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Background: Melastoma dodecandrum Lour. (MD), a traditional botanical drug known for its hypoglycemic, antioxidant, and anti-inflammatory properties, is commonly used to treat diabetes, osteoarthritis, and osteoporosis. However, its specific active components against diabetic osteoporosis remain unclear. Purpose: This study aimed to identify the key active components in MD using cell membrane chromatography coupled with mass spectrometry and validate their effects in vitro. Methods: An AGEs-induced osteoblast injury model was established. MTT assays measured cell viability, and ALP activity was assessed using a biochemical kit. Western blotting was employed to detect the expression levels of osteoblast-related proteins OCN and RUNX2 and the AGE receptor protein RAGE. ELISA was used to determine the levels of SOD, MDA, CAT, and GPx. PCR quantified TNF-α expression to evaluate the protective effects and potential mechanisms of MD. The AGEs-induced osteoblast cell membrane chromatography-mass spectrometry method facilitated the rapid identification of potentially active compounds based on their affinity for the osteoblast cell membrane. Cell experiments further validated the activity of the characteristic component isovitexin. Results: MD significantly improved cell viability in AGEs-damaged osteoblasts, enhanced ALP, SOD, CAT, and GPx activities, reduced MDA levels, increased OCN and RUNX2 protein expression, and decreased TNF-α mRNA and RAGE protein expression. Cell membrane chromatography identified 20 chemical constituents, including 13 flavonoids, 4 organic acids, 1 phenylpropanoids, 1 terpenoids, and 1 alkaloid. Cell experiments have confirmed that isovitexin has significant protective activity against osteoblasts and can inhibit the expression of specific receptor RAGE on the osteoblast membrane, consistent with the effect of MD. Conclusion: MD and its active component, isovitexin, provide protective effects against AGEs-induced osteoblast injury, offering a basis for subsequent drug development. [ABSTRACT FROM AUTHOR]

The influence of biostimulant treatments on Passiflora species was assessed by observing changes in the growth and leaf functional compounds of plants exposed to humic acids (HAs) and seaweed extracts (SEs) to determine their optimal application doses. Four different concentrations of HA irrigation (0, 144, 192, and 285 mg·L-1 per pot assigned as HI-1, 2, 3, and 4, respectively), HA spraying (0, 96, 128, and 192 mg·L-1 as HS-1, 2, 3, and 4, respectively), SE irrigation (SI-1~4 at 0, 1, 1.33, and 2 g·L21 per pot, respectively), and SE spraying (SS-1~4 at 0, 0.5, 0.67, and 1 g·L21, respectively) treatments were applied to 'Tainung No. 1' and Passiflora suberosa cultivars every week to study their responses in plant growth traits and metabolites. Results show that leaf dry weight (DW) and root DW of 'Tainung No. 1' plants under SS-3 and HI-4 treatments, respectively, were significantly increased compared with controls. Both HI-3 and HS-3 treatments remarkably increased vine length, fresh weight (FW), and DW of leaves and shoots in P. suberosa plants compared with controls. Furthermore, 'Tainung No. 1' and P. suberosa plants respectively subjected to HI-2 and SS-4 treatments contributed to developing biostimulant applications for obtaining higher total phenol and flavonoid content per plant. Both Passiflora species are recommended for treatment with SS-4 and SE to maximize orientin and isovitexin content, and for all their beneficial applications and sustainable use in agriculture. [ABSTRACT FROM AUTHOR]

Summary: Studies have recently highlighted potential health benefits of young rice leaves; however, optimization of extraction process was often overlooked. The present study aimed to assess impacts of extraction methods, namely, maceration and decoction, on total phenolics content and antioxidant activities based on FRAP, DPPH, and ABTS assays of extracts from Thai cultivar of Jasmine rice leaves. The study examined influences of ethanol concentration (0–100% (v/v) for maceration), boiling time (10–30 min for decoction) and solvent‐to‐solid ratio (20–40 mL g−1 for both maceration and decoction). Results showed that under its optimal condition (50% (v/v) ethanol concentration and solvent‐to‐solid ratio of 30 mL g−1), maceration yielded significantly higher total phenolic content, 12.54 ± 0.94 mg GAE/g DW. Furthermore, mechanisms of single electron transfer responsible for antioxidant activities were explored, identifying flavonoids as potential chemical markers in rice leaf extracts. Flavonoid derivatives, specifically isoorientin (3.33 ± 0.10 mg/g DW) and isovitexin (0.98 ± 0.03 mg/g DW), were subsequently quantified. This research contributed to improved understanding of relations between bioactive compounds and their antioxidant activities. The findings also underscore potential of Thai Jasmine rice leaves as natural additives in future functional foods production. [ABSTRACT FROM AUTHOR]

Four new flavonoids, isovitexin 4′-O-(2′′′-O-β-D-glucopyranosyl)-β-D-glucopyranoside (cucumoside H), isovitexin 4′-O-(6′′′-O-β-D-glucopyranosyl)-β-D-glucopyranoside (cucumoside I), isovitexin 4′-O-(6′′′-O-β-D-glucopyranosyl)-β-D-glucopyranoside-2′′-O-(6′′′′-O-p-coumaroyl)-β-D-glucopyranoside (cucumoside J), and isovitexin 4′-O-(6′′′-O-β-D-glucopyranosyl)-β-D-glucopyranoside-2′′-O-(6′′′′-O-feruloyl)-β-D-glucopyranoside (cucumoside K), were observed in leaves of Cucumis sativus L. (Cucurbitaceae, variety Gele Tros). Their structures were elucidated using chemical transformations, UV and NMR spectroscopy, and mass spectrometry. [ABSTRACT FROM AUTHOR]

Asystasia gangetica leaves were extracted sequentially with different solvent systems. The quantitative estimation of secondary metabolites along with antioxidant activities were evaluated. Methanol extract had the highest phenolics (12.82 mg of GAE g−1 DW), condensed tannins (13.81 mg of GAE g−1 DW), saponin (10.71 mg of DE g−1 DW) content along with highest DPPH radical (IC50 of 62.40 μg mL−1), ABTS radical (22.70 μg mL−1) scavenging activity, and CUPRAC (65.86 TE g−1 DW) total antioxidant activity. The mild antimitotic and antiproliferative effects of extracts suggest low toxicity. The extracts demonstrated potential in vitro anti-inflammatory activity. Polyphenols, including novel Isovitexin, Genestin, Syringic acid, and Caffeic acid were the major metabolites identified. [ABSTRACT FROM AUTHOR]

BackgroundMelastoma dodecandrum Lour. (MD), a traditional botanical drug known for its hypoglycemic, antioxidant, and anti-inflammatory properties, is commonly used to treat diabetes, osteoarthritis, and osteoporosis. However, its specific active components against diabetic osteoporosis remain unclear.PurposeThis study aimed to identify the key active components in MD using cell membrane chromatography coupled with mass spectrometry and validate their effects in vitro.MethodsAn AGEs-induced osteoblast injury model was established. MTT assays measured cell viability, and ALP activity was assessed using a biochemical kit. Western blotting was employed to detect the expression levels of osteoblast-related proteins OCN and RUNX2 and the AGE receptor protein RAGE. ELISA was used to determine the levels of SOD, MDA, CAT, and GPx. PCR quantified TNF-α expression to evaluate the protective effects and potential mechanisms of MD. The AGEs-induced osteoblast cell membrane chromatography-mass spectrometry method facilitated the rapid identification of potentially active compounds based on their affinity for the osteoblast cell membrane. Cell experiments further validated the activity of the characteristic component isovitexin.ResultsMD significantly improved cell viability in AGEs-damaged osteoblasts, enhanced ALP, SOD, CAT, and GPx activities, reduced MDA levels, increased OCN and RUNX2 protein expression, and decreased TNF-α mRNA and RAGE protein expression. Cell membrane chromatography identified 20 chemical constituents, including 13 flavonoids, 4 organic acids, 1 phenylpropanoids, 1 terpenoids, and 1 alkaloid. Cell experiments have confirmed that isovitexin has significant protective activity against osteoblasts and can inhibit the expression of specific receptor RAGE on the osteoblast membrane, consistent with the effect of MD.ConclusionMD and its active component, isovitexin, provide protective effects against AGEs-induced osteoblast injury, offering a basis for subsequent drug development.

Abstract Background The proliferation of porcine ovarian granulosa cells (GCs) is essential to follicular development and the ubiquitin–proteasome system is necessary for maintaining cell cycle homeostasis. Previous studies found that the deubiquitinase ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) regulates female reproduction, especially in ovarian development. However, the mechanism by which UCHL1 regulates porcine GC proliferation remains unclear. Results UCHL1 overexpression promoted GC proliferation, and knockdown had the opposite effect. UCHL1 is directly bound to cyclin B1 (CCNB1), prolonging the half-life of CCNB1 and inhibiting its degradation, thereby promoting GC proliferation. What’s more, a flavonoid compound-isovitexin improved the enzyme activity of UCHL1 and promoted the proliferation of porcine GCs. Conclusions UCHL1 promoted the proliferation of porcine GCs by stabilizing CCNB1, and isovitexin enhanced the enzyme activity of UCHL1. These findings reveal the role of UCHL1 and the potential of isovitexin in regulating proliferation and provide insights into identifying molecular markers and nutrients that affect follicle development.

