Rosmarinic Acid Ameliorates Acetaminophen-Induced Acute Liver Injury In Mice Via Rack1/Tnf-Alpha Mediated Antioxidant Effect

Context: Rosmarinic acid (RA) dose-dependently ameliorates acetaminophen (APAP) induced hepatotoxicity in rats. However, whether RA hepatoprotective effect is by regulating RACK1 and its downstream signals is still unclear.Objective: This study explores the RA protective effect on APAP-induced ALI and its mechanism.Materials and methods: Sixty Kunming mice 6-8 weeks old were randomly separated into six groups (n = 10) and pre-treated with normal saline, ammonium glycyrrhetate (AG) or RA (10, 20 or 40 mg/kg i.p./day) for two consecutive weeks. Then, APAP (300 mg/kg, i.g.) was administrated to induce ALI, except for the control. Serum alanine/aspartate aminotransferases (ALT and AST), malondialdehyde (MDA), superoxide dismutase (SOD) and histopathology were used to authenticate RA effect. The liver RACK1 and TNF-alpha were measured by western blot.Results: Compared with the APAP group, different dosages RA significantly decreased ALT (52.09 +/- 7.98, 55.13 +/- 10.19, 65.08 +/- 27.61 U/L, p < 0.05), AST (114.78 +/- 19.87, 115.29 +/- 31.91, 101.78 +/- 21.85 U/L, p < 0.05), MDA (2.37 +/- 0.87, 2.13 +/- 0.87, 1.86 +/- 0.39 nmol/mg, p < 0.01) and increased SOD (306.178 +/- 90.80, 459.21 +/- 58.54, 444.01 +/- 78.09 U/mg, p < 0.05). With increasing doses of RA, RACK1 and TNF-alpha expression decreased. Moreover, the RACK1 and TNF-alpha levels were positively correlated with MDA (r = 0.8453 and r = 0.9391, p < 0.01).Discussion and conclusions: Our findings support RA as a hepatoprotective agent to improve APAP-induced ALI and the antioxidant effect mediated through RACK1/TNF-alpha pathway.