Nutmeg is a Traditional Chinese Medicine used to treat gastrointestinal diseases. Some reports have indicated that nutmeg has hepatoprotective activity. In this study, a thioacetamide (TAA)-induced acute liver injury model in mice was used to explore the mechanism of the protective effects of nutmeg extract (NME), including its major bioactive component myrislignan. The results indicated that NME could effectively protect TAA-induced liver damage as assessed by recovery of increased serumtransaminases, decrease in hepatic oxidative stress, and lower hepatic inflammation. Metabolomics analysis further revealed that treatment with NME led to the recovery of a series of lipids including lysophosphatidylcholines that were decreased and a lowering of acylcarnitines that were increased in mouse plasma and liver after TAA exposure. Gene expression analysis demonstrated that the hepatoprotective effect of NME was achieved by modulation of the peroxisome proliferator-activated receptor alpha (PPARα) as well as the decrease in oxidative stress. NME could not protect from TAA-induced liver injury in Ppara-null mice, suggesting that its protective effect was dependent on PPARα. Myrislignan, a representative neolignan in nutmeg, showed potent protective activity against TAA-induced liver toxicity. These data demonstrate that nutmeg alleviates TAA-induced liver injury through the modulation of PPARα and that the lignan compounds in nutmeg such as myrislignan partly contributed to this action.

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PPARα介导肉豆蔻的保肝作用

肉豆蔻是用于治疗胃肠道疾病的中药。一些报道表明肉豆蔻具有保肝活性。在这项研究中，使用硫代乙酰胺（TAA）诱导的小鼠急性肝损伤模型来研究肉豆蔻提取物（NME）的保护作用机理，包括其主要的生物活性成分myrislignan。结果表明，通过增加血清转氨酶的恢复，降低肝氧化应激和降低肝脏炎症，NME可以有效保护TAA诱导的肝损伤。代谢组学分析进一步表明，用NME进行治疗可导致一系列脂质的恢复，包括在暴露于TAA后小鼠血浆和肝脏中降低的溶血磷脂酰胆碱和升高的酰基肉碱。基因表达分析表明，NME的肝保护作用是通过调节过氧化物酶体增殖物激活的受体α（PPARα）以及降低氧化应激来实现的。NME不能防止TAA诱导的肝损伤PPARA -敲除小鼠，暗示其保护作用依赖于PPARα。肉豆蔻中的代表性新木脂Myrislignan显示出对TAA诱导的肝毒性的有效保护活性。这些数据表明肉豆蔻通过调节PPARα减轻了TAA诱导的肝损伤，并且肉豆蔻中的木脂素化合物（例如肉豆蔻脑素）部分促成了这一作用。