Identification of oligopeptide components derived from Pseudostellaria heterophylla and its hypoglycemic effects in streptozotocin-induce type 2 diabetes mice.

BACKGROUND

Low molecular weight oligopeptides have attracted extensive attention in peptide-based diabetes treatment due to their high selectivity, low toxicity, reduced immunogenicity, and favorable therapeutic effect. Pseudostellaria heterophylla (P. heterophylla), a traditional Chinese medicinal herb, contains bioactive oligopeptides whose hypoglycemic effects have not been previously characterized.

OBJECTIVE

This study aimed to comprehensively characterize the oligopeptide compositions in P. heterophylla and evaluate their antidiabetic effects in type 2 diabetes mellitus (T2DM).

METHODS

Eight types of macroporous resins were screened for their capacity to enrich oligopeptides from P. heterophylla. The oligopeptide-enriched fraction was subsequently characterized using ultra-high pressure liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). The oligopeptide-enriched fraction was administered via oral gavage to a streptozotocin (STZ)-induced T2DM mouse model, and its effects on glucose metabolism, lipid regulation, inflammatory markers, and liver function were analyzed.

RESULTS

D101 resin was selected as optimal based on adsorption/desorption performance. A total of 57 oligopeptide components were identified, including 21 cyclic and 36 linear peptides, with 9 cyclic and 34 linear peptides being novel. The oligopeptide-enriched fraction significantly alleviated diabetic symptoms, reduced fasting blood glucose, improved glucose tolerance, decreased hepatic coefficient and lipid deposition, and modulated serum lipid profiles. It also elevated serum insulin and suppressed pro-inflammatory factors.

CONCLUSION

This study was the first to demonstrate that oligopeptides from P. heterophylla exhibited potent hypoglycemic and metabolic regulatory effects in STZ-induced diabetic mice, providing a scientific basis for further research on P. heterophylla-derived oligopeptides as potential therapeutic agents in the management of T2DM.