p38 MAPK-mediated protective autophagy and apoptosis associated with caspase-dependent cleavage of p70S6K. To the best of our knowledge, this study is the first to report on the implications of the p38 MAPK signaling pathway in targeting p70S6K to caspase cleavage. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessArticle
Ginseng Gintonin Attenuates Lead-Induced Rat Cerebellar Impairments during Gestation and Lactation
Biomolecules 2020, 10(3), 385; https://doi.org/10.3390/biom10030385 - 02 Mar 2020
Cited by 1
Abstract
Gintonin, a novel ginseng-derived lysophosphatidic acid receptor ligand, improves brain functions and protects neurons from oxidative stress. However, little is known about the effects of gintonin against Pb-induced brain maldevelopment. We investigated the protective effects of gintonin on the developing cerebellum after prenatal [...] Read more.
Gintonin, a novel ginseng-derived lysophosphatidic acid receptor ligand, improves brain functions and protects neurons from oxidative stress. However, little is known about the effects of gintonin against Pb-induced brain maldevelopment. We investigated the protective effects of gintonin on the developing cerebellum after prenatal and postnatal Pb exposure. Pregnant female rats were randomly divided into three groups: control, Pb (0.3% Pb acetate in drinking water), and Pb plus gintonin (100 mg/kg, p.o.). Blood Pb was increased in dams and pups; gintonin treatment significantly decreased blood Pb. On postnatal day 21, the number of degenerating Purkinje cells was remarkably increased while the number of calbindin-, GAD67-, NMDAR1-, LPAR1-immunoreactive intact Purkinje cells, and GABA transporter 1-immunoreactive pinceau structures were significantly reduced in Pb-exposed offspring. Following Pb exposure, gintonin ameliorated cerebellar degenerative effects, restored increased pro-apoptotic Bax, and decreased anti-apoptotic Bcl2. Gintonin treatment attenuated Pb-induced accumulation of oxidative stress (Nrf2 and Mn-SOD) and inflammation (IL-1β and TNFα,), restoring the decreased cerebellar BDNF and Sirt1. Gintonin ameliorated Pb-induced impairment of myelin basic protein-immunoreactive myelinated fibers of Purkinje cells. Gintonin attenuated Pb-induced locomotor dysfunctions. The present study revealed the ameliorating effects of gintonin against Pb, suggesting the potential use of gintonin as a preventive agent in Pb poisoning during pregnancy and lactation. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessArticle
Dried Leaf Artemisia Annua Improves Bioavailability of Artemisinin via Cytochrome P450 Inhibition and Enhances Artemisinin Efficacy Downstream
Biomolecules 2020, 10(2), 254; https://doi.org/10.3390/biom10020254 - 07 Feb 2020
Abstract
Artemisia annua L. and artemisinin, have been used for millennia to treat malaria. We used human liver microsomes (HLM) and rats to compare hepatic metabolism, tissue distribution, and inflammation attenuation by dried leaves of A. annua (DLA) and pure artemisinin. For HLM assays, [...] Read more.
Artemisia annua L. and artemisinin, have been used for millennia to treat malaria. We used human liver microsomes (HLM) and rats to compare hepatic metabolism, tissue distribution, and inflammation attenuation by dried leaves of A. annua (DLA) and pure artemisinin. For HLM assays, extracts, teas, and phytochemicals from DLA were tested and IC50 values for CYP2B6 and CYP3A4 were measured. For tissue distribution studies, artemisinin or DLA was orally delivered to rats, tissues harvested at 1 h, and blood, urine and feces over 8 h; all were analyzed for artemisinin and deoxyartemisinin by GC-MS. For inflammation, rats received an intraperitoneal injection of water or lipopolysaccharide (LPS) and 70 mg/kg oral artemisinin as pure drug or DLA. Serum was collected over 8 h and analyzed by ELISA for TNF-α, IL-6, and IL-10. DLA-delivered artemisinin distributed to tissues in higher concentrations in vivo, but elimination remained mostly unchanged. This seemed to be due to inhibition of first-pass metabolism by DLA phytochemicals, as demonstrated by HLM assays of DLA extracts, teas and phytochemicals. DLA was more effective than artemisinin in males at attenuating proinflammatory cytokine production; the data were less conclusive in females. These results suggest that the oral consumption of artemisinin as DLA enhances the bioavailability and anti-inflammatory potency of artemisinin. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessArticle
Potential Antidiabetic Activity of Extracts and Isolated Compound from Adenosma bracteosum (Bonati)
Biomolecules 2020, 10(2), 201; https://doi.org/10.3390/biom10020201 - 29 Jan 2020
Cited by 3
Abstract
Adenosma bracteosum Bonati. (A. bracteosum) has been used in traditional and modern medicine in Vietnam for curing hepatitis. In this study, ethanol and aqueous extracts of A. bracteosum were evaluated for their α-glucosidase inhibitory activities and anti-hyperglycemic effects on glucose loaded [...] Read more.
