Major Bioactive Flavonoid Research Articles

The Gastroprotective Effect of Sicyos angulatus Against Hydrochloric Acid/Ethanol-Induced Acute Gastritis and Gastric Ulcer in Mice.

Gastritis and gastric ulcers are common gastric diseases that are caused by infection, drugs, alcohol consumption, or stress. These conditions lead to increased inflammatory cytokines and recruitment of leukocytes, which damage the stomach mucosa and exacerbate disease severity. Sicyos angulatus (SA), an annual vine in the Cucurbitaceae family, is known to have an anti-inflammatory effect, but its efficacy for preventing gastritis and gastric ulcers has not yet been evaluated. In the present study, we investigated the gastroprotective effect of SA using a hydrochloric acid/ethanol-induced gastric mucosal injury mouse model and lipopolysaccharide (LPS)-stimulated KATO III cells. Macroscopic analysis revealed a reduction in gastric ulcer area. Similarly, histopathological analysis showed a dose-dependent decrease in gastric mucosal injury, with significant improvement at 750 mg/kg of SA treatment. Gene expressions of inflammatory cytokines, chemokines, and adhesion molecule were reduced in the SA-administered group. Immunohistochemical staining indicated that SA significantly decreased neutrophil infiltration in the lamina propria and epithelium of the stomach. Kaempferol, a major bioactive flavonoid of SA, also improved gastric injury by reducing macroscopic and microscopic lesions, inflammatory mediator gene expression, and neutrophil infiltration. Furthermore, both SA and kaempferol downregulated LPS-mediated increases in inflammatory cytokines and chemokines following inhibition of p38 and c-Jun N-terminal kinase (JNK) phosphorylation in KATO III cells. These results suggest that SA can ameliorate gastric mucosal injury by inhibiting the recruitment of inflammatory cells, particularly neutrophils, and by suppressing p38 and JNK phosphorylation.

In vitro Evaluation of Skin Related Enzyme Inhibitory Effect and Emulgel Formulation Development Studies of Onobrychis Argyrea subsp. Argyrea with Phytochemical Analysis.

Species of Onobrychis have been used to treat skin disorders such as wounds and cuts in folk medicine and Onobrychis argyrea subsp. argyrea (OA) commonly known as 'silvery sainfoin', is a member of this genus. In this study, it was aimed to investigate the skin-related biological activities and phytochemical characterization of OA. Moreover, an emulgel formulation was developed from the main methanolic extract of the plant (OAM). Initially, to identifiy of the active fractions, aerial parts of the plant material was extracted with methanol and fractionated by n-hexane, chloroform, ethyl acetate and n-butanol, respectively. Antioxidant activity was determined by CUPRAC, TOAC, FRAP and DPPH assays. Thereafter, the inhibition potential of OAM, novel formulation and all fractions was measured against elastase, collagenase, tyrosinase and hyaluronidase enzymes. OAM was analyzed and characterized by LC/MS-MS. The major bioactive flavonoids which are rutin and isoquercetin were measured and compared as qualitative and quantitative via high performance thin layer chromatography (HPTLC) analysis in OAM and fractions. The results showed that extracts of OA can be a potential cosmeceutical agent for skin related problems.

Chromosomal level genome assembly of medicinal plant Sophora flavescens

Sophora flavescens is a medicinal plant in the genus Sophora of the Fabaceae family. The root of S. flavescens is known in China as Kushen and has a long history of wide use in multiple formulations of Traditional Chinese Medicine (TCM). In this study, we used third-generation Nanopore long-read sequencing technology combined with Hi-C scaffolding technology to de novo assemble the S. flavescens genome. We obtained a chromosomal level high-quality S. flavescens draft genome. The draft genome size is approximately 2.08 Gb, with more than 80% annotated as Transposable Elements (TEs), which have recently and rapidly proliferated. This genome size is ~5x larger than its closest sequenced relative Lupinus albus L. . We annotated 60,485 genes and examined their expression profiles in leaf, stem and root tissues, and also characterised the genes and pathways involved in the biosynthesis of major bioactive compounds, including alkaloids, flavonoids and isoflavonoids. The assembled genome highlights the very different evolutionary trajectories that have occurred in recently diverged Fabaceae, leading to smaller duplicated genomes.

Casticin as potential anticancer agent: recent advancements in multi-mechanistic approaches.

