Flavonoid Glycosides Research Articles

IDENTIFICATION AND QUANTIFICATION OF FLAVONOIDS IN MEDICINAL PLANTS GROWING IN THE REPUBLIC OF UZBEKISTAN

Introduction. In recent years, the popularity of herbal medicine has been increasing. One of the most numerous classes of biologically active substances of plant origin are flavonoids, which have a wide range of biological activities: anticarcinogenic, antioxidant, antimicrobial, neuroprotective, immunomodulatory, hepatoprotective effects, and also capable of stimulating the damaged body tissues regeneration processes. The relevant area of the research is the search for medicinal plants with a high content of flavonoids for the development of herbal remedies with wound-healing activity. This problem can be solved through the use of plant raw materials from the Republic of Uzbekistan, which have a high content and a wide range of biologically active substances, thanks to the sharply continental climate of the country with consistently hot summers and increased levels of ultraviolet radiation. The purpose of the research is to select medicinal plant raw materials as a source of flavonoids for the development of wound healing agents. Material and methods. The object of the study was medicinal plant raw materials harvested on the territory of the Republic of Uzbekistan: oregano herb, sage leaves, St. John's wort herb, sandy everlasting flowers, bur beggar-ticks herb. Identification and quantification of flavonoids in the studied samples of medicinal plants was carried out using thin-layer chromatography, absorption spectrophotometry in the visible region using reaction with aluminum chloride and high-performance liquid chromatography-mass spectrometry. Results. It has been established that the content of flavonoids in the herb of oregano, leaves of medicinal sage, St. John's wort herb, flowers of sandy everlasting, harvested in the Republic of Uzbekistan, is significantly higher than in medicinal plant materials harvested in the territory of the Republic of Belarus and the Russian Federation. Using the method of thin-layer chromatography and high-performance liquid chromatography-mass spectrometry, kaempferol-3-β-D-glucopyranoside was identified in the extract of sandy everlasting flowers, and isoquercitrin was identified in the extract of St. John's wort herb. Conclusions. As a result of the research, sandy everlasting and St. John's wort, growing on the territory of the Republic of Uzbekistan, were selected as the sources of flavonoids (glycoside kaempferol and isoquercitrin) with regenerating properties for the development of wound healing agents.

UDP-glucosyltransferase 71C4 controls the flux of phenylpropanoid metabolism to shape cotton seed development

Seeds play a crucial role in plant reproduction, making it essential to identify genes that affect seed development. In this study, we focused on UDP-glucosyltransferase 71C4 (UGT71C4) in cotton, a member of the glycosyltransferase family that shapes seed width and length, thereby influencing seed index and seed cotton yield. Overexpression of UGT71C4 results in seed enlargement owing to its glycosyltransferase activity on flavonoids, which redirects metabolic flux from lignin to flavonoid metabolism. This shift promotes cell proliferation in the ovule via accumulation of flavonoid glycosides, significantly enhancing seed cotton yield and increasing the seed index from 10.66 g to 11.91 g. By contrast, knockout of UGT71C4 leads to smaller seeds through activation of the lignin metabolism pathway and redirection of metabolic flux back to lignin synthesis. This redirection leads to increased ectopic lignin deposition in the ovule, inhibiting ovule growth and development, and alters yield components, increasing the lint percentage from 41.42% to 43.40% and reducing the seed index from 10.66 g to 8.60 g. Our research sheds new light on seed size development and reveals potential pathways for enhancing seed yield.

Medicago truncatula β-glucosidase 17 contributes to drought and salt tolerance through antioxidant flavonoid accumulation.

Flavonoids are usually present in forms of glucosides in plants, which could be catabolized by β-glucosidase (BGLU) to form their corresponding flavonoid aglycones. In this study, we isolated three abiotic-responsive BGLU genes (MtBGLU17, MtBGLU21and MtBGLU22) from Medicago truncatula, and found only the recombinant MtBGLU17 protein could catalyse the hydrolysis of flavonoid glycosides. The recombinant MtBGLU17 protein is active towards a variety of flavonoid glucosides, including glucosides of flavones (apigenin and luteolin), flavonols (kaempferol and quercetin), isoflavones (genistein and daidzein)and flavanone (naringenin). In particular, the recombinant MtBGLU17 protein preferentially hydrolyses flavonoid-7-O-glucosides over their corresponding 3-O-glucosides. The content of luteoin-7-O-glucoside was reduced in the MtBGLU17 overexpression plants but increased in the Tnt-1 insertional mutant lines, whereas luteoin content was increased in the MtBGLU17 overexpression plants but reduced in the Tnt-1 insertional mutant lines. Under drought and salt (NaCl) treatment, the MtBGLU17 overexpression lines showed relatively higher DPPH content, and higher CAT and SOD activity than the wild type control. These results indicated that overexpression lines of MtBGLU17 possess higher antioxidant activity and thus confer drought and salt tolerance, implying MtBGLU17 could be potentially used as a candidate gene to improve plant abiotic stress tolerance.