Adenosma bracteosum Bonati. (A. bracteosum) has been used in traditional and modern medicine in Vietnam for curing hepatitis. In this study, ethanol and aqueous extracts of A. bracteosum were evaluated for their α-glucosidase inhibitory activities and anti-hyperglycemic effects on glucose loaded hyperglycemic and streptozotocin (STZ) induced diabetic mice. The α-glucosidase inhibition of the extracts was evaluated by colorimetric assays, and the anti-diabetic activity was tested on a STZ-induced diabetic mice model. The ethanol and aqueous extracts showed a significant α-glucosidase inhibitory activity, which was more effective than acarbose at the same concentration. In the STZ-induced diabetic mice, both extracts showed a strong anti-hyperglycemic activity, with the group receiving 50 mg/kg of ethanol extract and the group receiving 50 mg/kg of aqueous extract presenting 64.42% and 57.69% reductions, respectively, in the blood glucose levels when compared with the diabetic control group, on day 21 (p > 0.05). Isoscutellarein-8-O-β-D-glucopyranoside (IG) was identified from the ethanol extract, which showed a strong inhibitory activity against α-glucosidase, with a ten times higher potency compared with the positive control acarbose. The anti-hyperglycemic effect of IG was effectively similar to the standard drug, glibenclamide, at the same dose of 10 mg/kg (p > 0.05). These results indicated that A. bracteosum has a great antidiabetic potential. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessArticle
Super Critical Fluid Extracted Fatty Acids from Withania somnifera Seeds Repair Psoriasis-Like Skin Lesions and Attenuate Pro-Inflammatory Cytokines (TNF-α and IL-6) Release
Biomolecules 2020, 10(2), 185; https://doi.org/10.3390/biom10020185 - 25 Jan 2020
Cited by 1
Abstract
(1) Background: Withania somnifera Dunal (Ashwagandha) is a widely used medicinal herb in traditional medicinal systems with extensive research on various plant parts. Surprisingly, seeds of W. somnifera have never been investigated for their therapeutic potential. (2) Methods: W. somnifera seeds were extracted [...] Read more.
(1) Background: Withania somnifera Dunal (Ashwagandha) is a widely used medicinal herb in traditional medicinal systems with extensive research on various plant parts. Surprisingly, seeds of W. somnifera have never been investigated for their therapeutic potential. (2) Methods: W. somnifera seeds were extracted for fatty acids (WSSO) using super critical fluid extraction, and was analyzed by gas chromatography. Its therapeutic potential in psoriasis-like skin etiologies was investigated using a 12-O tetradecanoyl phorbol 13-acetate (TPA)-induced psoriatic mouse model. Psoriatic inflammation along with psoriatic lesions and histopathological scores were recorded. WSSO was also tested on murine macrophage (RAW264.7), human epidermoid (A431), and monocytic (THP-1) cells, stimulated with TPA or lipo poly-saccharide (LPS) to induce pro-inflammatory cytokine (IL-6 and TNF-α) release. NFκB promoter activity was also measured by luciferase reporter assay. (3) Results: Topical application of WSSO with concurrent oral doses significantly reduced inflammation-induced edema, and repaired psoriatic lesions and associated histopathological scores. Inhibition of pro-inflammatory cytokines release was observed in WSSO-treated A431 and THP-1 cells, along with reduced NFκB expression. WSSO also inhibited reactive nitrogen species (RNS) in LPS-stimulated RAW264.7 cells. (4) Conclusion: Here we show that the fatty acids from W. somnifera seeds have strong anti-inflammatory properties, along with remarkable therapeutic potential on psoriasis-like skin etiologies. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessReview
The Use of Euterpe oleracea Mart. As a New Perspective for Disease Treatment and Prevention
Biomolecules 2020, 10(6), 813; https://doi.org/10.3390/biom10060813 (registering DOI) - 26 May 2020
Abstract
Euterpe oleracea Mart. (EO), popularly known as açaí, belongs to the Arecaceae family and grows abundantly in Brazil. The fruit of this palm tree is widely used because of its anti-inflammatory and antioxidant properties. In this review, a search for literature and patent [...] Read more.