Plants, with their range of pharmacologically active molecules, represent the most promising source for the production of new anticancer drugs and for the formulation of adjuvants in chemotherapy treatments to reduce drug content and/or counteract the side effects of chemotherapy. Casticin is a major bioactive flavonoid isolated from several plants, mainly from the Vitex species. This compound is well known for its anti-inflammatory and antioxidant properties, which are mainly exploited in traditional medicine. Recently, the antineoplastic potential of casticin has attracted the attention of the scientific community for its ability to target multiple cancer pathways. The purpose of this review is, therefore, to present and critically analyze the antineoplastic potential of casticin, highlighting the molecular pathways underlying its antitumor effects. Bibliometric data were extracted from the Scopus database using the search strings "casticin" and "cancer" and analyzed using VOSviewer software to generate network maps to visualize the results. Overall, more than 50% of the articles were published since 2018 and even more recent studies have expanded the knowledge of casticin's antitumor activity by adding interesting new mechanisms of action as a topoisomerase IIα inhibitor, DNA methylase 1 inhibitor, and an upregulator of the onco-suppressive miR-338-3p. Casticin counteracts cancer progression through the induction of apoptosis, cell cycle arrest, and metastasis arrest, acting on several pathways that are generally dysregulated in different types of cancer. In addition, they highlight that casticin can be considered as a promising epigenetic drug candidate to target not only cancer cells but also cancer stem-like cells.

Oroxylin A inhibited autoimmune hepatitis-induced liver injury and shifted Treg/Th17 balance to Treg differentiation.

Autoimmune hepatitis (AIH) is a kind of autoimmune disease mediated by T cells, and its incidence is gradually increasing in the world. Oroxylin A (OA) is one of the major bioactive flavonoids that has been reported to inhibit inflammatory. Here, an AIH model of mouse was induced by Concanavalin A (Con A). It found that serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were decreased in mice with the treatment of OA. Hematoxylin-eosin staining showed that the liver injury was attenuated by OA, and TUNEL staining indicated that the cells apoptosis of liver was weakened in mice with OA treatment. ELISA analysis of cytokines and chemokines suggested that OA reduced the expression of IL-6, IL-17A, chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 1 (CXCL1) and CXCL10, but promoted the expression of IL-10 and TGF-β in mice. The mRNA levels of Il-17a in liver and spleen tissues were also significantly decreased, on the contrary, the mRNA levels of Il-10 in liver and spleen tissues were increased. The proportion of Treg/Th17 detected by flow cytometry revealed that OA promoted the differentiation of Treg and inhibited the differentiation of Th17 both in the liver and spleen. The results of this study demonstrated the inhibitory effects of OA on AIH-induced liver injury and the inflammatory response of AIH, and revealed that OA affected the balance of Treg/Th17 and shifted the balance toward Treg differentiation. It provided new potential drugs for the prevention of AIH.

Social isolation induces neuroinflammation and microglia overactivation, while dihydromyricetin prevents and improves them

BackgroundAnxiety disorders are the most prevalent mental illnesses in the U.S. and are estimated to consume one-third of the country’s mental health treatment cost. Although anxiolytic therapies are available, many patients still exhibit treatment resistance, relapse, or substantial side effects. Further, due to the COVID-19 pandemic and stay-at-home order, social isolation, fear of the pandemic, and unprecedented times, the incidence of anxiety has dramatically increased. Previously, we have demonstrated dihydromyricetin (DHM), the major bioactive flavonoid extracted from Ampelopsis grossedentata, exhibits anxiolytic properties in a mouse model of social isolation-induced anxiety. Because GABAergic transmission modulates the immune system in addition to the inhibitory signal transmission, we investigated the effects of short-term social isolation on the neuroimmune system.MethodsEight-week-old male C57BL/6 mice were housed under absolute social isolation for 4 weeks. The anxiety-like behaviors after DHM treatment were examined using elevated plus-maze and open field behavioral tests. Gephyrin protein expression, microglial profile changes, NF-κB pathway activation, cytokine level, and serum corticosterone were measured.ResultsSocially isolated mice showed increased anxiety levels, reduced exploratory behaviors, and reduced gephyrin levels. Also, a dynamic alteration in hippocampal microglia were detected illustrated as a decline in microglia number and overactivation as determined by significant morphological changes including decreases in lacunarity, perimeter, and cell size and increase in cell density. Moreover, social isolation induced an increase in serum corticosterone level and activation in NF-κB pathway. Notably, DHM treatment counteracted these changes.ConclusionThe results suggest that social isolation contributes to neuroinflammation, while DHM has the ability to improve neuroinflammation induced by anxiety.

