Ion-Channel Activity of Characteristic Alkaloids From Uncaria rhynchophylla.

Eleven characteristic monoterpenoid indole alkaloids from Uncaria rhynchophylla were isolated, structurally assigned, and evaluated in parallel for inhibitory effects on human Nav1.7, Nav1.5, Cav3.1, and Kv1.5 channels using whole-cell patch-clamp recordings. Nav1.7 and Nav1.5 showed the broadest responses, with active inhibitors displaying micromolar IC50 values against the two sodium channels. Corynanthe-type alkaloids were the main contributors to Cav3.1 inhibition, whereas Kv1.5 was less sensitive and responded mainly to rhynchophylline and isorhynchophylline. The observed channel preferences were associated with alkaloid chemotype and structural features. This comparative analysis reveals differential activity across the four ion channels examined and provides a basis for further electrophysiological and mechanistic studies.