Chlorogenic acid alleviates oxidative damage in hepatocytes by regulating miR-199a-5p/GRP78 axis

Chlorogenic acid (CGA) is a phenylpropanoid compound in chrysanthemum, which has a variety of biological activities. Nevertheless, CGA has not yet been studied concerning oxidative stress in hepatocytes. Our research aims to investigate whether chlorogenic acid can improve hepatic oxidative stress, and further illustrated its detailed mechanism. The results of free radicals measurement and Western blot showed that CGA suppressed the activation of JNK (c-Jun NH2-teminal kinase) signaling pathway by ameliorating endoplasmic reticulum stress in H2O2-treated hepatocytes, thereby eliminating excess intracellular free radicals. In addition, through RT-qPCR, we found that miR-199a-5p down-regulated in H2O2-induced L02 cells, which was restored by CGA. By inhibiting the expression of miR-199a-5p to promote the transcription of GRP78 gene, the antioxidant capacity of CGA was greatly weakened in hepatocytes. Our findings suggest that CGA treatment alleviated the H2O2-induced oxidative stress by targeting miR-199a-5p, thereby ameliorating ER stress and inhibiting JNK phosphorylation for anti-oxidant capacity enhancement. Based on our available results, CGA may be an alternative compound to mitigate hepatic oxidative damage through the miR-199a-5p/GPR78 axis.

Automated summary

This study aimed to investigate the effect of chlorogenic acid (CGA) in improving hepatic oxidative stress and elucidate its mechanism. The results showed that CGA suppressed the activation of the JNK signaling pathway by ameliorating endoplasmic reticulum stress, thereby reducing intracellular free radicals. Additionally, CGA attenuated oxidative stress by targeting miR-199a-5p, inhibiting JNK phosphorylation, and promoting the transcription of the GRP78 gene. These findings suggest that CGA may serve as an alternative compound to mitigate hepatic oxidative damage through the miR-199a-5p/GPR78 axis.