HPLC-DAD Fingerprints Combined With Multivariate Analysis of Epimedii Folium From Major Producing Areas in Eastern Asia: Effect of Geographical Origin and Species

The growth location and plant variety may influence the active components and biological activities of plants used in phytomedicine. In this study, nine sets of different Epimedii Folium, from different representative cultivation locations and Epimedium species, were collected for comparison, using HPLC-DAD combined with multivariate analysis. The objective was to investigate the influence of geographical origin and Epimedium species on the quality of Epimedii Folium, and provide applicable guidance for cultivation and quality control of Epimedii Folium. Several Epimedium spp. sets were used to establish the HPLC-DAD fingerprints and 91 peaks (compounds) were selected for the multivariate analysis. Major compounds were analyzed by HPLC-DAD combined with principal component analysis (PCA). HPLC quantitative analysis of known bioactive compounds was performed. Application of PCA to HPLC data showed that Epimedium samples sharing the same geographical origin or species clustered together, indicating that both species and geographical origin have impacts on the quality of Epimedii Folium. The major bioactive flavonoid compounds, epimedin C, icariin and baohuoside I, were identified and quantified. The concentration of bioactive compounds was significantly influenced both by species and geographical origin. E. sagittatum from Sichuan showed the highest content of bioactive compounds. The results showed that both Epimedium species and geographical origin have strong impact into quality of Epimedii Folium. HPLC data combined with multivariate analysis is a suitable approach to inform the selection of cultivation areas and choose Epimedium spp. most suitable for different geographical areas, resulting in improved quality of Epimedii Folium.

Microbial Transformation of Galangin Derivatives and Cytotoxicity Evaluation of Their Metabolites

Galangin (1), 3-O-methylgalangin (2), and galangin flavanone (3), the major bioactive flavonoids isolated from Alpinia officinarum, were biotransformed into one novel and four known metabolites (4–8) by application of the fungal strains Mucor hiemalis and Absidia coerulea as biocatalysts. Their structures were characterized by extensive spectroscopic analyses including one- and two-dimensional nuclear magnetic resonance spectroscopy and mass spectrometry. Compounds 1–7 were evaluated for their cytotoxic activities against cancer cell lines using the MTT assay. The new compound 3-O-methylgalangin-7-O-β-D-glucopyranoside (6) exhibited the most potent cytotoxic activity against MCF-7, A375P, B16F10, B16F1, and A549 cancer cell lines with the IC50 values at 3.55–6.23 μM.

Quercetin induces proteolysis of mesenchymal marker vimentin through activation of caspase-3, and decreases cancer stem cell population in human papillary thyroid cancer cell line.

Back groundEpithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) play an essential role in metastasis of papillary thyroid cancer (PTC), and vimentin is associated with lymph node metastasis and poor prognosis. Hence, inhibition of EMT and effective elimination of CSCs offers a novel target for developing new therapeutic agents. The objective of this study is to inspect the effect of quercetin, a major dietary bioactive flavonoid, on vimentin, CSCs and associated mechanism. MethodsThe first mechanism of quercetin mediated cytotoxicity was investigated in NPA cell line. Subsequently, the effect of quercetin was investigated on glycolysis, vimentin, CSCs, and the mechanism of vimentin degradation was also explored. ResultQuercetin effectively induces cytotoxicity by executing intrinsic apoptosis and activates caspase-3 through extracellular signal-regulated kinase (ERK) activation in NPA cell line having typical mesenchymal characters. Quercetin inhibits NPA cells migration and reduces extracellular acidification rate (ECAR), an indicator of enhanced glycolysis, required for cell migration. Quercetin treatment suppresses vimentin phosphorylation at lower concentrations, a critical step in cell migration, further proving its potential against cell migration. Phosphorylation of Vimentin is also crucial in the protection of vimentin from caspase-mediated proteolysis. Interestingly, quercetin activates caspase-3 at higher concentrations; hence, total vimentin levels were investigated, and caspase-3 mediated proteolysis of vimentin was observed. Vimentin and glycolysis are essential features of the mesenchymal state, which is required to maintain CSCs. Ours data also suggests quercetin mediated reduction in CSCs population. ConclusionWe report a novel mechanism of quercetin mediated inhibition of NPA cells migration by suppressing vimentin phosphorylation and subsequent proteolysis. Collectively our data suggest the potential of quercetin as an innovative anti-cancer therapeutic agent for PTC management.

