Chemical Composition, Antioxidant, and Antibacterial Activity of Ruta chalepensis L. Ethanolic Extract.

Ruta chalepensis L. is a versatile herb used in culinary arts and traditional medicine. The study aimed to determine the chemical composition of an ethanolic extract from R. chalepensis and the total phenolic and flavonoid content. Additionally, the extracts' antimicrobial and antioxidant activities were tested. The disc diffusion method and minimum inhibitory concentration (MIC) were used to test the antibacterial properties on four types of bacteria: Escherichia coli, Proteus penneri, Bacillus cereus, and Staphylococcus aureus. A colorimetric assay was used to evaluate the total phenolic and flavonoid content, and the DPPH method was used to assess the antioxidant activity. The phytochemical constituents were determined using LC-MS/MS. The results indicated that R. chalepensis ethanolic extract had 34 compounds, and the predominant compounds were quercetin (9.2 %), myricetin (8.8 %), and camphene (8.0 %). Moreover, the extract had a good level of polyphenols and flavonoids, as demonstrated by inhibiting free radicals (DPPH) (IC50 was 41.2±0.1). Also, the extract exhibited robust antimicrobial activity against P. penneri and S. aureus with an MIC of 12.5 and 25.0 µg/mL, respectively. In conclusion, the results suggest that the R. chalepensis ethanolic extract has good antioxidant and antibacterial properties that could be utilized to develop new antibacterial agents.

Pharmacophore-driven identification of human glutaminyl cyclase inhibitors from foods, plants and herbs unveils the bioactive property and potential of Azaleatin in the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of disabilities in old age and a rapidly growing condition in the elderly population. AD brings significant burden and has a devastating impact on public health, society and the global economy. Thus, developing new therapeutics to combat AD is imperative. Human glutaminyl cyclase (hQC), which catalyzes the formation of neurotoxic pyroglutamate (pE)-modified ß-amyloid (Aß) peptides, is linked to the amyloidogenic process that leads to the initiation of AD. Hence, hQC is an essential target for developing anti-AD therapeutics. Here, we systematically screened and identified hQC inhibitors from natural products by pharmacophore-driven inhibitor screening coupled with biochemical and biophysical examinations. We employed receptor-ligand pharmacophore generation to build pharmacophore models and Phar-MERGE and Phar-SEN for inhibitor screening through ligand-pharmacophore mapping. About 11 and 24 hits identified from the Natural Product and Traditional Chinese Medicine databases, respectively, showed diverse hQC inhibitory abilities. Importantly, the inhibitors TCM1 (Azaleatin; IC50 = 1.1 µM) and TCM2 (Quercetin; IC50 = 4.3 µM) found in foods and plants exhibited strong inhibitory potency against hQC. Furthermore, the binding affinity and molecular interactions were analyzed by surface plasmon resonance (SPR) and molecular modeling/simulations to explore the possible modes of action of Azaleatin and Quercetin. Our study successfully screened and characterized the foundational biochemical and biophysical properties of Azaleatin and Quercetin toward targeting hQC, unveiling their bioactive potential in the treatment of AD.

Integrated bioinformatics and network pharmacology to identify the therapeutic target and molecular mechanisms of Huangqin decoction on ulcerative Colitis.

