Gut microbiota-derived butyrate contributes to baicalin-induced attenuation of hypertensive vascular remodeling via adventitial immunity

Background Baicalin shows potent vasculoprotective effects against hypertension despite poor oral bioavailability. We investigated whether gut microbiota modulation contributes to the systemic vasculoprotective effects of orally administered baicalin. Methods We utilized an Angiotensin II-induced hypertensive mouse model, employing broad-spectrum antibiotics, 16S rRNA sequencing, metabolomics, and in vitro co-culture assays to map the gut-immune-vascular axis. Results Oral Baicalin significantly attenuated Ang II-induced blood pressure elevation and improved the intestinal barrier integrity. Antibiotic-induced microbiota depletion substantially weakened these protective effects, supporting a major microbiota contribution under the present experimental conditions. Baicalin reshaped the gut microbial community, enriched SCFA-supporting taxa, and restored a putative butyrate-associated microbial signature, enriching Akkermansia and Lactobacillus accompanied by increased cecal butyrate levels. Exogenous sodium butyrate recapitulated several major protective features of Baicalin treatment, including expansion of Foxp3+ regulatory T cells in mesenteric lymph nodes. These immune changes were accompanied by increased Foxp3+ regulatory immune-cell accumulation in the aortic adventitia. In vitro , butyrate-licensed Tregs suppressed Ang II-induced vascular smooth muscle cell (VSMC) proliferative responses, at least partly through IL-10-mediated inhibition of MAPK/ERK signalling. Conclusion Baicalin alleviates Ang II-associated vascular remodelling, at least in part, by reprogramming gut microbial ecology, increasing luminal butyrate availability, promoting regulatory immune responses, and suppressing VSMC proliferative signalling.