Phytochemical constituents and extracts of the roots of Scutellaria baicalensis exhibit in vitro and in vivo control efficacy against various phytopathogenic microorganisms

Scutellaria baicalensis is one of the most well-known medicinal herbs used in traditional Chinese herbal medicine. During our search of antimicrobial botanicals, the methanol extract from the roots of S. baicalensis displayed in vivo control efficacy against various fungal plant diseases and in vitro inhibition against phytopathogenic bacteria. In an in vitro antifungal bioassay, ethyl acetate-soluble extract was highly active against the growth of Magnaporthe oryzae and Phytophthora sp. mycelia in the range of 500 to 5000 µg/mL. Through antifungal activity-guided bioassay, bioactive flavonoids and an oligosaccharide were identified from the EtOAc soluble extract of S. baicalensis roots by ESI-MS and 1D- and 2D-NMR data analyses. These constituents were assessed for their in vitro and in vivo antifungal activities. The major bioactive flavonoids SB1 (wogonin), SB4 (baicalein), and SB5 (baicalin) in the extracts of S. baicalensis’s roots were quantified by HPLC method. Among these three compounds, SB1 exhibited the best in vitro antifungal effect against M. oryzae and in vivo efficacy (63%) against rice blast at 500 µg/mL. SB4 was the most active against plant bacteria Acidovorax avenae subsp. cattlyae, Clavibacter michiganensis subsp. michiganensis, and Ralstonia solanacearum with an MIC value of 19 µg/mL. Moreover, the emulsion-type formulation containing the ethyl acetate-soluble extract of S. baicalensis significantly suppressed the development of rice blast caused and rice leaf blight on the rice plants in vivo. This is the first report that demonstrated bioactive constituents and extracts derived from S. baicalensis plants, which are promising to develop botanical fungicide and bactericide to control various plant diseases.

Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy

The regenerative effect of Epimedium and its major bioactive flavonoid icariin (ICA) have been documented in traditional medicine, but their effect on sarcopenia has not been evaluated. The aim of this study was to investigate the effects of Epimedium extract (EE) on skeletal muscle as represented by differentiated C2C12 cells. Here we demonstrated that EE and ICA stimulated C2C12 myotube hypertrophy by activating several, including IGF-1 signal pathways. C2C12 myotube hypertrophy was demonstrated by enlarged myotube and increased myosin heavy chains (MyHCs). In similar to IGF-1, EE/ICA activated key components of the IGF-1 signal pathway, including IGF-1 receptor. Pre-treatment with IGF-1 signal pathway specific inhibitors such as picropodophyllin, LY294002, and rapamycin attenuated EE induced myotube hypertrophy and MyHC isoform overexpression. In a different way, EE induced MHyC-S overexpression can be blocked by AMPK, but not by mTOR inhibitor. On the level of transcription, EE suppressed myostatin and MRF4 expression, but did not suppress atrogenes MAFbx and MuRF1 like IGF-1 did. Differential regulation of MyHC isoform and atrogenes is probably due to inequivalent AKT and AMPK phosphorylation induced by EE and IGF-1. These findings suggest that EE/ICA stimulates pathways partially overlapping with IGF-1 signaling pathway to promote myotube hypertrophy.

Polygonum hydropiper extract attenuates ethanol-induced gastric damage through antioxidant and anti-inflammatory pathways.

