article · BMC Complementary Medicine and Therapies
Sceletium tortuosum is a Southern African indigenous plant known as kanna, used traditionally and commercially for its mood-elevating properties. Its major alkaloid, mesembrine, acts as a selective serotonin reuptake inhibitor (SSRI), a drug class linked to impaired bone mineralisation. This study evaluated whether aqueous and ethanolic extracts of the plant could counteract serotonin-induced suppression of bone formation using osteoblast-like cell models. While standard SSRIs disrupt bone mineral formation, extracts from Sceletium tortuosum promoted mineralisation in vitro and displayed potent intracellular and extracellular antioxidant activity. Analysis revealed that mesembrine and mesembrenone dominated the aqueous extract, though mesembrine alone only weakly induced mineralisation. The osteogenic effects appear to rely on combined interactions with serotonin receptors, transporters, and reactive oxygen species. Consequently, the plant extracts present potential therapeutic value as adjunct treatments to help mitigate osteoporosis risks linked with conventional antidepressants.
Common antidepressant treatments often carry adverse side effects, including impaired bone health and an increased risk of osteoporosis over long periods. Demonstrating that Sceletium tortuosum extracts support bone mineralisation alongside mood-altering properties indicates a route to safeguard skeletal integrity during depression therapies, combining traditional Southern African botanical knowledge with therapeutic safety research.
The findings point towards potential applications in pharmaceutical or nutraceutical development, particularly as adjunct therapies alongside antidepressants to protect bone health in patients at risk of osteoporosis. Target users would be clinicians, psychiatric patients, and supplement manufacturers. Because this research was conducted purely in vitro on cultured bone cells, the technology remains at an early laboratory stage and requires animal models and clinical testing before real-world therapeutic use.
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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.
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DOI: 10.1186/s12906-026-05540-x
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