Glycyrrhizic acid restores the downregulated hepatic ACE2 signaling in the attenuation of mouse steatohepatitis.

Autor: Zhou L; Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: 2462109418@qq.com., Chen S; Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: 418946336@qq.com., Wei Y; Department of Pharmacy, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. Electronic address: weiyuanyi2012@163.com., Sun Y; School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, 2006, Australia. Electronic address: vannysun014@gmail.com., Yang Y; Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, Sydney, NSW, 2000, Australia. Electronic address: yifanyang@sitcm.edu.au., Lin B; Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: 805114257@qq.com., Li Y; Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, Sydney, NSW, 2000, Australia. Electronic address: yuhao@sitcm.edu.au., Wang C; Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address: wangcx@smu.edu.cn.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2024 Mar 15; Vol. 967, pp. 176365. Date of Electronic Publication: 2024 Feb 03.
DOI: 10.1016/j.ejphar.2024.176365
Abstrakt: Glycyrrhizic acid (GA), one of the major active components derived from licorice root, exerts liver-protecting activity. Its molecular mechanisms of action, however, remain not completely understood. The angiotensin (Ang) converting enzyme (ACE) 2/Ang-(1-7)/Mas axis, regulated by ACE2 through converting Ang II into Ang-(1-7) to activate Mas receptor, counteracts the pro-inflammatory and pro-steatotic effects of the ACE/Ang II/Ang II receptor type 1 (AT1) axis. Here, it was found that pretreatment with GA suppressed LPS/D-galactosamine-induced serum hyperactivities of alanine aminotransferase and aspartate aminotransferase, hepatomegaly, pathological changes, and over-accumulation of triglycerides and fatty droplets in the liver of mice. GA also diminished LPS/free fatty acid-induced inflammation and steatosis in cultured hepatocytes. Mechanistically, GA restored hepatic protein hypoexpression of ACE2 and Mas receptor, and the decrease in hepatic Ang-(1-7) content. Hepatic overexpression of angiotensin II and AT1 was also suppressed. However, GA did not alter hepatic protein expression of renin and ACE. In addition, GA inhibited hepatic protein over-phosphorylation of the p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, extracellular signal-regulated kinase, and nuclear factor κB at Ser 536 . Hepatic overexpression of tumor necrosis factor α, interleukin 6, interleukin 1β, sterol regulatory element-binding protein 1c, and fatty acid synthase was also inhibited. GA-elicited recovery of ACE2 and Mas protein hypoexpression was further confirmed in the hepatocyte. Thus, the present results demonstrate that GA restores the downregulated hepatic ACE2-mediated anti-inflammatory and anti-steatotic signaling in the amelioration of steatohepatitis. We suggest that GA may protect the liver from injury by regulating the hepatic ACE2-mediated signaling.
Competing Interests: Declaration of competing interest The authors (Longyue Zhou, Shankang Chen, Yuanyi Wei, Yihui Sun, Yifan Yang, Bingqi Lin, Yuhao Li, and Chunxia Wang) declare no duality of competing financial interests or personal relationships to influence this study.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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