Ginsenoside Rk2, a dehydroprotopanaxadiol saponin, alleviates alcoholic liver disease via regulating NLRP3 and NLRP6 inflammasome signaling pathways in mice

Jian Zou; Rujie Yang; Ruibing Feng; Jiayue Liu; Jian-Bo Wan

doi:10.1016/j.jpha.2023.05.005

Ginsenoside Rk2, a dehydroprotopanaxadiol saponin, alleviates alcoholic liver disease via regulating NLRP3 and NLRP6 inflammasome signaling pathways in mice

J Pharm Anal. 2023 Sep;13(9):999-1012. doi: 10.1016/j.jpha.2023.05.005. Epub 2023 May 13.

Authors

Jian Zou¹, Rujie Yang¹, Ruibing Feng¹, Jiayue Liu¹, Jian-Bo Wan¹

Affiliation

¹ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.

Abstract

Heavy alcohol consumption results in alcoholic liver disease (ALD) with inadequate therapeutic options. Here, we first report the potential beneficial effects of ginsenoside Rk2 (Rk2), a rare dehydroprotopanaxadiol saponin isolated from streamed ginseng, against alcoholic liver injury in mice. Chronic-plus-single-binge ethanol feeding caused severe liver injury, as manifested by significantly elevated serum aminotransferase levels, hepatic histological changes, increased lipid accumulation, oxidative stress, and inflammation in the liver. These deleterious effects were alleviated by the treatment with Rk2 (5 and 30 mg/kg). Acting as an nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inhibitor, Rk2 ameliorates alcohol-induced liver inflammation by inhibiting NLRP3 inflammasome signaling in the liver. Meanwhile, the treatment with Rk2 alleviated the alcohol-induced intestinal barrier dysfunction via enhancing NLRP6 inflammasome in the intestine. Our findings indicate that Rk2 is a promising agent for the prevention and treatment of ALD and other NLPR3-driven diseases.

Keywords: Alcoholic liver disease; Ginsenoside Rk2; Intestinal barrier dysfunction; NLRP3 inflammasome; NLRP6 inflammasome.