The present study was conducted to investigate the underlying mechanisms and effective components of Polygonum hydropiper in ethanol-induced acute gastric mucosal lesions. The ethanol extract was purified on an AB-8 macroporous resin column and eluted with 60% ethanol and was then injected into the HPLC system for quantitative analysis. Sprague-Dawley rats were orally pretreated with P. hydropiper extract (PHLE; 50, 100, and 200 mg/kg) for 5 days and then absolute ethanol was administered to induce gastric mucosal damage. One hour after ethanol ingestion, the rats were euthanized and stomach samples were collected for biochemical analysis. Antioxidant enzymes and anti-inflammatory cytokines were quantified. Western blotting was used to detect the expression levels of proteins. Cell proliferation was assayed by CCK-8 assays. The proportion of total flavonoids in the final extract of P. hydropiper was 50.05%, which contained three major bioactive flavonoid constituents, including rutin, quercitrin, and quercetin. PHLE significantly increased cell viability and effectively protected human gastric epithelial cells-1 against alcohol-induced damage in vitro. PHLE pretreatment attenuated gastric mucosal injuries in a dose-dependent manner in rats, and increased the activity of superoxide dismutase, glutathione peroxidase, and glutathione, and decreased the levels of malondialdehyde in gastric tissue. Pretreatment with PHLE also reduced the generation of the pro-inflammatory cytokines tumor necrosis factor-α and interleukin-1β in gastric tissue by downregulating the expression of nuclear factor-kappa B. PHLE exerted protective effects against gastric injury through antioxidant and anti-inflammatory pathways. Flavonoids might be the main effective components of P. hydropiper against gastric mucosal injury.

Network pharmacology analysis and experimental validation to explore the mechanism of sea buckthorn flavonoids on hyperlipidemia

Ethnopharmacological relevanceSea buckthorn is popularly used as a herbal medicine and food additive in the world. Sea buckthorn flavonoids (SF) is reported to have an ameliorative effect on obesity and hyperlipidemia (HLP). AimTo identify the major bioactive compounds and the lipid-lowering mechanism of SF. MethodsWe used network pharmacology analysis and in vitro experiments to identify the major bioactive compounds and the lipid-lowering mechanism of SF. ResultsA total of 12 bioactive compounds, 60 targets related to SF and HLP were identified, and a component-target-disease network was constructed. The KEGG analysis revealed that SF regulated cholesterol metabolism, fat digestion and absorption, and PPAR signaling pathways in HLP. The experimental validation indicated that sea buckthorn flavonoids extract (SFE) and 4 bioactive compounds reduced lipid droplet accumulation, up-regulated the mRNA expression of PPAR-γ, PPAR-α, ABCA1 and CPT1A, etc, down-regulated SREBP-2 and its target gene LDLR, which are closely related to cholesterol conversion into bile acids, de novo synthesis and fatty acids oxidation. The major bioactive flavonoid isorhamnetin (ISOR) also increased the protein expression of PPAR-γ, LXRα and CYP7A1. ConclusionSF might promote cholesterol transformation into bile acids and cholesterol efflux, inhibit cholesterol de novo synthesis and accelerate fatty acids oxidation for ameliorating HLP.

Elucidating the Molecular Interactions of Chemokine CCL2 Orthologs with Flavonoid Baicalin.

An integrated and controlled migration of leukocytes is necessary for the legitimate functioning and maintenance of the immune system. Chemokines and their receptors play a decisive role in regulating the leukocyte migration to the site of inflammation, a phenomena often referred to as chemotaxis. Chemokines and their receptors have become significant targets for therapeutic intervention considering their potential to regulate the immune system. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a preeminent member of CC chemokine family that facilitates crucial roles by orchestrating the recruitment of monocytes into inflamed tissues. Baicalin (BA), a major bioactive flavonoid, has been reported to attenuate chemokine-regulated leukocyte trafficking. However, no molecular details pertaining to its direct binding to chemokine(s)/receptor(s) are available till date. In the current study, using an array of monomers/dimers of human and murine CCL2 orthologs (hCCL2/mCCL2), we have shown that BA binds to the CCL2 protein specifically with nanomolar affinity (Kd = 270 ± 20 nM). NMR-based studies established that BA binds CCL2 in a specific pocket involving the N-terminal, β1- and β3-sheets. Docking studies suggested that the residues T16, N17, R18, I20, R24, K49, E50, I51, and C52 are majorly involved in complex formation through a combination of H-bonds and hydrophobic interactions. As the residues R18, R24, and K49 of hCCL2 are crucial determinants of monocyte trafficking through receptor/glycosaminoglycans (GAG) binding in CCL2 human/murine orthologs, we propose that baicalin engaging these residues in complex formation will result in attenuation of CCL2 binding to the receptor/GAGs, thus inhibiting the chemokine-regulated leukocyte trafficking.