Huangqin decoction (HQD) is a Traditional Chinese Medicine formula for ulcerative colitis. However, the pharmacology and molecular mechanism of HQD on ulcerative colitis is still unclear. Combined microarray analysis, network pharmacology, and molecular docking for revealing the therapeutic targets and molecular mechanism of HQD against ulcerative colitis. TCMSP, DrugBank, Swiss Target Prediction were utilized to search the active components and effective targets of HQD. Ulcerative colitis effective targets were obtained by microarray data from the GEO database (GSE107499). Co-targets between HQD and ulcerative colitis are obtained by Draw Venn Diagram. PPI (Protein-protein interaction) network was constructed by the STRING database. To obtain the core target, topological analysis is exploited by Cytoscape 3.7.2. GO and KEGG enrichment pathway analysis was performed to Metascape platform, and molecular docking through Autodock Vina 1.1.2 finished. 161 active components with 486 effective targets of HQD were screened. 1542 ulcerative colitis effective targets were obtained with |Log2FC|> 1 and adjusted P-value < 0.05. The Venn analysis was contained 79 co-targets. Enrichment analysis showed that HQD played a role in TNF signaling pathway, IL-17 signaling pathway, Th17 cell differentiation, etc. IL6, TNF, IL1B, PTGS2, ESR1, and PPARG with the highest degree from PPI network were successfully docked with 19 core components of HQD, respectively. According to ZINC15 database, quercetin (ZINC4175638), baicalein (ZINC3871633), and wogonin (ZINC899093) recognized as key compounds of HQD on ulcerative colitis. PTGS2, ESR1, and PPARG are potential therapeutic targets of HQD. HQD can act on multiple targets through multi-pathway, to carry out its therapeutic role in ulcerative colitis.

Profiling of Antifungal Activities and In Silico Studies of Natural Polyphenols from Some Plants.

A worldwide increase in the incidence of fungal infections, emergence of new fungal strains, and antifungal resistance to commercially available antibiotics indicate the need to investigate new treatment options for fungal diseases. Therefore, the interest in exploring the antifungal activity of medicinal plants has now been increased to discover phyto-therapeutics in replacement to conventional antifungal drugs. The study was conducted to explore and identify the mechanism of action of antifungal agents of edible plants, including Cinnamomum zeylanicum, Cinnamomum tamala, Amomum subulatum, Trigonella foenumgraecum, Mentha piperita, Coriandrum sativum, Lactuca sativa, and Brassica oleraceae var. italica. The antifungal potential was assessed via the disc diffusion method and, subsequently, the extracts were assessed for phytochemicals and total antioxidant activity. Potent polyphenols were detected using high-performance liquid chromatography (HPLC) and antifungal mechanism of action was evaluated in silico. Cinnamomum zeylanicum exhibited antifungal activity against all the tested strains while all plant extracts showed antifungal activity against Fusarium solani. Rutin, kaempferol, and quercetin were identified as common polyphenols. In silico studies showed that rutin displayed the greatest affinity with binding pocket of fungal 14-alpha demethylase and nucleoside diphosphokinase with the binding affinity (Kd, -9.4 and -8.9, respectively), as compared to terbinafine. Results indicated that Cinnamomum zeylanicum and Cinnamomum tamala exert their antifungal effect possibly due to kaempferol and rutin, respectively, or possibly by inhibition of nucleoside diphosphokinase (NDK) and 14-alpha demethylase (CYP51), while Amomum subulatum and Trigonella foenum graecum might exhibit antifungal potential due to quercetin. Overall, the study demonstrates that plant-derived products have a high potential to control fungal infections.

Exploring the mechanism of Jianpi Qushi Huayu Formula in the treatment of chronic glomerulonephritis based on network pharmacology.

This study was to explore the effective components, potential targets, and pathways of Jianpi Qushi Huayu Formula (JQHF) for the treatment of chronic glomerulonephritics (CGN). First, the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), GeneCards, and OMIM databases were used to collect the major active components of JQHF and potential therapeutic targets of CGN. Then, functional enrichment analysis was performed to clarify the mechanisms of the JQHF on CGN. Subsequently, molecular docking was simulated to assess the binding ability of key targets and major active components. Finally, quantitative real-time PCR and western blot were performed for experimental verification of cells in vitro. A total of 55 active ingredients contained and 220 putative identified targets were screened from JQHF, of which 112 overlapped with the targets of CGN and were considered potential therapeutic targets. Then, we found quercetin and kaempferol are two key ingredients of JQHF, which may act on the top 10 screened targets of PPI, affecting CGN through related signal transduction pathways. Subsequently, molecular docking predicted that quercetin and kaempferol bind firm with the top 10 core targets of PPI. Further experiment verified some results and showed that JQHF has protected glomerular mesangial cells from lipopolysaccharide-induced inflammation by inhibiting expressions of IL6, TNF-α, and AKT1, and activating expressions of VEGFA. Based on network pharmacology, we explored the multi-component, multi-target, and multi-pathway characteristics of JQHF in treating CGN, and found that JQHF could act on IL6, TNF-α, VEGFA, and AKT1 to exert the effect of anti-CGN, which provided new ideas and methods for further research on the mechanism of JQHF in treating CGN.