Background: The proliferation of porcine ovarian granulosa cells (GCs) is essential to follicular development and the ubiquitin–proteasome system is necessary for maintaining cell cycle homeostasis. Previous studies found that the deubiquitinase ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) regulates female reproduction, especially in ovarian development. However, the mechanism by which UCHL1 regulates porcine GC proliferation remains unclear. Results: UCHL1 overexpression promoted GC proliferation, and knockdown had the opposite effect. UCHL1 is directly bound to cyclin B1 (CCNB1), prolonging the half-life of CCNB1 and inhibiting its degradation, thereby promoting GC proliferation. What's more, a flavonoid compound-isovitexin improved the enzyme activity of UCHL1 and promoted the proliferation of porcine GCs. Conclusions: UCHL1 promoted the proliferation of porcine GCs by stabilizing CCNB1, and isovitexin enhanced the enzyme activity of UCHL1. These findings reveal the role of UCHL1 and the potential of isovitexin in regulating proliferation and provide insights into identifying molecular markers and nutrients that affect follicle development. [ABSTRACT FROM AUTHOR]

Desmodium caudatum extracts (DCE) were investigated for their potential therapeutic effects on diabetic nephropathy (DN). In our study, the high-fat diet (HFD) / streptozotocin (STZ)-induced DN model in C57BL/6 mice was treated with 100 mg/kg, 200 mg/kg DCE. The results showed that DCE decreased biochemical parameters and proteinuria levels. The kidney sections staining indicated that DCE treatment recovered glomerular atrophy and alleviated lipid droplets in the glomerular. Additionally, DCE inhibited lipid and glycogen accumulation down-regulated the expression of sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FAS) proteins. DCE also reduced collagenous fibrous tissue and the expression of transforming growth factor-β1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) through Masson's trichrome staining and immunohistochemical analysis. We found that DCE alleviated hydroxyproline content, and epithelial-mesenchymal transition (EMT). Besides, the results shown that DCE enhanced the antioxidant enzymes to mitigate fibrosis by reducing oxidative stress. In conclusion, our study provided evidence of the protective effect of DCE which down-regulated hyperglycemia, hyperlipidemia and inhibition of TGF-β1 and EMT pathway but elevated antioxidant, suggesting its therapeutic implication for DN. [ABSTRACT FROM AUTHOR]

Prostate cancer is a malignant epithelial tumor of the prostate gland and is the most common malignant tumor of the male genitourinary system. Pharmacological therapies, including chemotherapy and androgen deprivation therapy, play a key role in the treatment of prostate cancer. However, drug resistance and side effects limit the use of these drugs and so there is a need for new drug therapies for prostate cancer patients. Flavonoids, with their wide range of sources and diverse biological activities, have attracted much attention in the field of anti-tumor drug screening. In 2016, at least 58 flavonoids were reported to have anti-prostate cancer activity. In recent years, six additional flavonoid compounds have been found to have anti-prostate cancer potential. In this review, we have collected a large amount of evidence on the anti-prostate cancer effects of these six flavonoids, including a large number of cellular experiments and a small number of preclinical animal experiments. In addition, we predicted their drug-forming properties using Schrödinger's QikProp software and ADMETlab due to the lack of in vivo pharmacokinetic data for the six compounds. In conclusion, this review has fully confirmed the anti-prostate cancer effects of these six flavonoids, summarized their mechanisms of action and predicted their druggability. It provides a reference for the further development of these compounds into anti-prostate cancer drugs. [ABSTRACT FROM AUTHOR]

Flavonoids are a diverse set of natural products with promising bioactivities including anti-inflammatory, anti-cancer, and neuroprotective properties. Previously, the oleaginous host Yarrowia lipolytica has been engineered to produce high titers of the base flavonoid naringenin. Here, we leverage this host along with a set of E. coli bioconversion strains to produce the flavone apigenin and its glycosylated derivative isovitexin, two potential nutraceutical and pharmaceutical candidates. Through downstream strain selection, co-culture optimization, media composition, and mutant isolation, we were able to produce168 mg/L of apigenin, representing a 46% conversion rate of 2-(R/S)-naringenin to apigenin. This apigenin platform was modularly extended to produce isovitexin by addition of a second bioconversion strain. Together, these results demonstrate the promise of microbial production and modular bioconversion to access diversified flavonoids. [Display omitted] • Apigenin and its flavone C-glucosides are promising bioactive natural products. • Apigenin produced through delayed multi-organism co-culture. • Bioconversion enhanced by host choice, media optimization, and mutant isolation. • Co-culture modularity enables downstream diversification to isovitexin. [ABSTRACT FROM AUTHOR]

Isovitexin is a main natural flavonoid component in various plants. Currently, the inhibitory effect of isovitexin on pancreatic lipase (PL) and its mechanism have not been elucidated yet. In the present study, we investigated the inhibitory effect of isovitexin on PL, as well as its interaction mechanism, using enzyme inhibition methods, spectroscopic analysis, and molecular simulations. Results showed that isovitexin possessed significant PL inhibitory activity, with IC50 values of 0.26 ± 0.02 mM. The interaction between isovitexin and PL was dominated by static quenching, and mainly through hydrogen bonding and hydrophobic interaction forces. Analysis of fluorescence spectroscopy confirmed that isovitexin binding altered the conformation of the PL. Circular dichroism (CD) spectrum indicated that isovitexin altered the secondary structure of PL by decreasing the α‐helix content and increasing the β‐fold content. Molecular simulations further characterize the conformational changes produced by the interaction between isovitexin with PL. The performed study may provide a new insight into the inhibitory mechanism of isovitexin as a novel PL inhibitor. [ABSTRACT FROM AUTHOR]

Seven new acylated C,O-glycosylflavones were isolated from leaves of Cucumis sativus L. (Cucurbitaceae) variety Gele Tros. The new compounds were isovitexin 4′-O-glucoside-2′′-O-(6′′′′-O-caffeyl)-glucoside (cucumoside A), isovitexin 4′-O-glucoside-2′′-O-(2′′′′-O-caffeyl)-glucoside (cucumoside B), isovitexin 4′-O-(2′′′-O-caffeyl)-glucoside-2′′-O-glucoside (cucumoside C), isovitexin 4′-O-glucoside-2′′-O-(6′′′′-O-sinapoyl)-glucoside (cucumoside D), isovitexin 4′-O-glucoside-2′′-O-(2′′′′-O-sinapoyl)-glucoside (cucumoside E), isovitexin 4′-O-glucoside-2′′-O-(2′′′′-O-feruloyl)-glucoside (cucumoside F), and isovitexin 4′-O-glucoside-2′′-O-(2′′′′-O-p-coumaroyl)-glucoside (cucumoside G). [ABSTRACT FROM AUTHOR]

Seed germination with selenium (Se) is promising for producing Se-biofortified foods. Mungbean (Vigna radiata (L.) Wilczek) sprout is freshly eaten as a salad dressed with sauce, making it superior for Se biofortification. Since the Se safety range for the human body is extremely narrow, it is imperative to evaluate the genotypic responses of mungbean sprouts to Se. This study evaluated the Se enrichment capacity and interaction with flavonoids and antioxidant systems in sprouts of 20 mungbean germplasms. Selenium treatment was done by immersing mungbean seeds in 20 μM sodium selenite solution for 8 h. Afterward, the biomass, Se amounts, flavonoid (particularly vitexin and isovitexin) contents, antioxidant capacity, and key biosynthetic gene expressions were measured. Sprout Se content was 2.0-7.0 μg g-1 DW among the 20 mungbean germplasms. Selenium treatment differentially affected the biomass, total flavonoid, vitexin, isovitexin, antioxidant enzyme activities, and antioxidant capacities of the mungbean germplasms. Eight germplasms showed increased biomass (p < 0.05), the highest increasing by 127%, but 13 did not phenotypically respond to Se treatment. Seven and six germplasms showed varied levels of vitexin and isovitexin increment after Se treatment, the highest measuring 2.67- and 2.87-folds for vitexin and isovitexin, respectively. Two mungbean flavonoid biosynthesis genes, chalcone synthase (VrCHS) and chalcone isomerase (VrCHI) were significantly up-regulated in the germplasms with increased vitexin and isovitexin levels (p < 0.05). Moreover, Se enrichment capacity was significantly correlated with the vitexin, isovitexin, and antioxidant capacities. In conclusion, mungbean sprouts could be a useful Se-biofortified food, but the Se enrichment capacity and nutritional response must be determined for each germplasm before commercialization. [ABSTRACT FROM AUTHOR]

Isovitexin is a highly bioactive food-derived flavonoid currently attracting attention for its signal transduction-based antioxidant effects. This study focused on the potential molecular mechanisms by which isovitexin protects HaCaT cells from oxidation-induced apoptosis. It was found that isovitexin significantly reversed oxidative stress-induced apoptosis by reducing ROS level. In addition, isovitexin inhibited apoptosis in a dose-dependent manner by upregulating the expression level of Bcl-xL and Bcl-2 and downregulating the expression level of Bax and caspase-3. It is important to note that the effect of isovitexin may be achieved by targeting miR-98-5p, an upstream target of Bcl-xL and Bcl-2, and overexpression of miR-98-5p counteracted isovitexin-mediated upregulation of antiapoptotic proteins. Isovitexin also inhibited apoptosis by reducing the level of IL-6, IL-1β and TNF-α, which was achieved by regulating MAPKs/NF-κB signaling pathway. Overall, this study confirmed the mechanism of multi-targeted inhibition of apoptosis by targeting miR-98-5p/Bcl-2/Bcl-xL and MAPKs/NF-κB signaling pathway by isovitexin.

