Rosmarinic acid ameliorates acetaminophen-induced acute liver injury in mice via RACK1/TNF-α mediated antioxidant effect. (1st January 2021)

• Record Type: Journal Article
• Authors: Yu, Yang; Wu, Yao; Yan, Hao-zheng; Xia, Zi-ru; Wen, Wen; Liu, Dan-yang; Wan, Li-hong
• Is Part Of: Pharmaceutical biology. Volume 59:Number 1(2021)
• Page Start: 1284
• Page End: 1291
• Publication Date: 2021-01-01
• Subjects: ALI -- non-steroidal anti-inflammatory drug -- antioxidative -- receptor for activated C kinase 1 -- tumour necrosis factor-α; Pharmacognosy -- Periodicals; Materia medica, Vegetable -- Periodicals; 615.321
• DOI: 10.1080/13880209.2021.1974059
• Languages: English
• ISSNs: 1388-0209

Abstract

Abstract: 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-α 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-α expression decreased. Moreover, the RACK1 and TNF-α 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-α pathway.