南方医科大学Chen Yu等研究人员合作发现，口服阿斯提宾通过调节肠道微生物群减轻小鼠对乙酰氨基酚诱导的急性肝损伤。2024年9月23日，《中国药理学报》杂志在线发表了这项成果。

研究人员表示，乙酰氨基酚（APAP）过量引发的急性肝损伤（ALI）以广泛的氧化应激为特征，目前对这种不良反应的临床干预仍然有限。阿斯提宾是一种存在于光果野葛根中的活性化合物，具有抗炎和抗氧化活性。由于其口服生物利用度低，阿斯提宾可以在肠道中积累，为其与肠道微生物群（GM）的相互作用提供了基础。

研究人员调查了阿斯提宾对APAP诱导的ALI的保护作用，重点关注阿斯提宾与GM的相互作用。小鼠接受了阿斯提宾（50 mg/kg每天，口服）为期7天。在最后一次阿斯提宾给药后2小时，小鼠接受了APAP（300 mg/kg，口服）以诱导ALI。结果表明，口服阿斯提宾显著减轻了APAP诱导的ALI，通过改变GM的组成并丰富有益代谢物（包括羟基酪醇）来实现。使用“抗生素鸡尾酒”或在口腔内给予阿斯提宾导致GM耗竭，从而消除了阿斯提宾的肝保护作用。

另一方面，给予羟基酪醇（10 mg/kg，口服）在APAP诱导的ALI小鼠中产生了类似的保护作用。肝脏组织的转录组分析显示，羟基酪醇抑制了APAP诱导ALI中的活性氧和炎症相关信号，并促进Nrf2信号通路的激活，以依赖于sirtuin-6的方式应对APAP引发的氧化应激。这些结果强调口服阿斯提宾通过调节肠道微生物群和代谢物，改善APAP诱导的ALI，并为缓解APAP诱导的ALI提供了一种替代治疗策略。

附：英文原文

Title: Oral administration of astilbin mitigates acetaminophen-induced acute liver injury in mice by modulating the gut microbiota

Author: Yang, Qin, He, Wen-hao, Xie, Li, Chen, Tao, Liu, Ruo-fan, Hu, Jia-jia, Guo, Jia-yin, Tan, Guo-zhu, Wu, Fu-ling, Gu, Peng, Chen, Peng, Chen, Yu

Issue&Volume: 2024-09-23

Abstract: Acetaminophen (APAP) overdose-induced acute liver injury (ALI) is characterized by extensive oxidative stress, and the clinical interventions for this adverse effect remain limited. Astilbin is an active compound found in the rhizome of Smilax glabra Roxb. with anti-inflammatory and antioxidant activities. Due to its low oral bioavailability, astilbin can accumulate in the intestine, which provides a basis for the interaction between astilbin and gut microbiota (GM). In the present study we investigated the protective effects of astilbin against APAP-induced ALI by focusing on the interaction between astilbin and GM. Mice were treated with astilbin (50mg·kg1·d1, i.g.) for 7 days. After the last administration of astilbin for 2h, the mice received APAP (300mg/kg, i.g.) to induce ALI. We showed that oral administration of astilbin significantly alleviated APAP-induced ALI by altering the composition of GM and enriching beneficial metabolites including hydroxytyrosol (HT). GM depletion using an “antibiotics cocktail” or paraoral administration of astilbin abolished the hepatoprotective effects of astilbin. On the other hand, administration of HT (10mg/kg, i.g.) caused similar protective effects in APAP-induced ALI mice. Transcriptomic analysis of the liver tissue revealed that HT inhibited reactive oxygen species and inflammation-related signaling in APAP-induced ALI; HT promoted activation of the Nrf2 signaling pathway to combat oxidative stress following APAP challenge in a sirtuin-6-dependent manner. These results highlight that oral astilbin ameliorates APAP-induced ALI by manipulating the GM and metabolites towards a more favorable profile, and provide an alternative therapeutic strategy for alleviating APAP-induced ALI.

DOI: 10.1038/s41401-024-01383-9

Source: https://www.nature.com/articles/s41401-024-01383-9