School of Pharmacy, Guangdong Pharmaceutical University, Guangdong, 510006, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
J Ethnopharmacol. 2023 Aug 10;312:116529. doi: 10.1016/j.jep.2023.116529. Epub 2023 Apr 20.
The Suxiao Jiuxin pill (SJP) is a Chinese medical patent drug on the national essential drug list of China, with well-established cardiovascular protective effects in the clinic. However, the mechanisms underlying the protective effects of SJP on cardiovascular disease have not yet been elucidated clearly, especially its relationship with the gut microbiota.
This study aimed to investigate the cardioprotective effect of SJP against isoproterenol-induced acute myocardial infarction (AMI) by integrating the gut microbiome and metabolome.
A rat model of AMI was generated using isoproterenol. Firstly, the effect of antibiotic (ABX) treatment on the blood absorption and excretion of the main components of SJP were studied. Secondly, 16S rRNA sequencing and untargeted metabolomics were used to discover the improvement of SJP treatment on gut microbiota and host metabolism in AMI rats. Finally, targeted metabolomics was used to verify the effects of SJP treatment on host metabolism in AMI rats.
The results showed that ABX treatment could affect the blood absorption and fecal excretion of the main active components of SJP. At the same time, SJP can restore the richness and diversity of gut microbiota, and multiple gut microbiota (including Jeotgalicoccus, Lachnospiraceae, and Blautia) are significantly associated with fatty acids. Untargeted metabolomics also found that SJP could restore the levels of various fatty acid metabolites in serum and cecal contents (p < 0.01, FC > 1.5 and VIP >1). Targeted metabolomics further confirmed that 41, 21, and 39 fatty acids were significantly altered in serum, cecal contents, and heart samples, respectively. Interestingly, these fatty acids belong to the class of eicosanoids, and SJP can significantly downregulate these eicosanoids in AMI rats.
The results of this study suggest that SJP may exert its cardioprotective effects by remodeling the gut microbiota and host fatty acid metabolism.
速效救心丸（SJP）是一种中国医学专利药物，已被列入中国国家基本药物目录，在临床上具有明确的心血管保护作用。然而，SJP 对心血管疾病的保护作用的机制尚未得到明确阐明，特别是它与肠道微生物群的关系。
本研究旨在通过整合肠道微生物群和代谢组学，研究 SJP 对异丙肾上腺素诱导的急性心肌梗死（AMI）的心脏保护作用。
使用异丙肾上腺素建立 AMI 大鼠模型。首先，研究抗生素（ABX）处理对 SJP 主要成分的血液吸收和排泄的影响。其次，采用 16S rRNA 测序和非靶向代谢组学技术，发现 SJP 治疗对 AMI 大鼠肠道微生物群和宿主代谢的改善作用。最后，采用靶向代谢组学技术验证 SJP 治疗对 AMI 大鼠宿主代谢的影响。
结果表明，ABX 处理会影响 SJP 主要活性成分的血液吸收和粪便排泄。同时，SJP 可以恢复肠道微生物群的丰富度和多样性，并且多种肠道微生物群（包括 Jeotgalicoccus、Lachnospiraceae 和 Blautia）与脂肪酸显著相关。非靶向代谢组学还发现，SJP 可以恢复血清和盲肠内容物中各种脂肪酸代谢物的水平（p<0.01，FC>1.5 和 VIP>1）。靶向代谢组学进一步证实，血清、盲肠内容物和心脏样本中分别有 41、21 和 39 种脂肪酸发生显著改变。有趣的是，这些脂肪酸属于类二十烷酸，SJP 可以显著下调 AMI 大鼠中的这些类二十烷酸。
本研究结果表明，SJP 可能通过重塑肠道微生物群和宿主脂肪酸代谢发挥其心脏保护作用。