Euterpe oleracea Mart. (EO), popularly known as açaí, belongs to the Arecaceae family and grows abundantly in Brazil. The fruit of this palm tree is widely used because of its anti-inflammatory and antioxidant properties. In this review, a search for literature and patent technological prospecting has been performed on the use of EO to treat and prevent diseases as well as to prepare pharmaceutical formulations. EO leaves, fruits, and oil stand out for their large number of pharmacological activities such as anti-inflammatory, antioxidant, antimicrobial, antinociceptive, anticancer, anti-atherogenic, and healing activities, protection against metabolic syndromes such as diabetes, hypertension, and hyperlipidemia, and protection of organs such as lung, kidney, liver, heart, and nervous system. While the phytochemical composition is intrinsically linked to identified biological activities, discoveries of the past decade concerning the use of this species have shown pharmacological alternatives mainly in the treatment and prevention of breast cancer and metabolic syndromes. Although studies and inventions on the use of EO though are believed to have been important in light of the pharmacological activities found, few clinical and toxicity tests have been performed. Nevertheless, with the increase of interest in EO, this species is believed to be only at the beginning of the breakthroughs in the development of promising products for the pharmaceutical industry. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Therapeutic Potential of Brassinosteroids in Biomedical and Clinical Research
Biomolecules 2020, 10(4), 572; https://doi.org/10.3390/biom10040572 - 09 Apr 2020
Abstract
Steroids are a pivotal class of hormones with a key role in growth modulation and signal transduction in multicellular organisms. Synthetic steroids are widely used to cure large array of viral, fungal, bacterial, and cancerous infections. Brassinosteroids (BRs) are a natural collection of [...] Read more.
Steroids are a pivotal class of hormones with a key role in growth modulation and signal transduction in multicellular organisms. Synthetic steroids are widely used to cure large array of viral, fungal, bacterial, and cancerous infections. Brassinosteroids (BRs) are a natural collection of phytosterols, which have structural similarity with animal steroids. BRs are dispersed universally throughout the plant kingdom. These plant steroids are well known to modulate a plethora of physiological responses in plants leading to improvement in quality as well as yield of food crops. Moreover, they have been found to play imperative role in stress-fortification against various stresses in plants. Over a decade, BRs have conquered worldwide interest due to their diverse biological activities in animal systems. Recent studies have indicated anticancerous, antiangiogenic, antiviral, antigenotoxic, antifungal, and antibacterial bioactivities of BRs in the animal test systems. BRs inhibit replication of viruses and induce cytotoxic effects on cancerous cell lines. Keeping in view the biological activities of BRs, this review is an attempt to update the information about prospects of BRs in biomedical and clinical application. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessReview
Plant-Based Natural Products for the Discovery and Development of Novel Anthelmintics against Nematodes
Biomolecules 2020, 10(3), 426; https://doi.org/10.3390/biom10030426 - 09 Mar 2020
Abstract
Intestinal parasitic nematodes infect approximately two billion people worldwide. In the absence of vaccines for human intestinal nematodes, control of infections currently relies mainly on chemotherapy, but resistance is an increasing problem. Thus, there is an urgent need for the discovery and development [...] Read more.
Intestinal parasitic nematodes infect approximately two billion people worldwide. In the absence of vaccines for human intestinal nematodes, control of infections currently relies mainly on chemotherapy, but resistance is an increasing problem. Thus, there is an urgent need for the discovery and development of new anthelmintic drugs, especially ones with novel mechanisms of action. Medicinal plants hold great promise as a source of effective treatments, including anthelmintic therapy. They have been used traditionally for centuries and are mostly safe (if not, their toxicity is well-known). However, in most medicinal plants the compounds active against nematodes have not been identified thus far. The free-living nematode C. elegans was demonstrated to be an excellent model system for the discovery of new anthelmintics and for characterizing their mechanism of action or resistance. The compounds discussed in this review are of botanical origin and were published since 2002. Most of them need further studies of their toxicity, mechanisms and structure-activity relationship to assess more fully their potential as drugs. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessReview
Traditional Uses, Bioactive Chemical Constituents, and Pharmacological and Toxicological Activities of Glycyrrhiza glabra L. (Fabaceae)
Biomolecules 2020, 10(3), 352; https://doi.org/10.3390/biom10030352 - 25 Feb 2020
Cited by 1
Abstract
Traditional herbal remedies have been attracting attention as prospective alternative resources of therapy for diverse diseases across many nations. In recent decades, medicinal plants have been gaining wider acceptance due to the perception that these plants, as natural products, have fewer side effects [...] Read more.
