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Zanthoxylum bungeanum leaves (ZBL) are of great medicinal value for being rich in hyperoside and quercitrin. In this study, a novel, efficient and economical continuous process was established. First, aqueous two-phase system (ATPS) composed of Triton X-100/(NH 4 ) 2 SO 4 was employed to enrich hyperoside and quercitrin from ZBL extracts and the recoveries reached 98.53% and 99.12%. Then back-extraction with dichloromethane-water system was adopted to separate hyperoside and quercitrin from Triton X-100 micelles which were recycled and the recoveries reached 86.58% and 85.19%. Finally, S-8 macroporous resin was used for removing the salt introduced in ATPS and the final recoveries reached 82.38% and 81.81%, much higher than the total flavonoids recovery as 69.08%. Furthermore, scale-up experiment certified that the continuous process was feasible for industrial production. Efficiently and economically, this method achieved a great breakthrough in purity and provided a novel reference for further purification and phase-forming component recycle.

Ethnopharmacological Relevance: Trifolium resupinatum L. (Fabaceae), known as Persian clover, ethnomedicinally used in Persian folk medicine to treat peritoneal inflammation, rheumatism, and back pain., Aim of the Study: To investigate the antineuropathic and antinociceptive activities of Trifolium resupinatum leaves essential oil (TREO) in male Wistar rats, as well as to explore the potential mechanisms of action., Materials and Methods: The antinociceptive activity of TREO and its main constituents, quercetin (Qc) was assessed using the formalin-induced paw licking test. Moreover, the potential mechanisms of antinociception were evaluated through various competitive and non-competitive antagonisms. Additionally, the antineuropathic potential was investigated using the cervical spinal cord hemi-contusion (CCS) model, and the role of phosphorylated Stat-3 was analyzed using Western blotting., Results: TREO exerted significant antinociceptive activity (P < 0.01) in both phases of the formalin-induced test; however, its effects were more pronounced in the second phase. Modulators of the NO-cGMP-K + channel pathway significantly reversed the antinociceptive activity of TREO (P < 0.05). Additionally, antagonists of TRPV1 and TRPV2, as well as CB1 and GABA A receptors, significantly reversed the antinociceptive effects of TREO (P < 0.05). In another study, both TREO and Qc significantly attenuated hyperalgesia and mechanical allodynia (P < 0.01) when evaluated using the CCS-induced nociception model. Notably, TREO also reduced the expression levels of interleukin-1 beta, interleukin-2, and tumor necrosis factor alpha in CCS-induced rats (P < 0.05)., Conclusion: TREO and Qc exhibit both antinociceptive and anti-neuropathic activities. The antinociceptive effects are partially mediated through the NO-cGMP-K + channel pathways, along with the activation of TRPV, GABA, and cannabinoid receptors. Furthermore, the anti-neuropathic activity of TREO may be partially regulated through the inhibition of cytokines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Every year, cardiovascular diseases (CVDs) account for about 17.9 million deaths, making them the primary cause of both morbidity and mortality. Conventional drugs, which are often prescribed to treat cardiovascular diseases, are costly and have adverse effects. Consequently, dietary modifications and other medications are needed. Traditional use of Solanum indicum as cardiotonic to treat hypertension and anticoagulant potency has been reported but poorly evaluated scientifically., Aim of the Study: This study investigated the in vivo anticoagulant activity and mechanism of anticoagulation of quercetin (QC), a bioactive compound isolated from S. indicum (SI) hydroethanolic fruit extract., Materials and Methods: Bioassay-guided fractionation (anticoagulant activity) extracted QC from hydroethanolic SI extract. QC was extensively characterized biochemically and pharmacologically. The interaction between QC and thrombin was investigated using spectrofluorometric and isothermal calorimetric methods. Cytotoxicity, antiplatelet, and thrombolytic studies were carried out in vitro. The Swiss albino mice were used to assess the in vivo, anticoagulant, and antithrombotic activities of QC., Results: QC exhibits anticoagulant activity via (i) uncompetitive inhibition of thrombin but not FXa with a Ki value of 33.11 ± 4.2 μM and (ii) a partial inhibition of thrombin-catalyzed platelet aggregation with an IC 50 value of 13.2 ± 1.2 μM. The experimental validation of the in silico study's prediction of QC's binding to thrombin was confirmed by spectrofluorometric and isothermal calorimetric analyses. QC was nontoxic to mammalian, non-hemolytic cells and demonstrated thrombolytic activity by activating plasminogen. QC demonstrated in vivo anticoagulant efficacy, preventing k-carrageen-induced thrombus formation in mice's tails. In the acute circulatory stasis paradigm in mice, QC reduces thromboxane B2 (TXB 2 ) and endothelin-1 (ET-1) while increasing nitric oxide synthase (eNOS) and 6-keto prostaglandin F1α (6-keto-PGF1 α)., Conclusion: Effective in vivo anticoagulant and antithrombotic properties of S. indicum's bioactive component QC point to the plant's potential use as a herbal anticoagulant medication for preventing and treating cardiovascular diseases linked to thrombosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Vachellia gummifera (Willd.) Kyal. & Boatwr. is a medicinal plant endemic to Morocco that has no documented studies on its chemical composition. In this study, the chemical composition of the water/methanol (4 : 1) extracts of air-dried leaf and stem samples of Moroccan V. gummifera was determined using UHPLC-MS and NMR. In total, over 100 metabolites were identified in our study. Pinitol was the major compound in both the leaf and stem extracts, being significantly more abundant in the former. Asparagine and 3-hydroxyheteroendrin were the second most abundant compounds in the stem and leaf extracts, respectively, though both compounds were present in each tissue. The other compounds included flavonoids based on quercetin, and phenolic derivatives. Eucomic acid, only identified in the stems and was the major aromatic compound distinguishing the leaf and stem profiles. Quercetin 3-O-(6''-O-malonyl)-β-D-glucopyranoside was identified as the major flavonoid in the leaves but was also present in the stems. Other malonylated derivatives that were all flavonol glycosides based on myricetin, kaempferol, and isorhamnetin in addition to quercetin were also identified. This is the first report of eucomic acid and malonylated compounds in Vachellia species. This report provides valuable insights into the chemotaxonomic significance of the Vachellia genus., (© 2024 The Authors. Chemistry & Biodiversity published by Wiley-VHCA AG.)

