1. Corosolic Acid Attenuates Hepatic Lipid Accumulation and Inflammatory Response via AMPK/SREBPs and NF-κB/MAPK Signaling Pathways.
- Author
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Zhang, Jian-Xiu, Feng, Wei-Jun, Liu, Guan-Cheng, Ma, Qian-Qian, Li, Hai-Lan, Gao, Xiao-Yan, Liu, Hui-Zhe, Piao, Guang-Chun, and Yuan, Hai-Dan
- Subjects
HEPATITIS prevention ,FATTY liver prevention ,ANALYSIS of variance ,ANIMAL experimentation ,ANTINEOPLASTIC agents ,ANTIOXIDANTS ,ASPARTATE aminotransferase ,CELL culture ,CELL physiology ,CELL separation ,CELLULAR signal transduction ,CHOLESTEROL ,GENE expression ,HIGH density lipoproteins ,HYDROCARBONS ,HYPERLIPIDEMIA ,HYPOGLYCEMIC agents ,IMMUNOHISTOCHEMISTRY ,LIVER ,LOW density lipoproteins ,MICE ,MOLECULAR structure ,PHOSPHORYLATION ,PHOSPHOTRANSFERASES ,POLYMERASE chain reaction ,RESEARCH funding ,RNA ,STATISTICS ,TRANSCRIPTION factors ,TRIGLYCERIDES ,TUMOR necrosis factors ,WESTERN immunoblotting ,DNA-binding proteins ,DATA analysis ,MITOGEN-activated protein kinases ,ALANINE aminotransferase ,CELL survival ,DESCRIPTIVE statistics - Abstract
Corosolic acid (CA) is the main active component of Lagetstroemia speciosa and has been known to serve as several different pharmacological effects, such as antidiabetic, anti-oxidant, and anticancer effects. In this study, effects of CA on the hepatic lipid accumulation were examined using HepG2 cells and tyloxapol (TY)-induced hyperlipidemia ICR mice. CA significantly inhibited hepatic lipid accumulation via inhibition of SREBPs, and its target genes FAS, SCD1, and HMGCR transcription in HepG2 cells. These effects were mediated through activation of AMPK, and these effects were all abolished in the presence of compound C (CC, an AMPK inhibitor). In addition, CA clearly alleviated serum ALT, AST, TG, TC, low-density lipoprotein cholesterol (LDL-C), and increased high-density lipoprotein cholesterol (HDL-C) levels, and obviously attenuated TY-induced liver steatosis and inflammation. Moreover, CA significantly upregulated AMPK, ACC, LKB1 phosphorylation, and significantly inhibited lipin1, SREBPs, TNF- α , F4/80, caspase-1 expression, NF- κ B translocation, and MAPK activation in TY-induced hyperlipidemia mice. Our results suggest that CA is a potent antihyperlipidemia and antihepatic steatosis agent and the mechanism involved both lipogenesis and cholesterol synthesis and inflammation response inhibition via AMPK/SREBPs and NF- κ B/MAPK signaling pathways. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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