Four novel Cit7GlcTs functional in flavonoid 7-O-glucoside biosynthesis are vital to flavonoid biosynthesis shunting in citrus.

Citrus fruits have abundant flavonoid glycosides (FGs), an important class of natural functional and flavor components. However, there have been few reports about the modification of UDP-glycosyltransferases (UGTs) on flavonoids in citrus. Notably, in flavonoid biosynthesis, 7-O-glucosylation is the initial and essential step of glycosylation prior to the synthesis of flavanone disaccharides, the most abundant and iconic FGs in citrus fruits. Here, based on the accumulation of FGs observed at the very early fruit development stage of two pummelo varieties, we screened six novel flavonoid 7-O-glucosyltransferase genes (7GlcTs) via transcriptomic analysis and then characterized them in vitro. The results revealed that four Cg7GlcTs possess wide catalytic activities towards various flavonoid substrates, with CgUGT89AK1 exhibiting the highest catalytic efficiency. Transient overexpression of CgUGT90A31 and CgUGT89AK1 led to increases in FG synthesis in pummelo leaves. Interestingly, these two genes had conserved sequences and consistent functions across different germplasms. Moreover, CitUGT89AK1 was found to play a role in the response of citrus to Huanglongbing infection by promoting FG production. The findings improve our understanding of flavonoid 7-O-glucosylation by identifying the key genes, and may help improve the benefits of flavonoid biosynthesis for plants and humans in the future.

Diosmetin attenuates fibromyalgia-like symptoms in a reserpine-induced model in mice.

Fibromyalgia is a potentially disabling idiopathic disease characterized by widespread chronic pain associated with comorbidities such as fatigue, anxiety, and depression. Current therapeutic approaches present adverse effects that limit adherence to therapy. Diosmetin, an aglycone of the flavonoid glycoside diosmin found in citrus fruits and the leaves of Olea europaea L., has antinociceptive, anti-inflammatory, and antioxidant properties. Here, we investigated the effect of diosmetin on nociceptive behaviors and comorbidities in an experimental fibromyalgia model induced by reserpine in mice. To induce the experimental fibromyalgia model, a protocol of subcutaneous injections of reserpine (1mg/kg) was used once a day for three consecutive days in adult male Swiss mice. Mice received oral diosmetin on the fourth day after the first reserpine injection. Nociceptive (mechanical allodynia, muscle strength, and thermal hyperalgesia) and comorbid (depressive-like and anxiety behavior) parameters were evaluated. Potential adverse effects associated with diosmetin plus reserpine (locomotor alteration, cataleptic behavior, and body weight and temperature changes) were also evaluated. Oral diosmetin (0.015-1.5mg/kg) reduced the mechanical allodynia, thermal hyperalgesia, and loss of muscle strength induced by reserpine. Diosmetin (0.15mg/kg) also attenuated depressive-like and anxiety behaviors without causing locomotor alteration, cataleptic behavior, and alteration in weight and body temperature of mice. Overall, diosmetin can be an effective and safe therapeutic alternative to treat fibromyalgia symptoms, such as pain, depression and anxiety.

Flavonoids glycosides from Camellia phanii

By combining chromatography methods, three new flavonoid glycosides, kaempferol 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranoside (1), kaempferol 3-O-(4-acetyl)-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranoside (2), and (2 R,3 S) 5,7,4′-tetrahydroxyflavanonol 3-O-(4-acetyl)-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranoside (3) as well as three known compounds, chrysandroside A (4), p-hydroxybenzaldehyde (5), and p-hydroxybenzoic acid (6) were isolated from the leaves of Camellia phanii Hakoda & Ninh. Their structure was elucidated by 1D and 2D-NMR spectra and compared to previously published in literature. In addition, all compounds were evaluated for their ability to inhibit α-glucosidase activity. As the results, flavonoid glycosides 1-3 inhibited α-glucosidase activity with IC50 values of 276.8 ± 19.4, 258.9 ± 24.3, and 341.4 ± 25.6 µM; phenolics (5 and 6) inhibited α-glucosidase activity with IC50 values of 295.5 ± 15.1 and 217.4 ± 23.6 µM, respectively.