Cucumber is an important agricultural crop that is cultivated under greenhouse conditions. Cucumber cultivation generates substantial quantities of green waste that require proper disposal. The lack of data on the chemical composition of cucumber greens and their biological activity emphasizes the necessity for research on useful products resulting from this widely available waste. Our examination of the flavonoid contents in the leaves and stems of 30 cucumber cultivars revealed 6 cultivars with high flavonoid contents. In addition, the cutting time did not cause negative effects, and we observed a positive effect with 0.05–0.10% organomineral fertilizer application on the flavonoid levels in the greens. Liquid chromatography–mass spectrometry detected 38 apigenin derivatives, including acylated and non-acylated cucumerins and C-, O-, and C,O-glycosides. Among these, 12 known flavonoids and 18 novel compounds were identified. The concentrations of these compounds in the six flavonoid extracts varied at 39.85–181.53 mg/g for the non-acylated flavones, 14.67–293.31 mg/g for the cucumerins, and 401.73–892.17 mg/g for the acylated flavones. Oral administration of the total flavonoid extracts (at a dosage of 100 g/kg/day) resulted in a hypolipidemic effect in hyperlipidemic hamsters, with subsequent normalization of their serum lipid profiles, malondialdehyde levels, and liver antioxidative enzyme activities. These results substantiate the lipid-lowering potential of cucumber waste extracts. Our investigation of the selected flavonoid activity showed that isovitexin-2′′-O-glucoside-6′′-O-p-coumarate (administered at 50 g/kg/day) had the highest hypolipidemic potency. These results can contribute to the practical use of cucumber green waste and the development of novel supplements for diseases linked to high-fat consumption. [ABSTRACT FROM AUTHOR]

Lipid metabolism disorders are a large group of diseases for the treatment of which various strategies are used, including the use of pancreatic lipase inhibitors that reduce the intake and adsorption of lipids. This study was the first that shows that agricultural wastes of cucumber (Cucumis sativus) can be a source of the effective lipase inhibitors. As a result of the chromatographic separation of metabolites in C. sativus leaves, seven acylated flavonoids were identified, including three new derivatives of isovitexin characterized by UV, NMR spectroscopy and mass spectrometry data as isovitexin-2"-O-glucoside-6"-O-ferulate (1), isovitexin-2"-O-glucoside-6"-O-p-coumarate (2), and isovitexin-2"-O-(6"-O-feruloyl)-glucoside-6"-O-ferulate (3). The quantitative HPLC data showed that the total content of the acylated flavonoids in the leaves of Russian varieties of C. sativus amounted to 3.78–7.44 mg/g of dry plant weight. Isolated compounds demonstrated the ability to inhibit the human pancreatic lipase; the effectiveness of compound 3 was the greatest and exceeded the activity of the reference compound Orlistat. This study has shown that C. sativus leaves can be a useful source of biologically active phytocomponents with hypolipidemic activity. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the anti-inflammatory effects and mechanism of isovitexin on ulcerative colitis mice and RAW264.7 cells. The results showed that isovitexin had strong antioxidant and anti-inflammatory effects, and could restore intestinal barrier integrity (p < 0.01). In addition, isovitexin inhibited the expression of MyD88, TLR4 and NF-κB p65 proteins. At the same time, isovitexin can inhibit the activation of MAPK/NF-κB signaling pathway in RAW264.7 cells. In conclusion, isovitexin has a protective effect on UC mice, and its improvement mechanism of UC might be related to MAPK/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Tinctures are medicinal plant extracts obtained by extraction with a hydroalcoholic solution (70%) by percolation (PER). This process takes about 26 h to prepare, in addition to using a large amount of solvent. In our research, passion fruit leaf tinctures were obtained using extract with the same pressurized hydroalcoholic solution as in an intermittent process. The objective was to demonstrate that this emerging technology can be economical and profitable. An optimization using Central Composite Rotatable Design (CCRD) was performed to evaluate the influence of process variables on the yields and compositions of the extracts. The temperature (T) was the factor that most influenced the responses. Extraction with pressurized liquid (PLE) provided total yields and total phenolic and flavonoid contents in greater amounts than PER. The optimized conditions of the process variables studied in the CCRD for the highest content of total phenolics (43.2 mg GAE/g) and flavonoids (58.8 mg QE/g) were at 100 °C with a rinse volume of 120% of the divided extractor volume in four cycles of the intermittent process. When adjusting the PLE in an intermittent process, and according to the one-dimensional mass transfer by the continuous diffusion of the Fick model, the effective diffusion coefficient (1.28 × 10−12 m2/s) was not affected by T. The kinetic curve of PLE extraction indicates that the adjusted intermittent process occurred in the period of the constant extraction rate when compared to the kinetics of the semi-continuous process. The yielded extracts were rich in isovitexin, and the highest levels were identified in the extracts obtained via PLE, indicating that this intermittent process can bring a product to market with the same quality but with a much shorter production time and the use of fewer solvents. Antioxidant activity, determined by DPPH, FRAP and ORAC, was also higher in extracts obtained via PLE. [ABSTRACT FROM AUTHOR]

Typhonium flagelliforme, a plant known for its medicinal properties, has numerous benefits in the treatment of certain diseases. This comprehensive research provides a detailed review of the phytochemical and pharmacological activities of this plant, with a specific focus on the utilization of its flavonoid compounds, namely vitexin and isovitexin, in the development of cosmetic formulas. The phytochemical compounds include flavonoid, coumaric acid, and other polyphenols compounds. These compounds exhibit a wide range of pharmacological activities, including antioxidant, anti-inflammatory, anti-cancer, reduced immunosuppressive effects by reducing lymphocyte proliferation, antibacterial, improved immune system activities, and cured gastric ulcers. Based on these pharmacological activities, this research summarizes the utilization of flavonoid compounds, vitexin, and isovitexin, in developing cosmetic preparations. Subsequently, isovitexin has been shown to possess anti-oxidant and anti-inflammatory, and it shares similar pharmacological effects with vitexin, likely due to its similar chemical structure. Considering the excellent antioxidant capacity of isovitexin, there is a favorable opportunity to utilize it in the creation of cosmetic formulations. Therefore, further research is needed to formulate topical preparations and cosmetics containing Typhonium flagelliforme extract. [ABSTRACT FROM AUTHOR]

Objective: The anti-inflammatory activities of apigenin-7-O-β-D-glucopyranoside, apigenin 5-O-glucoside, vitexin and isovitexin were evaluated. Methods: Changes of protein in THP-1 cells pretreated with flavonoids were measured by Western blot test. The differences of cytokines were analyzed by enzyme-linked immunosorbent assay and fluorescence quantitative polymerase chain reaction. Results: It showed that all the flavonoids tested could repress the gene expression of IL-10 (P

Abstract Pterocarpus santalinoides is used in Nigerian ethnomedicine to treat diabetes mellitus. This study aimed to establish the antidiabetic property of the plant, and isolate and characterize its active principle. Dried and pulverized leaves (500 g) of P. santalinoides were extracted with 1.8 L of 80 % hydromethanol by cold maceration. The dried extract (10 g) was partitioned into n-hexane, ethyl acetate (EtOAc), n-butanol, and water. Antidiabetic activitiy-guided isolation by column chromatographic separation of the EtOAc soluble and purification of the sub-fractions by repeated preparative thin layer chromatography (pTLC) yielded a C-glycosyl flavonoid, identified as isovitexin. The chemical structure was elucidated based on high-resolution mass spectroscopy, 1D, and 2D nuclear magnetic resonance spectroscopic analyses. Alloxan-induced diabetic rat model was adopted for antidiabetic screening. The extract of P. santalinoides (100-200 mg/kg), fraction F4 (50 mg/kg), sub-fraction F4.3 (10 mg/kg), and the semi-purified compound F4.3.2 (5 mg/kg) significantly (p 68 % recorded in glibenclamide (2 mg/kg) control. These results reveal that isovitexin is the antidiabetic principle in P. santalinoides.

