Paeoniflorin Modulates Oxidative Stress, Inflammation And Hepatic Stellate Cells Activation To Alleviate Ccl4-Induced Hepatic Fibrosis By Upregulation Of Heme Oxygenase-1 In Mice

JOURNAL OF PHARMACY AND PHARMACOLOGY(2021)

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摘要
Objectives The role of Paeoniflorin on hepatic fibrosis and the specific mechanisms has not yet been elucidated. Therefore, we explored whether Paeoniflorin exerted protective effects on carbon tetrachloride (CCl4)-induced hepatic fibrosis and the underlying mechanisms.Methods A model of hepatic fibrosis was induced by intraperitoneally injecting with CCl4 (10% 5 mu l/g) twice a week for 7 weeks. To explore the effects of Paeoniflorin, mice were treated with Paeoniflorin (100 mg/kg) by gavage once a day at 1 week after modeling until they were sacrificed.Key findings Paeoniflorin remarkably improved liver function and histopathological changes of hepatic tissues in CCl4-induced liver injury. Besides, the serum MAO enzyme activity and hydroxyproline contents were notably decreased following the intervention of Paeoniflorin. The decreased expression of Vimentin, alpha -SMA, Col1a and Desmin manifested the inhibition of the hepatic stellate cells (HSCs) activation. Interestingly, Paeoniflorin intervention significantly upregulated the expression of heme oxygenase-1, and attenuated the inflammatory cytokines production as well as the CCl4-induced oxidative stress imbalance.Conclusions Paeoniflorin could effectively alleviate CCl4-induced hepatic fibrosis by upregulation of heme oxygenase-1, and it might be a new effective option for the comprehensive treatment of hepatic fibrosis.
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paeoniflorin, hepatic fibrosis, hepatic stellate cell, inflammation, oxidative stress, heme oxygenase-1
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