Chlorogenic Acid Alleviated Liver Dysfunction Through Activating PINK1/Parkin Dependent Mitophagy
Abstract Background: Chlorogenic acid (CGA) is a natural polyphenolic compound with anti-inflammatory, antioxidant effects. It could improve mitochondrial dysfunction that was a key feature of acetaminophen (APAP) -induced liver injury. This study aimed to identify whether promoting mitophagy was associated with the hepatocyte protection for CGA.Methods: Acute hepatic injury model was induced by APAP in mice after CGA administration for 14 days. Survival rate was recoded within 24h of modeling. Serum aminotransferase, hepatic histopathology and TUNEL assays were simultaneously performed. The expression of apoptosis-related proteins (Bax and Bcl-2) and mitophagy-related genes and proteins (LC3Ⅱ, P62, PINK1 and Parkin) were analyzed. The fluorescence co-localization of LC3Ⅱ and Tom20 was analyzed with immunofluorescence.Results: Compared with APAP group, CGA pretreatment significantly increased survival rate of APAP-induced mice, inhibited the activity of ALT, AST and LDH in serum, and alleviated pathological features of liver such as inflammatory cell infiltration, necrosis of liver cells and vacuolation (p<0.05). Moreover, our data from the TUNEL and western blotting analysis showed that CGA significantly decreased the number of apoptotic cells and reversed the elevated Bax level and decreased Bcl-2 level(p<0.05). Furthermore, we found that CGA promoted the fluorescence co-localization of LC3Ⅱ and Tom20 and enhanced the protein expression of LC3Ⅱ (p<0.05). Finally, CGA significantly promoted mitophagy by exhibiting the increased gene and protein expression of PINK1 and Parkin.Conclusions: Our results demonstrated that CGA promoted PINK1/Parkin dependent mitophagy and inhibited hepatic apoptosis to exert protection against liver damage in APAP-induced mice.