It has been demonstrated that cancer stem cells (CSCs) go through metabolic changes that differentiate them from non-CSCs. The altered metabolism of CSCs plays a vital role in tumor initiation, progression, immunosuppression, and resistance to conventional therapy. Therefore, defining the role of CSC metabolism in carcinogenesis has emerged as a main focus in cancer research. Two natural flavonoids, apigenin and isovitexin, have been shown to act synergistically with conventional chemotherapeutic drugs by sensitizing CSCs, ultimately leading to improved therapeutic efficacy. The aim of this study is to present a critical and broad evaluation of the anti-CSC capability of apigenin and isovitexin in different cancers as novel and untapped natural compounds for developing drugs. A thorough review of the included literature supports a strong association between anti-CSC activity and treatment with apigenin or isovitexin. Additionally, it has been shown that apigenin or isovitexin affected CSC metabolism and reduced CSCs through various mechanisms, including the suppression of the Wnt/β-catenin signaling pathway, the inhibition of nuclear factor-κB protein expression, and the downregulation of the cell cycle via upregulation of p21 and cyclin-dependent kinases. The findings of this study demonstrate that apigenin and isovitexin are potent candidates for treating cancer due to their antagonistic effects on CSC metabolism. [ABSTRACT FROM AUTHOR]

The present work aimed to detail the mechanisms elicited by Allophylus africanus P. Beauv. stem bark extract in human stomach cancer cells and to identify the bioactives underlying the cytotoxicity. MTT reduction and LDH leakage assays allowed characterizing the cytotoxic effects in AGS cells, which were further detailed by morphological analysis using phalloidin and Hoechst 33258. Proapoptotic mechanisms were elucidated through a mitochondrial membrane potential assay and by assessing the impact upon the activity of caspase-9 and -3. The extract displayed selective cytotoxicity against AGS cells. The absence of plasma membrane permeabilization, along with apoptotic body formation, suggested that pro-apoptotic effects triggered cell death. Intrinsic apoptosis pathway activation was verified, as mitochondrial membrane potential decrease and activation of caspase-9 and -3 were observed. HPLC-DAD profiling enabled the identification of two apigenin-di-C-glycosides, vicenin-2 (1) and apigenin-6-C-hexoside-8-C-pentoside (3), as well as three mono-C-glycosides-O-glycosylated derivatives, apigenin-7-O-hexoside-8-C-hexoside (2), apigenin-8-C-(2-rhamnosyl)hexoside (4) and apigenin-6-C-(2-rhamnosyl)hexoside (5). Isovitexin-2″-O-rhamnoside (5) is the main constituent, accounting for nearly 40% of the total quantifiable flavonoid content. Our results allowed us to establish the relationship between the presence of vicenin-2 and other apigenin derivatives with the contribution to the cytotoxic effects on the presented AGS cells. Our findings attest the anticancer potential of A. africanus stem bark against gastric adenocarcinoma, calling for studies to develop herbal-based products and/or the use of apigenin derivatives in chemotherapeutic drug development. [ABSTRACT FROM AUTHOR]

Objective: Despite the development of several vaccines against severe acute respiratory syndrome coronavirus-2, the need for an additional prophylactic agent is evident. In recent in silico studies, isovitexin exhibited a higher binding affinity against the human angiotensin converting-enzyme 2 (hACE2) receptor than existing antiviral drugs. The research aimed to find out the point specificity of isovitexin for the hACE2 receptor and to assess its therapeutic potential, depending on the stability of the isovitexin–hACE2 complex. Materials and Methods: The pharmacokinetic profile of isovitexin was analyzed. The crystal structure of the hACE2 receptor and the ligand isovitexin were docked to form a ligand-protein complex following molecular optimization. To determine the isovitexin–hACE2 complex stability, their binding affinity, hydrogen bonding, and hydrophobic interactions were studied. Lastly, the root mean square deviation (RMSD), root mean square fluctuation, solvent accessible surface area, molecular surface area, radius of gyration (Rg), polar surface area, and principal component analysis values were found by simulating the complex with molecular dynamic (MD). Results: The predicted Lethal dose50 for isovitexin was 2.56 mol/kg, with an acceptable maximum tolerated dose and no hepatotoxicity or AMES toxicity. Interactions with the amino acid residues Thr371, Asp367, Glu406, Pro346, His345, Phe274, Tyr515, Glu375, Thr347, Glu402, and His374 of the hACE2 protein were required for the high binding affinity and specificity of isovitexin. Based on what was learned from the MD simulation, the hACE2 receptor-blocking properties of isovi¬texin were looked at. Conclusions: Isovitexin is a phytochemical with a reasonable bioactivity and safety profile for use in humans, and it can potentially be used as a hACE2-specific therapeutic to inhibit COVID-19 infection. [J Adv Vet Anim Res 2022; 9(2.000): 230-240]

Liang X, Xu C, Cao X, Wang W. Cancer Manag Res. 2019;11:8923–8936. We, the Editors and Publisher of Cancer Management and Research, have retracted the following article. Since publication, concerns have been raised about the integrity of the data in the article. This includes the duplication of images from Figure 2 with images from another article. Specifically, The western blot image for Figure 2J, DNMT1, has been duplicated with the image for Figure 3h, CD44, from Liang X, Xu C, Wang W, Li X, The DNMT1/miR-34a Axis Is Involved in the Stemness of Human Osteosarcoma Cells and Derived Stem-Like Cells. Stem Cells Int. 2019;2019:7028901. https://doi.org/10.1155/2019/7028901. When approached for an explanation, the authors did not respond to our queries, nor did they provide original data for their study. As the findings could not be verified the Editor and Publisher made the decision to retract the article and the authors were notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

This study detects the presence of an important flavonoids "isovitexin" present in the whole plant Anastitica hierochuntica L. cultivated in Iraq. The absence of any study concerning the isovitexin content of this medicinal plant in Iraq and the medicinal importance isovitexin depending on its uses for treatment some disease, acquired this study its value. This study concerned with extraction, identification, isolation, and purification of isovitexin from the whole plant Anastatica hierochuntica L. Extraction of this compound was carried out using two methods. Identification of this compound was done using thin layer chromatography (TLC) where different solvent systems had been tried. This identification was further augmented by using high performance liquid chromatography (HPLC) and then this flavonoid was isolated and purified. The identification of isolated isovitexin was carried out using Melting point (M.P), Thin layer chromatography (TLC), Infrared spectroscopy (IR) and High performance liqude chromatography (HPLC). This study confirms the presence of isovitexin in the whole plant Anastatica hierochuntica L. cultivated in Iraq. Also the result of this study showed that the extraction method NO.2 was the best, because the amount of both extract and isovitexin were higher than from extraction method NO.1. [ABSTRACT FROM AUTHOR]

Abstract Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in 2019 and is still an on-going pandemic. SARS-CoV-2 uses a human protease called furin to aid in cellular entry and its main protease (Mpro) to achieve viral replication. By targeting these proteins, scientists are trying to identify phytoconstituents of medicinal plants as potential therapeutics for COVID-19. Therefore, our study was aimed to identify promising leads as potential inhibitors of SARS-CoV-2 Mpro and furin using the phytocompounds reported to be isolated from Acacia pennata (L.) Willd. Results A total of 29 phytocompounds were reported to be isolated from A. pennata. Molecular docking simulation studies revealed 9 phytocompounds as having the top 5 binding affinities towards SARS-CoV-2 Mpro and furin. Among these phytocompounds, quercetin-3-O-α-L-rhamnopyranoside (C_18), kaempferol 3-O-α-L-rhamnopyranosyl-(1 → 4)-β-D-glucopyranoside (C_4), and isovitexin (C_5) have the highest drug score. However, C_18 and C_4 were not selected for further studies due to bioavailability issues and low synthetic accessibility. Based on binding affinity, molecular properties, drug-likeness, toxicity parameters, ligand interactions, bioavailability, synthetic accessibility, structure–activity relationship, and comparative analysis of our experimental findings with other studies, C_5 was identified as the most promising phytocompound. C_5 interacted with the active site residues of SARS-CoV-2 Mpro (GLU166, ARG188, GLN189) and furin (ASN295, ARG298, HIS364, THR365). Many phytocompounds that interacted with these amino acid residues were reported by other studies as potential inhibitors of SARS-CoV-2 Mpro and furin. The oxygen atom at position 18, the –OH group at position 19, and the 6-C-glucoside were identified as the pharmacophores in isovitexin (also known as apigenin-6-C-glucoside). Other in-silico studies reported apigenin as a potential inhibitor of SARS-CoV-2 Mpro and apigenin-o-7-glucuronide was reported to show stable conformation during MD simulations with SARS-CoV-2 Mpro. Conclusion The present study found isovitexin as the most promising phytocompound to potentially inhibit the cellular entry and viral replication of SARS-CoV-2. We also conclude that compounds having oxygen atom at position 18 (C-ring), –OH group at position 19 (A-ring), and 6-C-glucoside attached to the A-ring at position 3 on a C6–C3–C6 flavonoid scaffold could offer the best alternative to develop new leads against SARS-CoV-2.

