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Article ; Online: Jian-Gan-Xiao-Zhi decoction ameliorates high-fat high-carbohydrate diet-induced non-alcoholic fatty liver disease and insulin resistance by regulating the AMPK/JNK pathway

Xue-Hua Xie / Jia-Bao Liao / Fang Fang / Jie Zhao / Yong-Jun Cao / Huan-Tian Cui / Hong-Wu Wang / Zhai-Yi Zhang / Zhao-Hui Sun / Yuan Yin / Wei-Bo Wen

Traditional Medicine Research, Vol 6, Iss 1, Pp 4-

2021  Volume 4

Abstract: Background: Non-alcoholic fatty liver disease (NAFLD) can cause insulin resistance (IR) and diabetes. Our previous studies have demonstrated that Jian-Gan-Xiao-Zhi decoction (JGXZ) could be effective for the treatment of NAFLD and IR. However, the ... ...

Abstract Background: Non-alcoholic fatty liver disease (NAFLD) can cause insulin resistance (IR) and diabetes. Our previous studies have demonstrated that Jian-Gan-Xiao-Zhi decoction (JGXZ) could be effective for the treatment of NAFLD and IR. However, the possible mechanism underlying the effects of JGXZ on NAFLD and IR remains unknown. Methods: Fifty rats received a high-fat high-carbohydrate (HFHC) diet for 12 weeks to induce NAFLD. After 4 weeks of HFHC treatment, rats were orally treated with JGXZ (8, 16, and 32 g/kg weight) for 8 weeks. Ten rats in the control group received standard chow. In the positive control group, rats were orally treated with metformin (90 mg/kg weight) for 8 weeks. After JGXZ and metformin treatment, H&E staining was conducted on rat livers and serum biochemical markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and total cholesterol (TC), were measured using test kits. Moreover, a fasting blood glucose test and an oral glucose tolerance test (OGTT) were conducted. Serum levels of insulin were determined using ELISA kit, and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. The levels of total insulin receptor substrate-1 (IRS1), AMP-activated protein kinase-α (AMPKα) and c-Jun N-terminal kinase (JNK) as well as the levels of phosphorylation of IRS1 (p-IRS1), phosphorylation of AMPK (p-AMPK) and phosphorylation of JNK (p-JNK) were measured using western blotting. Results: The body weights in JGXZ low-, middle-, and high-dose groups were lower than those in the model group (P < 0.05, P < 0.01, P < 0.01, respectively). The serum levels of AST (P < 0.05 in JGXZ middle- and high-dose groups), ALT (P < 0.01 in JGXZ middle-dose group and P < 0.05 in JGXZ high-dose group), TG (P < 0.01 in JGXZ middle- and high-dose groups), and TC (P < 0.01) upon JGXZ treatment were lower those than in NAFLD model rats. H&E staining showed that JGXZ treatment reduced steatosis of the hepatocytes in NAFLD model rats. JGXZ decreased the levels of fasting blood glucose (P < 0.01), HOMA-IR (P < 0.01), AUC (area under the curve) of the OGTT (P < 0.05) and p-IRS1 (P < 0.01 in JGXZ middle- and high-dose groups, P < 0.05 in JGXZ low-dose groups). Moreover, JGXZ regulated the hepatic AMPKα/JNK pathway in NAFLD model rats, which reflected the induction of p-AMPKα and inhibition of p-JNK. Conclusion: This study showed that JGXZ improved liver function and reduced steatosis of the hepatocytes in NAFLD model rats. Moreover, JGXZ improved IR in NAFLD model rats. The possible mechanism underlying the effects of JGXZ on NAFLD and IR involves the modulation of the AMPK/JNK pathway.
Keywords jian-gan-xiao-zhi decoction ; non-alcoholic fatty liver disease ; insulin resistance ; ampk/jnk pathway ; Medicine ; R ; Miscellaneous systems and treatments ; RZ409.7-999
Subject code 630
Language English
Publishing date 2021-01-01T00:00:00Z
Publisher Hong Kong Gold Orchid Science and Technology Co., Limited
Document type Article ; Online
Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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