Staphylea , also called bladdernuts, is a genus of plants belonging to the family Staphyleaceae, widespread in tropical or temperate climates of America, Europe, and the Far East. Staphylea spp. produce bioactive metabolites with antioxidant properties, including polyphenols which have not been completely investigated for their phytotherapeutic potential, even though they have a long history of use for food. Here, we report the isolation of six flavonol glycosides from the hydroalcoholic extract of aerial parts of Staphylea pinnata L., collected in Italy, using a solid-phase extraction technique. They were identified using spectroscopic, spectrometric, and optical methods as three quercetin and three isorhamnetin glycosides. Among the flavonol glycosides isolated, isoquercetin and quercetin malonyl glucoside showed powerful antioxidant, antimicrobial, and wound healing promoting activity and thus are valuable as antiaging ingredients for cosmeceutical applications and for therapeutic applications in skin wound repair.

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) (IC 50 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., (© 2024 Wiley‐VHCA AG, Zurich, Switzerland.)

Flavonol and flavonoid compounds are important natural compounds with various biomedical activities. Therefore, it is of great significance to develop a strategy for the specific extraction of flavonol and flavonoid compounds. Quercetin is a well-studied flavonoid possessing many health benefits. This compound is a versatile antioxidant known to possess protective abilities against body tissue injury induced by pathological situations and various drug toxicities. Although quercetin is widely distributed in many plants, its content generally is not very high. Therefore, the specific extraction of quercetin as well as other flavonol and flavonoid compounds has profound significance. In this work, the quercetin molecularly imprinting polymer (QMIP) was successfully prepared, in which a typical flavonol quercetin was selected as the template molecule. QMIP was synthesized by performing the surface molecular imprinting technology on the surface of NH 2 -MIL-101(Fe). Our study results showed that QMIP exhibited quick binding kinetic behavior, a high adsorption capacity (57.04[Formula: see text]mg/g), and the specific recognition ability toward quercetin compared with structurally distinct compounds (selective [Formula: see text]). The specific adsorption ability of quercetin by QMIP was further explained using computation simulation that molecules with non-planar 3D conformations hardly entered the molecularly imprinted cavities on QMIP. Finally, QMIP was successfully used for the specific extraction of quercetin and five other flavonol and flavonoid compounds in the crude extracts from Sapium sebiferum . This study proposes a new strategy to synthesize the molecularly imprinted polymer based on a single template for enriching and loading a certain class of active ingredients with similar core structures from variable botanicals.

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 β-amyloid (Aβ) 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; IC 50 = 1.1 μM) and TCM2 (Quercetin; IC 50 = 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.

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 |Log 2 FC|> 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., (© 2022. The Author(s).)

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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cancer cells meet their energy need by predominantly increased uptake of glucose, high rate of glycolysis, and increased production of lactate even in the presence of adequate oxygen.  This process was proposed by Otto Warburg and named after him as the Warburg effect. The development of drugs that target glucose intake and aerobic glycolysis or lactic acid secretion of cancer cells is a newer approach for drug discovery. We have tested five purified plants-derived compounds such as curcumin, quercetin, ellagic acid, resveratrol, and indole-3-carbinol in HeLa cells for cytotoxicity, inhibition of metastasis, and modulation of lactate-pyruvate metabolism. Standard biochemical methods were used for glucose, lactic acid, and pyruvic acid measurement. The cell viability was determined by MTT assay. Cell migration was checked by wound healing assay. A dose-dependent cytotoxic effect and inhibition of cell migration were observed in all the tested compounds. A decrease in the lactate and increase in pyruvate level was observed in all the tested compounds except ellagic acid. Our finding suggests that tested phytocompounds are associated with the metabolic reprogramming of cancer cells and execute the cytotoxic effect. These compounds could be used for cancer prevention and therapy., (© 2020 International Union of Biochemistry and Molecular Biology, Inc.)

