Intestinal-targeted medicine-food homology ACE-inhibitory peptide microcapsules ameliorate hypertension in an L-NAME-induced gestational rat model via renin-angiotensin system modulation.

To develop intestinal-targeted microcapsules combining a medicine-food homology (MFH) complex with the ACE-inhibitory peptide IPP to enhance stability, achieve controlled release, and improve anti-hypertensive efficacy in an L-NAME-induced gestational hypertension rat model. Formulations were optimized by adjusting the complex-to-ACEIP ratio. Encapsulation efficiency, morphology, stability, and in vitro digestion were evaluated. Anti-hypertensive effects were assessed in L-NAME-treated pregnant rats by monitoring blood pressure, urinary protein, and renin-angiotensin system (RAS) biomarkers. The optimal 1:2 ratio showed the highest ACE-inhibitory activity. Spray-dried microcapsules reached 63.37% encapsulation efficiency, uniform morphology, and improved gastrointestinal stability. In vitro digestion showed intestinal-preferential release. In vivo, microcapsules significantly reduced L-NAME-induced hypertension and proteinuria, lowered angiotensin II, decreased ACE expression, and increased ACE2 levels. These microcapsules demonstrate enhanced stability, intestinal targeting, and strong RAS-modulating activity, effectively improving L-NAME-induced pregnancy hypertension and showing potential as a safe functional food ingredient for gestational hypertension management.