Diosmetin-7-O-ß-D-glucopyranoside from Pogostemonis Herba alleviated SARS-CoV-2-induced pneumonia by reshaping macrophage polarization and limiting viral replication.

ETHNOPHARMACOLOGICAL RELEVANCE: Viral pneumonia is the leading cause of death after SARS-CoV-2 infection. Despite effective at early stage, long-term treatment with glucocorticoids can lead to a variety of adverse effects and limited benefits. The Chinese traditional herb Pogostemonis Herba is the aerial part of Pogostemon Cablin (Blanco) Benth., which has potent antiviral, antibacterial, anti-inflammatory, and anticancer effects. It was used widely for treating various throat and respiratory diseases, including COVID-19, viral infection, cough, allergic asthma, acute lung injury and lung cancer. AIM OF THE STUDY: To investigate the antiviral and anti-inflammatory effects of chemical compounds from Pogostemonis Herba in SARS-CoV-2-infected hACE2-overexpressing mouse macrophage RAW264.7 cells and hACE2 transgenic mice. MATERIALS AND METHODS: The hACE2-overexpressing RAW264.7 cells were exposed with SARS-CoV-2. The cell viability was detected by CCK8 assay and cell apoptotic rate was by flow cytometric assay. The expressions of macrophage M1 phenotype markers (TNF-α and IL-6) and M2 markers (IL-10 and Arg-1) as well as the viral loads were detected by qPCR. The mice were inoculated intranasally with SARS-CoV-2 omicron variant to induce viral pneumonia. The levels of macrophages, neutrophils, and T cells in the lung tissues of infected mice were analyzed by full spectrum flow cytometry. The expressions of key proteins were detected by Western blot assay. RESULTS: Diosmetin-7-O-ß-D-glucopyranoside (DG) presented the strongest anti-SARS-CoV-2 activity. Intervention with DG at the concentrations of 0.625-2.5 µM not only reduced the viral replication, cell apoptosis, and the productions of inflammatory cytokines (IL-6 and TNF-α) in SARS-CoV-2-infected RAW264.7 cells, but also reversed macrophage polarity from M1 to M2 phenotype. Furthermore, treatment with DG (25-100 mg/kg) alleviated acute lung injury, and reduced macrophage infiltration in SARS-COV-2-infected mice. Mechanistically, DG inhibited SARS-COV-2 gene expression and HK3 translation via targeting YTHDF1, resulting in the inactivation of glycolysis-mediated NF-κB pathway. CONCLUSIONS: DG exerted the potent antiviral and anti-inflammatory activities. It reduced pneumonia in SARS-COV-2-infected mice via inhibiting the viral replication and accelerating M2 macrophage polarization via targeting YTHDF1, indicating its potential for COVID-19 treatment.

Application of a kosmotrope (Na2CO3) and chaotrope (NaCl) in chemometric optimization of aqueous two-phase extraction of bioactive compounds in Hypoxis iridifolia.

Enterolactone, coumaric acid and vitexin are polyphenolic compounds present in a variety of fruits, vegetables, cereals and plants. These bioactive compounds are in high demand due to their antioxidant property in various tissues and organs. The purpose of this study was to develop a simultaneous extraction method, an aqueous two-phase extraction (ATPE) method, that would enable the extraction of these compounds from Hypoxis iridifolia. This environmentally friendly extraction method only applied water and ethanol as extraction solvents for these analytes from the plant matrix. After phase separation, the analytes were salted-out from the aqueous phase into the organic phase with the aid of a chaotrope (NaCl) or kosmotrope (Na2CO3). Thereafter, the analytes were withdrawn by a micro-pipette for analysis on the high-performance liquid chromatography-photodiode array detector. Optimization was conducted using a central composite design, where three parameters were examined which involved percentage ethanol, centrifugation time and salt type. Generally, the optimized conditions for extraction were an ethanol percentage of 100% and a centrifugation time of 10 min, which yielded concentrations of 2942, 23,823 and 8881 mg kg-1 for enterolactone, vitexin and coumaric acid, respectively, in the presence of a kosmotrope. The optimized conditions of extraction in the presence of chaotrope were an ethanol percentage of 66% and a centrifugation time of 10 min with concentrations of 6727, 20,833 and 8618 mg kg-1 for enterolactone, vitexin and coumaric acid, respectively. The ATPE method involving Na2CO3 was a better extractant of all the compounds studied relative to that of NaCl. The superior extraction capability of Na2CO3 in ATPE could serve as a prototype for the development of efficient extraction methods to meet the high demand for medicinal compounds derived from natural products.