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 (K d , -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.

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The pharmacological characteristics of phytochemicals have prompted a lot of interest in their application in disease management. Due to the high incidence of cancer related mortality and morbidity throughout the world; experiments have concentrated on identifying the anticancer potential of natural substances. Many phytochemicals such as flavonoids and their derivatives produced from food offer a variety of new anti-cancer agents which prevent the cancer progression. Taxifolin, a unique bioactive flavonoid, is a dietary component that has grabbed the interest of dietitians and medicinal chemists due to its wide range of health benefits. It is a powerful antioxidant with a well-documented effect in the prevention of several malignancies in humans. Taxifolin has shown promising inhibitory activity against inflammation, malignancies, microbial infection, oxidative stress, cardiovascular disease, and liver disease. Anti-cancer activity has been shown to be relatively significant than other activities investigated in vitro and in vivo with a little or no side effects to the normal healthy cells. In summary this review offers the synopsis of recent breakthroughs in the use of taxifolin as a cancer treatment, as well as mechanisms of action. However, to develop a medicine for human usage, more study on pharmacokinetic profile, profound molecular mechanisms, and drug safety criteria should be conducted utilizing well-designed randomized clinical trials., (Copyright © 2021. Published by Elsevier Masson SAS.)

Background: Caulerpa lentillifera (CL) is a green seaweed, and its edible part represents added value as a functional ingredient. CL was dried and extracted for the determination of its active compounds and the evaluation of its biological activities. The major constituents of CL extract (CLE), including tannic acid, catechin, rutin, and isoquercetin, exhibited beneficial effects, such as antioxidant activity, anti-diabetic activity, immunomodulatory effects, and anti-cancer activities in in vitro and in vivo models. Whether CLE has an anti-inflammatory effect and immune response remains unclear., Methods: This study examined the effect of CLE on the inflammatory status and immune response of lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the mechanisms involved therein. RAW264.7 cells were treated with different concentrations of CLE (0.1-1000 µg/mL) with or without LPS (1 µg/mL) for 24 h. Expression and production of the inflammatory cytokines, enzymes, and mediators were evaluated., Results: CLE suppressed expression and production of the pro-inflammatory cytokines IL-6 and TNF-α. Moreover, CLE inhibited expression and secretion of the inflammatory enzyme COX-2 and the mediators PGE2 and NO. CLE also reduced DNA damage. Furthermore, CLE stimulated the immune response by modulating the cell cycle regulators p27, p53, cyclin D2, and cyclin E2., Conclusions: CLE inhibits inflammatory responses in LPS-activated macrophages by downregulating inflammatory cytokines and mediators. Furthermore, CLE has an immunomodulatory effect by modulating cell cycle regulators.

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.

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 G 2 /M checkpoint. Our findings provide novel insights into the apoptotic potential with promising anticancer and enzyme inhibitory effects of ROSW SPI., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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, β-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 SC 50 =12.43 μM. It was followed by lutein and quercetin-3,4'-di-O-rhamnoside, with 40.92 μM and 46.10 μM, respectively., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

Molecular imprinted polymers coated magnetic halloysite nanotubes (MHNTs-MIPs) were prepared through sol-gel method by using quercetin (Que), APTES and TEOS as template, monomer and cross-linker agent, respectively. The synthesized MHNTs-MIPs were characterized by fourier transform infrared, scanning electron microscope, transmission electron microscope, XRD and vibrating sample magnetometer. Various parameters influencing the binding capacity of the MHNTs-MIPs were investigated with the help of response surface methodology. Selectivity experiments showed that the MHNTs-MIPs exhibited the maximum selective rebinding to Que. Therefore, the MHNTs-MIPs was applied as a solid-phase extraction adsorbent for the extraction and preconcentration of quercetin and luteolin in serum and urine samples. The limits of detection for quercetin and luteolin range from 0.51 to 1.32 ng mL-1 in serum and from 0.23 to 1.05 ng mL-1 in urine, the recoveries are between 95.20 and 103.73% with the RSD less than 5.77%. While the recovery hardly decreased after several cycles. The designed MHNTs-MIP with high affinity, sensitivity and maximum selectivity toward Que in SPE might recommend a novel method for the extraction of flavonoids in other samples like natural products., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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 -β-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 .