Traditional herbal remedies have been attracting attention as prospective alternative resources of therapy for diverse diseases across many nations. In recent decades, medicinal plants have been gaining wider acceptance due to the perception that these plants, as natural products, have fewer side effects and improved efficacy compared to their synthetic counterparts. Glycyrrhiza glabra L. (Licorice) is a small perennial herb that has been traditionally used to treat many diseases, such as respiratory disorders, hyperdipsia, epilepsy, fever, sexual debility, paralysis, stomach ulcers, rheumatism, skin diseases, hemorrhagic diseases, and jaundice. Moreover, chemical analysis of the G. glabra extracts revealed the presence of several organic acids, liquirtin, rhamnoliquirilin, liquiritigenin, prenyllicoflavone A, glucoliquiritin apioside, 1-metho-xyphaseolin, shinpterocarpin, shinflavanone, licopyranocoumarin, glisoflavone, licoarylcoumarin, glycyrrhizin, isoangustone A, semilicoisoflavone B, licoriphenone, and 1-methoxyficifolinol, kanzonol R and several volatile components. Pharmacological activities of G. glabra have been evaluated against various microorganisms and parasites, including pathogenic bacteria, viruses, and Plasmodium falciparum, and completely eradicated P. yoelii parasites. Additionally, it shows antioxidant, antifungal, anticarcinogenic, anti-inflammatory, and cytotoxic activities. The current review examined the phytochemical composition, pharmacological activities, pharmacokinetics, and toxic activities of G. glabra extracts as well as its phytoconstituents. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessReview
Systematic Analysis of Monoterpenes: Advances and Challenges in the Treatment of Peptic Ulcer Diseases
Biomolecules 2020, 10(2), 265; https://doi.org/10.3390/biom10020265 - 10 Feb 2020
Abstract
Peptic ulcer disease (PUD) is a multifactorial and complex disease caused by an imbalance of protective and aggressive factors (endogenous and exogenous). Despite advances in recent years, it is still responsible for substantial mortality and triggering clinical problems. Over the last decades, the [...] Read more.
Peptic ulcer disease (PUD) is a multifactorial and complex disease caused by an imbalance of protective and aggressive factors (endogenous and exogenous). Despite advances in recent years, it is still responsible for substantial mortality and triggering clinical problems. Over the last decades, the understanding of PUD has changed a lot with the discovery of Helicobacter pylori infection. However, this disease continues to be a challenge due to side-effects, incidence of relapse from use of various anti-ulcer medicines, and the rapid appearance of antimicrobial resistance with current H. pylori therapies. Consequently, there is the need to identify more effective and safe anti-ulcer agents. The search for new therapies with natural products is a viable alternative and has been encouraged. The literature reports the importance of monoterpenes based on the extensive pharmacological action of this class, including wound healing and anti-ulcerogenic agents. In the present study, 20 monoterpenes with anti-ulcerogenic properties were evaluated by assessing recent in vitro and in vivo studies. Here, we review the anti-ulcer effects of monoterpenes against ulcerogenic factors such as ethanol, nonsteroidal anti-inflammatory drugs (NSAIDs), and Helicobacter pylori, highlighting challenges in the field. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Syzygium aromaticum L. (Myrtaceae): Traditional Uses, Bioactive Chemical Constituents, Pharmacological and Toxicological Activities
Biomolecules 2020, 10(2), 202; https://doi.org/10.3390/biom10020202 - 30 Jan 2020
Cited by 5
Abstract
Herbal medicinal products have been documented as a significant source for discovering new pharmaceutical molecules that have been used to treat serious diseases. Many plant species have been reported to have pharmacological activities attributable to their phytoconstituents such are glycosides, saponins, flavonoids, steroids, [...] Read more.