Bioactive Compounds From Coptidis Rhizoma Alleviate Pulmonary Arterial Hypertension by Inhibiting Pulmonary Artery Smooth Muscle Cells' Proliferation and Migration.

ABSTRACT: Pulmonary arterial hypertension (PAH) is a devastating disorder characterized by excessive proliferation and vasoconstriction of small pulmonary artery vascular smooth muscle cells (PASMCs). Coptidis rhizoma (CR) because of the complexity of the components, the underlying pharmacological role and mechanism of it on PAH remains unknown. In this article, the network pharmacological analysis was used to screen the main active constituents of CR and the molecular targets that these constituents act on. Then, we evaluated the importance of berberine and quercetin (biologically active components of CR) on the proliferation and migration of PASMCs and vascular remodeling in experimental models of PAH. Our results showed that berberine and quercetin effectively inhibited the proliferation and migration of hypoxia-induced PASMCs in a manner likely to be mediated by the suppression of MAPK1, NADPH oxidase 4 (NOX4), and cytochrome P450 1B1 (CYP1B1) expression. Furthermore, berberine and quercetin treatment attenuates pulmonary hypertension, reduces right ventricular hypertrophy, and improves pulmonary artery remodeling in monocrotaline-induced pulmonary hypertension in rat models. In conclusion, this research demonstrates CR might be a promising treatment option for PAH, and the network pharmacology approach can be an effective tool to reveal the potential mechanisms of Chinese herbal medicine.

Spiraeoside extracted from red onion skin ameliorates apoptosis and exerts potent antitumor, antioxidant and enzyme inhibitory effects.

Red onion skin waste (ROSW) was analyzed for extraction of naturally occurring 4'-O-glucoside of quercetin, spiraeoside (SPI) with promising biological activities. Reversed-phase high-performance liquid chromatography was used to determine the SPI content in three different solvent extracts of ROSW: water (12.2 mg/g), methanol (27.6 mg/g), and ethanol (32.5 mg/g). The ethanol extract and SPI showed significant radical-scavenging and anti-inflammatory activities. In addition, the anti-cancer effects of SPI on a HeLa cells was investigated. The results indicated that SPI treatment significantly inhibited cell growth, and the dose of 50 µg/mL exhibited the highest anti-cancer activity. SPI inhibited the expression of B-cell lymphoma 2 and BH3-interacting domain-death agonist and promoted apoptosis by activating caspase-9/-3 expression. Notably, SPI inhibited the expression of mu-2-related death-inducing gene, a molecule involved in death receptor-mediated apoptotic signaling. Cyclin-dependent kinase 2-cyclin-E expression was also inhibited after SPI treatment, particularly at the G2/M checkpoint. Our findings provide novel insights into the apoptotic potential with promising anticancer and enzyme inhibitory effects of ROSW SPI.

Selective separation of main flavonoids by combinational use of ionic liquid-loaded microcapsules from crude extract of Tartary buckwheat.

For selective adsorption of main flavonoids from crude Tartary buckwheat extract (rutin, 0.021 mg/mL; quercetin, 0.030 mg/mL; and kaempferol, 0.011 mg/mL), new ionic liquid-based sorbents were successfully prepared by encapsulating [Bmim]Br and [Bmim]Pro in regular spherical non-magnetic and magnetic microcapsules with polysulfone content of 8%, respectively. After appropriate loading process, the microcapsules were comprehensively characterized by infrared spectroscopy, thermogravimetry analysis and scanning electron microscopy. Then the separation strategy was designed to separate rutin and quercetin from kaempferol by combinational use of two kinds of IL-loaded microcapsules (ILLMs). The effects of solid-liquid ratio of ILLMs and extract, pH, time and adsorption temperature were all investigated. The experimental data fit well with the quasi-second-order kinetics model and Langmuir model. After desorption, target flavonoids were well recovered and the ILLMs showed good stability. As the result, a new IL-based separation technology for main flavonoids from food crop was developed for the first time.

