An in silico approach to identifying the potential anti-diabetic, anti-hypertensive and anti-cancer bioactivities of peptides derived from the edible pupae of the eri silkworm, Samia ricini

As emerging sustainable food sources, edible insects are rich in proteins with considerable therapeutic potential. The fate of edible insect proteins during human gastrointestinal (GI) digestion and the nature of released peptides under physiological digestive conditions remain poorly characterized. Conventional bioactive peptide discovery relies on enzymatic hydrolysis followed by extensive in vitro and in vivo experimental validation, which is time and resource intensive. Consequently, in silico approaches and molecular docking study are increasingly employed in bioactive peptide discovery and structure-function relationships directly from peptide sequences. In this study, high-confidence with an average local confidence (ALC) ≥95%, de novo peptide sequences of Samia ricini pupae protein were filtered out for downstream in silico analysis. Bioactive potential of the sequences was predicted using PepRank score, while antioxidant potential, toxicity, and physicochemical properties were evaluated using AnOxPePred, ToxinPred, and ProtParam, respectively. Peptides were further subjected to simulated gastrointestinal (GI) digestion to mimic the fate of peptides in the human GI digestive system, which were subsequently screened in the BIOPEP-UWMTM database to identify previously reported and potentially novel bioactive peptides. Simulated GI digestion released  multifunctional bioactive peptides with predicted antioxidant, antihypertensive, antidiabetic, anti-obesity, and anticancer activities. Molecular docking analysis of selected putative novel peptides against key therapeutic targets, including Dipeptidyl peptidase-4 (3W2T), Angiotensin-converting enzyme (1R4L), and Cathepsin L (7Z3T) revealed that the peptides SGL, YR and VSW respectively bind within the active sites of the targets, acting as potential inhibitors. Overall, this study identifies S. ricini pupae as a promising source of bioactive peptides.