Dracocephalum moldavica L. Extract Ameliorates Hypertension Through Modulating the Interaction Between miRNAs and Gut Microbiota in 2K1C Rats

Aim: To investigate the therapeutic effects of Dracocephalum moldavica L. extract (DME) against hypertension and elucidate the underlying molecular mechanism. Method: A two-kidney one-clip (2K1C) model was established in male Wistar rats, and DME or saline was administered via oral gavage for 4 weeks. Subsequently, the blood pressure was monitored. Fecal microRNAs (miRNAs), gut microbes, and host metabolites were evaluated through miRNA sequencing, 16S rRNA gene sequencing, and serum metabolomics analysis, respectively. Results: DME administration attenuated 2K1C-induced hypertension in rats. Additionally, DME alleviated the dysregulation of miRNA expression and gut microbiota dysbiosis in 2K1C rats. The correlation analysis confirmed the association of the differentially expressed miRNAs with gut microbes. Furthermore, non-targeted metabolomics analysis revealed different metabolic profiles in the serum of 2K1C rats compared to control rats. Interestingly, the changes in those serum metabolites were partially attenuated by DME. The metabolite enrichment analysis demonstrated that the differentially expressed metabolites were mainly involved in three metabolic pathways (Arachidonic acid metabolism, TCA cycle, and Alanine, aspartate and glutamate metabolism). Conclusion: DME can be suggested as an effective intervention in the prevention of hypertension through modulating the miRNAs, gut microbiota, and host metabolites. Our findings may give new insights regarding the treatment of hypertension.