Search Results (13)

Farrerol, a bioactive compound found in Folium Rhododendri daurici, demonstrates various biological and pharmacological effects. Nevertheless, the stereoselectivity of in vivo processes and bioactivity between its enantiomers have not been thoroughly investigated. This study aimed to explore the stereoselectivity and pharmacological activity variations in farrerol enantiomers, focusing on stereoselective pharmacokinetics, tissue distribution, in vitro metabolism using liver microsomes, in vivo intestinal absorption, molecular simulations of binding affinity with antiproliferative target, and cell viability assessed through the CCK-8 assay. The findings indicated that the pharmacokinetic characteristics of farrerol in rats’ plasma, liver, and kidney tissues displayed enantioselectivity after intragastric administration. Then, no chiral transformation between farrerol enantiomers was observed in the rat plasma when (+)-farrerol and (−)-farrerol were orally administered. Additionally, there are notable stereoselective differences in the inhibition of CYP 1A2, CYP 2C9, CYP 2C19, and CYP 3A4/5 enzymes by (+)-farrerol and (−)-farrerol (p < 0.01). These differences may contribute to the stereoselectivity observed in the hepatic metabolism of the two enantiomers of farrerol. In addition, there were selective differences in the binding of farrerol enantiomers to anti-proliferative targets, including UCHL3, STAT3β, PTP1B, and GSK3β. Farrerol enantiomers exhibited similar growth inhibitory effects in HT-29 cell. Overall, our work will provide a solid theoretical basis and experimental reference for the further development and utilization of farrerol enantiomers. Full article

Vascular endothelial growth factor (VEGF), also known as VEGF-A, has been linked to various diseases, such as wet age-related macular degeneration (wAMD) and cancer. Even though there are VEGF inhibitors that are currently commercially available in clinical applications, severe adverse effects have been associated with these treatments. There is still a need to develop novel VEGF-based therapeutics against these VEGF-related diseases. Here, we established a series of VEGF-based computational docking analyses and cell models, such as a wound healing assay in HaCaT cells and an evaluation of NF-κB performance in macrophages, to screen a large library of flavonoid-type phytochemicals. Three flavonoids, namely, farrerol, ononin and (−)-epicatechin, were shown to express binding affinities to VEGF protein and inhibit VEGF-mediated biological activities. The investigation evidently suggested that the three flavonoids above could be considered potential anti-VEGF agents for the following drug development against VEGF-mediated diseases. Full article

Neofusicoccum laricinum is the causal agent of larch shoot blight, a fungal disease affecting several species of larch. It causes severe damage, including stunting and mortality. This study aims to address the severe impact of larch shoot blight by evaluating the effect of farrerol on the inhibition of Neofusicoccum laricinum in Larix olgensis. We used LC-MS/MS and weighted gene co-expression network analysis to investigate farrerol’s effects on Neofusicoccum laricinum and identify associated genes in resistant and susceptible larch. Our study identified significant differences in metabolite profiles between resistant and susceptible cultivars, with higher concentrations of farrerol showing complete inhibition of N. laricinum. Additionally, specific genes associated with farrerol content were up-regulated in resistant larch. Farrerol at higher concentrations completely inhibited N. laricinum, showing a strong correlation with increased disease resistance. This research suggests that farrerol enhances disease resistance in larch and provides a foundation for developing disease-resistant larch varieties based on antifungal metabolite traits. Full article