Discovery of vitexin as a novel VDR agonist that mitigates the transition from chronic intestinal inflammation to colorectal cancer.

Colitis-associated colorectal cancer (CAC) frequently develops in patients with inflammatory bowel disease (IBD) who have been exposed to a prolonged state of chronic inflammation. The investigation of pharmacological agents and their mechanisms to prevent precancerous lesions and inhibit their progression remains a significant focus and challenge in CAC research. Previous studies have demonstrated that vitexin effectively mitigates CAC, however, its precise mechanism of action warrants further exploration. This study reveals that the absence of the Vitamin D receptor (VDR) accelerates the progression from chronic colitis to colorectal cancer. Our findings indicate that vitexin can specifically target the VDR protein, facilitating its translocation into the cell nucleus to exert transcriptional activity. Additionally, through a co-culture model of macrophages and cancer cells, we observed that vitexin promotes the polarization of macrophages towards the M1 phenotype, a process that is dependent on VDR. Furthermore, ChIP-seq analysis revealed that vitexin regulates the transcriptional activation of phenazine biosynthesis-like domain protein (PBLD) via VDR. ChIP assays and dual luciferase reporter assays were employed to identify the functional PBLD regulatory region, confirming that the VDR/PBLD pathway is critical for vitexin-mediated regulation of macrophage polarization. Finally, in a mouse model with myeloid VDR gene knockout, we found that the protective effects of vitexin were abolished in mid-stage CAC. In summary, our study establishes that vitexin targets VDR and modulates macrophage polarization through the VDR/PBLD pathway, thereby alleviating the transition from chronic colitis to colorectal cancer.

Effects of Purified Vitexin and Iso-Vitexin from Mung Bean Seed Coat on Antihyperglycemic Activity and Gut Microbiota in Overweight Individuals' Modulation.

Exceeding a healthy weight significantly elevates the likelihood of developing type 2 diabetes (T2DM). A commercially available singular constituent, available as either purified vitexin or iso-vitexin, has been associated with a decreased risk of T2DM, but its synergistic effect has not been reported yet. Vitexin and iso-vitexin were extracted using an ethanol-based solvent from mung bean seed coat (MBCE) and subsequently purified using preparative liquid chromatography (Prep-LC). Eleven mixture ratios of vitexin and/or iso-vitexin were determined for their antioxidant and antihyperglycemic activities. The 1:1.5 ratio of vitexin to iso-vitexin from MBCE demonstrated the most synergistic effects for enzyme inhibition and glucose uptake in HepG2 cells within an insulin-resistant system, while these ratios exhibited a significantly lower antioxidant capacity than that of each individual component. In a gut model system, the ratio of 1:1.5 (vitexin and iso-vitexin) regulated the gut microbiota composition in overweight individuals by decreasing the growth of Enterobacteriaceae and Enterococcaceae, while increasing in Ruminococcaceae and Lachnospiraceae. The application of vitexin/iso-vitexin for 24 h fermentation enhanced a high variety of abundances of 21 genera resulting in five genera of Parabacteroides, Ruminococcus, Roseburia, Enterocloster, and Peptacetobacter, which belonged to the phylum Firmicutes, exhibiting high abundant changes of more than 5%. Only two genera of Proteus and Butyricicoccus belonging to Proteobacteria and Firmicutes decreased. The findings suggest that these phytochemicals interactions could have synergistic effects in regulating glycemia, through changes in antihyperglycemic activity and in the gut microbiota in overweight individuals. This optimal ratio can be utilized by industries to formulate more potent functional ingredients for functional foods and to create nutraceutical supplements aimed at reducing the risk of T2DM in overweight individuals.