In order to study the changes in the content of vitexin and isovitexin in different varieties of mung beans during the germination process, a method based on high performance liquid chromatography for the determination of vitexin and isovitexin in mung beans was established. The study used four varieties of mung beans as the study objects, with acetic acid water and acetonitrile as mobile phases, and the diode array detector was used for measurement. Under the optimized conditions, the linear relationship of the nine kinds of vitexin and isovitexin were good in a certain mass concentration range, the correlation coefficient was greater than 0.995, the detection limits of vitexin and isovitecin were 0.04173 μg/mL and 0.023255 μg/mL, the recovery of the method was 80.05–101.54%, the relative standard deviation less than 5.0%. The results showed that vitexin and isovitexin showed a downward trend during the germination process of mung bean. Compared with the existing methods, this method is sensitive, fast and applicable, and can effectively determine the content changes of vitexin and isovitecin during the germination process of mung bean. [ABSTRACT FROM AUTHOR]

In order to study the effect of germinated mung bean powder on the quality and nutrition of yogurt,different varieties of mung bean were selected in this paper,germinated mung bean sprout powder and pure milk as raw materials,Lactobacillus bulgaricus and Streptococcus thermophilus as fermentation strains,solidified germinated mung bean yoghurt was developed by single factor and orthogonal test; The contents of vitexin,isovitexin and cellulose in the germination mung bean powder were determined by high performance liquid chromatography and enzyme-weight method to explore the effects of adding germination mung bean powder on the quality and nutrition of yogurt.The results showed that the addition of germinated mung bean powder could strengthen the tissue structure of yogurt,increase the number of viable lactic acid bacteria,and give the yogurt a unique mung bean flavor; Moreover,the addition of germinated mung bean powder could enhance the antioxidant properties of yogurt,increase soluble dietary fiber,beneficial ingredients such as vitexin and isovitexin,and give yogurt physiological health functions.The best process for coagulated germination mung bean yogurt was:adding 2% germination mung bean powder,7% sucrose,0.3% CMC stabilizer,adding starter at the ratio of 1.5 g/L,and incubating at 42 ℃ for 5 hours.Under these conditions the germinated mung bean yogurt had a stable structure and good flavor and taste.

Melastoma dodecandrum (MD), a traditional ethnomedicine, has been widely used for the treatment of fractures, osteoarthritis, and osteoporosis due to its remarkable anti-inflammatory activity. However, the specific active components responsible for its therapeutic effects on orthopedic conditions remain unidentified. This study aimed to screen and identify key active components in MD using a combination of cell membrane chromatography and mass spectrometry, followed by cellular validation. A TNF-α-induced osteoblast injury model and an osteoblast membrane chromatography screening system were established to select and identify chemical components of MD that directly act on osteoblasts. The protective effects of MD on osteoblasts were assessed by evaluating cell viability, alkaline phosphatase (ALP) activity, cell mineralization and the expression of osteogenesis-related proteins OCN, RUNX2, and the TNF-α receptor protein TNFR1. Validation of the activity of individual components was also conducted. MD significantly improved the viability of osteoblasts under TNF-α-induced injury, enhanced ALP activity, stimulated the expression of OCN and RUNX2 proteins, and decreased the expression of TNFR1. Cell membrane chromatography screening identified 32 chemical components, including 21 flavonoids, 6 organic acids, 2 phenylpropanoids, 2 terpenes, and 1 nucleotide. Molecular docking revealed that isovitexin could bind to the specific receptor TNFR1 on the cell membrane. Furthermore, cellular validation demonstrated that isovitexin significantly protected osteoblasts. MD and its pharmacologically active component, isovitexin, exhibit protective effects against TNF-α-induced inflammatory injury in osteoblasts, laying a solid foundation for future drug development. [Display omitted] • Established TNF-α Induced osteoblast injury model and osteoblast membrane chromatographic screening system. • A total of 32 chemical constituents of Melastoma dodecandrum which act directly on osteoblasts were found. • Identified isovitexin as an active component of Melastoma dodecandrum with the ability to ameliorate TNF-α mediated osteoblast injury. [ABSTRACT FROM AUTHOR]

Xiaofen Hu,1,2,* Ruijie Li,1,2,* Ming Sun,1,2 Ying Kong,1,2 Haifeng Zhu,1,2 Fujiang Wang,1 Quanqing Wan1,2 1The Third Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, 310005, People’s Republic of China; 2Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Quanqing WanThe Third Affiliated Hospital of Zhejiang Chinese Medicine University, 219 Moganshan Road, Hangzhou, 310005, Zhejiang, People’s Republic of ChinaEmail 13003678819@163.comPurpose: Osteoarthritis (OA) is a multifactorial joint disease and inflammatory processes contribute to joint destruction. Isovitexin (IVX) is a flavone component found in passion flower, Cannabis and, and the palm that is known for its anti-inflammatory properties.Materials and Methods: This study investigated in vitro the role and underlying mechanism used by IVX in its regulation of OA development. Effects of IVX on the viability of chondrocytes were measured by CCK-8 assays. The phenotypes of extracellular matrix (ECM) degeneration and inflammation were measured by qPCR, Western blot, and ELISA; and NF-κB pathway was detected by immunofluorescence and Western blot. Molecular docking was applied to predict the interacting protein of IVX, while Nrf2 was knocked down by siRNAs to confirm its role.Results: We demonstrated that IVX suppressed ECM degeneration and suppressed pro-inflammatory factors in IL-1β-treated chondrocytes. Additionally, IVX impact on NF-κB signaling in IL-1β-exposed chondrocytic cells; Mechanistically, it was also demonstrated in molecular docking and knock down studies that IVX might bind to Nrf2 to suppress NF-κB pathway.Conclusion: Our data suggest that IVX halts OA disease advancement through the Nrf2/NF-κB axis, suggesting a possibility of IVX as a target for OA therapy.Keywords: osteoarthritis, isovitexin, extracellular matrix, NF-κB, Nrf2

Adiponectin plays key roles in energy metabolism and ameliorates inflammation, oxidative stress, and mitochondrial dysfunction via its primary receptors, adiponectin receptors −1 and 2 (AdipoR1 and AdipoR2). Systemic depletion of adiponectin causes various metabolic disorders, including MASLD; however adiponectin supplementation is not yet achievable owing to its large size and oligomerization-associated complexities. Small-molecule AdipoR agonists, thus, may provide viable therapeutic options against metabolic disorders. Using a novel luciferase reporter-based assay here, we have identified Apigenin-6-C-glucoside (ACG), but not apigenin, as a specific agonist for the liver-rich AdipoR isoform, AdipoR2 (EC 50 : 384 pM) with >10000X preference over AdipoR1. Immunoblot analysis in HEK-293 overexpressing AdipoR2 or HepG2 and PLC/PRF/5 liver cell lines revealed rapid AMPK, p38 activation and induction of typical AdipoR targets PGC-1α and PPARα by ACG at a pharmacologically relevant concentration of 100 nM (reported cMax in mouse; 297 nM). ACG-mediated AdipoR2 activation culminated in a favorable modulation of key metabolic events, including decreased inflammation, oxidative stress, mitochondrial dysfunction, de novo lipogenesis, and increased fatty acid β-oxidation as determined by immunoblotting, QRT-PCR and extracellular flux analysis. AdipoR2 depletion or AMPK/p38 inhibition dampened these effects. The in vitro results were recapitulated in two different murine models of MASLD, where ACG at 10 mg/kg body weight robustly reduced hepatic steatosis, fibrosis, proinflammatory macrophage numbers, and increased hepatic glycogen content. Together, using in vitro experiments and rodent models, we demonstrate a proof-of-concept for AdipoR2 as a therapeutic target for MASLD and provide novel chemicobiological insights for the generation of translation-worthy pharmacological agents. [Display omitted] • ACG activates AdipoR2 with an EC 50 of 384 pM. • ACG specifically activates AdipoR2 with >10000X selectivity over AdipoR1. • ACG ameliorates lipotoxicity via AdipoR-associated signaling pathways. • ACG ameliorates MASLD in genetically dyslipidemic mice fed a Western diet. • ACG ameliorates MASLD in a diet-induced rodent model. [ABSTRACT FROM AUTHOR]

