Bioactive chromatographic fractions from Uncaria sclerophylla (W.Hunter) Roxb. leaves on dipeptidyl peptidase-4 inhibition and antioxidant capacity, phytochemicals, and compound profiling using UPLC-ESI-QToF-MS/MS

Context: Uncaria sclerophylla (W.Hunter) Roxb., a traditional antidiabetic drug for Kalimantan people, has never been scientifically reported as an antidiabetic agent, especially in dipeptidyl peptidase-4 (DPP-4) inhibition and as an antioxidant. Aims: To identify the leaf's extract most active chromatographic fraction in DPP-4 inhibition and as an antioxidant and determine the compounds contained. Methods: Extraction was carried out using the four-grade maceration method, fractionation used column chromatography techniques, and bioassay used spectrofluorometric principles. Compound profiling was performed using liquid chromatography combined with electrospray ionization and quadrupole time-of-flight mass spectrometry (UPLC-ESI-QToF-MS/MS), and molecular docking was used to investigate interactions between major compounds and DPP-4. Results: This study highlights the potential of methanol leaf extract as an antidiabetic agent with a DPP-4 inhibition mechanism (IC50: 79.67 ± 2.95 µg/mL) and antioxidant mechanism with EC50 value of 9.50 ± 0.319 µg/mL (FRAP method) and 9.94 ± 0.1572 µg/mL (DPPH method). The methanol extract of the leaves has been proven to produce the best chromatographic fraction (FMet5) as a DPP-4 enzyme inhibitor agent, with an IC50 value of 50.71 ± 1.22 µg/mL, and as an antioxidant, with an EC50 value of 8.89 ± 0.1701 µg/mL (FRAP method) and 6.07 ± 0.125 µg/mL (DPPH method). UPLC-ESI-QToF-MS/MS profiling of the compounds in FMet5 revealed the presence of various alkaloid and flavonoid compounds like dehydrosilybin, 19-epi-3-isoajmalicine, procyanidin A2, cinchonain I b, maokonine, and cuscohygrine. Conclusions: Extracts and chromatographic fractions derived from the leaves of U. sclerophylla have potent antioxidant and DPP-4 inhibitory properties, indicating their potential as an antidiabetic agent with DPP-4 inhibition and antioxidant mechanisms.