Comprehensive investigation of network pharmacology, computational modeling, and pharmacokinetic assessment to evaluate the efficacy of flavonoids in rheumatoid arthritis.

Rheumatoid arthritis is a chronic autoimmune disease characterized by inflammation and joint damage, imposing a significant burden on affected individuals worldwide. Flavonoids, a class of natural compounds abundant in various plant-based foods, have shown promising anti-inflammatory and immunomodulatory effects, suggesting their potential as therapeutic agents for RA. In this study, we conducted a comprehensive investigation of identified LCMS compounds utilizing network pharmacology, computational modeling, in silico approaches, and pharmacokinetic assessment to evaluate the efficacy of flavonoids in RA treatment. The study identified 5 flavonoid structures with common targets via LCMS and Integration of network pharmacology approaches enabled a comprehensive evaluation of the pharmacological profile of flavonoids in the context of RA treatment, guiding the selection of promising candidates for further experimental validation and clinical development. The top 10 targets were AKT1, PI3KR1, CDK2, EGFR, CDK6, NOS2, FLT3, ALOX5, CCNB1, and PTPRS via PPI network. The investigation emphasized several pathways, including the AGE-RAGE signaling pathway, resistance to EGFR tyrosine kinase inhibitors, the PI3K-AKT signaling network, and the Rap 1 signaling pathway. In silico studies estimated binding affinities that ranged from - 7.0 to - 10.0 kcal/mol. Schaftoside and Vitexin showed no toxicity in computational approach and found suitable for further investigations. Overall, our study underscores the potential of flavonoids as therapeutic agents for RA and highlights the utility of integrative approaches combining network pharmacology, computational modeling, in silico methods, and pharmacokinetic assessment in drug discovery and development processes.

Vitexin Mitigates Haloperidol-Induced Orofacial Dyskinesia in Rats through Activation of the Nrf2 Pathway.

Vitexin (VTX), a C-glycosylated flavone found in various medicinal herbs, is known for its antioxidant, anti-inflammatory, and neuroprotective properties. This study investigated the protective effects of VTX against orofacial dyskinesia (OD) in rats, induced by haloperidol (HPD), along with the neuroprotective mechanisms underlying these effects. OD was induced by administering HPD (1 mg/kg i.p.) to rats for 21 days, which led to an increase in the frequency of vacuous chewing movements (VCMs) and tongue protrusion (TP). VTX (10 and 30 mg/kg) was given intraperitoneally 60 min after each HPD injection during the same period. On the 21st day, following assessments of OD, the rats were sacrificed, and nitrosative and oxidative stress, antioxidant capacity, mitochondrial function, neuroinflammation, and apoptosis markers in the striatum were measured. HPD effectively induced OD, while VTX significantly reduced HPD-induced OD, decreased oxidative stress, enhanced antioxidant capacity, prevented mitochondrial dysfunction, and reduced neuroinflammatory and apoptotic markers in the striatum, and the protective effects of VTX on both behavioral and biochemical aspects of HPD-induced OD were significantly reduced when trigonelline (TGN), an inhibitor of the nuclear factor erythroid-2-related factor 2 (Nrf2)-mediated pathway, was administered. These findings suggest that VTX provides neuroprotection against HPD-induced OD, potentially through the Nrf2 pathway, indicating its potential as a therapeutic candidate for the prevention or treatment of tardive dyskinesia (TD) in clinical settings. However, further detailed research is required to confirm these preclinical findings and fully elucidate VTX's therapeutic potential in human studies.

Evaluation of Cytotoxicity and Acute Oral Toxicity of Saline Extract and Protein-Rich Fraction from Moringa oleifera Lam. Leaves.

