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）以炎症不堪和大量肝细胞凋亡为特征，威胁生命，死亡率高。天麻（GTD），从天麻中提取的酚类糖苷发挥抗凋亡和抗炎作用。在本研究中，我们旨在评估GTD处理是否可以减轻脂多糖和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治疗可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介素（IL）-1β，IL-6和肿瘤坏死因子来显着保护LPS / GalN诱导的FH（ TNF）-α分泌。此外，GTD治疗通过调节过氧化物酶体增殖物激活受体（PPAR），P53和caspase-3 / 9减轻了肝细胞凋亡。此外，GTD治疗可以显着抑制LPS / GalN激活的炎症相关信号通路，包括抑制核苷酸结合域（NOD）样受体蛋白3（NLRP3）和核因子-κB（NF-κB）激活。重要的是，GTD治疗有效地恢复了LPS / GalN的表达，但并未诱导其降低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保护中起着至关重要的作用，这可能与抑制NLRP3炎性小体和NF-κB活化，调节凋亡相关蛋白的表达以及抑制肝细胞凋亡密切相关。 AMPK / ACC /自噬的恢复。GTD处理有效恢复但不诱导LPS / GalN降低AMP活化蛋白激酶（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保护中起着至关重要的作用，这可能与抑制NLRP3炎性小体和NF-κB活化，调节凋亡相关蛋白的表达以及抑制肝细胞凋亡密切相关。 AMPK / ACC /自噬的恢复。GTD处理有效恢复但不诱导LPS / GalN降低AMP活化蛋白激酶（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通过缓解肝细胞凋亡和炎症反应在肝脏保护中起着至关重要的作用，这可能与抑制NLRP3炎性小体和NF-κB活化，调节凋亡相关蛋白的表达以及抑制肝细胞凋亡密切相关。 AMPK / ACC /自噬的恢复。