Indole Alkaloids Inhibiting Neural Stem Cell from Uncaria rhynchophylla

Uncaria rhynchophylla is commonly recognized as a traditional treatment for dizziness, cerebrovascular diseases, and nervous disorders in China. Previously, the neuro-protective activities of the alkaloids from U. rhynchophylla were intensively reported. In current work, three new indole alkaloids ( 1–3 ), identified as geissoschizic acid ( 1 ), geissoschizic acid N 4 -oxide ( 2 ), and 3 β -sitsirikine N 4 -oxide ( 3 ), as well as 26 known analogues were isolated from U. rhynchophylla . However, in the neural stem cells (NSCs) proliferation assay for all isolated compounds, geissoschizic acid ( 1 ), geissoschizic acid N 4 -oxide ( 2 ), isocorynoxeine ( 6 ), isorhynchophylline ( 7 ), (4 S )-akuammigine N -oxide ( 8 ), and (4 S )-rhynchophylline N -oxide ( 10 ) showed unexpected inhibitory activities at 10 μM. Unlike previous neuro-protective reports, as a warning or caution, our finding showcased a clue for possible NSCs toxicity and the neural lesions risk of U. rhynchophylla , while the structure–activity relationships of the isolated compounds were discussed also.