GABA-enriched Lactobacillus buchneri XBMU-C1 fermentation broth lowers blood pressure in L-NAME-induced hypertensive rats via RAAS suppression and PI3K/Akt/eNOS activation.

γ-Aminobutyric acid (GABA)-producing lactic acid bacteria are promising natural alternatives for hypertension management. Here, we isolated a novel high GABA-yielding strain, Lactobacillus buchneri XBMU-C1 (1.45 g/L), from traditional homemade sauerkraut. The strain exhibited excellent tolerance to acid (83.6% survival at pH 3.0), bile salts (85.1% survival at 1 g/L after 4 h), and simulated gastrointestinal fluid (12.2% survival). In an Nω-Nitro-L-arginine methyl ester (L-NAME) induced hypertensive rat model, oral administration of XBMU-C1 fermentation broth for 6 weeks dose-dependently reduced mean arterial pressure (MAP), with the high dose (150 mg·kg-1·d-1) lowering MAP by 22.15 mmHg. Mechanistically, the fermentation broth significantly decreased serum levels of angiotensin-converting enzyme (ACE) and angiotensin II (Ang II), while increasing serum nitric oxide (NO) content. Western blot analysis revealed upregulated protein expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and endothelial nitric oxide synthase (eNOS) in vascular tissues. Histopathological examination showed that the fermentation broth alleviated hypertension-induced myocardial injury, vascular smooth muscle hyperplasia, and intestinal villus damage. Collectively, Lactobacillus buchneri XBMU-C1 fermentation broth exerts antihypertensive effects through dual modulation of renin-angiotensin-aldosterone system (RAAS) suppression and PI3K/Akt/eNOS-mediated NO enhancement, offering a safe and effective natural intervention for hypertension.