Ginsenoside Rb1 Reduces D-GalN/LPS-induced Acute Liver Injury by Regulating TLR4/NF-κB Signaling and NLRP3 Inflammasome

Yimei Liu; Ninghua Liu; Yujing Liu; Hongyu He; Zhe Luo; Wenjun Liu; Nan Song; Minjie Ju

doi:10.14218/JCTH.2021.00072

Ginsenoside Rb1 Reduces D-GalN/LPS-induced Acute Liver Injury by Regulating TLR4/NF-κB Signaling and NLRP3 Inflammasome

J Clin Transl Hepatol. 2022 Jun 28;10(3):474-485. doi: 10.14218/JCTH.2021.00072. Epub 2021 Aug 19.

Authors

Yimei Liu¹, Ninghua Liu², Yujing Liu³, Hongyu He¹, Zhe Luo¹, Wenjun Liu¹, Nan Song², Minjie Ju¹

Affiliations

¹ Department of Critical Care Medicine, Zhongshan Hospital of Fudan University, Shanghai, China.
² Department of Facial Plastic and Reconstructive Surgery, Eye & ENT Hospital of Fudan University, Shanghai, China.
³ Department of Nursing, Zhongshan Hospital of Fudan University, Shanghai, China.

Abstract

Background and aims: The effect of ginsenoside Rb1 on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury (ALI) is unknown. The aim of this study was to evaluate the effect of ginsenoside Rb1 on ALI and its underlying mechanisms.

Methods: Mice were pretreated with ginsenoside Rb1 by intraperitoneal injection for 3 days before D-GalN/LPS treatment, to induce ALI. The survival rate was monitored every hour for 24 h, and serum biochemical parameters, hepatic index and histopathological analysis were evaluated to measure the degree of liver injury. ELISA was used to detect oxidative stress and inflammatory cytokines in hepatic tissue and serum. Immunohistochemistry staining, RT-PCR and western blotting were performed to evaluate the expression of toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), and NLR family, pyrin domain-containing 3 protein (NLRP3) in liver tissue and Kupffer cells (KCs).

Results: Ginsenoside Rb1 improved survival with D-GalN/LPS-induced ALI by up to 80%, significantly ameliorated the increased alanine and aspartate transaminase, restored the hepatic pathological changes and reduced the levels of oxidative stress and inflammatory cytokines altered by D-GalN/LPS. Compared to the control group, the KCs were increased in the D-GalN/LPS groups but did not increase significantly with Rb1 pretreatment. D-GalN/LPS could upregulate while Rb1 pretreatment could downregulate the expression of interleukin (IL)-1β, IL-18, NLRP3, apoptosis associated speck-like protein containing CARD (ASC) and caspase-1 in isolated KCs. Furthermore, ginsenoside Rb1 inhibited activation of the TLR4/NF-κB signaling pathway and NLRP3 inflammasome induced by D-GalN/LPS administration.

Conclusions: Ginsenoside Rb1 protects mice against D-GalN/LPS-induced ALI by attenuating oxidative stress and the inflammatory response through the TLR4/NF-κB signaling pathway and NLRP3 inflammasome activation.

Keywords: Chemical and drug induced liver injury; Ginsenosides; NLR family, pyrin domain-containing 3 protein; Toll-like receptor 4.