Liu Yimei, Liu Ninghua, Liu Yujing, He Hongyu, Luo Zhe, Liu Wenjun, Song Nan, Ju Minjie
Department of Critical Care Medicine, Zhongshan Hospital of Fudan University, Shanghai, China.
Department of Facial Plastic and Reconstructive Surgery, Eye & ENT Hospital of Fudan University, Shanghai, China.
J Clin Transl Hepatol. 2022 Jun 28;10(3):474-485. doi: 10.14218/JCTH.2021.00072. Epub 2021 Aug 19.
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.
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).
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.
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.
人参皂苷Rb1对D-氨基半乳糖（D-GalN）/脂多糖（LPS）诱导的急性肝损伤（ALI）的影响尚不清楚。本研究旨在评估人参皂苷Rb1对ALI的影响及其潜在机制。
在D-GalN/LPS处理前3天，通过腹腔注射用人参皂苷Rb1预处理小鼠，以诱导ALI。每小时监测24小时的存活率，并评估血清生化参数、肝脏指数和组织病理学分析，以测量肝损伤程度。采用ELISA法检测肝组织和血清中的氧化应激和炎性细胞因子。进行免疫组织化学染色、RT-PCR和western印迹，以评估肝组织和库普弗细胞（KC）中Toll样受体4（TLR4）、核因子κB（NF-κB）和含pyrin结构域的NLR家族3蛋白（NLRP3）的表达。
人参皂苷Rb1使D-GalN/LPS诱导的ALI小鼠存活率提高了80%，显著改善了丙氨酸和天冬氨酸转氨酶的升高，恢复了肝脏病理变化，并降低了D-GalN/LPS改变的氧化应激和炎性细胞因子水平。与对照组相比，D-GalN/LPS组的KC增加，但Rb1预处理后未显著增加。D-GalN/LPS可上调而Rb1预处理可下调分离的KC中白细胞介素（IL）-1β、IL-18、NLRP3、含半胱天冬酶激活和招募结构域的凋亡相关斑点样蛋白（ASC）和半胱天冬酶-1的表达。此外，人参皂苷Rb1抑制了D-GalN/LPS给药诱导的TLR4/NF-κB信号通路和NLRP3炎性小体的激活。
人参皂苷Rb1通过TLR4/NF-κB信号通路和NLRP3炎性小体激活减轻氧化应激和炎症反应，从而保护小鼠免受D-GalN/LPS诱导的ALI。
