Protective effect of chrysophanol on LPS/d-GalN-induced hepatic injury through the RIP140/NF-κB pathway

Abstract

Chrysophanol (Chr), one of the major anthraquinones extracted from rhubarb, has been reported to possess various pharmacological properties including anti-cancer, antimicrobial and anti-inflammatory effects. The purpose of this current study was to investigate the possible protective effects of chrysophanol for the intervention in lipopolysaccharide (LPS)/D-galactosamine (GalN)-challenged acute liver injury in mice. LPS (50 μg kg⁻¹) and D-GalN (800 mg kg⁻¹) were injected intraperitoneally 1 h after chrysophanol (1.10 mg kg⁻¹) pretreatment on day 7. The results demonstrated that chrysophanol showed a trend for protection against acute liver injury, as evidenced by the alleviation of hepatic pathological damage and serum ALT and AST levels, as well as the serum and hepatic production of tumor necrosis factor-a (TNF-α), interleukin-6 (IL-6) and IL-10. Moreover, the treatment with Chr modified the levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GSH-Px) in hepatic tissues. Chrysophanol also significantly attenuated hepatic iNOS expression by inhibiting RIP140 and NF-κB activation, which could be observed through western blotting analysis. Simultaneously, in this present study, treatment with chrysophanol decreased the ratio of Bax/Bcl-2 and caspase-3 and caspase-8 expression, which suggested an anti-apoptotic property. Taken together, the conclusion, mirrored by our results, was that chrysophanol prevented LPS/D-GalN-induced liver injury through the induction of antioxidant defence, suppression of apoptosis and reduction of inflammatory response via inhibition of the RIP140/NF-κB pathway.