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 β-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 β-secretase inhibitors was determined by estimation of kinetic parameters (K m , V max , K I , and K IS ). Binding affinities (K SV ) 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 β-secretase inhibition with IC 50 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 β-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 (K SV ) 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 β-secretase, which is a critical factor for AD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Current pharmacological treatments for insomnia carry several and long-term side effects. Therefore, natural products without side effects are warranted. In this study, the sleep-promoting activity of the lotus leaf ( Nelumbo nucifera ) extract was assessed using ICR mice and Sprague Dawley rats. A pentobarbital-induced sleep test and electroencephalogram analysis were conducted to measure sleep latency time, duration, and sleep architecture. The action mechanism of the extract was evaluated through ligand binding experiments. A high dose (300 mg/kg) of the ethanolic lotus leaf extract significantly increased sleep duration compared to the normal group ( p < 0.01). Administration of low (150 mg/kg) and high doses (300 mg/kg) of the extract significantly increased sleep quality, especially the relative power of theta waves ( p < 0.05), compared to the normal group. Furthermore, caffeine and lotus leaf extract administration significantly recovered caffeine-induced sleep disruption ( p < 0.001), and the sleep quality was similar to that of the normal group. Additionally, ligand binding assay using [ 3 H]-flumazenil revealed that quercetin-3 -O- glucuronide contained in the lotus leaf extract (77.27 μg/mg of extract) enhanced sleep by binding to GABA A receptors. Collectively, these results indicated that the lotus leaf extract, particularly quercetin-3- O -glucuronide, exhibits sleep quantity- and quality-enhancing activity via the GABAergic pathway.

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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Taxifolin is a kind of dihydroflavone and is usually used as a food additive and health food for its antioxidant, anti-inflammatory, and anti-tumor activities. The purpose of this research is to probe into the hepatoprotective activity and the molecular mechanism of taxifolin., Materials and Methods: The liver fibrosis model was established by intraperitoneal injection of 5 mL/kg body weight of CCl 4 (20% CCl 4 peanut oil solution), and taxifolin was dissolved with 0.9% physiological saline and administered intragastrically to mice., Results: The results indicated that CCl 4 -induced significantly increased the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mice. Histopathological examination showed severe hepatocyte necrosis and hepatic tissue lesion. Immunohistochemical staining and rt-PCR analysis demonstrated that the expressions of inducible nitric oxide synthetase (iNOS), cyclooxygenase-2 (COX-2), IL-1β, IL-6, and TNF-α were increased. These changes were significantly reversed when treated with taxifolin. In addition, TUNEL staining and Bcl-2/Bax pathway confirmed that taxifolin significantly inhibited hepatocyte apoptosis. Besides, the research confirmed that taxifolin also inhibited the activation of hepatic stellate cells and the production of extracellular matrix (ECM) by regulating PI3K/AKT/mTOR and TGF-β1/Smads pathways., Conclusion: Taxifolin inhibited inflammation, and attenuated CCl 4 -induced oxidative stress and cell apoptosis by regulating PI3K/AKT/mTOR and TGF-β1/Smads pathways, which might in part contributed to taxifolin anti-hepatic fibrosis, further demonstrating that taxifolin may be an efficient hepatoprotective agent., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Liu et al.)

Sirtuin 1 (SIRT1), an NAD + -dependent deacetylase, is a crucial regulator that produces multiple physiological benefits, such as the prevention of cancer and age-related diseases. SIRT1 is activated by sirtuin-activating compounds (STACs). Here, we report that quercetin 3,5,7,3',4'-pentamethyl ether (KPMF-8), a natural STAC from Thai black ginger Kaempferia parviflora, interacts with SIRT1 directly and stimulates SIRT1 activity by enhancing the binding affinity of SIRT1 with Ac-p53 peptide, a native substrate peptide without a fluorogenic moiety. The binding affinity between SIRT1 and Ac-p53 peptide was enhanced 8.2-fold by KPMF-8 but only 1.4-fold by resveratrol. The specific binding sites of KPMF-8 to SIRT1 were mainly localized to the helix2-turn-helix3 motif in the N-terminal domain of SIRT1. Intracellular deacetylase activity in MCF-7 cells was promoted 1.7-fold by KPMF-8 supplemented in the cell medium but only 1.2-fold by resveratrol. This work reveals that KPMF-8 activates SIRT1 more effectively than resveratrol does.

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 IC 50 values of 12.35, 13.53 and 12.93 µg/mL and with IC 90 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 -β-d-galactopyranoside ( 6 ) and myricetin-3'- O -β-d-glucopyranoside ( 7 ). Myricetin-3'- O -β-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 IC 50 and IC 90 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.

