Accelerative effects of carbazole-type alkaloids from Murraya koenigii on neurite outgrowth and their derivative's in vivo study for spatial memory.

Abstract

Murraya koenigii is a medicinal plant that contains several carbazole-type alkaloids as its characteristic constituents. Blood-brain barrier permeable constituents of M. koenigii accelerated neurite outgrowth in PC-12 cells. Nine compounds were isolated from M. koenigii and their effects on neurite outgrowth were examined. Murrayamine-E (8) at 10 μM showed significant effect. Focusing on the carbazole skeleton, we synthesized derivatives to attenuate cytotoxicity. 9-Benzyl-9H-carbazol-4-ol (15) exhibited strong neurite outgrowth accelerative effect. In addition, the novel object recognition test and the Morris water maze test were performed to evaluate memory improvement of 15 in APdE9 mice. Compound 15 tended to improve spatial memory in the Morris water maze test. These results suggest that carbazole derivative 15 would be a seed compound for Alzheimer's disease drug.

• Authors: Mamiko Yano, Souichi Nakashima, Shiori Kasa, Seikou Nakamura, Kaneyasu Nishimura, Yoshimi Oda, Kazuyuki Takata, Hisashi Matsuda
• Journal: Journal of natural medicines (J Nat Med) Vol. 74 Issue 2 Pg. 448-455 (Mar 2020) ISSN: 1861-0293 [Electronic] Japan
• PMID: 31960209 (Publication Type: Journal Article)

Chemical References

• Alkaloids
• Carbazoles
• Plant Extracts
• carbazole

Topics

• Alkaloids (chemistry)
• Alzheimer Disease (drug therapy)
• Animals
• Carbazoles (chemistry)
• Female
• Mice
• Murraya (chemistry)
• Neuronal Outgrowth (drug effects)
• PC12 Cells
• Plant Extracts (chemistry)
• Plants, Medicinal (drug effects)
• Rats
• Spatial Memory (drug effects)