Obstructive uropathy is a clinical condition that can lead to chronic kidney disease. However, treatments that can prevent the progression of renal injury and fibrosis are limited. Farrerol (FA) is a natural flavone with potent antioxidant and anti-inflammatory properties. Here, we investigated the effect of FA on renal injury and fibrosis in a mouse model of unilateral ureteral obstruction (UUO). Mice underwent a sham or UUO operation and received intraperitoneal injections of FA (20 mg/kg) daily for 8 consecutive days. Histochemistry, immunohistochemistry and immunofluorescence staining, TdT-mediated dUTP nick end labeling assay, Western blotting, gene expression analysis, and biochemical tests were performed. FA attenuated renal dysfunction (p < 0.05) and ameliorated renal tubular injury (p < 0.01) and interstitial fibrosis (p < 0.001) in UUO mice. FA alleviated 4-hydroxynonenal expression (p < 0.001) and malondialdehyde levels (p < 0.01) by regulating pro-oxidant and antioxidant enzymes. Apoptosis in the kidneys of UUO mice was inhibited by FA (p < 0.001), and this action was accompanied by decreased expression of cleaved caspase-3 (p < 0.01). Moreover, FA alleviated pro-inflammatory cytokine production (p < 0.001) and macrophage infiltration (p < 0.01) in the kidneys of UUO mice. These results suggest that FA ameliorates renal injury and fibrosis in the UUO model by inhibiting oxidative stress, apoptosis, and inflammation. Full article

(1) Background: Senescence represents the final stage of plant growth and development, which transfers nutrients to growing seeds and directly affects the yield and quality of crops. However, little is known about chlorophyll degradation in developing and maturing seeds, in contrast to leaf senescence; (2) Methods: RNA-Seq was used to analyze the differentially expressed genes of different late-senescent germplasms. A widely untargeted metabolic analysis was used to analyze differential metabolites. In addition, qRT-PCR was conducted to detect gene expression levels; (3) Results: Transcriptome analysis revealed that ZX12 seeds have a higher expression level of the chlorophyll synthesis genes in the early stage of maturity, compared with ZX4, and have a lower expression level of chlorophyll degradation genes in the late stage of maturity. Flavonoids were the primary differential metabolites, and ZX12 contains the unique and highest expression of three types of metabolites, including farrerol-7-O-glucoside, cyanidin-3-o-(6′-o-feruloyl) glucoside, and kaempferide-3-o-(6′-malonyl) glucoside. Among them, farrerol-7-O-glucoside and cyanidin-3-o-(6′-o-feruloyl) glucoside are flavonoid derivatives containing mono and dihydroxy-B-ring chemical structures, respectively; and (4) Conclusions: It is speculated that the two metabolites can slow down the degradation process of chlorophyll by scavenging oxygen-free radicals in the chloroplast. Full article

Rhododendron ferrugineum, commonly named Alpine rose, is an emblematic medicinal plant of European mountains. In this study, the chemical profile of a glycerol/water extract developed from this plant as a cosmetic ingredient is investigated to understand the extract constituent(s) that could mostly contribute to its senolytic activity and skin-rejuvenation effects. For this purpose, the dereplication method “CARAMEL”, which combines Centrifugal Partition Chromatography to Nuclear Magnetic Resonance data interpretation, was directly applied to the hydro-glycerinated extract, leading to the unambiguous identification of fourteen Alpine rose metabolites, despite the strong presence of the heavy solvent glycerol. Flavonoids derived from taxifolin, quercetin, and (+)-catechin were identified as significant constituents of the extract, followed by flavanones, orcinol derivatives, phloroacetophenone, and phenolic acids, as well as the pentacyclic triterpene lupeol. Given that senolytic molecules are known to selectively induce the death of senescent cells without affecting healthy proliferating cells, which can be achieved by the selective inhibition or downregulation of the anti-apoptotic Bcl-2 protein, and considering the well-recognized pro-apoptotic activity of hyperoside, taxifolin, naringenin and farrerol, the senolytic activity of the glycerol/water Alpine rose extract can be explained by the abundance of flavonoids present in the extract. Full article

