Rehmannia glutinosa (Gaertn.) DC Repressing Excessive Mitophagy through PINK1/Parkin Pathway to Alleviate Liver Toxicity of Tripterygium wilfordii Hook. F.

Background: Tripterygium wilfordii Hook. F. (TW) has significant anti-inflammatory, anti-tumor, and immunosuppressive effects, and is often used in the treatment of rheumatic immune diseases, inflammation, and tumors; however, its liver toxicity is also prominent. Combination treatment with Rehmannia glutinosa (Gaertn.) DC (RG) and TW for detoxification originates from the Qingluotongbi formula and are also representative of a combination of strengthening the body’s resistance to attenuation (Fuzheng Zhidu). Objective: This study aimed to explore the protective effect of RG against TW-induced liver injury and its regulatory mechanism of mitophagy to explain the connotation of combination of strengthening body resistance to attenuation. Materials and Methods: After the administration of RG and TW and their main and active ingredients (triptolide [TP] and catalpol [CAT]), C57BL/6J mice and HL7702 cells were tested for liver pathological changes, liver function indicators, and mitophagy index. The protein and gene expression of the PTEN-induced putative kinase 1 (PINK1)/Parkin pathway were analyzed. In HL7702 cells, PINK1 mRNA was knocked down using siRNA to verify the role of the PINK1/Parkin pathway in mitophagy regulation. Results: RG/CAT reduced the pathological injury and alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels, while reversing the protein and gene levels of microtubule-associated proteins 1A/1B-light chain 3, sequestosome-1, and dynamin-related protein 1 and inhibiting the PINK1/Parkin pathway caused by TW/TP. Knockdown of the PINK1/Parkin pathway in vitro alleviates TP-induced hepatotoxicity in HL7702 cells. Conclusions: RG inhibited excessive mitophagy to reduce TW-induced hepatotoxicity by downregulating the PINK1/Parkin pathway, providing research support for explaining the connotation of RG’s combination of strengthening the body resistance and attenuating the hepatotoxicity of TW.