Zhang Pin, Fang Zhengyu, Zhao Min, Yi Bojiao, Huang Yihe, Yang Hongjun, Guo Na, Zhao Chunjie
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China.
Phytother Res. 2023 Dec;37(12):5932-5946. doi: 10.1002/ptr.8005. Epub 2023 Sep 11.
Acute myocardial infarction (AMI) is a multifactorial disease with high mortality rate worldwide. Ethanol extract of Pueraria lobata (EEPL) has been widely used in treating cardiovascular diseases in China. This study aimed to explore the underlying therapeutic mechanism of EEPL in AMI rats.
We first evaluated the anti-AMI efficacy of EEPL through immunohistochemistry staining and biochemical indexes. Then, UPLC-MS/MS, 16S rDNA, and shotgun metagenomic sequencing were used to analyze the alterations in bile acid metabolism and intestinal flora. Finally, the influence of EEPL on ilem bile acid metabolism, related enzymes expression, and transporter proteins expression in rats were verified by mass spectrometry image and ELISA.
The results showed that EEPL can reduce cardiac impairment in AMI rats. Besides, EEPL effectively increased bile acid levels and regulated gut microbiota disturbance in AMI rats via increasing CYP7A1 expression and restoring intestinal microbiota diversity, separately. Moreover, it can increase bile acids reabsorption and fecal excretion through inhibiting FXR-FGF15 signaling pathway and increasing OST-α expression, which associated with Lachnoclostridium.
Our findings demonstrated that EEPL alleviated AMI partially by remediating intestinal dysbiosis and promoting bile acid biosynthesis, which provided new targets for AMI treatment.
急性心肌梗死(AMI)是一种多因素疾病,在全球范围内死亡率很高。葛根乙醇提取物(EEPL)在中国已被广泛用于治疗心血管疾病。本研究旨在探讨EEPL对急性心肌梗死大鼠的潜在治疗机制。
我们首先通过免疫组化染色和生化指标评估了EEPL的抗急性心肌梗死疗效。然后,采用超高效液相色谱-串联质谱法(UPLC-MS/MS)、16S核糖体DNA(rDNA)和鸟枪法宏基因组测序分析胆汁酸代谢和肠道菌群的变化。最后,通过质谱成像和酶联免疫吸附测定(ELISA)验证了EEPL对大鼠回肠胆汁酸代谢、相关酶表达和转运蛋白表达的影响。
结果表明,EEPL可以减轻急性心肌梗死大鼠的心脏损伤。此外,EEPL分别通过增加细胞色素P450 7A1(CYP7A1)表达和恢复肠道微生物群多样性,有效提高急性心肌梗死大鼠的胆汁酸水平并调节肠道微生物群紊乱。此外,它可以通过抑制法尼酯X受体(FXR)-成纤维细胞生长因子15(FGF15)信号通路和增加与迟缓梭菌相关的有机溶质转运蛋白α(OST-α)表达,增加胆汁酸的重吸收和粪便排泄。
我们的研究结果表明,EEPL通过改善肠道菌群失调和促进胆汁酸生物合成,部分缓解了急性心肌梗死,为急性心肌梗死的治疗提供了新的靶点。