Abstract

DO THE SCELETIUM TORTUOSUM PLANT ALKALOIDS, MESEMBRINE AND MESEMBRENONE HAVE AN EFFECT ON N-METHYL-D-ASPARTATE RECEPTOR?

Yuying Ye, Yangwen Luo, Srinivas Patnala, Isadore Kanfer, Luchen Shan*, Pei Yu*

ABSTRACT

Sceletium tortuosum is a South African herb, medicinally used as a mood elevator by the native people in the Western and Karoo regions of the country. Sceletium plant is reported for its antidepressant and antianxiety effects attributed to its alkaloidal components - mainly mesembrine-type alkaloidal structures. Among them mesembrine and mesembrenone were reported to be PDE4 and 5-HT transporter inhibitors. Although these effects contributed to the antidepressant-like activity, it is still possible that these two alkaloids or other constituents in Sceletium tortuosum may act on other targets such as the N-methyl- D-aspartate receptor (NMDAR) to exert rapid action. Therefore, it is necessary to study the effect of Sceletium tortuosum extract and its alkaloids on NMDAR which contribute to the neuropharmacological activities. This work aimed to explain whether Sceletium tortuosum could affect the activity of NMDAR to exert its rapid antidepressant-like activity, especially the effect of mesembrine and mesembrenone. The extracts of Sceletium tortuosum and its two main compounds, mesembrine and mesembrenone, were prepared. The whole cell patch clamp recording experiments were performed to test their inhibitory effect on NMDAR. The results showed that both its extract and main alkaloids, mesembrine and mesembrenone have caused a slight inhibition on NMDAR, which may partially contribute to the pharmacological activities of Sceletium tortuosum.

Keywords: Sceletium tortuosum;Mesembrine; Mesembrenone; N-methyl-D-aspartate receptors; Whole-cell patch clamp; Hippocampus neurons; Molecular Docking.