[논문]Iridoids of Valeriana fauriei contribute to alleviating hepatic steatosis in obese mice by lipophagy

Lee, Da-Hye; Park, So-Hyun; Huh, Yang Hoon; Jung Kim, Min; Seo, Hyo-Deok; Ha, Tae-Youl; Ahn, Jiyun; Jang, Young-Jin; Jung, Chang Hwa

doi:10.1016/j.biopha.2020.109950

[해외논문] Iridoids of Valeriana fauriei contribute to alleviating hepatic steatosis in obese mice by lipophagy 원문보기

Biomedicine & pharmacotherapy = Biomédecine & pharmacothérapie, v.125, 2020년, pp.109950 -

Lee, Da-Hye (Research Division of Food Functionality, Korea Food Research Institute) , Park, So-Hyun (Research Division of Food Functionality, Korea Food Research Institute) , Huh, Yang Hoon (Center for Electron Microscopy Research, Korea Basic Science Institute) , Jung Kim, Min (Research Division of Food Functionality, Korea Food Research Institute) , Seo, Hyo-Deok (Research Division of Food Functionality, Korea Food Research Institute) , Ha, Tae-Youl (Research Division of Food Functionality, Korea Food Research Institute) , Ahn, Jiyun (Research Division of Food Functionality, Korea Food Research Institute) , Jang, Young-Jin (Research Division of Food Functionality, Korea Food Research Institute) , Jung, Chang Hwa (Research Division of Food Functionality, Korea Food Research Institute)

Abstract ▼ AI-Helper

Abstract Nonalcoholic fatty liver disease (NAFLD) is a common risk factor for metabolic syndrome that increases the risk of future cardiovascular disease, stroke, and diabetes. Recently, autophagy has been proposed as a means to prevent NAFLD. We investigated whether substances with autophagy-inducing activity alleviate NAFLD. The Valeriana fauriei (V. fauriei) was selected as a potential autophagy inducer among various natural materials using a Cyto-ID autophagy detection kit. V. fauriei 70 % ethanol extract (VFE) increased LC3II levels in the presence of the lysosomal inhibitor and reduced the GFP/mCherry puncta ratio, suggesting that VFE enhanced autophagy. VFE reduced oleic acid (OA)-induced lipid accumulation and increased the number of autophagosome in hepatocytes. Autophagy induction by VFE is due to inhibition of mTORC1 activity. VFE supplementation reduced fatty liver by downregulating lipogenesis-related genes and increased the autophagy, as revealed by TEM and IHC analysis in the fatty liver. We identified iridoids as main compounds of VFE; didrovaltrate (DI), valeriotriate B (VAL B), valeriotetrate C (VAL C), valtrate (VAL), and valechlorine (VC) were shown to enhance autophagy. These compounds also reduced OA-induced lipid accumulation in an Atg5-dependent manner. Taken together, VFE and its iridoids might be effective in alleviating fatty liver by acting as autophagy enhancers to break down LDs. Highlights V. fauriei extract enhanced autophagy activity in hepatocytes. V. fauriei extract reduced number of oleic acid-induced lipid droplets via lipophagy. V. fauriei extract increased autophagy in the liver of obese mice. Iridoids (valtrate, valetriotriate B, didrovaltrate, valechlorine, and valeriotetrate C) are major components of V. fauriei. These iridoids are responsible for inducing lipophagy. Graphical abstract [DISPLAY OMISSION]

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