A Rare Dirhamnosyl Flavonoid and Other Radical-Scavenging Metabolites from Cynophalla mollis (Kunth) J.†Presl and Colicodendron scabridum (Kunt) Seem. (Capparaceae) of Ecuador.

The phytochemistry of Cynophalla mollis (Kunth) J. Presl and Colicodendron scabridum (Kunth), both belonging to the family Capparaceae, were investigated in this study for the first time. Lupeol, betulin, lutein, stachydrine and quercetin-3,4'-di-O-rhamnoside were isolated from C. mollis, whereas C. scabridum afforded lupeol, lutein, stachydrine, ß-sitosterol, stigmasterol, betonicine and narcissoside. All these compounds were purified by preparative liquid chromatography, in both open column and instrumental (MPLC) separation systems. Preparative TLC was also applied. They were all identified by 1 H- and 13 C-NMR experiments. The complete structure of the very rare flavonoid quercetin-3,4'-di-O-rhamnoside was fully elucidated through DEPT-135, COSY, HMQC and HMBC experiments, together with UV/VIS and FT-IR spectrophotometry. Complete NMR data for quercetin-3,4'-di-O-rhamnoside in deuterated methanol were presented here for the first time. All the extracts did not exert antioxidant activity at the maximum tested dose of 1 mg/mL. Three out of the nine isolated compounds exerted a good spectrum of antioxidant capacity, being narcissoside the most active against ABTS radicals, with SC50 =12.43 µM. It was followed by lutein and quercetin-3,4'-di-O-rhamnoside, with 40.92 µM and 46.10 µM, respectively.

Proposed Mechanism for the Antitrypanosomal Activity of Quercetin and Myricetin Isolated from Hypericum afrum Lam.: Phytochemistry, In Vitro Testing and Modeling Studies.

The in vitro activity of L. donovani (promastigotes, axenic amastigotes and intracellular amastigotes in THP1 cells) and T. brucei, from the fractions obtained from the hydroalcoholic extract of the aerial part of Hypericum afrum and the isolated compounds, has been evaluated. The chloroform, ethyl acetate and n-butanol extracts showed significant antitrypanosomal activity towards T. brucei, with IC50 values of 12.35, 13.53 and 12.93 µg/mL and with IC90 values of 14.94, 19.31 and 18.67 µg/mL, respectively. The phytochemical investigation of the fractions led to the isolation and identification of quercetin (1), myricitrin (2), biapigenin (3), myricetin (4), hyperoside (5), myricetin-3-O-ß-d-galactopyranoside (6) and myricetin-3'-O-ß-d-glucopyranoside (7). Myricetin-3'-O-ß-d-glucopyranoside (7) has been isolated for the first time from this genus. The chemical structures were elucidated by using comprehensive one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) spectroscopic data, as well as high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). These compounds have also been evaluated for their antiprotozoal activity. Quercetin (1) and myricetin (4) showed noteworthy activity against T. brucei, with IC50 and IC90 values of 7.52 and 5.71 µM, and 9.76 and 7.97 µM, respectively. The T. brucei hexokinase (TbHK1) enzyme was further explored as a potential target of quercetin and myricetin, using molecular modeling studies. This proposed mechanism assists in the exploration of new candidates for novel antitrypanosomal drugs.

Inhibitory mechanism of O-methylated quercetins, highly potent ß-secretase inhibitors isolated from Caragana balchaschensis (Kom.) Pojark.