In this research, two nonlinear models, namely; adaptive neuro-fuzzy inference system and feed-forward neural network and a classical linear model were employed for the prediction of retention time of isoquercitrin in Coriander sativum L. using the high-performance liquid chromatography technique. The prediction employed the use of composition of mobile phase and pH as the corresponding input parameters. The performance indices of the models were evaluated using root mean square error, determination co-efficient, and correlation co-efficient. The results obtained from the simple models showed that subclustering-adaptive-neuro fuzzy inference system gave the best results in both the training and testing phases and boosted the performance accuracy of the simple models. The overall comparison of the results showed that subclustering-adaptive-neuro fuzzy inference system ensemble demonstrated outstanding performance and increased the accuracy of the single models and ensemble models in the testing phase, up to 35% and 3%, respectively., (© 2021 Wiley-VCH GmbH.)

Our study describes in detail the binding mechanism between the main flavonoids that were extracted from onion skins by supercritical CO 2 and peptides from whey proteins, from the perspective of obtaining multifunctional ingredients, with health-promoting benefits. The supercritical CO 2 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 Val 15 -Ser 21 . 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., (© 2020 Institute of Food Technologists®.)

Ethnopharmacological Relevance: Epilobium species are generally known as "Yakı 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-β-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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Smilax brasiliensis is a medicinal species of the Brazilian Cerrado. The extract and fractions of this plant were analysed by LC-DAD-MS. Identified constituents included glycosylated and non-glycosylated flavonoids, especially quercetin, and phenylpropanoids, such as chlorogenic acids. The antioxidant activity was significantly more pronounced for the methanol extract and fractions than that of the commercial antioxidant 2,6-di-tert-butyl-4-methylphenol (BHT). Maximum larvicidal activity of 85.83% was recorded in the dichloromethane fraction (LC 50 = 469.78 µg mL -1 ). The methanol extract and fractions presented low toxicity to larvae of the shrimp brine Artemia salina, indicating selectivity for C. quinquefasciatus . These results contribute to the phytochemical study of S. brasiliensis . These compounds were identified for the first time in this species and encourage additional work on the isolation of compounds present in the extract and fractions of S. brasiliensis to evaluate the possibility of using them as natural sources of antioxidants, since cytotoxic effects were not demonstrated.

A novel acylated quercetin glycoside, floralpanasenoside A ( 1 ) and five known flavonoid glycosides, panasenoside ( 2 ), quercetin 3- O -(2''- β -D-glucopyranosyl)- β -D- galactopyranoside ( 3 ), trifolin ( 4 ) kaempferol 7- O - α -L-rhamnoside ( 5 ), and afzelin ( 6 ) were isolated from the flower buds of Panax ginseng . Their structures were established by spectroscopic data and comparison with the literature values. Four of the six isolated compounds including 1 (IC 50 = 62.4) exhibited α -glucosidase inhibitory activity with IC 50 values lower than acarbose (385.2 μM). The molecular docking study indicated that 1 bound to the active site of α -glucosidase with numerous hydrogen bond interactions.

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., Competing Interests: Declaration of Competing Interest The authors declare that there are no competing interests associated with the manuscript., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In vitro acetylholinesterase (AChE) inhibitory activity of an autochthonous sample of the mushroom Coprinus comatus (encompassing fruiting body FB, mycelia M and filtrate F from the submerged cultivation) was the subject of this study. C. comatus F extract exhibited rather potent anti-AChE activity (73.0 ± 1.5%) at in liquid conditions, comparable to those of the conventional drug donepezil (80.6 ± 1.4%). Also, the same extract exhibited high anti-AChE activity (1 µg) in solid . While its FTIR spectrum indicated the presence of phenolic compounds, quercetin (28.1 µg g -1 d.w.) was found to affect the observed bioactivity (59.8 ± 0.9%). This is the first report of profound anti-AChE activity of any C. comatus extract, a medicinal mushroom that has been successfully cultivated in P.R. China, due to the demanding needs of food industry.

The objective of this work was the development of an on-line extraction/fractionation method based on the coupling of pressurized liquid extraction and solid-phase extraction for the separation of phenolic compounds from apple pomace. Several variables of the process were evaluated, including the amount of water of the first stage (0-120 mL), temperature (60-80 °C), solid-phase extraction adsorbent (Sepra, Isolute, Strata X and Oasis) and activation/elution solvent (methanol and ethanol). The best results were observed with the adsorbent Sepra. The temperature had a small effect on recovery, but significant differences were observed for phlorizin and a quercetin derivative. Results indicate that ethanol can be used to replace methanol as an activation, extraction/elution solvent. While using mostly green solvents (water, ethanol, and a small amount of methanol that could be reused), the developed method produced higher or similar yields of acids (2.85 ± 0.19 mg/g) and flavonoids (0.97 ± 0.11 mg/g) than conventional methods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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.

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.

