College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang Bayi, China.
College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang Bayi, China.
Int Immunopharmacol. 2020 Aug;85:106627. doi: 10.1016/j.intimp.2020.106627. Epub 2020 May 27.
Fulminant hepatitis (FH), characterized by overwhelmed inflammation and massive hepatocyte apoptosis, is a life-threatening and high mortality rate. Gastrodin (GTD), a phenolic glucoside extracted from Gastrodiaelata Blume, exerts anti-apoptosis, and anti-inflammatory activities. In the present study, we aimed to evaluate whether GTD treatment could alleviate lipopolysaccharide and d-galactosamine (LPS/GalN)-induced FH in mice and its potential mechanisms. These data suggested that GTD treatment remarkably protected against LPS/GalN-induced FH by enhancing the survival rate of mice, reducing ALT and AST levels, attenuating histopathological changes, and suppressing interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α secretion. In addition, GTD treatment relieved hepatic apoptosis by the regulation of peroxisome proliferator-activated receptors (PPARs), P53 and caspase-3/9. Furthermore, GTD treatment could significantly inhibit inflammation-related signaling pathways activated by LPS/GalN, including the suppression of nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) and nuclear factor-kappa B (NF-κB) activation. Importantly, GTD treatment effectively restored but not induced LPS/GalN-reduced the expression of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, as well as the level of pro-autophagy proteins. Taken together, our investigation indicated that GTD played an essential role in liver protection by relieving hepatocyte apoptosis and inflammation reaction, which may be closely involved in the inhibition of NLRP3 inflammasome and NF-κB activation, regulation of apoptosis-related proteins expression, and the recovery of AMPK/ACC/autophagy.
暴发性肝炎（FH）的特征是炎症过度活跃和大量肝细胞凋亡，是一种危及生命和高死亡率的疾病。天麻素（GTD）是从天麻中提取的酚糖苷，具有抗凋亡和抗炎作用。在本研究中，我们旨在评估 GTD 治疗是否能减轻脂多糖和 D-半乳糖胺（LPS/GalN）诱导的小鼠 FH 及其潜在机制。这些数据表明，GTD 治疗通过提高小鼠的存活率、降低 ALT 和 AST 水平、减轻组织病理学变化以及抑制白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子（TNF）-α的分泌，显著地减轻了 LPS/GalN 诱导的 FH。此外，GTD 治疗通过调节过氧化物酶体增殖物激活受体（PPARs）、P53 和半胱天冬酶-3/9 来缓解肝凋亡。此外，GTD 治疗能显著抑制 LPS/GalN 激活的炎症相关信号通路，包括抑制核苷酸结合寡聚化结构域（NOD）样受体蛋白 3（NLRP3）和核因子-κB（NF-κB）的激活。重要的是，GTD 治疗有效地恢复了 LPS/GalN 降低的 AMP 激活的蛋白激酶（AMPK）和乙酰辅酶 A 羧化酶（ACC）磷酸化的表达，以及自噬蛋白的水平。综上所述，我们的研究表明，GTD 通过减轻肝细胞凋亡和炎症反应在肝脏保护中发挥了重要作用，这可能与抑制 NLRP3 炎性体和 NF-κB 的激活、调节凋亡相关蛋白的表达以及恢复 AMPK/ACC/自噬有关。