Miconia chamissois Naudin is a species from the Cerrado, which is being increasingly researched for its therapeutic potential. The aim of this study was to obtain a standardized extract and to evaluate seasonal chemical variations. Seven batches of aqueous extracts from leaves were produced for the standardization. These extracts were evaluated for total solids, polyphenol (TPC) and flavonoid content (TFC), vitexin derivative content, antioxidant activity; thin-layer chromatography (TLC), and high-performance liquid chromatography (HPLC) profiles were generated. For the seasonal study, leaves were collected from five different periods (May 2017 to August 2018). The results were correlated with meteorological data (global radiation, temperature, and rainfall index). Using chromatographic and spectroscopic techniques, apigenin C-glycosides (vitexin/isovitexin) and derivatives, luteolin C-glycosides (orientin/isoorientin) and derivatives, a quercetin glycoside, miconioside B, matteucinol-7-O-β-apiofuranosyl (1 → 6) -β-glucopyranoside, and farrerol were identified. Quality parameters, including chemical marker quantification by HPLC, and biological activity, are described. In the extract standardization process, all the evaluated parameters showed low variability. The seasonality study revealed no significant correlations (p < 0.05) between TPC or TFC content and meteorological data. These results showed that it is possible to obtain extracts from M. chamissois at any time of the year without significant differences in composition. Full article

Farrerol (FA) is a flavanone isolated from the Chinese herbal medicine “Man-shan-hong” (Rhododendron dauricum L.). In the present study, FA decreased the viability of SKOV3 cells in a dose- and time-dependent manner, and it induced G2/M cell cycle arrest and cell apoptosis. Cell cycle distribution analysis via flow cytometry showed that FA decreased G1 populations and increased G2/M populations in SKOV3 cells. Additionally, Western blotting confirmed an increase in the expression level of proteins involved in the cell cycle, e.g., CDK and cyclins. FA-induced apoptosis in SKOV3 cells was also investigated using a TUNEL assay, and increased expression levels of proapoptotic factors, including Caspase-3 and poly ADP ribose polymerase (PARP), through the Extracellular signal-regulated kinase (ERK)/MAPK pathway were investigated. Proinflammatory cytokines (e.g., IL-6, TNF-α, and IL-1) have been identified as a driver of the pathological mechanisms underlying involuntary weight loss and impaired physical function, i.e., cachexia, during cancer; in the present study, we showed that farrerol attenuates TNF-α-induced lipolysis and increases adipogenic differentiation in 3T3-L1 cells. Thus, farrerol could potentially be used as an anticancer agent or anticachetic drug. Full article

Although farrerol, a characteristically bioactive constituent of Rhododendron dauricum L., exhibits extensive biological and pharmacological activities (e.g., anti-oxidant, anti-immunogenic, and anti-angiogenic) as well as a high drug development potential, its metabolism remains underexplored. Herein, we employed ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry coupled with multiple data post-processing techniques to rapidly identify farrerol metabolites produced in vivo (in rat blood, bile, urine and feces) and in vitro (in rat liver microsomes). As a result, 42 in vivo metabolites and 15 in vitro metabolites were detected, and farrerol shown to mainly undergo oxidation, reduction, (de)methylation, glucose conjugation, glucuronide conjugation, sulfate conjugation, N-acetylation and N-acetylcysteine conjugation. Thus, this work elaborates the metabolic pathways of farrerol and reveals the potential pharmacodynamics forms of farrerol. Full article

Farrerol, a type of 2, 3-dihydro-flavonoid, is obtained from Rhododendron. Previous studies have shown that Farrerol performs multiple biological activities, such as anti-inflammatory, antibacterial, and antioxidant activity. In this study, we aim to investigate the effect of Farrerol on colonic inflammation and explore its potential mechanisms. We found that the effect of Farrerol was evaluated via the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model in mice and found that Farrerol has a protective effect on TNBS-induced colitis. Farrerol administration significantly improved the weight change, clinical scores, colon length, and intestinal epithelium barrier damage and markedly decreased the inflammatory cytokines production in TNBS-induced mice. The protective effect of Farrerol was also observed in LPS-induced RAW264.7 cells. We found that Farrerol observably reduced the production of inflammatory mediators including IL-1β, IL-6, TNF-α, COX-2, and iNOS in LPS-induced RAW264.7 cells via suppressing AKT, ERK1/2, JNK1/2, and NF-κB p65 phosphorylation. In conclusion, the study found that Farrerol has a beneficial effect on TNBS-induced colitis and might be a natural therapeutic agent for IBD treatment. Full article

