Hirsutanines H-O, monoterpene indole alkaloids from Uncaria hirsuta with neuroprotective effects

Abstract

Hirsutanines H-O (1-8), eight previously undescribed monoterpene indole alkaloids, along with five known analogues (9-13), were isolated from the stems and leaves of Uncaria hirsuta. Compounds 1-4 represent a rare subclass of 3-oxo-3,7-seco-oxindole alkaloids. The structures of 1-13 were elucidated by spectroscopic, computational, and chemical means. All the isolates were evaluated for their neuroprotective effects against sodium nitroprusside-induced damage in PC-12 cells. Among them, compounds 1, 4, and 9 exhibited pronounced activity, being comparable to that of the positive control, edaravone. Mechanistic studies revealed that 1, the most active compound, exerted its neuroprotective effect via attenuating oxidative stress.

Keywords: 3-Oxo-3,7-seco-oxindole alkaloids; Monoterpene indole alkaloids; N-oxide; Neuroprotective effect; PC-12 cells; Rubiaceae; Uncaria hirsuta.