ETHNOPHARMACOLOGICAL RELEVANCE: Caragana has a standing history of implementation in Traditional Chinese Medicine (TCM). Most species of this genus have been explored for multi-functional purposes, such as promoting blood circulation and curing neuralgia, fatigue, migraine, arthritis, and vascular hypertension (Meng et al., 2009). Among them, the well-known species C. sinica showed the most promising potential to increase the expression of ADAM10 among 313 tested medicinal plants, which is one of the promising approach for the treatment of Alzheimer's disease (AD). (Schuck et al., 2015). AIM OF THIS STUDY: The aim of this work is to explore ß-secretase inhibitory activity of compounds isolated from the aerial part of endemic Caragana balchaschensis (Kom.) Pojark. We provided a full characterization of their inhibitory mechanisms, binding affinities, and binding modes. MATERIALS AND METHODS: The isolation of quercetin derivatives was accomplished by various chromatographical approaches and their structures were annotated by spectroscopic analysis. The detailed kinetic behavior of ß-secretase inhibitors was determined by estimation of kinetic parameters (Km, Vmax, KI, and KIS). Binding affinities (KSV) and binding modes of inhibitors were elucidated by fluorescence quenching and molecular docking studies, respectively. RESULTS: O-methylated quercetins (2-7) were significantly effective in ß-secretase inhibition with IC50 ranging from 1.2 to 6.5 µM. The most active one (6) was 20-fold effective than the mother skeleton, quercetin. The O-methyl motif was a critical factor in ß-secretase inhibition: tri-O-methylated (1.2 µM) > di-O-methylated (3.5 µM) > mono-O-methylated (6.5 µM) > quercetin (25.2 µM). In the kinetic study, all quercetins (1-7) showed a noncompetitive inhibition, but glucoside ones (8 and 9) were mixed type I inhibitors. The binding affinities (KSV) were agreed with inhibitory potencies. The O-methylated quercetins were annotated as the most natural abundant metabolites in the aerial part by LC-ESI-TOF/MS. Binding modes of inhibitors to enzyme were elucidated by molecular docking experiments. CONCLUSION: This study disclosed that most of the major phenolic metabolites of the aerial part of C. balchaschensis are O-methylated quercetins, which have a significant inhibitory effect on ß-secretase, which is a critical factor for AD.

A new anti-inflammatory flavonoid glycoside from tetraena aegyptia.

The chromatographic reinvestigation the methanol extract of Tetraena aegyptia led to the separation of a new flavonoid glycoside, isorhamnetin-3-O-[2```,3```-O-isopropylidene-α-L-rhamnopyranosyl]-(1```→6``)-O-ß-D-glucopyranoside (1), together with two known flavonoids, isorhamnetin (2) and isorhamnetin-3-O-glucoside (3), isolated for the first time from the plant. The new compound was evaluated for the anti-inflammatory activity by using LPS-induce RAW 264.7 cells model. Compound 1 showed significant inhibitory effect on NO release. ELISA assay showed a pronounced effect of 1 on the secretion of cytokines IL-6 and TNF-α, in a dose-dependent manner. Consistent results were obtained by qRT-PCR which revealed that compound 1 markedly reduced the mRNA expression of IL-6 and TNF-α. Together these data, we demonstrated the anti-inflammatory activity of compound 1.

Phytochemical identification and quantification of quercetin in Triplaris gardneriana wedd. leaves by HPLC-DAD with evaluation of antibacterial activity.

Triplaris gardneriana is used by traditional medicine. The objective of this work was the leaves chemical study with isolate, identify and quantify the chemical constituent, validate the analytical method and evaluate the antibacterial activity. The ethyl acetate and chloroform fractions were subjected to column chromatography for isolation of the compounds quercetin and lupeol, respectively. For the identification, quantification of quercetin in the samples and validation of method were performed using HPLC-DAD. The antibacterial activity was evaluated by the microdilution method. The isolated phytochemicals are being reported for the first time in the species. The ethyl acetate fraction showed a higher content of quercetin with 9.967 ± 1.01 mg.g-1. The method was validated. The samples showed good antibacterial activity. In this study, quercetin was isolated and quantified in the species being a great alternative as a producer of this secondary metabolite, which can be safely applied in the quality control analysis.

