Mitigation of serotonin-caused suppression of osteoblast function by extracts of the psychoactive indigenous plant Sceletium tortuosum

Abstract

Abstract Background Sceletium tortuosum is an endemic plant in Southern Africa, traditionally used as kanna by the indigenous people and also exploited commercially due to its mood-elevating properties. Mesembrine, a major alkaloid from this plant, acts as a selective serotonin reuptake inhibitor (SSRI), a group of drugs commonly used in antidepressant therapy but with the undesirable side effect of impairing bone mineral formation. The aim of this study was to investigate the potential effects and mechanisms of extracts from this plant on mineralization. Methods Both aqueous and ethanolic extracts were prepared from S. tortuosum . Their effects on mineralization were studied using bone-forming SaOS-2 cells. In addition to the effects on cell viability and alkaline phosphatase (ALP) activity, the radical scavenging activity of the extracts was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2’,7’-dichlorodihydrofluorescein diacetate (H 2 DCF-DA) assays. The alkaloid composition was analyzed by liquid chromatography–mass spectrometry (LC-MS). Results It is shown that the S. tortuosum extracts, in contrast to SSRIs, have a significant mineralization-promoting activity in vitro. This result was obtained despite the fact that, as is characteristic for SSRIs, the transient attenuation of the serotonin-induced suppression of cell viability that occurs with increasing serotonin concentrations was inhibited in SaOS-2. The activity of ALP, a marker of differentiated osteoblasts, remained unchanged. It was found that the plant extracts exhibit a pronounced radical scavenging activity not only in the DPPH assay, but also intracellularly using the cell-permeant probe H 2 DCF-DA. The alkaloid fraction of the aqueous extract of S. tortuosum consists primarily of the two bioactive alkaloids mesembrine and mesembrenone. Mesembrine proved to be only a weak inducer of mineralization. Conclusions The results suggest that the observed osteogenic effects of S. tortuosum are due to a tuned interaction with signaling pathways involving serotonin receptors, serotonin transporters and reactive oxygen species. Due to its mineralization-promoting properties, we conclude that S. tortuosum is of potential interest for the long-term treatment of depressive disorders as an adjunct to antidepressant drugs that increase the risk of osteoporosis.