Prickly pear fruit peel constitutes a high percentage of the fruit and could be a natural, economic agro-industrial waste of potential use in the nutraceutical industry. This study aimed to isolate and characterize the main constituents of the fruit peel and evaluate its antibacterial activity. A methanol extract was successively fractionated using hexane, chloroform and ethyl acetate. The n-hexane fraction was evaluated for its fatty acid content using gas chromatography mass spectrometry (GC-MS), revealing linolenic acid (omega-3) as the major fatty acid (60.56%), while an ethyl acetate fraction was analyzed using ultra-performance liquid chromatography electrospray tandem mass spectrometry (UPLC-ESI-MS/MS), resulting in the identification of 6 phenolic acids and 9 flavonoids, where caffeic acid (43.69%) and quercetin (14%) were found the most abundant. The ethyl acetate fraction was subjected to column chromatography, resulting in the isolation of four flavanols, viz. astragalin (1), quercetin 5,4'-dimethyl ether (2), isorhamnetin-3-O-glucoside (3) and isorhamnetin (4). Antibacterial evaluation revealed that the EtOAc fraction is the most potent active fraction against the selected pneumonia pathogens, and quercetin 5,4'-dimethyl ether (2) is the most active among the isolated compounds. Virtual docking of the isolated compounds showed promising in silico anti-quorum sensing efficacy, indicating that they could represent natural antibacterial agents. These findings indicate that the unused waste from prickly pear fruits contains valuable constituents that have beneficial potential against some pneumonia pathogens.

We previously reported that the ethyl acetate (EtOAc) fraction of a 70% ethanol extract of Elaeocarpus sylvestris (ESE) inhibits varicella-zoster virus (VZV) and human cytomegalovirus (HCMV) replication in vitro. PGG (1,2,3,4,6-penta-O-galloyl-ß-D-glucose) is a major chemical constituent of the EtOAc fraction of ESE that inhibits VZV but not HCMV replication. In this study, we comprehensively screened the chemical compounds identified in the EtOAc fraction of ESE for potential antiviral properties. Among the examined compounds, quercetin and isoquercitrin displayed potent antiviral activities against both VZV and HCMV with no significant cytotoxic effects. Both compounds strongly suppressed the expression of VZV and HCMV immediate-early (IE) genes. Our collective results indicated that, in addition to PGG, quercetin and isoquercitrin are bioactive compounds in the EtOAc fraction of ESE that effectively inhibit human herpesvirus replication.

In this work, to improve the availability of the recognition sites of molecularly imprinted polymers (MIPs), ordered macroporous molecularly imprinted polymers (OMMIPs) were facilely prepared by grafting a quercetin-MIPs layer on the pore walls of the ordered macroporous thiol group functionalized silica. The pore structures were characterized by FTIR, Raman, SEM, BET and TGA measurements. The results indicated that OMMIPs possessed a nanoscale polymer layer, a more regular macroporous structure and a greater porosity compared with the traditional bulk MIPs (TBMIPs). The polymer content of OMMIPs was about 49.7%. Kinetic and isothermal adsorption experiments indicated that OMMIPs exhibited higher affinity and selectivity towards quercetin than its structural analogues. Moreover, OMMIPs could improve the intra-particle adsorption and thus provide a significant improvement in recognition sites availability over TBMIPs. Using the quercetin-OMMIPs as SPE sorbent, quercetin was directly extracted from the crude Gingko leaves extract with a satisfying selectivity and elution recovery., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Extraction behaviors of the 3 flavonoids taxifolin, diosmin, and quercetin have been investigated in Abies nephrolepis leaves and bark. The following operation parameters-ethanol volume fraction, liquid-solid ratio, temperature, ultrasound irradiation power and time, and ultrasound frequency-were varied to study their effect on the yield of the 3 flavonoids during extraction. The results showed that a low extraction efficiency occurred at 293.15 K due to slow kinetics, while the situation was significantly improved at 333.15 K. The kinetic data for the extraction yields of the 3 flavonoids achieved good fits by the first-order kinetic model. From the thermodynamic analysis results, we realized that the ultrasound-assisted extraction of taxifolin, diosmin, and quercetin from the leaves and bark of A. nephrolepis was a spontaneous and endothermic process in which the disorder increased (Δ G 0 < 0, Δ H 0 > 0, and Δ S 0 > 0). According to the response surface methodology (RSM) analysis, under the optimal operation conditions (ethanol concentration of 50%, liquid-solid ratio of 20 mL/g, frequency of 45 kHz, extraction time of 39.25 min, ultrasound irradiation power of 160 W and temperature of 332.19 K), the total yield of the 3 flavonoids were 100.93 ± 4.01 mg/g from the leaves of A. nephrolepis (with 31.03 ± 1.51 mg/g, 0.31 ± 0.01 mg/g, 69.59 ± 2.57 mg/g for taxifolin, diosmin, and quercetin, respectively), and under the optimal operation conditions (ethanol concentration of 50%, liquid-solid ratio of 20 mL/g, frequency of 45 kHz, extraction time of 36.80 min, ultrasound irradiation power of 150 W and temperature of 328.78 K), 16.05 mg/g ± 0.38 mg/g were obtained from the bark of A. nephrolepis (with 1.44 ± 0.05 mg/g, 0.47 ± 0.01 mg/g, 14.14 ± 0.38 mg/g for taxifolin, diosmin, and quercetin, respectively), which were close to the prediction values.