Sophorin mitigates flutamide-induced hepatotoxicity in wistar rats

Flutamide is frequently used in the management of prostate cancer, hirsutism, and acne. It is a non-steroidal anti-androgenic drug and causes hepatotoxicity. The current study's objective is to evaluate sophorin's hepatoprotective effectiveness against flutamide-induced hepatotoxicity in Wistar rats. Sophorin is a citrus flavonoid glycoside, also known as rutin, which is a low molecular weight polyphenolic compound with natural antioxidant properties and reported to have promising hepatoprotective efficacy. In this study, sophorin was used at a dose of 100 mg/kg body weight in purified water via oral route for 4 week daily whereas, flutamide was used at a dose of 100 mg kg/b.wt for 4 weeks daily in 0.5% carboxy methyl cellulose (CMC) through the oral route for the induction of hepatotoxicity. Flutamide administration leads to enhanced reactive oxygen species (ROS) generation, an imbalance in redox homeostasis and peroxidation of lipid resulted in reduced natural antioxidant level in liver tissue. Our result demonstrated that sophorin significantly abrogate flutamide induced lipid peroxidation, protein carbonyl (PC), and also significantly increasesed in enzymatic activity/level of tissue natural antioxidant such as reduced glutathione(GSH), glutathione reductase(GR), catalase, and superoxide dismutase(SOD). Additionally, sophorin reduced the activity of cytochrome P450 3A1 in liver tissue which was elevated due to flutamide treatment. Furthermore, sophorin treatment significantly decreased the pro-inflammatory cytokines (TNF-α and IL-6) level. Immunohistochemical analysis for the expression of inflammatory proteins (iNOS and COX-2) in hepatic tissue was decreased after sophorin treatment against flutamide-induced hepatotoxicity. Moreover, sophorin suppressed the infiltration of mast cells in liver tissue which further showed anti-inflammatory potential of sophorin. Our histological investigation further demonstrated sophorin's hepatoprotective function by restoring the typical histology of the liver. Based on the aforementioned information, we are able to come to the conclusion that sophorin supplementation might benefit wistar rats with flutamide-induced hepatic damage by reducing oxidative stress and hepatocellular inflammation.

Combinatorial metabolic engineering of Bacillus subtilis enables the efficient biosynthesis of isoquercitrin from quercetin

BackgroundIsoquercitrin (quercetin-3-O-β-D-glucopyranoside) has exhibited promising therapeutic potentials as cardioprotective, anti-diabetic, anti-cancer, and anti-viral agents. However, its structural complexity and limited natural abundance make both bulk chemical synthesis and extraction from medical plants difficult. Microbial biotransformation through heterologous expression of glycosyltransferases offers a safe and sustainable route for its production. Despite several attempts reported in microbial hosts, the current production levels of isoquercitrin still lag behind industrial standards.ResultsHerein, the heterologous expression of glycosyltransferase UGT78D2 gene in Bacillus subtilis 168 and reconstruction of UDP-glucose (UDP-Glc) synthesis pathway led to the synthesis of isoquercitrin from quercetin with titers of 0.37 g/L and 0.42 g/L, respectively. Subsequently, the quercetin catabolism blocked by disruption of a quercetin dioxygenase, three ring-cleavage dioxygenases, and seven oxidoreductases increased the isoquercitrin titer to 1.64 g/L. And the hydrolysis of isoquercitrin was eliminated by three β-glucosidase genes disruption, thereby affording 3.58 g/L isoquercitrin. Furthermore, UDP-Glc pool boosted by pgi (encoding glucose-6-phosphate isomerase) disruption increased the isoquercitrin titer to 10.6 g/L with the yield on quercetin of 72% and to 35.6 g/L with the yield on quercetin of 77.2% in a 1.3-L fermentor.ConclusionThe engineered B. subtilis strain developed here holds great potential for initiating the sustainable and large-scale industrial production of isoquercitrin. The strategies proposed in this study provides a reference to improve the production of other flavonoid glycosides by engineered B. subtilis cell factories.

