Salidroside Modulates Insulin Signaling in a Rat Model of Nonalcoholic Steatohepatitis

Li, Hongshan; Ying, Hao; Hu, Airong; Li, Dezhou; Hu, Yaoren

doi:10.1155/2017/9651371

Cited by 9 publications

(10 citation statements)

References 23 publications

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“…We found that salidroside-stimulated AMPK activation could reduce lipid accumulation in muscle and liver tissues of db/db mice, suggesting that salidroside may be used for the treatment of NAFLD [ 25 ]. Yang et al [ 36 ] and Li et al [ 44 ] reported that salidroside could prevent liver injury in the rat or mice NASH model induced by HFD feeding, and these findings raised that the antioxidant and hepatic insulin signaling regulation are involved in the action of salidroside, respectively. However, whether or not salidroside is suitable for NAFLD, treatment and mechanisms underlying its effects have not been fully elucidated yet.…”

Section: Discussionmentioning

confidence: 99%

Salidroside Attenuates High‐Fat Diet‐Induced Nonalcoholic Fatty Liver Disease via AMPK‐Dependent TXNIP/NLRP3 Pathway

Zheng

Yang

et al. 2018

Oxidative Medicine and Cellular Longevity

101

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Our previous studies suggested that salidroside could alleviate hepatic steatosis in type 2 diabetic C57BLKS/Leprdb (db/db) mice. The aim of the present study was to evaluate the therapeutic effect of salidroside on high-fat diet- (HFD-) induced nonalcoholic fatty liver disease (NAFLD) by investigating underlying mechanisms. Mice were fed with HFD or regular diet, randomly divided into two groups, and treated with salidroside or vehicle for 8 weeks. Then, biochemical analyses and histopathological examinations were conducted in vivo and in vitro. Salidroside administration attenuated HFD-induced obesity, blood glucose variability, and hepatic lipid deposition, markedly increasing insulin sensitivity in HFD mice. In addition, salidroside suppressed oxidative stress, thioredoxin-interacting protein (TXNIP) expression, and NLRP3 inflammasome activation in the liver. In cultured hepatocytes, salidroside dose dependently regulated lipid accumulation, reactive oxygen species (ROS) generation, and NLRP3 inflammasome activation as well as improved AMP-activated protein kinase (AMPK) activity and insulin sensitivity. The inhibition of AMPK activation by inhibitor or short interfering RNA (siRNA) resulted in the suppression of the beneficial effects of salidroside in hepatocytes. Our findings demonstrated that salidroside protects against NAFLD by improving hepatic lipid metabolism and NLRP3 inflammasome activation, and these actions are related to the regulation of the oxidative stress and AMPK-dependent TXNIP/NLRP3 pathways.

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Section: Discussionmentioning

confidence: 99%

Salidroside Attenuates High‐Fat Diet‐Induced Nonalcoholic Fatty Liver Disease via AMPK‐Dependent TXNIP/NLRP3 Pathway

Zheng

Yang

et al. 2018

Oxidative Medicine and Cellular Longevity

101

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“…HE staining was performed on 4-μm-thick sections according to the standard published protocols [23]. Sections were examined by experienced liver pathologists.…”

Section: Histopathological Examinationmentioning

confidence: 99%

Gypenosides regulate farnesoid X receptor-mediated bile acid and lipid metabolism in a mouse model of non-alcoholic steatohepatitis

Xin

et al. 2020

Nutr Metab (Lond)

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Background Gypenosides (Gyp) are the main ingredient of the Chinese medicine, Gynostemma pentaphyllum. They are widely used in Asia as a hepatoprotective agent. Here, we elucidated the mechanism of Gyp in non-alcoholic steatohepatitis (NASH) with a focus on farnesoid X receptor (FXR)-mediated bile acid and lipid metabolic pathways. Methods NASH was induced in mice by high-fat diet (HFD) feeding, while mice in the control group were given a normal diet. At the end of week 10, HFD-fed mice were randomly divided into HFD, HFD plus Gyp, and HFD plus obeticholic acid (OCA, FXR agonist) groups and were given the corresponding treatments for 4 weeks. Next, we analyzed the histopathological changes as well as the liver triglyceride (TG) level and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood glucose (FBG), fasting insulin (FINS), TG, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels as well as the bile acid profile. We carried out RT-PCR and western blotting to detect HFD-induced alterations in gene/protein expression related to bile acid and lipid metabolism. Results The HFD group had histopathological signs of hepatic steatosis and vacuolar degeneration. The liver TG and serum ALT, AST, FBG, FINS, TC, and LDL-C levels as well as the total bile acid level were significantly higher in the HFD group than in the control group (P < 0.01). In addition, we observed significant changes in the expression of proteins involved in bile acid or lipid metabolism (P < 0.05). Upon treatment with Gyp or OCA, signs of hepatic steatosis and alterations in different biochemical parameters were significantly improved (P < 0.05). Further, HFD-induced alterations in the expression genes involved in bile acid and lipid metabolism, such as CYP7A1, BSEP, SREBP1, and FASN, were significantly alleviated. Conclusions Gyp can improve liver lipid and bile acid metabolism in a mouse model of NASH, and these effects may be related to activation of the FXR signaling pathway.

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“…Thus, they have the potential to hinder the progression of NASH to HCC. Salidroside (31) reduced hepatic lipid accumulation, the inflammatory response and insulin resistance in NAFLD rats ( Li et al, 2017 ). In an HFD-induced NASH model in mice, salidroside (31) treatment significantly improved HFD-induced intestinal bacterial and bile acid disturbances, thus demonstrating the potential role of salidroside (31) in NASH treatment via the intestinal microbial-bile acid-FXR axis ( Li H. et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

The Pathogenesis of HCC Driven by NASH and the Preventive and Therapeutic Effects of Natural Products

Shao

Liu

et al. 2022

Front. Pharmacol.

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Nonalcoholic steatohepatitis (NASH) is a clinical syndrome with pathological changes that are similar to those of alcoholic hepatitis without a history of excessive alcohol consumption. It is a specific form of nonalcoholic fatty liver disease (NAFLD) that is characterized by hepatocyte inflammation based on hepatocellular steatosis. Further exacerbation of NASH can lead to cirrhosis, which may then progress to hepatocellular carcinoma (HCC). There is a lack of specific and effective treatments for NASH and NASH-driven HCC, and the mechanisms of the progression of NASH to HCC are unclear. Therefore, there is a need to understand the pathogenesis and progression of these diseases to identify new therapeutic approaches. Currently, an increasing number of studies are focusing on the utility of natural products in NASH, which is likely to be a promising prospect for NASH. This paper reviews the possible mechanisms of the pathogenesis and progression of NASH and NASH-derived HCC, as well as the potential therapeutic role of natural products in NASH and NASH-derived HCC.

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Salidroside Modulates Insulin Signaling in a Rat Model of Nonalcoholic Steatohepatitis

Cited by 9 publications

References 23 publications

Salidroside Attenuates High‐Fat Diet‐Induced Nonalcoholic Fatty Liver Disease via AMPK‐Dependent TXNIP/NLRP3 Pathway

Salidroside Attenuates High‐Fat Diet‐Induced Nonalcoholic Fatty Liver Disease via AMPK‐Dependent TXNIP/NLRP3 Pathway

Gypenosides regulate farnesoid X receptor-mediated bile acid and lipid metabolism in a mouse model of non-alcoholic steatohepatitis

The Pathogenesis of HCC Driven by NASH and the Preventive and Therapeutic Effects of Natural Products

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