Figure 12.

Schema of the underlying mechanism of withaferin A inhibition of liver fibrosis. Withaferin A enters into hepatic stellate cells and activates SIRT3 (mainly located in mitochondria), then SIRT3 activation causes the decreased MDA level and increased GSH level. In addition, SIRT3 activation also increases the activities of antioxidant enzymes such as CAT, SOD, and GPx leading to the inhibition of oxidative stress, thus exerting the antiliver fibrotic effect. However, the antioxidative stress and antifibrotic effects of withaferin A can only be observed in WT mice but not in SIRT3 KO mice. Overall, withaferin A inhibits liver fibrosis by suppressing oxidative stress in a SIRT3-dependent manner.