Moringa oleifera Lam. (horseradish tree) leaves demonstrate high nutritional value, are rich in proteins, and are widely used in folk medicine and food. This study investigated the presence of secondary metabolites and antinutritional proteins in leaf extract (LE) and the protein-rich fraction (PRF) derived from M. oleifera leaves, as well as the cytotoxicity to human cells, hemolytic activity, and in vivo acute toxicity and genotoxicity in mice. The flavonoids rutin and vitexin as well as trypsin inhibitors and lectins were detected in LE and PRF. Neither sample demonstrated toxicity against human peripheral blood mononuclear cells and both showed low hemolytic action. In vivo, LE and PRF did not show antinutritional effects and caused no death. The hematological parameters of the animals in the treated group were similar to those of the control. A significant increase in the serum levels of alanine aminotransferase and a discrete leukocyte infiltration with cytoplasmic vacuolization of the hepatocytes in the liver were detected in LE-treated animals. The preparations were not genotoxic or mutagenic. This study shows that LE and PRF are not antinutritional agents and presented low acute toxicity and no genotoxicity or mutagenicity. The present study contributes to the determination of the safety of using M. oleifera leaf proteins.

Unveiling the Potential of Bergenia Phenolics: Vitexin's Role in Allosteric Modulation of PBP2a as a Strategy against MRSA Resistance.

BACKGROUND: For cell wall biosynthesis, drug-resistant S. aureus uses a special protein called PBP2a, even when antibiotics are present and stop its natural processes from working. To combat this, novel therapies are required to specifically target PBP2a with greater efficacy. METHODS: Using computational approaches, we screened nine phenolic compounds from other Bergenia species, including Bergenia ciliata, Begenia ligulata, Bergenia purpurascens, and Ber-genia stracheyi, against the PBP2a allosteric site to explore the potential interaction between phe-nolic compounds and a specific region of PBP2a known as the allosteric site. RESULTS: Based on interaction patterns and estimated affinity, vitexin has been found to be the most prominent phenolic compound. We performed MD simulations on vitexin and ceftazidime as control molecules based on the docking results. The binding free energy estimates of vitexin (-94.48 +/- 17.92 kJ/mol) using MM/PBSA were lower than those of the control (-67.61 +/- 12.29 kJ/mol), which suggests that vitexin may be able to inhibit PBP2a activity in MRSA. CONCLUSION: It has been intriguing to observe a correlation between the affinity of the lead com-pounds at the allosteric site and the modification of Tyr446, the active site gatekeeper residue in PBP2a. Our findings have implied that lead compounds can either directly or indirectly decrease PBP2a activity by inducing allosteric site change in conventional medicine.

Vitexin attenuates neuropathic pain by regulating astrocyte autophagy flux and polarization via the S1P/ S1PR1-PI3K/ Akt axis.

Neuropathic pain (NP) is associated with astrocytes activation induced by nerve injury. Reactive astrocytes, strongly induced by central nervous system damage, can be classified into A1 and A2 types. Vitexin, a renowned flavonoid compound, is known for its anti-inflammatory and analgesic properties. However, its role in NP remains unexplored. This study aims to investigate the effects of vitexin on astrocyte polarization and its underlying mechanisms. A mouse model of NP was established, and primary astrocytes were stimulated with sphingosine-1-phosphate (S1P) to construct a cellular model. The results demonstrated significant activation of spinal astrocytes on days 14 and 21. Concurrently, reactive astrocytes predominantly differentiated into the A1 type. Western blot analysis revealed an increase in A1 astrocyte-associated protein (C3) and a decrease in A2 astrocyte-associated protein (S100A10). Serum S1P levels increased on days 14 and 21, alongside a significant upregulation of Sphingosine-1-phosphate receptor 1 (S1PR1) mRNA expression and elevated expression of chemokines. In vitro, stimulation with S1P inhibited the Phosphatidylinositol 3-kinase and protein kinase B (PI3K/Akt) signaling pathway and autophagy flux, promoting polarization of astrocytes towards the A1 phenotype while suppressing the polarization of A2 astrocytes. Our findings suggest that vitexin, acting on astrocytes but not microglia, attenuates S1P-induced downregulation of PI3K/Akt signaling, restores autophagy flux in astrocytes, regulates A1/A2 astrocyte ratio, and reduces chemokine and S1P secretion, thereby alleviating neuropathic pain caused by nerve injury.