Research Progress on Anti-Inflammatory Effects and Related Mechanisms of Astragalin.

Chronic inflammation is a significant contributor to the development of cancer, cardiovascular disease, diabetes, obesity, autoimmune disease, inflammatory bowel disease, and other illnesses. In the academic field, there is a constant demand for effective methods to alleviate inflammation. Astragalin (AST), a type of flavonoid glycoside that is the primary component in several widely used traditional Chinese anti-inflammatory medications in clinical practice, has garnered attention from numerous experts and scholars. This article focuses on the anti-inflammatory effects of AST and conducts research on relevant literature from 2003 to 2023. The findings indicate that AST demonstrates promising anti-inflammatory potential in various models of inflammatory diseases. Specifically, AST is believed to possess inhibitory effects on inflammation-related factors and protein levels in various in vitro cell models, such as macrophages, microglia, and epithelial cells. In vivo studies have shown that AST effectively alleviates neuroinflammation and brain damage while also exhibiting potential for treating moderate diseases such as depression and stroke; it also demonstrates significant anti-inflammatory effects on both large and small intestinal epithelial cells. Animal experiments have further demonstrated that AST exerts therapeutic effects on colitis mice. Molecular biology studies have revealed that AST regulates complex signaling networks, including NF-κB, MAPK, JAK/STAT pathways, etc. In conclusion, this review will provide insights and references for the development of AST as an anti-inflammatory agent as well as for related drug development.

<i>In Silico</i> Screening of a Phytochemical Naringin, Isolated from <i>Citrus decumana</i> var. <i>paradisi</i> Against the Genes of Polycystic Ovary Syndromenes of Polycystic Ovary Syndrome

Polycystic Ovary Syndrome (PCOS) is a complex hormonal and metabolic disorder. The overproduction of androgens is the primary feature of PCOS. The currently available pharmacological agents recommended for the treatment of PCOS are linked with several adverse effects. Therefore, herbal-based drugs with lesser side effects, have become a favourable trend among people. A flavonoid glycoside, naringin isolated from different fruit parts of Citrus decumana var. paradisi (Macfad.) H.H.A. Nicholls exhibits a wide range of therapeutic properties. In the traditional system of medicine, it is used to improve ovarian health. To set down scientific evidence, molecular docking analysis was performed to find out the binding affinity of compound naringin with the protein CYP 17-cytochrome P 450, attributing to hyperandrogenism due to its overexpression, leading to PCOS. The docking score values were compared with the standard drug metformin to interpret the effectiveness of flavonoid naringin in the treatment of PCOS.

Drosophila melanogaster as a model organism for diabetes II treatment by the ethyl acetate fraction of Atriplex halimus L.

Type 2 diabetes (T2D) is the most common metabolic disorder. The undesirable effects of synthetic drugs demand a search for safe antidiabetic agents. This study aimed to assess the antidiabetic activity of different fractions of Atriplex halimus (petroleum ether 60-80, methylene chloride, ethyl acetate, and n-butanol) using Drosophila melanogaster larvae. Titers of total glucose and trehalose, as well as larval weight, were measured and compared with those of control and diabetic larvae. The expression of Drosophila insulin-like peptides (DILP2 and DILP3) and adipokinetic hormone (AKH) was evaluated. The results revealed a significant increase in total glucose, trehalose, and a decrease in body weight in the larvae fed a high-sugar diet compared with those in the control. When larvae fed diets containing the tested fractions, the total glucose and trehalose decreased to the control level, and the body weight increased. DILP2, DILP3, and AKH exhibited significant decreases upon treatment with A. halimus ethyl acetate. Metabolomic profiling of the ethyl acetate fraction of A. halimus revealed the presence of flavonoids and flavonoid glycosides. After docking screening to predict the most powerful moiety, we discovered that flavonoid glycosides (especially eriodictyol-7-O-neohesperidoside) have a greater affinity for the pocket than the other moieties. The results indicated the therapeutic activity of the A. halimus ethyl acetate fraction against induced T2D in Drosophila larvae. The antidiabetic activity may be attributed to flavonoids, which are the main components of the A. halimus ethyl acetate fraction.

