Anti-diabetic compounds from Uvaria dulcis Dunal

Medicinal plants have long been a source of lead compounds for drug discovery. Among these, the Annonaceae family has gained recognition for its potential to yield novel compounds, particularly those that can be used in the development of drugs targeting chronic diseases like diabetes mellitus (DM). We employed various chromatographic methods to isolate bioactive compounds from the roots, leaves, and twigs of Uvaria dulcis Dunal. We used spectroscopic methods to determine the chemical structures of these compounds. We successfully identified twelve known compounds from various parts of U. dulcis: patchoulenon, polygochalcone, 2'3'-dihydroxy-4',6'-dimethoxydihydrochalcone, 2',3'-dihydroxy-4',6'-dimethoxychalcone, chrysin, techochrysin, 8-hydroxy-5,7-dimethoxyflavanone, pinocembrin, 3-farnesylindole, onysilin, cinchonain la, and cinchonain lb. Interestingly, cinchonain la and cinchonain lb exhibited more potent anti-α-glucosidase activity than acarbose (standard drug), with IC₅₀ values of 11.88 ± 1.41 μg/mL and 15.18 ± 1.19 μg/mL, respectively. Cinchonain la inhibited the DPP-IV enzyme, with IC₅₀ value lower than the standard compound (diprotin A) at 81.78 ± 1.42 μg/mL. While 2',3'-dihydroxy-4',6'-dimethoxychalcone show more potent inhibitory effect than standard drug with IC₅₀ value of 8.62 ± 1.19 μg/mL. Additionally, at a concentration of 10 μg/mL, cinchonain lb and 2',3'-dihydroxy-4',6'-dimethoxychalcone promoted glucose uptake in L6 myotubes cells to the same extent as 100 nM insulin. These findings suggest that cinchonain la, cinchonain lb, and 2',3'-dihydroxy-4',6'-dimethoxychalcone are the U. dulcis-derived bioactive compounds that hold promise as potential structures to use in the development of anti-diabetic drugs.