A mixture of quercetin 4'-O-rhamnoside and isoquercitrin from Tilia americana var. mexicana and its biotransformation products with antidepressant activity in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The aerial parts of Tilia americana var. mexicana (Malvaceae, formerly Tiliaceae) or "sirimo" are used in Mexican traditional medicine for the relief of mild symptoms of mental stress, commonly referred to as "nerve diseases". Individuals use this plant to fall asleep, to calm states of nervous excitement, headaches, mood disorders, and general discomfort. Recent studies indicated that fractions standardized in their flavonoid content possess antidepressant activity in behavioral assays in mice. The present study aims to focus on the evaluation of the antidepressant effect of the mixture of two flavonoids (FMix), and its interaction with serotonergic drugs. Also, the pharmacological effect of the products of the metabolism of aglycone, quercetin, was evaluated in mice subjected to forced swimming test (FST) and open field test (OFT). MATERIALS AND METHODS: A methanol-soluble extract obtained from leaves of Tilia americana was fractionated in an open column chromatographic separation. One of the fractions contained FMix wich is constituted of the mixture of quercetin 4'-O-rhamnoside (1, 47%) y isoquercitrin (2, 53%). The mice were divided into the several following groups: FMix (0.01, 0.1, 0.5, 1.0, and 2 mg/kg); FMix (1.0 mg/kg) and agonist DOI (2.0 mg/kg); FMix (1.0 mg/kg) and antagonist ketanserin (KET, 0.03 mg/kg) of 5-HT2A receptors; FMix (1.0 mg/kg) and selective agonist 8-OH-DPAT (8-OH, 0.01 mg/kg); FMix (1.0 mg/kg) and antagonist WAY100635 (WAY, 0.5 mg/kg) of 5HT1 receptors; Phloroglucinol (PHL); 3,4-dihydroxy-phenyl acid (DOPAC); p-hydroxyphenyl acetic acid (p-HPAA); and m-hydroxyphenyl acetic acid (m-HPAA) were tested in FST or OFT. RESULTS: FMix induced dependent-dose antidepressant activity and, at the highest dose administered, a sedative effect was also observed. The 8-OH-DPAT, or the DOI, or the KET combination with FMix (1.0 mg/kg) induced a higher antidepressant effect than compounds alone; there was no effect exerted with WAY. The activity on OFT increased only with the FMix and KET combination. At the same time, the products of the aglycone metabolism of quercetin, that is, DOPAC and p-HPAA, decreased the immobility time of the mice in FST at 1.0 mg/kg, and a dose-curve was formed for these. CONCLUSION: The antidepressant effect of FMix could depend, at least in part, on the degradation products of quercetin and with a possible action mode through interaction with the serotoninergic system.

Bovine ß-lactoglobulin peptides as novel carriers for flavonoids extracted with supercritical fluids from yellow onion skins.

Our study describes in detail the binding mechanism between the main flavonoids that were extracted from onion skins by supercritical CO2 and peptides from whey proteins, from the perspective of obtaining multifunctional ingredients, with health-promoting benefits. The supercritical CO2 extract had 202.31 ± 11.56 mg quercetin equivalents/g DW as the major flavonoid and antioxidant activity of 404.93±1.39 mM Trolox/g DW. The experiments on thermolysin-derived peptides fluorescence quenching by flavonoids extract allowed estimating the binding parameters, in terms of binding constants, and the number of binding sites. The thermodynamic analysis indicated that the main forces involved in complex formation were hydrogen bonds and van der Waals interactions. Molecular docking tests indicated that peptide fluorescence quenching upon gradual addition of onion skin extract might be due to flavonoids binding by Val15 -Ser21 . All 7 to 14 amino acids long peptides appeared to have affinity toward quercetin-3,4'-O-diglucoside and quercetin-4'-O-monoglucoside. The study is important as a potential solution for reuse of valuable resources, underutilized, such as whey peptides and yellow onion skins flavonoids for efficient microencapsulation, as a holistic approach to deliver healthy and nutritious food. PRACTICAL APPLICATION: A growing interest was noticed in the last years in investigating the interactions between proteins and different biologically active compounds, such as to provide knowledge for efficient development of new food, pharmaceutical, and cosmetic products. Recent studies suggest that flavonoid-protein complexes may be designed to improve the functional performance of the flavonoids. The results obtained in this study bring certain benefits in terms of exploiting the bioactive potential of both flavonoids and bioactive peptides, for developing of formulas with improved functional properties.