Constructed the metabolic compound accumulation profiles of daylily at different main producing areas using multi-omics techniques

Daylily flower buds (DFB) are widely cultivated in China. The discernible disparities exist in the nutritional composition of daylilies across different primary production areas. However, limited studies about the chemical composition and biosynthetic mechanisms of the principal constituents of DFB. This study systematically investigated daylilies from seven distinct growing regions by integrated metabolomics and transcriptomic sequencing to elucidate the environmental impact on DFB quality and metabolite biosynthesis mechanisms. In DFB, flavonoids constituting the majority, followed by phenolic acids and lipids. The total flavonoid and polyphenol content exhibited the highest levels in northern China (Ningxia, Gansu), and the lowest levels in southern regions (Hunan, Fujian). Correspondingly, antioxidant enzyme activity and free radical scavenging capacity mirrored these regional disparities. Thus, northern-producing areas demonstrated a propitious environment for the accumulation of secondary metabolites, particularly flavonoids and phenolic acids. In contrast, southern production areas exhibited a less conducive environment for the accumulation of flavonoid glycosides in daylilies. Furthermore, distinctive variations in the key metabolites were observed in FJQZ, a region characterized by diverse flower colors. Key enzymes and transcription factors were identified and validated through RT-qPCR. These results contribute valuable insights into the daylily quality formation mechanisms, offering a foundation for high-quality breeding strategies.

Microscopical, phytochemical, and LC/MS analysis of Ginkgo biloba leaves

Every medicinal practitioner knows Ginkgo as the plant source of an extract that is good for memory improvement. Ginkgo biloba extract is classified as one of the medicines in the treatment of dementia and social exclusion brought by vascular or neurodegenerative disorders. In such disorders, the extract was reported to be successful in improving symptoms such as depression, attention, memory disturbances, vertigo, tinnitus, and anxiety. The aerial part of Ginkgo bioloba was obtained from China, Utilizing fresh leaves allows for a microscopic inspection, the concentrated extracts by soxhlet were screened by standard methods for the qualitative investigation of secondary metabolites present in the plant, and a small quantity of extract was analyzed by LC/MS instrument. Microscopical examination shows diacytic stomata, helical vessels, fiber, and unicellular unbranched trichomes. Qualitative analysis is positive for tannin, glycoside, flavonoid, terpene, and phenolic compounds detected while saponin, coumarin, and alkaloid gave a negative result. While LC/MS shows important compounds that have important biological activities such as phenolic acids, flavonoids, and flavonoid glycosides which are reported for their different pharmacological activity, the Ginkgo plant is a promising drug that can help in the treatment of different diseases and required further studies.

The manufacturing process provides green teas with differentiated nonvolatile profiles and influences the deterioration of flavor during storage at room temperature

Hundreds of green tea products are available on the tea market and exhibit different characteristics. In the present study, seven types of green tea were processed, and their nonvolatile profiles were analyzed by liquid chromatography–mass spectrometry. Non-spreading green tea contained higher concentrations of catechins and flavonoid glycosides, but lower concentrations of amino acids, caffeine, and theaflavins. Non-rolling green teas with a straight appearance contained higher concentrations of flavonoid glycosides and theaflavins. In contrast, leaf-rolling green teas contained much lower concentrations of flavonoid glycosides and catechins. These seven green tea qualities all decreased following prolonged storage, concurrent with increasing concentrations of proanthocyanidins, catechins dimers, theaflavins, and organic acids. The leaf-rolling green teas exhibited reduced levels of deterioration during storage in terms of their nonvolatile profile and sensory quality. Findings show that moderate destruction on tea leaves during green tea processing is beneficial to both tea flavor and quality maintenance during storage.

A Flavonoid Glycoside Compound from Siraitia grosvenorii with Anti-Inflammatory and Hepatoprotective Effects In Vitro.

Inflammation is a pivotal factor in the development and advancement of conditions like NAFLD and asthma. Diet can affect several phases of inflammation and significantly influence multiple inflammatory disorders. Siraitia grosvenorii, a traditional Chinese edible and medicinal plant, is considered beneficial to health. Flavonoids can suppress inflammatory cytokines, which play a crucial role in regulating inflammation. In the present experiments, kaempferol 3-O-α-L-rhamnoside-7-O-β-D-xylosyl(1→2)-O-α-L-rhamnoside (SGPF) is a flavonoid glycoside that was first isolated from S. grosvenorii. A series of experimental investigations were carried out to investigate whether the flavonoid component has anti-inflammatory and hepatoprotective effects in this plant. The researchers showed that SGPF has a stronger modulation of protein expression in LPS-induced macrophages (MH-S) and OA-induced HepG2 cells. The drug was dose-dependent on cells, and in the TLR4/NF-κB/MyD88 pathway and Nrf2/HO-1 pathway, SGPF regulated all protein expression. SGPF has a clear anti-inflammatory and hepatoprotective function in inflammatory conditions.

