Unlocking Probiotic Potential: Lactiplantibacillus plantarum Targets ACE to Mitigate High-Salt Diet-Induced Multiorgan Injury

Hypertension is a prevalent chronic disease related to multiorgan injury. Lactic acid bacteria (LAB) produce angiotensin-converting enzyme-inhibitory peptides (ACEIPs) to regulate blood pressure. This study aimed to screen LAB with high ACE inhibitory activity and investigate their protective effects against high-salt diet (HSD)-induced hypertension and organ injury. From diverse sample sources, Lactiplantibacillus plantarum T4-1 exhibited the highest ACE inhibitory activity (98%). Four highly active ACEIPs were identified via peptidomics analysis, molecular docking, and in vitro ACE inhibition assays. Among them, Peptide 1 showed the strongest inhibition (IC50 = 0.8622 μg/mL). Whole genome sequencing of Lactiplantibacillus plantarum T4-1 revealed related functional gene loci. Subsequently, animal experiments demonstrated that oral administration of T4-1 suspension significantly reduced mean arterial pressure by about 18 mmHg and mitigated multiorgan injury in HSD mice. This work enriches antihypertensive probiotic resources and provides theoretical support for developing functional food-derived ACEIPs.