Myricetin and dihydromyricetin as JNK1 inhibitors protect against ROS-mediated oxidative stress and apoptosis

Reactive oxygen species (ROS)-mediated oxidative stress and apoptosis contribute to the pathogenesis and pathological conditions of various diseases induced by food and environmental pollutants. Myricetin and dihydromyricetin, as natural flavonoids, can counteract oxidative damage, apoptosis, and associated diseases. Molecular docking analysis, ELISA, fluorescence spectroscopy, and Western blot techniques were applied to examine the potential of the two flavonoids as effective therapeutics for ROS-mediated diseases and the mechanism(s) underlying their protective effects against ethanol/H₂O₂-induced damage. In Kunming mice and HepG2 cells, myricetin and dihydromyricetin inhibited ethanol/H₂O₂-induced liver damage, ROS accumulation, and oxidative stress and apoptosis. Molecular docking showed that myricetin and dihydromyricetin interacted with JNK1 via hydrophobic interactions and hydrogen bonds, thereby exerting their protective effects. The significant differences in their binding patterns to JNK1 resulted from the different bond types between C2 and C3 on their C ring. Myricetin and dihydromyricetin likely protected liver injury via counteracting ROS/JNK1-mediated oxidative stress and apoptosis. The finding that the suppression of ROS-mediated oxidative stress and apoptosis by flavonoids via interacting with functional proteins, such as kinase, may represent an alternative strategy for treating excessive ROS-induced health problems.