Recent studies on the ethnomedicinal use of Clinacanthus nutans suggest promising anti-inflammatory, anti-tumorigenic, and antiviral properties for this plant. Extraction of the leaves with polar and nonpolar solvents has yielded many C-glycosyl flavones, including schaftoside, isoorientin, orientin, isovitexin, and vitexin. Aside from studies with different extracts, there is increasing interest to understand the properties of these components, especially regarding their ability to exert anti-inflammatory effects on cells and tissues. A major focus for this review is to obtain information on the effects of C. nutans extracts and its phytochemical components on inflammatory signaling pathways in the peripheral and central nervous system. Particular emphasis is placed on their role to target the Toll-like receptor 4 (TLR4)-NF-kB pathway and pro-inflammatory cytokines, the antioxidant defense pathway involving nuclear factor erythroid-2-related factor 2 (NRF2) and heme oxygenase 1 (HO-1); and the phospholipase A2 (PLA2) pathway linking to cyclooxygenase-2 (COX-2) and production of eicosanoids. The ability to provide a better understanding of the molecular targets and mechanism of action of C. nutans extracts and their phytochemical components should encourage future studies to develop new therapeutic strategies for better use of this herb to combat inflammatory diseases. [ABSTRACT FROM AUTHOR]

The Ocotea genus exhibits a variety of pharmacological, antibacterial and antioxidant effects. The aim of the present study was to evaluate the antioxidant potential and antibacterial properties of the ethyl acetate fraction of Ocotea nutans leaves. Isolation and identification of the phenolic compounds from the fraction was also carried out. The isolated compounds were characterised by one- and two-dimensional nuclear magnetic resonance analysis and identified as vitexin (1) and isovitexin (2). The ethyl acetate fraction of Ocotea nutans leaves demonstrated considerable antioxidant potential. The observed minimum inhibitory concentration of 250 µg.mL−1 was classified as a moderate antibacterial activity against Enterococcus faecalis. Findings from this study demonstrate the utility of this plant as a potential source of antioxidant and antibacterial agents. [ABSTRACT FROM AUTHOR]

Objective: Despite the development of several vaccines against severe acute respiratory syndrome coronavirus-2, the need for an additional prophylactic agent is evident. In recent in silico studies, isovitexin exhibited a higher binding affinity against the human angiotensin converting-enzyme 2 (hACE2) receptor than existing antiviral drugs. The research aimed to find out the point specificity of isovitexin for the hACE2 receptor and to assess its therapeutic potential, depending on the stability of the isovitexin-hACE2 complex. Materials and Methods: The pharmacokinetic profile of isovitexin was analyzed. The crystal structure of the hACE2 receptor and the ligand isovitexin were docked to form a ligand-protein complex following molecular optimization. To determine the isovitexin-hACE2 complex stability, their binding affinity, hydrogen bonding, and hydrophobic interactions were studied. Lastly, the root mean square deviation (RMSD), root mean square fluctuation, solvent accessible surface area, molecular surface area, radius of gyration (Rg), polar surface area, and principal component analysis values were found by simulating the complex with molecular dynamic (MD). Results: The predicted Lethal dose50 for isovitexin was 2.56 mol/kg, with an acceptable maximum tolerated dose and no hepatotoxicity or AMES toxicity. Interactions with the amino acid residues Thr371, Asp367, Glu406, Pro346, His345, Phe274, Tyr515, Glu375, Thr347, Glu402, and His374 of the hACE2 protein were required for the high binding affinity and specificity of isovitexin. Based on what was learned from the MD simulation, the hACE2 receptor-blocking properties of isovitexin were looked at. Conclusions: Isovitexin is a phytochemical with a reasonable bioactivity and safety profile for use in humans, and it can potentially be used as a hACE2-specific therapeutic to inhibit COVID-19 infection. [ABSTRACT FROM AUTHOR]

The current outbreak of the COVID-19 threatens public health worldwide, and WHO declares this as a global pandemic. Effective oral drug therapy against coronavirus did not discover yet. In order to find out an effective drug, we docked 23 compounds within the active site of 6LU7 protein of coronavirus. Among all, some antivirals exhibited very promising results against coronavirus and may be considered as a potential drug for treating COVID-19 disease. Molecular docking study revealed that isovitexin and apigenin found from nishinda (Vitex sp.) as well as our newly prepared compound (E)-4-((3,5-dibromo-2-hydroxybenzylidene)amino)-N-(5-methylisoxazol-3-yl)benzenesulfonamide showed exce-llent activity as compared to danoprevir, lopinavir, remdesivir and ritonavir. Isovitexin showed a binding affinity of -8.00 kcal/mol, whereas the binding affinity of sulfonamide compound with the coronavirus protein was -7.30 kcal/mol, which was relatively high compared to other antiviral drugs. Besides, the synthesized sulfonamide compound's absorption, distribution, metabolism, excretion, and toxicity profiles were also carried out. The compound showed excellent drug-like properties and percentage of human oral absorption. Moreover, it was found to be safe for the human body in toxicological risk assessment. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is an ultimately fatal, degenerative brain disease in the elderly people. In the current work, we assessed the defensive capability of isovitexin (IVX) through an intracerebroventricular injection of streptozotocin (STZ)-induced AD mouse model.

Yebei Qiu,1,2,* Xiaocheng Cao,1,2,* Lihua Liu,3,4 Xiaozheng Cao,3,4 Qing Yuan,5 Xiang Li,5 Yinghong Cui,1,5 Chang Xu,1,2 Chang Zou,4,6 Kaiqun Ren,1,2 Jianguo Cao1,2 1The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Medical College, Hunan Normal University, Changsha 410013, People’s Republic of China; 2The Key Laboratory of Study and Discover of Small Targeted Molecules of Hunan Province, Medical College, Hunan Normal University, Changsha 410013, People’s Republic of China; 3Pharmacy Department, The Second Clinical Medical School of Jinan University, Shenzhen People’s Hospital, Shenzhen 518020, People’s Republic of China; 4Shenzhen Public Service Platform on Tumor Precision Medicine and Molecular Diagnosis, Shenzhen People’s Hospital, Shenzhen 518020, People’s Republic of China; 5Department of Preclinical Medicine, Medical College, Hunan Normal University, Changsha, Hunan 410013, People’s Republic of China; 6Clinical Medical Research Center, The Second Clinical Medical School of Jinan University, Shenzhen People’s Hospital, Shenzhen 518020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianguo Cao; Kaiqun RenKaiqun Ren the Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Medical College, Hunan Normal University, Changsha 410013, People’s Republic of ChinaTel +86-0731-88912434Email caojianguo2005@126.com; kaiqunren@126.comBackground: Manganese superoxide dismutase (MnSOD) induces FoxM1 expression, subsequently contributing to migration in several cancer cells. Isovitexin (ISOV) was recently found to downregulate MnSOD and FoxM1, decreasing stemness in hepatocellular carcinoma (HCC) stem-like cells (HCSLCs). The current study aimed to determine whether inhibition of migration, invasion and EMT in HCSLCs by ISOV results from MnSOD/FoxM1 signaling blockade and subsequent Twist1, Slug, ZEB1 and MMP-2 downregulation.Materials and Methods: We examined the migratory and invasive capabilities and EMT phenotype in HCC cells and their HCSLCs, respectively, by wound-healing assay, transwell invasion assay and Western blot after treatment with non-cytotoxic concentrations of ISOV, and explored the mechanism by which ISOV affects migration, invasion and EMT by MnSOD or FoxM1 knockdown and/or overexpression in HCSLCs or HCC cells.Results: The results showed that ISOV not only downregulated MnSOD and FoxM1 but also suppressed the migratory and invasive capabilities and reversed the EMT phenotype in HCSLCs, which was reflected by elevated E-cadherin protein amounts, and reduced N-cadherin, Twist1, Slug, ZEB1 and MMP-2 protein levels. The suppressive effects of ISOV on the migratory and invasive capabilities and EMT phenotype could be potentiated by MnSOD or FoxM1 knockdown in HCSLCs, and attenuated by MnSOD or FoxM1 overexpression in HCC cells. Importantly, FoxM1 overexpression reversed MnSOD knockdown combined with ISOV suppression on the migratory and invasive capabilities and EMT phenotype in HCSLCs, while having little effects on MnSOD expression.Conclusion: Collectively, the above findings demonstrated that ISOV suppresses migration, invasion and EMT in HCSLCs by blocking MnSOD/FoxM1 signaling subsequently inhibiting the expression of EMT-related transcription factors and MMP-2.Keywords: hepatocellular carcinoma, cancer stem cell, isovitexin, epithelial-mesenchymal transition, MnSOD, FoxM1, Twist1, MMP-2

It has been demonstrated that cancer stem cells (CSCs) go through metabolic changes that differentiate them from non-CSCs. The altered metabolism of CSCs plays a vital role in tumor initiation, progression, immunosuppression, and resistance to conventional therapy. Therefore, defining the role of CSC metabolism in carcinogenesis has emerged as a main focus in cancer research. Two natural flavonoids, apigenin and isovitexin, have been shown to act synergistically with conventional chemotherapeutic drugs by sensitizing CSCs, ultimately leading to improved therapeutic efficacy. The aim of this study is to present a critical and broad evaluation of the anti-CSC capability of apigenin and isovitexin in different cancers as novel and untapped natural compounds for developing drugs. A thorough review of the included literature supports a strong association between anti-CSC activity and treatment with apigenin or isovitexin. Additionally, it has been shown that apigenin or isovitexin affected CSC metabolism and reduced CSCs through various mechanisms, including the suppression of the Wnt/β-catenin signaling pathway, the inhibition of nuclear factor-κB protein expression, and the downregulation of the cell cycle via upregulation of p21 and cyclin-dependent kinases. The findings of this study demonstrate that apigenin and isovitexin are potent candidates for treating cancer due to their antagonistic effects on CSC metabolism.

