Identification of dipeptidyl peptidase-4 inhibitory compounds of Paederia foetida twigs by nuclear magnetic resonance metabolomics, in silico models, and liquid chromatography–mass spectrometry profiling

Authors

Dai Chuan Tan
Nur Kartinee Kassim
Intan Safinar Ismail
Siok Geok Chong

Abstract

Paederia foetida is a climber that has been traditionally used to treat various diseases, including diabetes. This study aims to investigate the dipeptidyl peptidase-4 (DPP-4) inhibitory activity of P. foetidaI/i> twig extracts and identification of the bioactive compounds by nuclear magnetic resonance (NMR) metabolomics, liquid chromatography–mass spectrometry (LC-MS), and in silico docking study. P. foetida twigs were extracted using organic solvents, namely hexane, chloroform, and methanol and submitted to DPP-4 inhibition assay. Ten milligram of each sample extract was diluted in 700 μL CDCl3 with 0.03% TMS and 1H-NMR spectra were recorded at 25°C on a JEOL FT-NMR spectrometer. The multivariate data analysis, similarity coefficients, and molecular docking study were performed in the study. In vitro assay revealed that the chloroform extract exhibited the highest DPP-4 inhibition (67.40%). The orthogonal partial least square model and LC-MS profiling revealed the presence of 13 metabolites including β-sitosterol, stigmasterol, α-terpineol, scopoletin, rutin, geniposide, apigenin, linarin, lupeol, campesterol, embelin, epifriedelanol, and ursolic acid. In silico molecular docking using the DPP-4 (PDB ID: 1 × 70) crystal structure showed linarin, epifriedelanol, stigmasterol, and ursolic acid (−10.5, −9.3,−9.1, and −8.8 kcal/mol) which were comparable to sitagliptin (−8.8 kcal/mol). This research provided valuable data on the potential biomarker’s antidiabetic inhibitors in P. foetida twigs, suggesting the potential of this plant for the management of diabetes.