Acute liver injury and its terminal phase, hepatic failure, trigger a series of complications, including hepatic encephalopathy, systematic inflammatory response syndrome, and multiorgan failure, with relatively high morbidity and mortality. Liver transplantation is the ultimate intervention, but the shortage of donor organs has limited clinical success. Mangiferin (MF), a xanthone glucoside, has been reported to have excellent anti-inflammatory efficacy. Here, a lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury mouse model was established to investigate the protective role of MF and the underlying mechanisms of action. Pretreatment with MF improved survival, decreased serum aminotransferase activities, and inhibited hepatic TNF-α production in LPS/D-GalN-challenged mice. Through Kupffer cell (KC) deletion by GdCl₃ and KC adoptive transfer, KCs were confirmed to be involved in these beneficial effects of MF. MF reduced LPS-mediated TNF-α production via the suppression of the TLR4/NF-κB signaling pathway in vitro. MF promoted HO-1 expression, but the knockdown of HO-1 prevented TNF-α inhibition, suggesting that the damage-resistance effects of HO-1 occurred via the suppression of TNF-α synthesis. When HO-1-silenced KCs were transferred to the liver with KC deletion, the protective effect of MF against LPS/D-GalN-induced acute liver injury was reduced, illustrating the role of KC-derived HO-1 in the anti-injury effects of MF. Collectively, MF attenuated acute liver injury induced by LPS/D-GalN via the inhibition of TNF-α production by promoting KCs to upregulate HO-1 expression.

急性肝损伤及其末期，肝功能衰竭引发一系列并发症，包括肝性脑病，系统性炎症反应综合征和多器官衰竭，具有较高的发病率和死亡率。肝移植是最终的干预措施，但是供体器官的短缺限制了临床成功。芒果黄素（MF）是一种th吨酮苷，具有出色的抗炎功效。在这里，建立了脂多糖（LPS）/ D-半乳糖胺（D-GalN）诱导的急性肝损伤小鼠模型，以研究MF的保护作用及其潜在的作用机制。用MF预处理可改善LPS / D-GalN攻击小鼠的存活率，降低其血清氨基转移酶活性，并抑制肝脏TNF-α的产生。GdCl通过Kupffer细胞（KC）缺失₃和KC过继转移证实，KC参与了MF的这些有益作用。MF通过抑制TLR4 /NF-κB信号通路减少LPS介导的TNF-α的产生体外。MF促进了HO-1的表达，但敲除HO-1阻止了TNF-α的抑制，这表明HO-1的抗损伤作用是通过抑制TNF-α的合成而产生的。当沉默HO-1的KCs转移至肝脏并缺失KC时，MF对LPS / D-GalN诱导的急性肝损伤的保护作用减弱，这说明KC衍生的HO-1在抗损伤中的作用MF的影响。总体而言，MF通过促进KCs上调HO-1表达来抑制TNF-α的产生，从而减轻了LPS / D-GalN诱导的急性肝损伤。