Chemical characterization and DPP-IV inhibitory activity evaluation of tripeptides from Gynura divaricata (L.) DC

Gynura divaricata (L.) DC. (GD), a herbal medicine, has been used for the prevention and treatment of hyperglycemia in China. However, hypoglycemic ingredients within GD have not yet been well studied.

The aim of this study was to explore undiscovered compounds with dipeptidyl peptidase IV (DPP-IV) inhibitory activity within GD.

A four-step strategy was developed to explore undiscovered DPP-IV inhibitors within GD. First, the components were preliminarily characterized using UHPLC-HRMS combined with a library search. Second, preliminarily characterized compounds were searched for potential bioactivity. Third, a mixture of these preliminarily characterized compounds was isolated and thoroughly characterized based on fragmentation patterns associated with molecular networking. Fourth, the activities of these compounds were verified using DPP-IV inhibitory assay and molecular docking.

Diprotin A, a tripeptide inhibitor against DPP-IV, was identified. Thereafter, a mixture of twenty-five diprotin A analogs was isolated and characterized, which exhibited IC₅₀ of 0.40 mg/mL for DPP-IV. Molecular docking results also confirmed the interactions between the tripeptide analogs and DPP-IV mainly via H-bonds and hydrophobic interactions.

This is the first report of DPP-IV inhibitors within GD. These findings demonstrate that the extract of GD might be beneficial for the treatment of type 2 diabetes mellitus, and is expected to promote further development and utilization of GD in herbal medicine.