Farrerol has been proved to have an anti-inflammatory effect. However, the effects of farrerol on mastitis have not been investigated. This study was aimed to investigate the effect and mechanism of farrerol in lipopolysaccharide (LPS)-induced mouse mastitis and LPS-induced inflammatory response of mouse mammary epithelial cells (mMECs). In vivo, LPS were injected to the tetrad pair of nipples for establishing mouse mastitis, and then tested the effect of farrerol on histopathological changes, inflammatory response and activation degree of protein kinase B (AKT), nuclear factor-kappa B p65 (NF-κB p65), p38, extracellular regulated protein kinase (ERK1/2). In vitro, the mMECs were incubated by farrerol for 1 h following by stimulating with LPS, and then the inflammatory response and the related signaling pathways were detected. The in vivo results found that farrerol could improve pathological injury of mammary gland, attenuate the activity of myeloperoxidase (MPO), inhibit the production of pro-inflammatory mediators and the phosphorylation of AKT, NF-κB p65, p38 and ERK1/2. The in vitro results also found farrerol inhibited inflammatory response and the related signaling pathways. Collectively, this study revealed that farrerol inhibits the further development of LPS-induced mastitis by inhibiting inflammatory response via down regulating phosphorylation of AKT, NF-κB p65, p38, and ERK1/2. These findings suggest that farrerol may be used as an anti-inflammatory drug for mastitis. Full article

Background: This study examined the chemistry and safety of Heteromeles arbutifolia, also called toyon or California holly, which is a traditional California Indian food and treatment for Alzheimer’s disease. Methods: Plant extracts were examined by HPLC/MS, NMR and other techniques to identify compounds. Volunteers were recruited to examine the acute safety of the plant medicine using a standard short-term memory test. Results: The plant was found to contain icariside E4, dihydroxyoleanenoic acid, maslinic acid, betulin, trihydroxyoxo-seco-ursdienoic acid, catechin, vicenin-2, farrerol, kaempferide and tetrahydroxyoleanenoic acid. These compounds are anti-inflammatory agents that may protect the blood-brain barrier and prevent inflammatory cell infiltration into the brain. The dried berries were ingested by six volunteers to demonstrate the safety of the medicine. Conclusion: The plant medicine was found to contain several compounds that may be of interest in the treatment of Alzheimer’s disease. The plant medicine was found to be safe. Full article

Farrerol, isolated from Rhododendron dauricum L., has been proven to be an important multifunctional physiologically active component, but its vasoactive mechanism is not clear. The present study was performed to observe the vasoactive effects of farrerol on rat aorta and to investigate the possible underlying mechanisms. Isolated aortic rings of rat were mounted in an organ bath system and the myogenic effects stimulated by farrerol were studied. Intracellular Ca²⁺ ([Ca²⁺]_in) was measured by molecular probe fluo-4-AM and the activities of L-type voltage-gated Ca²⁺ channels (LVGC) were studied with whole-cell patch clamp in cultured vascular smooth muscle cells (VSMCs). The results showed that farrerol significantly induced dose-dependent relaxation on aortic rings, while this vasorelaxation was not affected by N^G-nitro-l-arginine methylester ester or endothelium denudation. In endothelium-denuded aortas, farrerol also reduced Ca²⁺-induced contraction on the basis of the stable contraction induced by KCl or phenylephrine (PE) in Ca²⁺-free solution. Moreover, after incubation with verapamil, farrerol can induce relaxation in endothelium-denuded aortas precontracted by PE, and this effect can be enhanced by ruthenium red, but not by heparin. With laser scanning confocal microscopy method, the farrerol-induced decline of [Ca²⁺]_in in cultured VSMCs was observed. Furthermore, we found that farrerol could suppress Ca²⁺ influx via LVGC by patch clamp technology. These findings suggested that farrerol can regulate the vascular tension and could be developed as a practicable vasorelaxation drug. Full article