Bavachin induces apoptosis through mitochondrial regulated ER stress pathway in HepG2 cells

抄録

As a traditional herbal medicine, the fruits of Psoralea corylifolia L. (FP) have been widely used for the treatment of various skin diseases for hundred years. Recently, the emerging FP-induced toxic effects, especially hepatotoxicity, in clinic are getting the public’s attention. However, its exact toxic components and mechanisms underlying remain unclear. Bavachin, one of flavonoids in FP, has been documented as a hepatotoxic substance, and the present study aimed to determine the toxicity caused by bavachin and the possible toxic mechanisms involved using HepG2 cells. Our results showed that bavachin could significantly inhibited cell proliferation and trigger the endoplasmic reticulum stress (ER stress) in a dose dependent manner. Downregulating ER stress using tauroursodeoxycholic acid (TUDCA) obvious attenuated Bavachin-triggerd cell apoptosis. Then, siRNA knock-down of Mitofusion 2 (Mfn2) resulted in a remarkable aggravation of ER stress through the inhibition of the phosphorylation of protein kinase B (Akt). Additionally, suppression of reactive oxygen species (ROS) by ROS Scavenger (NAC) also reduced Bavachin-induced ER stress. Taken together, our study demonstrated that Bavachin-induced ER stress caused cell apoptosis by Mfn2-Akt pathway, and that ROS may participate upstream in this mechanism. Here, we not only provide a new understanding of ROS/Mfn2/Akt pathway in Bavachin-induced cytotoxicity via the ER stress, but also identify a new specific intervention to prevent FP-induced hepatotoxicity in the future.