Cellular target of isoquercetin from Passiflora ligularis Juss for glucose uptake in rat soleus muscle.

Quercetin 3-O-beta-d-glucopyranoside (isoquercetin) is one of the most frequent metabolites of the Passiflora ligularis Juss. The purpose of this study was to investigate the effect of the aqueous extract and ethanol fraction from P. ligularis Juss leaves on glycaemia and the mechanism of action of isoquercetin on glucose uptake. In the glucose tolerance test, the aqueous extract and ethanol fraction from P. ligularis Juss (125 mg/kg to 500 mg/kg o. g.) reduced glycaemia and increased the hepatic and muscular glycogen content. Phytochemical analysis evidenced the dominant presence of isoquercetin in the extract and fraction from leaves of P. ligularis Juss. Isoquercetin mediates the stimulatory effect on glucose uptake independent of insulin receptor activation but, involve PI3K, MAPK, MEK/ERK pathways and de novo protein synthesis to GLUT-4 translocation. Overall findings revealed that isoquercetin and aqueous extract and ethanol fraction of P. ligularis Juss leaves might be a promising functional food or medicine for the treatment or prevention of diabetes.

Modulatory properties of cardiac and quercetin glycosides from Dacryodes edulis seeds during L-NAME-induced vascular perturbation.

Background Numerous food wastes have been identified to possess potent bioactive compounds used for the treatment of several diseases. Therefore this study evaluated the potentials of cardiac and quercetin glycosides extracted from Dacryodes edulis seeds to reverse vascular and endothelial damage (VAED). Methods The glycoside composition of the seeds was extracted using standard methods and characterized by gas chromatography. We then recruited rats with L-NAME-induced VAED based on confirmatory biomarkers cardiac troponin (CnT), cellular adhesion molecule (VCAM-1), lipoprotein associated phospholipase A2 (Lp-PLA2), RAAS, VWF, endothelin, eNOx, and homocysteine. Only rats that showed total alterations of all biomarkers were recruited into the respective experimental groups and treated with either metaprolol succinate (met.su) + losartan or glycoside extracts of D. edulis seeds (NPSG). Results Chromatographic isolation of glycosides in the seed showed predominance of artemetin (1.59 mg/100 g), amygdalin (3.68 mg/100 g), digitoxin (19.21 mg/100 g), digoxin (27.23 mg/100 g), avicularin (133.59 mg/100 g), and hyperoside (481.76 mg/100 g). We observed decreased water intake and higher heart beats under vascular damage as the experiment progressed up to the fourth week. The met.su + losartan and H.D NPSG proved effective in restoring troponin, but both doses of NPSG normalized the VCAM-1 and RAAS activities excluding aldosterone and Lp-PLA2. Among the endothelial dysfunction biomarkers, H.D NPSG produced equivalent effects to met.su + losartan towards restoring the eNOx and VWF activities, but showed higher potency in normalizing the endothelin and Hcy levels. Conclusions We thus propose that the synergistic effect of the isolated glycosides from D. edulis shown in our study proved potent enough at high doses in treatment of vascular and endothelial dysfunction.

Bioassay-Guided Separation of Centipeda minima Using Comprehensive Linear Gradient Centrifugal Partition Chromatography.

A comprehensive linear gradient solvent system for centrifugal partition chromatography (CPC) was developed for the bioassay-guided isolation of natural compounds. The gradient solvent system consisted of three different ternary biphasic solvents types: n-hexane-acetonitrile-water (10:2:8, v/v), ethyl acetate-acetonitrile-water (10:2:8, v/v), and water-saturated n-butanol-acetonitrile-water (10:2:8, v/v). The lower phase of the n-hexane-acetonitrile-water (10:2:8, v/v) was used as the stationary phase, while its upper phase, as well as ethyl acetate-acetonitrile-water (10:2:8), and water-saturated n-butanol-acetonitrile-water (10:2:8, v/v) were pumped to generate a linear gradient elution, increasing the mobile phase polarity. We used the gradient CPC to identify antioxidant response elements (AREs), inducing compounds from Centipeda minima, using an ARE-luciferase assay in HepG2 cells, which led to the purification of the active molecules 3-methoxyquercetin and brevilin A. The developed CPC solvent systems allow the separation and isolation of compounds with a wide polarity range, allowing active molecule identification in the complex crude extract of natural products.

