Gypenosides improves nonalcoholic fatty liver disease induced by high-fat diet induced through regulating LPS/TLR4 signaling pathway. Issue 22 (16th November 2020)

• Record Type: Journal Article
• Authors: Shen, Shuhua; Wang, Kungen; Zhi, Yihui; Shen, Wei; Huang, Liquan
• Is Part Of: Cell cycle. Volume 19:Issue 22(2020)
• Page Start: 3042
• Page End: 3053
• Publication Date: 2020-11-16
• Subjects: Gypenosides -- nonalcoholic fatty liver disease -- lipid metabolism -- insulin resistance -- LPS/TLR4 signaling pathway; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2020.1829800
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: Background The contents of lipopolysaccharide (LPS) and Toll-like receptor 4 (TLR4) are significantly increased during the progression of nonalcoholic fatty liver disease (NAFLD). The study investigated the role of the LPS/TLR4 signaling pathway in improving gypenosides (Gyp) on NAFLD. Methods NAFLD model were established in rats and treated by Gyp. Pathological changes of liver tissues were observed by Hematoxylin and Eosin (HE) staining. Lipid metabolism and insulin resistance were measured. Expressions of inflammatory factors and protein of LPS/TLR4 downstream pathway were detected by qRT-PCR and Western blotting. THLE-2 cells were treated by free-fatty acid (FFA), Gyp, and LPS, and then transfected with TLR4. Next, cell viability was detected by MTT. Lipid droplet deposition and Triglyceride (TG) content were determined by Oil Red O staining and ELISA. Results Gyp protected fatty liver tissues in NAFLD model, and significantly reversed cholesterol increased by high-fat diet. Moreover, Gyp increased SOD content and decreased the contents of AST, ALT, MDA, HSI, FBG, FINS, HOMA-IR, IL-1β, and TNF-α, and promoted the expressions of TLR4, LPS, MyD88, p-IκBα, and reduced the expressions of p-p65 and IκBα in the NAFLD model. Gyp treatment significantly reduced lipid droplet deposition, increased TG content and MyD88, p-IκBα, p-p65 in FFA-induced liver cells, but LPS and TLR4 greatly reversed improvement of FFA by Gyp. Conclusion Gypenosides could improve liver function, lipid metabolism, insulin resistance, and levels of inflammatory factors in NAFLD model by regulating LPS/TLR4 signaling pathway in vitro and in vivo .