Investigating the molecular mechanism of vitexin targeting CDK1 to inhibit colon cancer cell proliferation via GEO chip data mining, computer simulation, and biological activity verification.

The objective of this study is to explore the antiproliferative activity of the traditional Chinese medicine monomer vitexin on colon cancer HCT-116 cells and its underlying mechanism. The in vitro antiproliferative activity of vitexin on colon cancer HCT-116 cells was evaluated using the CCK-8 assay. Potential drug targets for colon cancer were identified through GEO chip data mining, and molecular docking using Schrödinger software was conducted. Molecular dynamics simulations were employed to deeply analyze the interaction between candidate compounds and target proteins. Flow cytometry was employed to examine the cell cycle. The impact of vitexin on the expression of CDK1/cyclinB proteins in HCT-116 cells was assessed through Western blot analysis, immunofluorescence, and CDK inhibition assay. Vitexin exhibited inhibitory effects on colon cancer HCT-116 cells, with a half inhibitory concentration (IC50) value of 203.27 ± 9.85 µmol/L. The analysis of differential gene expression in GEO and TCGA datasets, along with the GENECARD dataset of related disease genes, identified 91 disease targets, including "CDK1." Vitexin induced cell cycle arrest in the G2/M phase of HCT-116 cells. Molecular docking revealed a strong interaction between Vitexin and CDK1 (Docking score - 9.497), with molecular dynamics simulations confirming the stability of the Vitexin-CDK1 complex and comparable inhibitory effects to Flavopiridol. Vitexin can inhibit the expression of CDK1/cyclin B proteins in HCT-116 cells, with an IC50 of 58.06 ± 3.07 µmol/L. Vitexin may inhibit colon cancer HCT-116 cell proliferation by suppressing CDK1/cyclin B expression, leading to cell cycle arrest in the G2/M phase.

The Protective Effect of Vitexin on Hypertensive Nephropathy Rats.

INTRODUCTION: Vitexin is a natural flavonoid compound extracted from Vitex leaves or seeds, exhibiting various pharmacological activities including anticancer, antihypertensive, anti-inflammatory, and spasmolytic effects. However, its protective effects on hypertensive nephropathy (HN) and the underlying mechanisms remain unclear. METHODS: Spontaneous hypertension rats were fed a high-sugar and high-fat diet for 8 weeks to induce the disease HN model. From the 5th week, the rats were administered vitexin via gavage. Blood pressure was measured biweekly using the tail-cuff method. Histopathological changes were assessed using HE staining, and biochemical analyses were performed to evaluate the effects of vitexin on HN rats. The underlying mechanisms of vitexin treatment were investigated through western blotting. RESULTS: The data demonstrated that vitexin significantly lowered systolic, diastolic, and mean arterial pressures and ameliorated histopathological changes in HN rats. Biochemical analyses revealed that vitexin reduced the levels of creatinine (Cr), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), total protein (TP), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and advanced glycation end products (AGEs), while increasing the levels of albumin (ALB) and superoxide dismutase (SOD). Western blotting results indicated that vitexin treatment decreased the expression of TNF-α, IL-6, and nuclear factor kappa-B (NF-κB), while increasing the expression of SOD. CONCLUSION: The findings of this study suggest that vitexin exerts protective effects against HN, providing pharmacological evidence for its potential use in HN treatment.

Vitexin promotes the anti-senescence effect via inhibiting JAK2/STAT3 in D-Galactose-induced progeria mice and stress-induced premature senescence.

