Salvianolic acid A attenuates CCl4-induced liver fibrosis by regulating the PI3K/AKT/mTOR, Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways
Authors Wang R, Song F, Li S, Wu B, Gu Y, Yuan Y
Received 15 November 2018
Accepted for publication 8 April 2019
Published 31 May 2019 Volume 2019:13 Pages 1889—1900
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Cristiana Tanase
Rong Wang*, Fuxing Song*, Shengnan Li, Bin Wu, Yanqiu Gu, Yongfang Yuan
Department of Pharmacy, Shanghai 9th People‘s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, People’s Republic of China
*These authors contributed equally to this work
Background: Liver fibrosis occurs due to chronic liver disease due to multiple pathophysiological causes. The main causes for this condition are chronic alcohol abuse, nonalcoholic steatohepatitis, and infection due to hepatitis C virus. Currently, there is more and more information available about the molecular as well as cellular mechanisms, which play a role in the advancement of liver fibrosis. However, there is still no effective therapy against it.
Purpose: In order to find an effective treatment against liver fibrosis, our study explored whether salvianolic acid A (SA-A), a traditional Chinese medicine extracted from the plant Danshen, could effectively inhibit the liver fibrosis, which is induced by CCl4 in vivo.
Methods: The effects of SA-A were evaluated by assessing the parameters related to liver fibrosis such as body weight, histological changes, and biochemical parameters. Thereafter, the related protein or gene levels of P13K/AKT/mTOR, Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways were determined by western blotting, real-time PCR or immunohistochemistry staining.
Results: According to the results of our study, SA-A could reduce liver fibrosis by inhibiting liver function, liver fibrosis index, collagen deposition, and improving the degree of liver fibrosis in rats. Mechanistically, the PI3K/AKT/mTOR signaling cascade was inhibited by SA-A to prevent the stimulation of hepatic stellate cell, as well as the synthesis of extracellular matrix, and regulated Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways to prevent hepatocyte apoptosis.
Conclusion: The novel findings of this study suggested that SA-A could reduce liver fibrosis and the molecular mechanisms behind it are closely associated with the regulation of PI3K/AKT/mTOR, Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways.
Keywords: liver fibrosis, salvianolic acid A, AKT/mTOR, Bcl-2/Bax, caspase-3/cleaved caspase-3
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