Ziziphora clinopodioides flavonoids based on network pharmacology attenuates atherosclerosis in rats induced by high-fat emulsion combined with vitamin D3 by down-regulating VEGF/AKT/NF-κB signaling pathway

Ziziphora clinopodioides flavonoids (ZCF) is a major bioactive total flavonoids compound isolated from Ziziphora clinopodioides Lam. It has been long used as an anti-atherosclerosis (AS) in clinics. However, anti-AS effects of ZCF have not been fully investigated. The objective of this study is to further investigate the anti-AS activities and mechanisms of ZCF in vivo. The main chemical components, action targets and signal pathways of Ziziphora clinopodioides Lam were predicted and analyzed by network pharmacology technology. The main bioactive components of Ziziphora clinopodioides Lam were identified using high performance liquid chromatography-mass spectrometry (HPLC-MS). In vivo experiments, atherosclerosis in rats induced by high-fat emulsion combined with vitamin D3 and treated with simvastatin (0.45 mg/kg/d), ZCF (6.25, 12.5, 25 g/kg/d) for 7 weeks.We found that ZCF significantly reduced blood lipid levels (TG, TC, and LDL-C), and decreased lipid deposition in the aorta and atherosclerotic lesion size, inhibited mitochondrial mem- brane potential (MMP2/9/12/13) impairment. Meanwhile, ZCF may down-regulated the levels of VEGF, AKT, NF-κB, ICAM-1 and VCAM-1 proteins, indicating ZCF may play an anti-atherosclerotic role by down-regulating the VEGF/AKT/NF-κB signaling pathway.Results from this study demonstrated that ZCF have an anti-AS ability to lower lipid concentrations and protect endothelial function, antioxidant and anti-inflammatory activity, and suggested that ZCF might be a potential therapeutic drug in the prevention of AS.

Optimization of Solvent Systems for the Extraction of Vitexin as the Major Bioactive Flavonoid in <i>Prosopis farcta</i>

Prosopis farcta, a plant belongs to the mimosoideae, is characterized by a very wide spectrum of various bioactive and medical constituents. Vitexin, the marker flavonoid found in Prosopis, has potent and broad antitumour efficacy in preclinical models. Many studies had been done for the isolation of flavonoids (vitexin) by completely different chromatographically methodology. During this study, vitexin was isolated from Prosopis farcta by 6 different extraction methods in which parameters as the type, concentration and pH of the extracting solvents considered. Among different solvent systems used, methanol-water (40%, containing acetic acid 0.5%) was found to be the best solvent generating the highest yield (0.554 mg·g-1 DW) from Prosopis leaves. The present work suggests an efficient method for estimation the greatest content of vitexin analyzed by HPLC technique and introduces Prosopis farcta as a suitable source of this flavonoid with several pharmacological properties.

Baicalin protects against ethanol-induced chronic gastritis in rats by inhibiting Akt/NF-κB pathway

AimsCurrently, chronic gastritis is a high incidence of digestive diseases, along with loss of appetite, abdominal pain and diarrhea. Baicalin belongs to the major bioactive flavonoids compounds from Scutellariae Radix, it exhibited anti-inflammatory and anti-bacteria activities. Nonetheless, the protective effects of baicalin on ethanol-induced gastritis have not been completely clarified. Our study was designed to evaluate the protective activity of baicalin on ethanol-induced chronic gastritis. Main methodsRat with chronic gastritis model was induced by the administration of 56% ethanol for four weeks. Baicalin (50 and 100 mg/kg) were orally administered for seven days to evaluate its curative effect, respectively. The production of TNF-α, interleukin (IL)-8, IL-1β, NO, ET-1, PGE2, LDH and COX-2 were determined by ELISA. The activities of Akt, p-Akt, IκBα, p-IκBα, NF-κBp65 and NF-κBp-p65 were tested by western blot. Immunofluorescence staining was employed to assess the location of NF-κBp65. Key findingsThe changes of the histopathological analysis and the levels of NO, ET-1, PGE2, LDH and COX-2 demonstrated that baicalin treatment ameliorated ethanol-induced gastritis. ELISA analysis showed that baicalin inhibited the levels of TNF-α, IL-8 and IL-1β. Besides, Akt, p-Akt, IκBα, p-IκBα, NF-κBp65 and NF-κBp-p65 expression were significantly suppressed by baicalin. Meanwhile, baicalin suppressed the translocation of NF-κBp65 to the cell nucleus through immunofluorescence staining, molecular docking analysis showed that baicalin had affinity with Akt and NF-κBp65. SignificanceAll results demonstrated that baicalin effectively alleviated chronic gastritis via suppressing the levels of inflammatory regulators and inhibiting Akt/NF-κB activation.