In vivo bioactivity assessment on Epilobium species: A particular focus on Epilobium angustifolium and its components on enzymes connected with the healing process.

ETHNOPHARMACOLOGICAL RELEVANCE: Epilobium species are generally known as "Yaki Otu" in Turkey, which mens "plaster herb" in English. Young shoots of Epilobium angustifolium L., Epilobium stevenii Boiss., and Epilobium hirsutum L. are consumed as salad or meal. These species have been used as a poultice for the treatment of mouth wounds in traditional medicine. An ointment prepared from leaves is used for skin disorders in children. AIM OF THE STUDY: We aimed to evaluate the ethnopharmacological use of Epilobium angustifolium, E. stevenii, and E. hirsutum by using in vivo and in vitro experimental models, and to identify the active wound-healer compound(s) and to explain the probable mechanism of the wound-healing activity. MATERIALS AND METHODS: Evaluation of wound healing effects of plant extracts was performed in rats and mice by linear incision and circular excision wound models. Determination of total phenolic constituents and antioxidant capacities, which are known to promote the wound healing process, were carried out through Folin-Ciocalteau method and 2,2 Diphenyl 1 picrylhydrazyl (DPPH) scavenging assay as well as determination of total antioxidant status (TAS) and total oxidant status (TOS) on the treated tissues. The active ethyl acetate (EtOAc) sub-extract of E. angustifolium was fractionated by different chromatographic separation techniques. The structures of isolated compounds were elucidated via detailed analyzes (NMR and LC/MS). In addition, in vitro collagenase, hyaluronidase, and elastase enzymes inhibitory activity tests were performed on the isolated compounds to discover the activation pathways of the samples. RESULTS: Among the methanol (MeOH) extracts, E. angustifolium had the highest wound healing activity. Among the sub-extracts, EtOAc showed the highest wound healing activity. Thus, EtOAc sub-extract was subjected to chromatography to isolate the active compounds. Five known flavonoids namely hyperoside (quercetin-3-O-ß-D-galactoside) (1), kaempferol (2), kaempferol-3-O-α-L-rhamno pyranoside (3), quercetin-3-O-α-L-rhamno pyranoside (4), and quercetin-3-O-α-L-arabino pyranoside (5) were isolated from the EtOAc sub-extract of E. angustifolium. In vitro tests showed that hyperoside could be the compound responsible for the wound-healing activity by its significant anti-hyaluronidase, anti-collagenase, and antioxidant activities. CONCLUSION: The EtOAc sub-extract of the aerial part of Epilobium angustifolium displayed remarkable wound-healing activity with anti-hyaluronidase, anti-collagenase, and antioxidant activities. Hyperoside was detected as the primary active compound of the aerial parts. According to the results, we suggest that EtOAc sub-extract of E. angustifolium and hyperoside may be a potent nominee to be used for the improvement of a wound-healing agent.

Isorhamnetin: A review of pharmacological effects.

Isorhamnetin is one of the most important active ingredients in the fruits of Hippophae rhamnoides L. and the leaves of Ginkgo biloba L., which possesses extensive pharmacological activities. At present, there have been numerous investigations on isorhamnetin, which has the effects of cardiovascular and cerebrovascular protection, anti-tumor, anti-inflammatory, anti-oxidation, organ protection, prevention of obesity, etc. The related mechanisms involve the regulation of PI3K/AKT/PKB, NF-κB, MAPK and other signaling pathways as well as the expression of related cytokines and kinases. Isorhamnetin has a high value of development and application. However, the investigations on its mechanism of action are limited and lack of detailed scientific validation. The manuscript reviewed the pharmacological effects of isorhamnetin and related mechanisms of action for the development of its medicinal properties further.