作者: Yan, Honghao ; Zhao, Jinkai ; Du, Yu ; Jiang, He ; Hong, Chunlan ; Qiu, Ping ; Lou, Dayong ; Huang, Shuo ; Luo, Qihan ; Kong, Yu ; Chen, Fangming ; Kong, Desong ; Ma, Qing ; Mi, Ai ; Qiu, Jiang ; Li, Changyu ; Chen, Yufan ; Efferth, Thomas

BACKGROUNDAlcohol-related liver damage is the most prevalent chronic liver disease, which creates a heavy public health burden worldwide. The leaves of Ampelopsis grossedentata have been considered a popular tea and traditional herbal medicine in China for more than one thousand years, and possess anti-inflammatory, antioxidative, hepatoprotective, and antiviral activities.PURPOSEWe explored the protective effects of Ampelopsis grossedentata extract (AGE) against chronic alcohol-induced hepatic injury (alcoholic liver disease, ALD), aiming to elucidate its underlying mechanisms.METHODSFirstly, UPLC-Q/TOF-MS analysis and network pharmacology were used to identify the constituents and elucidate the potential mechanisms of AGE against ALD. Secondly, C57BL/6 mice were pair-fed the Lieber-DeCarli diet containing either isocaloric maltodextrin or ethanol, AGE (150 and 300 mg/kg/d) and silymarin (200 mg/kg) were administered to chronic ethanol-fed mice for 7 weeks to evaluate the hepatoprotective effects. Serum biochemical parameters were determined, hepatic and ileum sections were used for histologic examination, and levels of inflammatory cytokines and oxidative stress in the liver were examined. The potential molecular mechanisms of AGE in improving ALD were demonstrated by RNA-seq, Western blotting analysis, and immunofluorescence staining.RESULTSTen main constituents of AGE were identified using UPLC-Q/TOF-MS and 274 potential ALD-related targets were identified. The enriched KEGG pathways included Toll-like receptor signaling pathway, NF-κB signaling pathway, and necroptosis. Moreover, in vivo experimental studies demonstrated that AGE significantly reduced serum aminotransferase levels and improved pathological abnormalities after chronic ethanol intake. Meanwhile, AGE improved ALD in mice by down-regulating oxidative stress and inflammatory cytokines. Furthermore, AGE notably repaired damaged intestinal epithelial barrier and suppressed the production of gut-derived lipopolysaccharide by elevating intestinal tight junction protein expression. Subsequent RNA-seq and experimental validation indicated that AGE inhibited NF-κB nuclear translocation, suppressed IκB-α, RIPK3 and MLKL phosphorylation and alleviated hepatic necroptosis in mice.CONCLUSIONIn this study, we have demonstrated for the first time that AGE protects against alcoholic liver disease by regulating the gut-liver axis and inhibiting the TLR4/NF-κB/MLKL-mediated necroptosis pathway. Therefore, our present work provides important experimental evidence for AGE as a promising candidate for protection against ALD.

2019-05-01·European Journal of Clinical Nutrition3区 · 医学

Ampelopsis grossedentata supplementation effectively ameliorates the glycemic control in patients with type 2 diabetes mellitus

3区 · 医学

Article

作者: Ran, Li ; Lang, HeDong ; Qin, Yu ; Mi, ManTian ; Liu, Huan ; Xu, Jing ; Wang, Jian ; Wang, XiaoLan

BACKGROUNDSome animal and cellular experiments showed that ampelopsis grossedentata (APL) was helpful to improve insulin resistance or glucose uptake.OBJECTIVEThe aim of this study was to assess the effects of APL on blood glucose metabolism, lipid, and renal function parameters in adults with type 2 diabetes mellitus (T2DM).METHODSEighty participants with T2DM were randomly assigned to the APL group (n = 40, 10 g of APL daily contained 970 mg of dihydromyricetin) or to the placebo group (n = 40, 10 g of APL daily deleted dihydromyricetin) for 1 month in a double-blind, randomized clinical trial. Blood levels of glucose and insulin, lipids, and renal function parameters were assayed.RESULTSSeventy subjects completed the trial (36 in the APL group and 34 in the placebo group). The baseline characteristics were similar between the two groups. Compared with the placebo group, the levels of fasting plasma glucose, glycated albumin, cystatin C, and retinol binding protein-4 significantly decreased (all p < 0.05). Meanwhile, the levels of other lipids, apolipoproteins, and other parameters did not change.CONCLUSIONSOne-month supplementation with APL obviously improved the glycemic control and parameters of renal function in adults with T2DM. Our findings suggested that a potential role for APL in the prevention and treatment of T2DM.

2018-04-07·World Journal of Gastroenterology3区 · 医学

Systems pharmacology approach reveals the antiinflammatory effects of Ampelopsis grossedentata on dextran sodium sulfate-induced colitis

3区 · 医学

Article

作者: Tang, Zhi-Peng ; Dai, Yan-Cheng ; Zhang, Ya-Li ; Chen, You-Lan

AIMTo investigate the protective effects of Ampelopsis grossedentata (AMP) on dextran sulfate sodium (DSS)-induced colitis in mice based on systems pharmacology approach.METHODSSystems pharmacology approach was used to predict the active ingredients, candidate targets and the efficacy of AMP on ulcerative colitis (UC) using a holistic process of active compound screening, target fishing, network construction and analysis. A DSS-induced colitis model in C57BL/6 mice (n = 10/group) was constructed and treated with 5-aminosalicylic acid (100 mg/kg/d) and AMP (400 mg/kg/d) to confirm the underlying mechanisms and effects of AMP on UC with western blot analyses, polymerase chain reaction, histological staining and immunohistochemistry.RESULTSThe therapeutic effects of AMP against DSS-induced colitis were determined in the beginning, and the results showed that AMP significantly improved the disease in general observations and histopathology analysis. Subsequent systems pharmacology predicted 89 corresponding targets for the four candidate compounds of AMP, as well as 123 candidate targets of UC, and protein-protein interaction networks were constructed for the interaction of putative targets of AMP against UC. Enrichment analyses on TNF-α and RANKL/RANK, a receptor activator of NF-κB signaling pathways, were then carried out. Experimental validation revealed that inflammation-related signaling pathways were activated in the DSS group, and AMP significantly suppressed DSS-induced high expression of IRAK1, TRAF6, IκB and NF-κB, and inhibited the elevated expression levels of TNF-α, IL-1β, IL-6 and IL-8.CONCLUSIONAMP could exert protective effects on UC via suppressing the IRAK1/TRAF6/NF-κB-mediated inflammatory signaling pathways.

100 项与显齿蛇葡萄总黄酮含片相关的药物交易

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