New Monoterpenoid Indole Alkaloids as Potential Neuroprotective Agents from Uncaria hirsuta Haviland

Nineteen monoterpene indole alkaloids, including twelve new ones, were successfully isolated and identified from the stems and leaves of Uncaria hirsuta (Havil.). The planar structures were elucidated by nuclear magnetic resonance (NMR), high-resolution mass (HRMS), and ultraviolet (UV) analyses. The absolute configurations of new compounds were determined using electron circular dichroism calculations in conjunction with NMR calculations. The acetylcholinesterase inhibitory activity of the isolated compounds was evaluated in vitro. In further biological evaluation, the isolated compounds were evaluated for their neuroprotective effects on HT22 neuronal cells. Six compounds demonstrated significant protective activity. Their intracellular reactive oxygen species (ROS) levels were measured using the DCFH-DA fluorescent probe, which markedly attenuated glutamate-induced ROS accumulation. The results not only enrich the knowledge on the structural diversity of monoterpene indole alkaloids but also offer substantial evidence for further pharmacological exploration.