Vitexin is a natural flavonoid glycoside compound extracted from the leaves and seeds of Vitex negundo. It is widely distributed in the leaves and stems of numerous plants and exhibites remarkable anti-tumor, anti-inflammatory, and anti-hypertensive properties. However, whether vitexin presents the anti-aging and senescence prevention effect has not been fully elucidated. The purpose of this study is to investigate the effect of vitexin on progeria mice and cellular senescence, as well as its underlying molecular mechanisms. To generate a premature aging/senescence model in vivo and in vitro, we used D-galactose (D-gal), hydrogen peroxide (H2O2), and adriamycin (ADR), respectively. Our findings demonstrated that vitexin potentially delays D-gal-induced progeria mice; similar effects were observed in stress-induced premature senescent fibroblasts in culture. Interestingly, this effect of vitexin is closely correlated with the reduction of the senescence-associated secretory phenotype (SASP) and the inhibition of the SASP-related JAK2/STAT3 pathway. Furthermore, we determined that vitexin meets the pharmacological parameters using the freely available ADMET web tool. Collectively, our findings demonstrate that vitexin possesses anti-senescence and anti-aging properties due to the inhibition of SASP and suppression of JAK2/STAT3 signaling pathway.

Essential oil composition of passiflora foetida L. (passifloraceae) flowers and chemical-biology study of the leaves extracts and isolated compound.

Passiflora foetida is a climbing herb employed in ethno-medicine for the treatment of various ailments. The essential oil from flowers of P. foetida was obtained by hydrodistillation. The ethanol extract of the leaves was dissolved in water, then partitioned with n-hexane and n-butanol to obtain the various fractions; the fractions and isolated compound were subjected to in vitro antioxidant activity. Gas chromatography-mass spectrometry afforded the identification of forty-two constituents in the floral oil, dominated by ß-caryophyllene (17.2%), cedrol (11.5%), and α-humulene (11.5%). The n-butanol fraction was the most active (70% inhibition and absorbance 0.401; 100 µg/mL) in the 2,2-diphenyl-1-picrylhydrazyl radicals and ferric reducing power assays, respectively. Chromatographic analysis facilitated the isolation of 8-C-ß-d-glucosylapigenin (vitexin) from the butanol fraction of P. foetida. Vitexin demonstrated good antioxidant activities (75% inhibition and absorbance 0.424; 100 µg/mL) compared with ascorbic acid. The volatile metabolites of P. foetida flowers are reported for the first time.

Based on Virtual Screening and Simulation Exploring the Mechanism of Plant-Derived Compounds with PINK1 to Postherpetic Neuralgia.

Accumulating evidence strongly supports that PINK1 mutation can mediate mitochondrial autophagy dysfunction in dopaminergic neurons. This study was conducted to determine the role of PINK1 in the pathogenesis of postherpetic neuralgia (PHN) and find new targets for its treatment. A rigorous literature review was conducted to identify 2801 compounds from more than 200 plants in Asia. Virtual screening was used to shortlist the compounds into 20 groups based on their binding energies. MM/PBSA was used to further screen the compound dataset, and vitexin, luteoloside, and 2'-deoxyadenosine-5'-monophosphate were found to have a score of - 59.439, - 52.421, and - 47.544 kcal/mol, respectively. Pain behavioral quantification, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, western blotting, and transmission electron microscopy were used to confirm the effective mechanism. Vitexin had the most significant therapeutic effect on rats with PHN followed by luteoloside; 2'-deoxyadenosine-5'-monophosphate had no significant effect. Our findings suggested that vitexin could alleviate PHN by regulating mitochondrial autophagy through PINK1.

Pearl millet flour and green gram milk based probiotic beverage.

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.

Potential Health Benefits of Fermented Vegetables with Additions of Lacticaseibacillus rhamnosus GG and Polyphenol Vitexin Based on Their Antioxidant Properties and Prohealth Profiles.

