Biopharmaceutics, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Department of Pharmaceutical, Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong, China.
Drug Dev Res. 2021 Jun;82(4):575-580. doi: 10.1002/ddr.21776. Epub 2020 Dec 30.
Acute liver injury (ALI) is a serious syndrome that is associated with high mortality, but there are few effective treatments. The activation of NLRP3 inflammasome is associated with ALI. Oridonin is a natural substance with an anti-inflammatory effect and has been reported to be an inhibitor of NLRP3. The aim of this study was to investigate the protective effect of oridonin on d-galactosamine (d-GalN)/lipopolysaccharide (LPS)-induced ALI and whether the effect is mediated by NLRP3. Mice were pretreated with oridonin (5 or 10 mg/kg) for 3 days. Then, they were injected with d-GalN (400 mg/kg) and LPS (40 μg/kg). The levels of inflammatory factors were measured by RT-PCR, Western blot, and enzyme-linked immunosorbent assay. We confirmed that oridonin significantly alleviated ALI induced by d-GalN/LPS in mice. Oridonin markedly decreased the inflammatory response by reducing the levels of inflammatory cytokines. More importantly, oridonin markedly reduced the expression of NLRP3, caspase-1, IL-18, and IL-1β. This study showed that oridonin has a protective effect on d-GalN/LPS-induced ALI, and the underlying mechanisms may be associated with the inhibition of the NLRP3 inflammatory pathways.
急性肝损伤 (ALI) 是一种死亡率较高的严重综合征，但目前有效的治疗方法较少。NLRP3 炎性小体的激活与 ALI 有关。冬凌草甲素是一种具有抗炎作用的天然物质，据报道其是 NLRP3 的抑制剂。本研究旨在探讨冬凌草甲素对 D-半乳糖胺(D-GalN)/脂多糖(LPS)诱导的 ALI 的保护作用及其是否通过 NLRP3 介导。小鼠用冬凌草甲素(5 或 10mg/kg)预处理 3 天。然后，它们被注射 D-GalN(400mg/kg)和 LPS(40μg/kg)。通过 RT-PCR、Western blot 和酶联免疫吸附试验测量炎症因子的水平。我们证实冬凌草甲素显著减轻了 D-GalN/LPS 诱导的小鼠 ALI。冬凌草甲素通过降低炎症细胞因子的水平显著减轻炎症反应。更重要的是，冬凌草甲素显著降低了 NLRP3、半胱天冬酶-1、IL-18 和 IL-1β 的表达。本研究表明，冬凌草甲素对 D-GalN/LPS 诱导的 ALI 具有保护作用，其潜在机制可能与抑制 NLRP3 炎症途径有关。
