In vitro simulated gastrointestinal digestion stability and in vivo antihypertensive effect of the peptide KYPHVF and its network pharmacology

Previous study showed KYPHVF has a high angiotensin-converting enzyme (ACE) inhibitory activity. This study aimed to further explore the in vitro simulated gastrointestinal digestion stability, in vivo antihypertensive, and network pharmacology of KYPHVF. Results showed that KYPHVF was stable during simulated gastrointestinal digestion in vitro. KYPHVF was absorbed in intact form by Caco-2 cell monolayer with a transport percentage of 2.00%, and KYPHVF was partially hydrolyzed to produce YPHVF and PHVF through the Caco-2 cell monolayer. The blood pressures of Spontaneous hypertensive rats (SHRs) decreased after the oral administration of KYPHVF, and KYPHVF might produce antihypertensive effect by lowering the ACE contents of serum and kidney in SHRs. Furthermore, the results of network pharmacology indicated that KYPHVF had 44 potential antihypertensive targets, showing multi-target and multi-pathway antihypertensive characteristics. Molecular docking results showed that KYPHVF had strong binding force and affinity with key antihypertensive targets.