Fermented vegetables are increasingly being recognized as an important dietary component, particularly of plant-based diets, to achieve a sustainable healthy gut because of their microbial diversity and antioxidant properties. However, the functional relevance of fermented vegetables varies based on the raw ingredients used and nutrient supplementation. Therefore, in the present study, we investigated the microbial diversity and antioxidant activity of three formulas of fermented vegetables (standard, supplemented with Lacticaseibacillus rhamnosus GG, and supplemented with polyphenol vitexin) at days 0 and 15. The bacterial community profiles were determined through 16S rRNA sequencing analysis, and antioxidant activity was analyzed using 2,2-diphenyl-1-picrylhydrazyl and by measuring the oxygen radical absorbance capacity, the ferric reducing ability of plasma, and the total phenolic content. The results confirm microbial diversity in the taxonomic composition of the different formulas of fermented vegetables, with different bacteria predominating, particularly lactic acid bacteria including the genera Weissella, Pedicocccus, Leuconostoc, and Lactobacillus. Spearman's correlation analysis showed significant differences in the specific bacteria present in the different formulas of fermented vegetables that conferred antioxidant capacity. Our findings show that supplementation with L. rhamnosus GG and polyphenol vitexin may effectively enhance the functional relevance of foods by promoting cellular protection against oxidative stress.

Examination of the effects of vitexin and vitexin-loaded solid lipid nanoparticles on neuropathic pain and possible mechanisms of action.

This research aims to investigate the possible antiallodynic and antihyperalgesic effects of pure vitexin and vitexin-loaded solid lipid nanoparticles (SLN) on neuropathic pain and the pathways mediating these effects. Chronic constriction nerve injury was induced in female rats, and the effects of vitexin at the doses of 5, 10, 20, 40 mg/kg were evaluated. Ketanserin, ondansetron, WAY-100635, yohimbine and bicuculin, which are antagonists of receptors on pain pathways. were used to examine the mechanisms of the effects of vitexin. Pure vitexin exhibited antiallodynic activity at all administered doses, whereas antihyperalgesic activity was not observed at 5 mg/kg vitexin dose. SLN formulation was prepared with 5 mg/kg vitexin, the lowest dose. Vitexin-loaded formulation significantly increased antiallodynic and antihyperalgesic effects. Ondansetron, WAY-100635, yohimbine, and bicuculine antagonized the antiallodynic and antihyperalgesic effects of vitexin. So, it was concluded that serotonin (5-hydroxtryptamine, 5-HT) receptor subtypes 5-HT3 and 5-HT1A, alpha-2 adrenergic, and γ-Aminobutyric acid type A (GABA-A) receptors are involved in the antiallodynic and antihyperalgesic activity of vitexin. In conclusion, vitexin and vitexin-loaded formulation have the potential for clinical use in neuropathic pain management, and different pain pathways contributed to this effect. And also, it is thought that vitexin-loaded SLN formulation is more effective than pure vitexin, which will provide an advantage in treatment.

An enhanced cardio-protective effect of nanoparticles loaded with active components from Polygonum orientale L. against isoproterenol-induced myocardial ischemia in rats.

In this study, nanoparticles loaded with active components from Polygonum orientale L. (PO), a traditional Chinese herb known for its anti-myocardial ischemic properties, were investigated for cardio-protective properties. Specifically, OVQ-Nanoparticles (OVQ-NPs) with Orientin (Ori), Vitexin (Vit), and Quercetin (Que) was obtained by double emulsion-solvent evaporation method. The OVQ-NPs exhibited a spherical shape, with a uniform size distribution of 136.77 ± 3.88 nm and a stable ζ-potential of -13.40 ± 2.24 mV. Notably, these nanoparticles exhibited a favorable sustained-release characteristic, resulting in an extended circulation time within the living organism. Consequently, the administration of these nanoparticles resulted in significant improvements in electrocardiograms and heart mass index of myocardial ischemic rats induced by isoproterenol, as well as decreased serum levels of CK, LDH, and AST. Furthermore, the results of histopathological examination, such as H&E staining and TUNEL staining, confirmed a reduced level of cardiac tissue pathology and apoptosis. Moreover, the quantification of biochemical indicators (SOD, MDA, GSH, NO, TNF-α, and IL-6) demonstrated that OVQ-NPs effectively mitigated myocardial ischemia by regulating oxidative stress and inflammatory pathways. In conclusion, OVQ-NPs demonstrate promising therapeutic potential as an intervention for myocardial ischemia, providing a new perspective on traditional Chinese medicine treatment in this area.