The present work aimed to detail the mechanisms elicited by Allophylus africanus P. Beauv. stem bark extract in human stomach cancer cells and to identify the bioactives underlying the cytotoxicity. MTT reduction and LDH leakage assays allowed characterizing the cytotoxic effects in AGS cells, which were further detailed by morphological analysis using phalloidin and Hoechst 33258. Proapoptotic mechanisms were elucidated through a mitochondrial membrane potential assay and by assessing the impact upon the activity of caspase-9 and -3. The extract displayed selective cytotoxicity against AGS cells. The absence of plasma membrane permeabilization, along with apoptotic body formation, suggested that pro-apoptotic effects triggered cell death. Intrinsic apoptosis pathway activation was verified, as mitochondrial membrane potential decrease and activation of caspase-9 and -3 were observed. HPLC-DAD profiling enabled the identification of two apigenin-di-C-glycosides, vicenin-2 (1) and apigenin-6-C-hexoside-8-C-pentoside (3), as well as three mono-C-glycosides-O-glycosylated derivatives, apigenin-7-O-hexoside-8-C-hexoside (2), apigenin-8-C-(2-rhamnosyl)hexoside (4) and apigenin-6-C-(2-rhamnosyl)hexoside (5). Isovitexin-2″-O-rhamnoside (5) is the main constituent, accounting for nearly 40% of the total quantifiable flavonoid content. Our results allowed us to establish the relationship between the presence of vicenin-2 and other apigenin derivatives with the contribution to the cytotoxic effects on the presented AGS cells. Our findings attest the anticancer potential of A. africanus stem bark against gastric adenocarcinoma, calling for studies to develop herbal-based products and/or the use of apigenin derivatives in chemotherapeutic drug development.

Alternative strategies to control weeds are required at the field level to reduce herbicides and derived pollution. As cover crop, rye (Secale cereale L.) is adopted mainly because of its allelopathic weed control, which takes place through a strong inhibition of germination and seedling growth in several types of grass and broad-leaved weeds. The present study consisted of: i) a field trial, focused on the evaluation of biomass production and allelochemical concentration in the biomass, and in situ weed control at 30 days after termination (with two termination timings: T1 - heading phase and T2 - 10 days later) of 8 rye varieties; ii) a pot experiment, focused on the inhibition effect of mulches derived by those 8 rye varieties on four summer weeds: velvetleaf (Abutilon theophrasti Med.), lambsquarters (Chenopodium album L.), redroot pigweed (Amaranthus retroflexus L.), and common purslane (Portulaca oleracea L). Results showed that biomass production was the highest with Protector, closely followed by Primizia, Sito 70, Hellvus, Forestal, and Hymonta. In any case, rye mulching always reduced the weed biomass, especially with Fasto and Forestal. The allelochemical concentration in the biomass was the highest with Fasto and Forestal and decreased on average from T1 to T2 (--38% for total benzoxazinoids and --57% for isovitexin). Conversely, the rye biomass production increased (on average + 77%), passing from T1 to T2. We also found that the reduction of weed biomass, compared with the control, is highly correlated with the allelochemical content in rye biomass in the case of T1 termination, while with the biomass production in the case of T2. In pots, a strong inhibitory effect on seedling growth due to rye mulching was observed for C. album (--76%), A. retroflexus (- 56%), and P. olearcea (--84%), while not for A. theophrasti. We concluded that, regardless of the variety, adopting rye as a cover crop may be considered as a suitable practice to reduce weed pressure at the field level. Among all the varieties tested, Forestal and Protector showed the most significant weed suppression potential, due to the high amount of allelochemicals production for Forestal and high biomass production for Protector. [ABSTRACT FROM AUTHOR]

Qiu Y, Cao X, Liu L, et al. Cancer Manag Res. 2020;12:5759‒5771. The Editor and Publisher of Cancer Management and Research wish to retract the published article. Concerns were raised regarding the alleged duplication of cell migration and invasion images throughout the article. Specifically, Figure 1B, panel 0h HCSLC, appears to have been duplicated with the image from Figure 2C, panel 0h 0.0 µM ISOV. Figure 3B, panel 24h Ad-shMnSOD, appears to have been duplicated with the image from Figure 5G, panel 24h Mock. Figure 4G, panel 24h Ad-GFP+/Ad-MnSOD-/ISOV (10µM)-, appears to have been duplicated with the image from Figure 4G, panel 24h Ad-GFP+/Ad-MnSOD-/ISOV (10µM)+. Figure 1B, panel 24h HCSLC, appears to have been duplicated with an image from Figure 5c, panel 24h Isovitexin (0µg/mL) Ad-GFP from Liu et al, 2021 (https://doi.org/10.1155/2021/9972057). The authors responded to our initial queries but were unable to provide a satisfactory explanation for the alleged image duplication, nor were they able to provide adequate original data for their study. The decision was made to retract the article and the authors agreed with this decision. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

It has been reported that Celtis sinensis Pers. is employed as a folk medicine for the treatment of inflammatory diseases. But the mechanism supporting its use as anti-inflammatory remains unclear. To investigate the anti-inflammatory of Celtis sinensis Pers. ICR mice were provided Celtis sinensis Pers. leaf extract (CLE) at 100, 200 mg/kg after ginkgolic acids (GA) sensitization. Our data showed that CLE and the main flavonoid isovitexin in CLE could ameliorate GA-induced contact dermatitis in mice. Ear swelling, inflammatory cell infiltration and splenomegaly were inhibited significantly by isovitexin, while the weight loss of mice in the isovitexin-treated group was much better than that in the dexamethasone-treated group (positive control drug). It has been reported in previous research that GA-induced inflammation is closely related to the T cell response. Therefore, T cells were the focus of the anti-inflammatory effect of isovitexin in this paper. The in vivo results showed that isovitexin (10, 20 mg/kg) inhibited the expression of proinflammatory cytokines (TNF-α, IFN-γ, IL-2 and IL-17A) in lymph nodes, inhibited the secretion of cytokines into the serum from mice with contact dermatitis and promoted the expression of apoptosis-related proteins. In vitro, isovitexin also induced apoptosis and inhibited proinflammatory cytokine expression in Con A-activated T cells. Further study showed that the MAPK and STAT signaling pathways and the phosphorylation of SHP2 were inhibited by isovitexin. Both molecular docking and biological experiments indicated that SHP2 may be an anti-inflammatory target of isovitexin in T cells. Taken together, isovitexin can serve as a potential natural agent for the treatment or prevention of GA-induced inflammatory problems.

It has been reported that Celtis sinensis Pers. is employed as a folk medicine for the treatment of inflammatory diseases. But the mechanism supporting its use as anti-inflammatory remains unclear. To investigate the anti-inflammatory of Celtis sinensis Pers. ICR mice were provided Celtis sinensis Pers. leaf extract (CLE) at 100, 200 mg/kg after ginkgolic acids (GA) sensitization. Our data showed that CLE and the main flavonoid isovitexin in CLE could ameliorate GA-induced contact dermatitis in mice. Ear swelling, inflammatory cell infiltration and splenomegaly were inhibited significantly by isovitexin, while the weight loss of mice in the isovitexin-treated group was much better than that in the dexamethasone-treated group (positive control drug). It has been reported in previous research that GA-induced inflammation is closely related to the T cell response. Therefore, T cells were the focus of the anti-inflammatory effect of isovitexin in this paper. The in vivo results showed that isovitexin (10, 20 mg/kg) inhibited the expression of proinflammatory cytokines (TNF-α, IFN-γ, IL-2 and IL-17A) in lymph nodes, inhibited the secretion of cytokines into the serum from mice with contact dermatitis and promoted the expression of apoptosis-related proteins. In vitro , isovitexin also induced apoptosis and inhibited proinflammatory cytokine expression in Con A-activated T cells. Further study showed that the MAPK and STAT signaling pathways and the phosphorylation of SHP2 were inhibited by isovitexin. Both molecular docking and biological experiments indicated that SHP2 may be an anti-inflammatory target of isovitexin in T cells. Taken together, isovitexin can serve as a potential natural agent for the treatment or prevention of GA-induced inflammatory problems. [ABSTRACT FROM AUTHOR]

