Exploration of ACE inhibitory peptides from sea cucumber viscera with DPP-IV inhibitory activity: Virtual screening, characterization, and potential mechanism investigation.

Sea cucumber is a protein-rich food that has great potential to release bioactive compounds with diverse functionalities. Inhibition of angiotensin-converting enzyme (ACE) and dipeptidyl peptidase-IV (DPP-IV) using peptides has emerged as part of new therapeutic strategy for complementing treatment of hypertension and type 2 diabetes. The present study aimed to explore novel ACE inhibitory peptides with DPP-IV inhibitory activity from sea cucumber viscera hydrolysate combining virtual screen and molecular docking approaches. Four ACE inhibitory peptides WEPFP, GFPGLP, FPGGPP, and LPPGPFP were explored from the constructed peptide database, exhibiting ACE inhibitory activity by non-competitive or competitive action modes. GFPGLP displayed the strongest activity against DPP-IV through non-competitive pattern. Human umbilical vein cell fusion cells (EA. Hy926) and insulin-resistant-HepG2 (IR-HepG2) cell model demonstrated their potential hypoglycemic and hypotensive effects on cellular functions. Network pharmacological analysis subsequently suggested that GFPGLP might exert antihypertensive and antidiabetic activity trough regulation of multiple signal pathways and interactions with commonly core targets such as TGFB1, ACE, REN, CCL2, IGF1, and PPARG. These results uncover the development of novel ACE inhibitory peptides with DPP-IV inhibitory activity and the potential action mechanism, as well as explore peptides served as functional food ingredients for management of hypertension and diabetes.