Protective Effect of Vitexin Against IL-17-Induced Vascular Endothelial Inflammation Through Keap1/Nrf2-Dependent Signaling Pathway.

SCOPE: Vitexin, a C-glycosylated flavonoid, is abundant in food sources and has potential health-beneficial properties. However, the targets for its beneficial effects remain largely unknown. This study aims to establish an in vitro cell model of vascular low-grade inflammation and explore the antiinflammatory mechanism of vitexin. METHODS AND RESULTS: Low-dose TNFα and IL-17 are combined to establish a cell model of vascular low-grade inflammation. Cell-based studies show that low-dose TNFα (1 ng mL-1) alone has a slight effect, but its combination with IL-17 can potently induce protein expression of inflammatory cytokines, leading to an inflammatory state. However, the vascular inflammation caused by low-dose TNF plus IL-17 does not lead to oxidative stress, and reactive oxygen species (ROS) does not involved in developing this inflammation. Vitexin can be absorbed by human umbilical vein endothelial (HUVEC) cells to increase the Nrf2 protein level and attenuate inflammation. In addition, the antiinflammatory effect of vitexin is blocked by the knockdown of Nrf2. Further localized surface plasmon resonance, drug affinity responsive target stability, and molecular docking demonstrate that vitexin can directly interact with Keap1 to disrupt Keap1-Nrf2 interaction and thus activate Nrf2. Treatment of mice with a bolus oral gavage of vitexin (100 mg kg-1 body weight) or a high-fat diet supplemented with vitexin (5 mg kg-1 body weight per day) for 12 weeks confirms the rapid increase in blood vitexin levels and subsequent incorporation into blood vessels to activate Nrf2 and ameliorate inflammation in vivo. CONCLUSION: The findings provide a reliable cell model of vascular low-grade inflammation and indicate Nrf2 protein as the potential target of vitexin to inhibit vascular inflammation.

Deciphering the metabolic signatures of Trigonella microgreens as a function of photoperiod and temperature using targeted compound analysis and non-targeted UHPLC-QTOF-IMS based approach.

Trigonella foenum-graecum L. (Fenugreek) is an annual herb that belongs to Fabaceae family. The compositional make-up of microgreens depends on prevailing environmental conditions. So, Trigonella microgreens were cultivated under different photoperiod and temperature conditions and evaluated for plant height, total chlorophyll content (TCC), targeted compound analysis and non-targeted UHPLC-QTOF-IMS based metabolomic profile. The plant height and TCC of Trigonella microgreens increased by approximately 22 % and 20 %, respectively under T1 conditions (longer photoperiod of 22 h with 22 °C in light and 17 °C in dark). The targeted phenolic profile analysis revealed the dominant presence of gallic acid, p-coumaric acid and apigenin in Trigonella microgreens. Also, the concentration of p-coumaric acid concentration raised from 3.51 mg/g to 5.83 mg/g as a response of T1 conditions. The sugar profile revealed augmented concentration of myo-inositol, glucose, fructose, xylose, maltose, and sucrose in longer photoperiod with T1 conditions. The microgreens were also rich in amino acids like aspartic acid, glutamic acid, leucine, isoleucine, and phenylalanine. Notably, the concentration of proline increased from 10.40 mg/g to 16.92 mg/g as a response to T1 growth conditions. The concentration of these metabolites varied significantly under different photoperiod and temperature conditions. The comprehensive non-targeted UHPLC-QTOF-IMS analysis of microgreens revealed different class of metabolites like organic compounds, alkaloids, coumarin-derivatives, phenolic and flavonoid derivatives, terpenoids, sugars, amino acids and few nucleic acid derivatives. The multivariate PLS-DA explained different expression level of metabolites under different growing conditions. The T1 growing condition resulted in the increased biosynthesis of phenolic compounds and various metabolites. The expression level of terpenoid derivatives specifically of Trigonelloside C and Trigoneoside XIIa/b increased under T1 conditions. The substantial alteration in the metabolites due to growing conditions may alter the microgreen's dietary benefits. So, additional research may be warranted.