Luteolin-7-O-β-d-glucuronide Ameliorates Cerebral Ischemic Injury: Involvement of RIP3/MLKL Signaling Pathway.

Luteolin-7-O-β-d-glucuronide (LGU) is a major active flavonoid glycoside compound that is extracted from Ixeris sonchifolia (Bge.) Hance, and it is a Chinese medicinal herb mainly used for the treatment of coronary heart disease, angina pectoris, cerebral infarction, etc. In the present study, the neuroprotective effect of LGU was investigated in an oxygen glucose deprivation (OGD) model and a middle cerebral artery occlusion (MCAO) rat model. In vitro, LGU was found to effectively improve the OGD-induced decrease in neuronal viability and increase in neuronal death by a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and a lactate dehydrogenase (LDH) leakage rate assay, respectively. LGU was also found to inhibit OGD-induced intracellular Ca2+ overload, adenosine triphosphate (ATP) depletion, and mitochondrial membrane potential (MMP) decrease. By Western blotting analysis, LGU significantly inhibited the OGD-induced increase in expressions of receptor-interacting serine/threonine-protein kinase 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL). Moreover, molecular docking analysis showed that LGU might bind to RIP3 more stably and firmly than the RIP3 inhibitor GSK872. Immunofluorescence combined with confocal laser analyses disclosed that LGU inhibited the aggregation of MLKL to the nucleus. Our results suggest that LGU ameliorates OGD-induced rat primary cortical neuronal injury via the regulation of the RIP3/MLKL signaling pathway in vitro. In vivo, LGU was proven, for the first time, to protect the cerebral ischemia in a rat middle cerebral artery occlusion (MCAO) model, as shown by improved neurological deficit scores, infarction volume rate, and brain water content rate. The present study provides new insights into the therapeutic potential of LGU in cerebral ischemia.

LC-MS/MS metabolomics approach for chemical characterization of Beta vulgaris subspecies maritima extract through untargeted molecular networking, in correlation to its renoprotective activity in renal ischemia/reperfusion induced injury model in rats

This study evaluates the reno-protective effect of Beta vulgaris subspecies maritima lyophilized 70% ethanolic extract (BVLE) in renal ischemia/reperfusion (I/R) induced injury model in rats. Detailed investigation of the effects of its oral administration was checked. serum blood urea nitrogen (BUN), which was reduced to 0.7 ± 0.04 mmol/L at a dose of 200 mg/Kg of BVLE compared to 1.9 ± 0.08 mmol/L for the I/R group. And creatinine levels were reduced to 1.2 ± 0.06 nmol/L at a dose of 200 mg/Kg of BVLE compared to 4.7 ± 0.12 nmol/L for the I/R group. Oxidative stress biomarkers including MDA (reduced to 0.4 ± 0.03 compared to 1.7 ± 0.05 nmol/mg protein of I/R a dose of 200 mg/Kg) and GSH levels (increased to 1.3 ± 0.03 compared to 0.3 ± 0.02 nmol/mg protein of I/R a dose of 200 mg/Kg). Meanwhile, inflammatory mediators including TNF-α and IL-6 levels were lowered to 46.7 ± 0.60 and 32.1 ± 1.78 pg/mg protein, respectively. Oxidative stress genetic pathways including Nrf2/HO-1 signaling pathway via testing Nrf2 and its dependent HO-1 mRNA expression levels were studied as well. Metabolomic profiling of BVLE was achieved by UPLC-HR-ESIMS coupled with molecular networking. BVLE significantly improved renal inflammatory markers, oxidative stress biomarkers and renal functions test, in dose dependent manner. Thirty-nine compounds were tentatively identified in BVLE by UPLC-MS/MS. Mainly flavonoid glycosides, triterpenoidal saponins and fatty acids. Among identified saponins five unreported betavulgaroside derivatives were tentatively described for the first time.

