Chemical components from Uncaria gambir (W.Hunter) Roxb. and their preliminary bioactivities in CDC25B phosphatase inhibition and vasodilatory activity.

The endangered Uncaria gambir (W.Hunter) Roxb. (U. gambir) remains largely unexplored in chemical constituents and bioactivities. Therefore, fifteen compounds (1-15), comprising monoterpene indole alkaloids, lignans, flavonoids, triterpenoids, coumarins, and fatty acids, were isolated from this species. Their inhibitory effects against cell division cycle 25B (CDC25B) phosphatase and vasodilatory activities were then evaluated. Results showed that compound 1 (strictosamide) exhibited a notable inhibitory effect on CDC25B phosphatase, with the IC50 value of 5.4 μM, comparable to the positive control (Na3VO4). Compound 3 (3α-dihydrocadambine) effectively revealed strong vasodilatory activity with EC50 values of 2.4 μM and 2.1 μM, respectively, similar levels comparable to the positive control (verapamil). Interestingly, these activities of compounds 1 and 3 were evaluated for the first time in this work. Moreover, network pharmacology and molecular docking predicted compound 1 to correlate with the p53-Hippo-TGF-β antitumor signalling pathway and compound 3 with the cAMP/cGMP-PKG cardiovascular signalling pathway. This work provides preliminary experimental data for the development of potential lead compounds from U. gambir.