Corn silk extract as a prebiotic exerts antihypertensive effects via gut microbiota modulation in hypertensive rats.

Corn silk extract (CSE), a traditional medicinal food rich in polysaccharides, flavonoids, and saponins, has been used as a natural antihypertensive agent, but its mechanism remains unclear. This study aimed to evaluate whether CSE can lower blood pressure through gut microbiota modulation. Spontaneously hypertensive rats received oral CSE for 4 weeks, followed by a 4-week drug-free observation. The treatment significantly reduced blood pressure, increased microbial diversity, decreased the Firmicutes/Bacteroidetes ratio, and enriched beneficial genera, such as Akkermansia and Lactobacillus. These changes were accompanied by reduced serum lipopolysaccharide and pro-inflammatory cytokines, elevated nitric oxide (NO) levels, and restored endothelial function. Permutational multivariate analysis of variance (PERMANOVA) and correlation analyses showed that microbiota and inflammatory markers were more strongly associated with blood pressure improvements than urinary indices. Structural equation modeling suggested a potential mechanistic pathway involving gut microbiota-inflammation-NO regulation. Importantly, fecal microbiota transplantation using post-treatment donor samples reproduced the antihypertensive and anti-inflammatory effects, confirming the microbiota's critical mediating role. These findings provide the first experimental evidence that CSE functions as a prebiotic to improve gut microbial balance and vascular health, offering a promising natural strategy for microbiota-targeted blood pressure control. IMPORTANCE: This study identifies corn silk extract (CSE) as a novel plant-derived prebiotic with antihypertensive effects mediated through gut microbiota modulation. Using a spontaneously hypertensive rat model, we demonstrated that CSE reshapes gut microbial composition, enhances microbial diversity, and promotes beneficial genera while reducing systemic inflammation and restoring nitric oxide (NO)-mediated vascular function. Importantly, fecal microbiota transplantation confirmed the causal role of gut microbiota in mediating these effects. These findings highlight a gut microbiota-inflammation-NO axis as a key pathway through which CSE regulates blood pressure. As a safe, accessible, and food-compatible intervention, CSE represents a promising strategy for non-pharmacological blood pressure management and broadens the application scope of prebiotics in cardiovascular health.