Natural Product Glycosylation: Biocatalytic Synthesis of Quercetin-3,4'-O-diglucoside.

Flavonoids have gained much attention for their proposed positive effects for human health. Glycosylation is a significant method for the structural modification of various flavanols, resulting in glycosides with increased solubility, stability, and bioavailability compared with the corresponding aglycone. Natural product glycosylation by using enzymes has emerged as a topic of interest as it offers a sustainable and economical alternative source so as to address supply scalability limitations associated with plant-based production. Quercetin-3,4'-O-diglucoside, as one of the major but trace bioactive flavonoids in onion (Allium cepa), is superior or at least equal to quercetin aglycone in its bioavailability. In the present study, the onion-derived enzyme, UGT73G1, coupled with sucrose synthase, StSUS1, from Solanum tuberosum formed a circulatory system to produce quercetin-3,4'-O-diglucoside from quercetin, which preferred sucrose as a sugar donor and quercetin as a sugar acceptor. The optimal conditions were determined in order to increase the production of quercetin-3,4'-O-diglucoside. The maximum concentration of quercetin-3,4'-O-diglucoside achieved in a 10-mL reaction was 427.11mg/L, from the conversion of 1g/L of quercetin for 16h at 40°C and pH 7.2.

Dihydromyricetin ameliorates memory impairment induced by acute sleep deprivation

Dihydromyricetin (DHM), the major bioactive flavonoid ingredient extracted from the leaves of Ampelopsis grossedentata (Hand.-Mazz) W.T. Wang displays multiple pharmacological activities, including oxidation resistance, anti-tumour properties and free radical scavenging capacities. However, the role of DHM in sleep deprivation (SD)-induced memory impairments and its underlying molecular mechanisms are unclear. The aim of the present study was to evaluate the effects of DHM on oxidative stress and its role in ameliorating memory impairment induced by acute SD. DHM (100, 50, 25 mg/kg) and melatonin (10 mg/kg) were administered to mice via oral gavage. The open field test was used to evaluate motor function. Spatial learning and memory were assessed using the Morris water maze task. Malondialdehyde, glutathione, and glutathione disulfide levels, as well as superoxide dismutase enzyme activity, were assessed to determine the level of oxidative stress. In addition, we employed quantitative real-time PCR assays to examine the gene expression of 29 key proteins, including protein kinase A (PKA), cAMP response element binding protein (CREB), and adcy1. The levels of proteins including those of GABABRS, GABAARα5, GluR1, BDNF and PSD95, were detected by western blotting. The results showed that DHM significantly attenuated SD-induced spatial learning and memory impairments (P < 0.01). The possible underlying mechanisms of DHM may be attributed to its ability to reduce oxidative stress and restore synaptic plasticity.

Baicalein protects tert‑butyl hydroperoxide‑induced hepatotoxicity dependent of reactive oxygen species removal.

Baicalein (BA), one of the major bioactive flavonoids isolated from ScutellariaeRadix, possesses various pharmacological activities. The present study aimed to investigate the protective effects of BA on tert‑butyl hydroperoxide (t‑BHP)‑induced hepatotoxicity, and to investigate the potential mechanisms in LO2 cells. BA was demonstrated to possess protective properties against t‑BHP injury in LO2 cells, as evidenced by MTT and lactate dehydrogenase assays. BA significantly prevented t‑BHP‑induced depolarization of mitochondrial membrane potential (MMP), decreased the percentage of apoptotic cells caused by t‑BHP, and prevented intracellular reactive oxygen species (ROS) generation in LO2 cells. Furthermore, BA slightly triggered autophagy in LO2 cells, as evidenced by the elevation of LC3‑II expression, while BA combined treatment with an autophagy inhibitor (chloroquine) or activator (rapamycin) did not alter the hepatoprotective properties. In conclusion, BA may possess a hepatoprotective effect against t‑BHP‑induced liver cell injury, dependent on ROS removal. Therefore, BA may represent a potential drug candidate in protecting hepatotoxicity.