Isoliquiritigenin, an antioxidant flavonoid from licorice, inhibits high‐fat diet‐induced hepatic steatosis and oxidative injury through JNK1 inhibition

Abstract

Isoliquiritigenin (ILQ), a flavonoid originated from Glycyrrhizae species, has an anti‐oxidant effect. This study investigated the potential of ILQ for inhibiting liver X receptor‐alpha (LXRalpha)‐mediated lipogenesis and steatosis in hepatocytes, and the underlying molecular basis. Treatment of ILQ antagonized the ability of LXRalpha agonist (T0901317) to activate sterol regulatory element binding protein‐1c, thereby repressing downstream lipogenic genes induction. ILQ treatment inhibited activating phosphorylation of JNK1 elicited by palmitate or TNFalpha. JNK1, but not JNK2, increased LXRalpha phosphorylation at serine residues, promoting LXRalpha activation. The ability of ILQ to inhibit JNK1 led to the repression of T0901317‐inducible LXRalpha activation. In mice fed a high‐fat diet, ILQ treatment inhibited hepatic steatosis, as shown by a decrease in fat accumulation and repression of lipogenic genes. The results of blood chemistry and histopathology confirmed attenuation of high‐fat diet‐induced liver injury by ILQ. Moreover, ILQ inhibited oxidative stress, as shown by decreases in thiobarbituric acid reactive substance formation, iNOS and COX‐2 induction, and nitrotyrosinylation. Our results demonstrate that ILQ has the ability to repress LXRalpha‐dependent hepatic steatosis through JNK1 inhibition, and protect hepatocytes from oxidative injury induced by fat accumulation.