Rhinacanthin C Ameliorates Insulin Resistance and Lipid Accumulation in NAFLD Mice via the AMPK/SIRT1 and SREBP-1c/FAS/ACC Signaling Pathways

Zhiqiang Gong; Sha Han; Chenlin Li; Tianxiu Meng; Yu Huo; Xianfu Liu; Yanhong Huang; Lifang Yang

doi:10.1155/2023/6603522

Rhinacanthin C Ameliorates Insulin Resistance and Lipid Accumulation in NAFLD Mice via the AMPK/SIRT1 and SREBP-1c/FAS/ACC Signaling Pathways

Evid Based Complement Alternat Med. 2023 Jan 10:2023:6603522. doi: 10.1155/2023/6603522. eCollection 2023.

Authors

Zhiqiang Gong^{1

2}, Sha Han², Chenlin Li², Tianxiu Meng², Yu Huo², Xianfu Liu², Yanhong Huang², Lifang Yang¹

Affiliations

¹ School of Chemistry and Chemical Engineering, Guangxi Minzu University, Guangxi Key Laboratory for Polysaccharide Materials and Modifications, Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, Nanning, Guangxi, China.
² Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine, Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine Nanning, Nanning, Guangxi, China.

Abstract

Rhinacanthin C (RC) is a naphthoquinone ester with an anti-inflammatory activity extracted from Rhinacanthus nasutus (L.) Kurz (Rn). It has been proven to improve hyperglycemia and hyperlipidemia, but the prevention and mechanism of RC in nonalcoholic fatty liver disease (NAFLD) are not clear. In the current study, we first extracted RC from Rn using ethyl acetate and identified it by HPLC, MS, and NMR. At the same time, molecular docking analysis of RC with AMPK and SREBP-1c was performed using AutoDock software. In addition, the mouse model of NAFLD was induced by a high-fat diet in vivo, and low, medium, and high concentrations of RC were used for intervention. The results showed that RC significantly reduced the body mass and liver body coefficient of NAFLD mice, inhibited liver inflammation and fat accumulation, and improved insulin resistance. Further studies showed that RC significantly reduced the levels of serum leptin and resistin, upregulated the expression levels of adiponectin and adiponectin receptor in the liver, and inhibited the expression levels of MCP-1, TNF-α, and IL-6. In terms of mechanism, RC upregulates the expression of p-AMPK and SIRT1 and downregulates the expression of p-p65, SREBP-1c, Fas, Acc-α, PPAR-γ, and SCD1. These studies suggest that RC improves insulin resistance and lipid accumulation in NAFLD by activating the AMPK/SIRT1 and SREBP-1c/Fas/ACC pathways, respectively.