In this study, an attempt has been made to devise a method for a large-scale production of quercetin from a medicinal plant. The natural products are first isolated from plants and then synthesized commercially. During their synthesis, a number of impurities or side products are also formed, most of which are carcinogenic. Plant products have limited side effects. Therefore, they are considered safe to be used for systemic uses. In the Rubus fruticosus fruit, the ethyl acetate extract was loaded to 50 optimized silica gel columns. The effluents of columns were passed through the membrane system for concentration. A 100% recovery was achieved from the drain pipe in case of reverse osmosis membrane when the specified rely of the pilot plant was set on 25% rejection. About 95% recovery was achieved through the NF membrane while the 5% loss in permeate was recovered through magnetic carbon nanocomposite (characterized through a bar magnet, SEM, XRD, and EDX). The equilibrium time of adsorption was 83 min and followed by pseudo-first-order kinetics. The adsorption equilibrium data fitted well to the Langmuir isotherm model. Through the devised method, quercetin was successfully concentrated with high efficiencies; however, further studies are needed to validate the method., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Muhammad Zahoor et al.)

Sea buckthorn ( Hippophae rhamnoides ) berries are well known for their content in bioactive compounds, high acidity, bright yellow color, pleasant taste and odor, thus their addition in a basic food such as bread could be an opportunity for modern food producers. The aim of the present research was to investigate the characteristics and the effects of the berry' flour added in wheat bread (in concentration of 1%, 3% and 5%) on sensory, physicochemical and antioxidant properties, and also bread shelf life. Berry flour contained total polyphenols-1467 mg gallic acid equivalents (GAE)/100 g, of which flavonoids-555 mg GAE/100 g, cinnamic acids-425 mg caffeic acid equivalents (CAE)/100 g, flavonols-668 mg quercetin equivalents (QE)/100 g. The main identified phenolics were catechin, hyperoside, chlorogenic acid, cis- and trans-resveratrol, ferulic and protocatechuic acids, procyanidins B1 and B2, epicatechin, gallic acid, quercetin, p - and m -hydroxybenzoic acids. The antioxidant activity was 7.64 mmol TE/100 g, and carotenoids content 34.93 ± 1.3 mg/100 g. The addition of berry flour increased the antioxidant activity of bread and the shelf life up to 120 h by inhibiting the development of rope spoilage. The obtained results recommend the addition of 1% Hippophae rhamnoides berry flour in wheat bread, in order to obtain a product enriched in health-promoting biomolecules, with better sensorial and antioxidant properties and longer shelf life.

Phenolamines and flavonoids are two important components in bee pollen. There are many reports on the bioactivity of flavonoids in bee pollen, but few on phenolamines. This study aims to separate and characterize the flavonoids and phenolamines from rape bee pollen, and compare their antioxidant activities and protective effects against oxidative stress. The rape bee pollen was separated to obtain 35% and 50% fractions, which were characterized by HPLC-ESI-QTOF-MS/MS. The results showed that the compounds in 35% fraction were quercetin and kaempferol glycosides, while the compounds in 50% fraction were phenolamines, including di-p-coumaroyl spermidine, p-coumaroyl caffeoyl hydroxyferuloyl spermine, di-p-coumaroyl hydroxyferuloyl spermine, and tri-p-coumaroyl spermidine. The antioxidant activities of phenolamines and flavonoids were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), and ferric reducing antioxidant power (FRAP) assays. It was found that the antioxidant activity of phenolamines was significantly higher than that of flavonoids. Moreover, phenolamines showed better protective effects than flavonoids on HepG2 cells injured by AAPH. Furthermore, phenolamines could significantly reduce the reactive oxygen species (ROS), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and increase the superoxide dismutase (SOD) and glutathione (GSH) levels. This study lays a foundation for the further understanding of phenolamines in rape bee pollen.

