Achyranthes bidentata alleviates hypertension alongside selective expansion of the relative abundance of Dubosiella and remodeling of arachidonic acid metabolism

Abstract Hypertension remains a major risk factor worldwide. The traditional Chinese medicine Achyranthes bidentata (Ab) regulates the gut microbiota, but how its anti-hypertensive activity relates to the gut microbiota and metabolism remains unclear. Here we show that Ab significantly lowers blood pressure and ameliorates renal injury in L-NAME/high-salt hypertensive mice, without significant changes in circulating inflammatory cytokines or aldosterone. High-throughput 16 S rRNA gene amplicon sequencing revealed significant treatment-driven community divergence that widened over time, whereas α-diversity based on the Shannon, Faith PD, and Observed-feature indices showed no significant difference after Ab treatment. Differential abundance and random-forest analyses identified Dubosiella and Lactobacillus as the principal Ab-enriched genera negatively correlated with blood pressure, with the relative abundance of Dubosiella expanding from 0.1% to 26.5%. Metabolomic profiling showed that Ab remodeled gut arachidonic acid metabolism, with elevated PGE2 p-acetamidophenyl ester. Network analysis associated Dubosiella abundance with arachidonic acid–related metabolites and lower blood pressure, and Procrustes analysis confirmed microbiota–metabolome concordance. In vitro, Ab promoted the growth and biofilm formation of Dubosiella newyorkensis DSM103457, supporting the Ab-associated increase in the relative abundance of Dubosiella . These data indicate that Ab acts as an anti-hypertensive herbal prebiotic whose effect is associated with an increase in the relative abundance of Dubosiella and with remodeling of arachidonic acid metabolism, providing correlative evidence for microbiota-targeted hypertension therapy.