Herbal medicinal products have been documented as a significant source for discovering new pharmaceutical molecules that have been used to treat serious diseases. Many plant species have been reported to have pharmacological activities attributable to their phytoconstituents such are glycosides, saponins, flavonoids, steroids, tannins, alkaloids, terpenes, etc. Syzygium aromaticum (clove) is a traditional spice that has been used for food preservation and possesses various pharmacological activities. S. aromaticum is rich in many phytochemicals as follows: sesquiterpenes, monoterpenes, hydrocarbon, and phenolic compounds. Eugenyl acetate, eugenol, and β-caryophyllene are the most significant phytochemicals in clove oil. Pharmacologically, S. aromaticum has been examined toward various pathogenic parasites and microorganisms, including pathogenic bacteria, Plasmodium, Babesia, Theileria parasites, Herpes simplex, and hepatitis C viruses. Several reports documented the analgesic, antioxidant, anticancer, antiseptic, anti-depressant, antispasmodic, anti-inflammatory, antiviral, antifungal, and antibacterial activity of eugenol against several pathogenic bacteria including methicillin-resistant Staphylococcus epidermidis and S. aureus. Moreover, eugenol was found to protect against CCl4−induced hepatotoxicity and showed a potential lethal efficacy against the multiplication of various parasites including Giardia lamblia, Fasciola gigantica, Haemonchus contortus, and Schistosoma mansoni. This review examines the phytochemical composition and biological activities of clove extracts along with clove essential oil and the main active compound, eugenol, and implicates new findings from gas chromatography-mass spectroscopy (GC-MS) analysis. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessReview
Vascular Epiphytic Medicinal Plants as Sources of Therapeutic Agents: Their Ethnopharmacological Uses, Chemical Composition, and Biological Activities
Biomolecules 2020, 10(2), 181; https://doi.org/10.3390/biom10020181 - 24 Jan 2020
Abstract
This is an extensive review on epiphytic plants that have been used traditionally as medicines. It provides information on 185 epiphytes and their traditional medicinal uses, regions where Indigenous people use the plants, parts of the plants used as medicines and their preparation, [...] Read more.
This is an extensive review on epiphytic plants that have been used traditionally as medicines. It provides information on 185 epiphytes and their traditional medicinal uses, regions where Indigenous people use the plants, parts of the plants used as medicines and their preparation, and their reported phytochemical properties and pharmacological properties aligned with their traditional uses. These epiphytic medicinal plants are able to produce a range of secondary metabolites, including alkaloids, and a total of 842 phytochemicals have been identified to date. As many as 71 epiphytic medicinal plants were studied for their biological activities, showing promising pharmacological activities, including as anti-inflammatory, antimicrobial, and anticancer agents. There are several species that were not investigated for their activities and are worthy of exploration. These epipythes have the potential to furnish drug lead compounds, especially for treating cancers, and thus warrant indepth investigations. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessReview
Avocado–Soybean Unsaponifiables: A Panoply of Potentialities to Be Exploited
Biomolecules 2020, 10(1), 130; https://doi.org/10.3390/biom10010130 - 13 Jan 2020
Cited by 1
Abstract
Avocado and soybean unsaponifiables (ASU) constitute vegetable extracts made from fruits and seeds of avocado and soybean oil. Characterized by its potent anti-inflammatory effects, this ASU mixture is recommended to act as an adjuvant treatment for osteoarthritic pain and slow-acting symptomatic treatment of [...] Read more.
Avocado and soybean unsaponifiables (ASU) constitute vegetable extracts made from fruits and seeds of avocado and soybean oil. Characterized by its potent anti-inflammatory effects, this ASU mixture is recommended to act as an adjuvant treatment for osteoarthritic pain and slow-acting symptomatic treatment of hip and knee osteoarthritis; autoimmune diseases; diffuse scleroderma and scleroderma-like states (e.g., morphea, sclerodactyly, scleroderma in bands). Besides, it was reported that it can improve the mood and quality of life of postmenopausal women in reducing menopause-related symptoms. This article aims to summarize the studies on biological effects of the avocado–soybean unsaponifiable, its chemical composition, pharmacotherapy as well as applications in autoimmune, osteoarticular and menopausal disorders. Finally, we will also discuss on its safety, toxicological and regulatory practices. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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