Zhang Han, Hui Xianrui, Wang Yule, Wang Yi, Lu Xiaoyan
Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, China.
Front Pharmacol. 2022 Sep 15;13:1001422. doi: 10.3389/fphar.2022.1001422. eCollection 2022.
Angong Niuhuang Pill (ANP) is a famous traditional Chinese patent medicine and is used for treating ischemic or hemorrhagic stroke for centuries. However, the mechanism of action of ANP in stroke treatment has rarely been reported. With increasing evidence for a mechanistic link between acute ischemic stroke and gut microbiota alterations, this study aimed to determine the mechanism of action of ANP in treating acute ischemic stroke from the perspective of the gut microbiota. A mouse model of acute ischemic stroke by middle cerebral artery occlusion (MCAO) was established, and 16S ribosomal RNA (rRNA) gene sequencing and metabolomic analysis were performed on the cecal content samples collected from the sham, model, and ANP-treated MCAO mice. The results showed that ANP significantly ameliorated cerebral infarct volume, improved neurological deficits, and reduced histopathological injuries in the ipsilateral ischemic cortex, hippocampus, and striatum. The latter effects included inhibition of neuronal death, increased Nissl bodies, and decreased cell apoptosis. Moreover, ANP reversed gut microbiota dysbiosis by modulating the abundance of bacteria whose effects may mitigate MCAO damage, such as the phyla and , the families and , and the genera and . Microbial metabolites related to inflammation and neuroprotection, such as prostaglandin I2 and uridine, were also regulated by ANP treatment. Uridine, guanosine, and inosine might be potential neuromodulators produced by the gut microbiota in the ANP-treated group. Spearman correlation analysis revealed that these metabolites were intimately related to certain genera, including , , , , , and . Our results demonstrated that alleviating gut microbiota dysbiosis is one of the mechanisms by which ANP protects against ischemic stroke and suggest that targeting , , , , , and might be a potential anti-stroke therapy.
安宫牛黄丸（ANP）是一种著名的传统中成药，数世纪以来一直用于治疗缺血性或出血性中风。然而，安宫牛黄丸治疗中风的作用机制鲜有报道。随着急性缺血性中风与肠道微生物群改变之间存在机制联系的证据越来越多，本研究旨在从肠道微生物群的角度确定安宫牛黄丸治疗急性缺血性中风的作用机制。通过大脑中动脉闭塞（MCAO）建立急性缺血性中风小鼠模型，并对从假手术组、模型组和安宫牛黄丸治疗的MCAO小鼠收集的盲肠内容物样本进行16S核糖体RNA（rRNA）基因测序和代谢组学分析。结果表明，安宫牛黄丸显著改善了脑梗死体积，改善了神经功能缺损，并减少了同侧缺血皮质、海马和纹状体的组织病理学损伤。后一种作用包括抑制神经元死亡、增加尼氏体和减少细胞凋亡。此外，安宫牛黄丸通过调节可能减轻MCAO损伤的细菌丰度来逆转肠道微生物群失调，如门 和 、科 和 以及属 和 。与炎症和神经保护相关的微生物代谢产物，如前列腺素I2和尿苷，也受到安宫牛黄丸治疗的调节。尿苷、鸟苷和肌苷可能是安宫牛黄丸治疗组中由肠道微生物群产生的潜在神经调节剂。Spearman相关性分析显示，这些代谢产物与某些属密切相关，包括 、 、 、 、 和 。我们的结果表明，减轻肠道微生物群失调是安宫牛黄丸预防缺血性中风的机制之一，并表明靶向 、 、 、 、 和 可能是一种潜在的抗中风疗法。