Icariin attenuates vascular endothelial dysfunction by inhibiting inflammation through GPER/Sirt1/HMGB1 signaling pathway in type 1 diabetic rats

Icariin, a flavonoid glycoside, is extracted from Epimedium. This study aimed to investigate the vascular protective effects of icariin in type 1 diabetic rats by inhibiting high-mobility group box 1 (HMGB1)-related inflammation and exploring its potential mechanisms. The impact of icariin on vascular dysfunction was assessed in streptozotocin (STZ)-induced diabetic rats through vascular reactivity studies. Western blotting and immunofluorescence assays were performed to measure the expressions of target proteins. The release of HMGB1 and pro-inflammation cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The results revealed that icariin administration enhanced acetylcholine-induced vasodilation in the aortas of diabetic rats. It also notably reduced the release of pro-inflammatory cytokines, including interleukin-8 (IL-8), IL-6, IL-1β, and tumor necrosis factor-alpha (TNF-α) in diabetic rats and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs). The results also unveiled that the pro-inflammatory cytokines in the culture medium of HUVECs could be increased by rHMGB1. The increased release of HMGB1 and upregulated expressions of HMGB1-related inflammatory factors, including advanced glycation end products (RAGE), Toll-like receptor 4 (TLR4), and phosphorylated p65 (p-p65) in diabetic rats and HG-induced HUVECs, were remarkably suppressed by icariin. Notably, HMGB1 translocation from the nucleus to the cytoplasm in HUVECs under HG was inhibited by icariin. Meanwhile, icariin could activate G protein-coupled estrogen receptor (GPER) and sirt1. To explore the role of GPER and Sirt1 in the inhibitory effect of icariin on HMGB1 release and HMGB-induced inflammation, GPER inhibitor and Sirt1 inhibitor were used in this study. These inhibitors diminished the effects of icariin on HMGB1 release and HMGB1-induced inflammation. Specifically, the GPER inhibitor also negated the activation of Sirt1 by icariin. These findings suggest that icariin activates GPER and increases the expression of Sirt1, which in turn reduces HMGB1 translocation and release, thereby improving vascular endothelial function in type 1 diabetic rats by inhibiting inflammation.

Unveiling the Molecular Mechanism of Diosmetin and its Impact on Multifaceted Cellular Signaling Pathways.

Diosmetin is an O-methylated flavone and the aglycone part of the flavonoid glycosides diosmin that occurs naturally in citrus fruits. Pharmacologically, diosmetin is reported to exhibit anticancer, antimicrobial, antioxidant, oestrogenic, and anti-inflammatory activities. This comprehensive review was aimed to critically explore diverse pharmacological activities exhibited by diosmetin. Along with that, this review can also identify potential research areas with an elucidation of the multifactorial underlying signaling mechanism of action of diosmetin in different diseases. A comprehensive collection of evidence and insights was obtained from scientific journals and books from physical libraries and electronic platforms like Google Scholar and PubMed. The time frame selected was from year 1992 to July 2023. The review delves into diosmetin's impact on cellular signaling pathways and its potential in various diseases. Due to its ability to modulate signaling pathways and reduce oxidative stress, it can be suggested as a potential versatile therapeutic agent for mitigating oxidative stressassociated pathogenesis. The amalgamation of the review underscores diosmetin's promising role as a multifaceted therapeutic agent, highlighting its potential for drug development and clinical applications.

Integrated Full-Length Transcriptomics and Metabolomics Reveal Glycosyltransferase Involved in the Biosynthesis of Flavonol Glycosides in Laportea bulbifera.

Many species of the Urticaceae family are important cultivated fiber plants that are known for their economic and industrial values. However, their secondary metabolite profiles and associated biosynthetic mechanisms have not been well-studied. Using Laportea bulbifera as a model, we conducted widely targeted metabolomics, which revealed 523 secondary metabolites, including a unique accumulation of flavonol glycosides in bulblet. Through full-length transcriptomic and RNA-seq analyses, the related genes in the flavonoid biosynthesis pathway were identified. Finally, weighted gene correlation network analysis and functional characterization revealed four LbUGTs, including LbUGT78AE1, LbUGT72CT1, LbUGT71BX1, and LbUGT71BX2, can catalyze the glycosylation of flavonol aglycones (kaempferol, myricetin, gossypetin, and quercetagetin) using UDP-Gal and UDP-Glu as the sugar donors. LbUGT78AE1 and LbUGT72CT1 showed substrate promiscuity, whereas LbUGT71BX1 and LbUGT71BX2 exhibited different substrate and sugar donor selectivity. These results provide a genetic resource for studying Laportea in the Urticaceae family, as well as key enzymes responsible for the metabolism of valuable flavonoid glycosides.