In this study, the phenolic profiles and bioactivities of five representative cultivars of okra collected in China were investigated. Noticeable variations of phenolic compounds and their bioactivities were observed among these different cultivars of okra. The contents of total flavonoids (TFC) in "Shuiguo", "Kalong 8", "Kalong 3", "Wufu", and "Royal red" ranged from 1.75 to 3.39 mg RE/g DW, of which "Shuiguo" showed the highest TFC. Moreover, five individual phenolic compounds were found in okra by high performance liquid chromatography analysis, including isoquercitrin, protocatechuic acid, quercetin-3-O-gentiobioside, quercetin, and rutin, while isoquercitrin and quercetin-3-O-gentiobioside were detected as the main phenolic compounds in okra. Moreover, all tested okra exhibited significant antioxidant activities (2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity, 2,2'-azino-bis (3-ethylenzthiazoline-6-sulphonic acid) radical scavenging capacity, and ferric reducing antioxidant power) and inhibitory effects on digestive enzymes (lipase, α-glucosidase, and α-amylase). Indeed, "Shuiguo" exhibited much better antioxidant activities and inhibitory activities on digestive enzymes, which might be attributed to its high TFC. Results suggested that okra, especially "Shuiguo", could be developed as natural antioxidants and inhibitors against hyperlipidemia and hyperglycemia in the fields of functional foods and pharmaceuticals, which could meet the increasing demand for high-quality okra with health-promoting properties in China.

The aim of the present study was to develop self-microemulsifying drug delivery systems (SMEDDS) of the extract of Moringa oleifera, a herbal medicinal plant. Kaempferol and quercetin, the flavonoids present in the leaf extract of M. oleifera, were chosen as markers for quantification. The optimized formulation of SMEDDS consisted of propylene glycol dicaprylocaprate, polysorbate 80, and polyethylene glycol 400 (PEG 400) in a percentage ratio of 20:60:20 (m/m). SMEDDS emulsified immediately (within 20 s) after dilution in water, resulting in transparent microemulsions with a droplet size of 49 nm. SMEDDS could increase the solubility of kaempferol and quercetin to nearly 100 % within 15 min, whereas only a 30 % improvement in solubility was achieved in the case of crude extract. These results demonstrated SMEDDS to be a promising strategy to improve the solubility of M. oleifera extract-derived drugs, which, in turn, could prove beneficial to the herbal medicine field.

Fireweed has recently been recognized as a plant with high antioxidant potential and phenolic content. Its leaves can be fermented to prepare an infusion with ideal antioxidant activity. The aim of this study was to investigate and to determine the influence of solid-phase fermentation of different durations on the variation of polyphenols in the leaves of fireweed. Laboratory experiments were conducted in 2017-2018. The leaves of fireweed, naturally growing, were fermented for different periods of time: not fermented (control) and fermented for 24 and 48 h. The evaluation of polyphenols and antioxidant activity in leaves was performed using high- performance liquid chromatography (HPLC). Additionally, principal component analysis was used to characterize differences in bioactive compounds between fireweed samples fermented at different durations. Solid-phase fermented leaves were characterized by higher contents of oenothein B, quercetin and benzoic acid but had lower contents of quercetin-3- O -rutinoside, luteolin and chlorogenic and gallic acids. Antioxidant activity in short- (24 h) and long-term (48 h) fermentation (compared to control) gave the highest level of regression in 2017, but in 2018 the effect was observed only with short-term fermentation and control. In conclusion, solid-phase fermentation can be used to modulate biologically active compounds in fireweed leaves., Competing Interests: The authors declare no conflict of interest.

This study aimed to compare the biological activities of 35 herbal hydroethanolic extracts and select high potential extract, which showed antioxidative activity and inhibitory activities of α-glucosidase, lipase, and hyaluronidase, and to investigate the isolation, structural elucidation, and biological activities of five phenolic compounds from the selected extracts of Rosa gallica. On the basis of one-dimensional nuclear magnetic resonance together with the comparison with the literature values, the phenolic compounds were identified as methyl gallate (1), kaempferol-3-O-arabinofuranoside (2), multinoside A acetate (3), kaempferol (4), and quercetin (5), respectively. The results suggest that the extracts from R. gallica show the strongest biological activities in 35 herbal extracts and that 1, 4, and 5 among the five isolated compounds from rose extracts are effective in promoting antioxidative and enzymatic inhibitory activities.

Quercetin (QC) is one of the most prominent dietary antioxidants present in vegetables/fruits, specifically in onions that rank second in consumption following tomato. QC with proven health benefits is now largely utilized as a nutritional supplement. In this work that aims to isolate QC from red onion peels forming a huge agricultural waste, a QC-molecularly imprinted polymer (QC-MIP) in a molar ratio of 1:4:20 (QC:4-vinylpyridine:ethylene glycol dimethacrylate) was prepared thermally through bulk polymerization. Molecularly imprinted solid phase extraction (MISPE) procedures were applied for the selective pre-concentration and purification of QC from both red onion peel methanolic extract with 58% recovery and from the extract hydrolyzate with 86% recovery. The hydrolysis process increased both the QC amount as expected and the recovery yield due to changing matrix components. The results demonstrated that onion peel can easily and efficiently be converted to a valuable product, QC, using QC-MIP as SPE sorbent., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)