Exploring the effects of Danshen-Honghua herb pair on the intestinal flora of rats with acute myocardial ischemia and its microbial transformation in vitro

Background: The Danshen-Honghua herb pair (DHHP) is a common modern Chinese medicine pair for activating blood circulation and resolving blood stasis. It has been used for centuries to treat cardiovascular and cerebrovascular diseases and is often found in some herbal compounds for treating cardiovascular diseases. The aim of this study was to explore the effects of DHHP on the intestinal flora of rats with acute myocardial ischemia and its microbial transformation in vitro. Methods: In this study, we investigated the protective effect of DHHP on isoproterenol-induced acute myocardial ischemia in rats based on metagenomic sequencing technology, and further characterized the in vitro metabolic transformation products of DHHP, so as to investigate its anti-myocardial ischemic efficacy material basis. Results: Pharmacodynamic results demonstrated that DHHP significantly ameliorated pathological changes and improved abnormal cardiac enzyme levels in acute myocardial ischemia rats. In addition, metagenomic analysis showed the efficacy of DHHP in ameliorating the isoproterenol-induced modifications of the intestinal flora in rats. Specifically, DHHP promoted the growth of the intestinal potential probiotics such as Lactobacillus while suppressing the pathogenic bacteria, including Escherichia and Streptococcus. The in vitro metabolism results showed that the DHHP's active components underwent primarily phase I metabolism through hydroxylation, decarboxylation, and dehydration inversions in the isolated intestinal flora of acute myocardial ischemia rats and in phase II through sulfation esterification and methylation reactions. Conclusion: The results suggest that there may be a bidirectional regulatory effect between DHHP and intestinal flora, which is important to explain the pharmacological mechanism of DHHP.