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
Rong Wang*, Fuxing Song*, Shengnan Li, Bin Wu, Yanqiu Gu, Yongfang YuanDepartment 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:...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-05-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://www.dovepress.com/salvianolic-acid-a-attenuates-ccl4-induced-liver-fibrosis-by-regulatin-peer-reviewed-article-DDDT |
| _version_ | 1819226315030528000 |
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| author | Wang R Song F Li S Wu B Gu Y Yuan Y |
| author_facet | Wang R Song F Li S Wu B Gu Y Yuan Y |
| author_sort | Wang R |
| collection | DOAJ |
| description | Rong Wang*, Fuxing Song*, Shengnan Li, Bin Wu, Yanqiu Gu, Yongfang YuanDepartment 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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| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-23T10:23:32Z |
| publishDate | 2019-05-01 |
| publisher | Dove Medical Press |
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| series | Drug Design, Development and Therapy |
| spelling | doaj.art-e3d6e7c40f054364bdd30e68aa32054e2022-12-21T17:50:38ZengDove Medical PressDrug Design, Development and Therapy1177-88812019-05-01Volume 131889190046225Salvianolic acid A attenuates CCl4-induced liver fibrosis by regulating the PI3K/AKT/mTOR, Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathwaysWang RSong FLi SWu BGu YYuan YRong Wang*, Fuxing Song*, Shengnan Li, Bin Wu, Yanqiu Gu, Yongfang YuanDepartment 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-3https://www.dovepress.com/salvianolic-acid-a-attenuates-ccl4-induced-liver-fibrosis-by-regulatin-peer-reviewed-article-DDDTliver fibrosissalvianolic acid AAKT/mTORBcl-2/BaxCaspase-3/Cleaved caspase-3 |
| spellingShingle | Wang R Song F Li S Wu B Gu Y Yuan Y 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 Drug Design, Development and Therapy liver fibrosis salvianolic acid A AKT/mTOR Bcl-2/Bax Caspase-3/Cleaved caspase-3 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | liver fibrosis salvianolic acid A AKT/mTOR Bcl-2/Bax Caspase-3/Cleaved caspase-3 |
| url | https://www.dovepress.com/salvianolic-acid-a-attenuates-ccl4-induced-liver-fibrosis-by-regulatin-peer-reviewed-article-DDDT |
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