The probiotic beverage was developed using germinated and ungerminated pearl millet flour and green gram milk. The germinated and ungerminated pearl millet flour was added to green gram milk at different concentrations (0.5–2.5 %) along with sugar and cardamom. The mixtures were then inoculated with probiotic bacteria Lactobacillus acidophilus incubated at 37 °C for 6 h. Characterization of probiotic beverages was carried out during storage at (4 ± 1)°C for 21 days. The germinated flour beverage had high acidity as compared to the ungerminated flour beverage. The probiotic count in germinated and ungerminated flour beverages ranged from 8.19 to 8.77 × 107 and 8.04 to 8.52 × 107 log CFU/mL, respectively. Antioxidant activity, polyphenol content increased with an increase in the concentration of flour in the beverage. The LC-MS analysis found the existence of vitexin and isovitexin as the main polyphenolic compounds in the probiotic beverage. Non-dairy probiotic beverage prepared with 0.5 % germinated millet flour gave the best taste, color, texture, and rheological properties. • Probiotic beverages were prepared using pearl millet flour and green gram milk. • Lactobacillus acidophilus was used as probiotic inoculum for beverage. • Good viability of probiotic bacteria was observed till three weeks at 4 °C temperature. • Cereal probiotic beverage is very nutritious and potential alternative to dairy probiotic. • Sensory analysis found probiotic beverage with 0.5 g germinated pearl millet flour scored maximum. [ABSTRACT FROM AUTHOR]

Xiao Liang,1 Chang Xu,2 Xiaocheng Cao,2 Wanchun Wang1 1Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; 2Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha 410013, ChinaCorrespondence: Wanchun WangDepartment of Orthopaedics, The Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, Hunan 410011, People’s Republic of ChinaTel +86-13607482026Email wanchun.wang@csu.edu.cnXiaocheng CaoDepartment of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha 410013, People’s Republic of ChinaTel +86-18773127496Fax +86-0731-88912434Email caocheng268@163.comBackground: Isovitexin (apigenin-6-C-glucoside, ISOV) is a natural flavonoid that exhibits tumor suppressive activity on various types of cancer. However, it is unknown whether the mechanism of its action in osteosarcoma (OS) is associated with epigenetic regulation and whether it involves DNA methyltransferase 1 (DNMT1), microRNAs and their targets.Materials and methods: The present study investigated the effects of ISOV on DNMT1 activation and miR-34a and Bcl-2 expression levels in order to explain the mechanism underlying ISOV-mediated repression of proliferation and stemness. In addition, the induction of apoptosis in the spheres derived from OS cells was investigated.Results: The results indicated that ISOV significantly repressed survival, induced apoptosis and decreased the level of CD133, CD44, ABCG2 and ALDH1 mRNA in the spheres derived from U2OS (U2OS-SC) and MG63 cells (MG63-SC). ISOV further reduced the sphere formation rate of U2OS-SC and MG63-SC. It is important to noted that, ISOV inhibited tumor growth and reduced tumor size of U2OS-SC xenografts in nude mice, which was accompanied by decreased CD133 protein levels, elevated apoptotic index, downregulation of proliferating cell nuclear antigen (PCNA) expression, reduced DNMT1 activity and expression, increased miR-34a and decreased Bcl-2 levels. We identified that Bcl-2 as a direct functional target of miR-34a. Furthermore, ISOV exhibited a synergistic effect with 5-aza-2′-deoxycytidine, the miR-34a mimic or ABT-263 in order to repress cell survival, induce apoptosis, downregulate CD133, CD44, ABCG2 and ALDH1 mRNA expression levels and reduce sphere formation rates of U2OS-SC and MG63-SC cells.Conclusion: The findings suggested that ISOV-mediated epigenetic regulation involved the DNMT1/miR-34a/Bcl-2 axis and caused the suppression of stemness and induction of apoptosis in the spheres derived from OS cells. The data indicated that ISOV exhibited a novel efficient potential for the treatment of OS.Keywords: osteosarcoma, cancer stem cell, isovitexin, DNMT1, miR-34a, Bcl-2

Abstract Background Manganese superoxide dismutase (MnSOD) upregulating FoxM1 have previously been demonstrated promoting lung cancer stemness. Isovitexin exhibits antitumor activities in various cancers. This study aimed to assess whether isovitexin inhibits hepatic carcinoma stem-like cells (HCSLCs) features via regulating MnSOD and FoxM1 expression. Methods Second-generation spheres from the hepatic carcinoma cell lines, respectively, were used as HCSLCs. Protein amounts of MnSOD, FoxM1 and stemness-associated markers (CD133, CD44, ALDH1, Bmi1, Nanog and Oct4) were determined by immunoblotting. In vitro carcinogenicity was evaluated by sphere- and colony-formation assays. The effects of isovitexin on HCSLC carcinogenicity and stemness were examined in vitro and in xenograft models. An adenoviral delivery system was employed to manipulate MnSOD and/or FoxM1. Luciferase reporter assay was performed to verify isovitexin downregulated FoxM1 by inhibiting MnSOD-mediated effects of E2F1 and/or Sp1 on activation of FoxM1 promoter. Results FoxM1 upregulation by MnSOD contributed to carcinogenicity and stemness, with increased sphere- and colony-formation capabilities, upregulated stemness-associated markers and CD133+ subpopulation as well as elevated oncogenicity in vivo in HCSLCs compared with hepatic carcinoma cells. Isovitexin substantially decreased sphere and colony formation rates, and stemness-associated markers in cultured HCSLCs by suppressing MnSOD and FoxM1 expression. Importantly, isovitexin significantly inhibited tumor growth of in nude mice bearing HCSLCs and reduced CD133 protein expression of xenograft in nude mice. MnSOD or FoxM1 knockdown enhanced the effects of isovitexin suppression on carcinogenicity and stemness in HCSLC. MnSOD or FoxM1 overexpression attenuated the effects of isovitexin. Additionally, isovitexin and MnSOD knockdown could inhibit FoxM1 reporter activity via a decreased binding of E2F1 and/or Sp1 onto FoxM1 promoter. FoxM1 overexpression reversed the effects of isovitexin combined with MnSOD knockdown, without affecting MnSOD expression. Moreover, MnSOD knockdown plus thiostrepton, a FoxM1 specific inhibitor, cooperated with isovitexin to repress xenograft tumor growth and downregulate MnSOD and FoxM1 in nude mice bearing HCSLCs from MHCC97H cells. Conclusions Isovitexin inhibits carcinogenicity and stemness in HCSLCs by downregulating FoxM1via inhibition of MnSOD.

Recent studies on the ethnomedicinal use of Clinacanthus nutans suggest promising anti-inflammatory, anti-tumorigenic, and antiviral properties for this plant. Extraction of the leaves with polar and nonpolar solvents has yielded many C-glycosyl flavones, including schaftoside, isoorientin, orientin, isovitexin, and vitexin. Aside from studies with different extracts, there is increasing interest to understand the properties of these components, especially regarding their ability to exert anti-inflammatory effects on cells and tissues. A major focus for this review is to obtain information on the effects of C. nutans extracts and its phytochemical components on inflammatory signaling pathways in the peripheral and central nervous system. Particular emphasis is placed on their role to target the Toll-like receptor 4 (TLR4)-NF-kB pathway and pro-inflammatory cytokines, the antioxidant defense pathway involving nuclear factor erythroid-2-related factor 2 (NRF2) and heme oxygenase 1 (HO-1); and the phospholipase A2 (PLA2) pathway linking to cyclooxygenase-2 (COX-2) and production of eicosanoids. The ability to provide a better understanding of the molecular targets and mechanism of action of C. nutans extracts and their phytochemical components should encourage future studies to develop new therapeutic strategies for better use of this herb to combat inflammatory diseases.

Isovitexin is a main natural flavonoid component in various plants. Currently, the inhibitory effect of isovitexin on pancreatic lipase (PL) and its mechanism have not been elucidated yet. In the present study, we investigated the inhibitory effect of isovitexin on PL, as well as its interaction mechanism, using enzyme inhibition methods, spectroscopic analysis, and molecular simulations. Results showed that isovitexin possessed significant PL inhibitory activity, with IC 50 values of 0.26 ± 0.02 mM. The interaction between isovitexin and PL was dominated by static quenching, and mainly through hydrogen bonding and hydrophobic interaction forces. Analysis of fluorescence spectroscopy confirmed that isovitexin binding altered the conformation of the PL. Circular dichroism (CD) spectrum indicated that isovitexin altered the secondary structure of PL by decreasing the α-helix content and increasing the β-fold content. Molecular simulations further characterize the conformational changes produced by the interaction between isovitexin with PL. The performed study may provide a new insight into the inhibitory mechanism of isovitexin as a novel PL inhibitor., (© 2024 John Wiley & Sons Ltd.)