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• W4386385220 abstract "Sceletium tortuosum (L.) N.E.Br. (ST) is an alkaloid-rich succulent plant with various mechanisms of action that infer psychotropic effects. These actions correlate with clinical evidence suggesting efficacy in the treatment of depression and anxiety, in line with its use by indigenous populations. Its low side effect profile suggests potential of ST to improve the overall wellbeing and compliance of millions of patients that experience severe side effects and/or do not respond to current prescription medication. However, to elucidate specific physiological effects of ST extracts, it is necessary to first understand which of its constituents are the major contributors to beneficial effects demonstrated for ST in this context. To determine an anxiolytic- and antidepressant-like effective concentration of a ST extract by means of a dose response in zebrafish (ZF) larvae, and to assess relative contributions of equivalent concentrations of isolated alkaloids contained in the effective concentration(s). A dose response study employing a light-dark transition test (LDTT) was done in ZF larvae (<5 days post fertilization) to track locomotor activity in terms of anxiety-like (hyperlocomotion) and depression-like (hypolocomotion) behaviour. Larvae were treated for 1 h directly before the LDTT with escalating concentrations of a ST extract commercially known as Zembrin® (Zem) ranging from 0.25 to 500 μg/mL and compared to an untreated control group (n = 12 per treatment concentration). LDTT was repeated after 24 h to evaluate long-term exposure toxicity. The concentration that best attenuated hyperlocomotion during the dark phase following light-dark transition was identified as the anxiolytic-like concentration. This concentration, plus one higher and one lower concentration, were used for subsequent tests. The percentage content of each alkaloid (mesembrine, mesembrenone, mesembrenol, and mesembranol) in these concentrations were calculated and applied to additional larvae to identify the most effective anxiolytic-like alkaloid in the LDTT. To identify antidepressant-like therapeutic concentration and equivalent alkaloid concentration, the same treatment concentrations were tested in larvae (n = 12 per treatment concentration) pre-exposed to reserpine for 24 h. Depending on normality of data distribution, Brown-Forsythe and Welch, or Kruskal-Wallis ANOVA were used, with Dunnett or Dunn's multiple comparisons tests. Only the extreme concentration of Zem (500 μg/mL) elicited toxicity after treatment for 24 h. Zem 12.5 μg/mL was the most effective anxiolytic-like concentration as it significantly decreased locomotor activity (P = 0.05) in the LDTT. Low (5 μg/mL), optimal (12.5 μg/mL) and high (25 μg/mL) Zem concentrations, as well as treatment solutions of single alkaloids (mesembrine, mesembrenone, mesembranol and mesembrenol), prepared to contain equivalent concentrations of each major alkaloid contained within these three concentrations of Zem, were tested further. Only mesembrine concentrations equal to that contained within the optimal and high dose of Zem (12.5 and 25 μg/mL) showed significant anxiolytic-like effects (P < 0.05). Only the highest Zem concentration (25 μg/mL) reversed the effects of reserpine - indicating antidepressant-like properties (P < 0.05) - while isolated alkaloids failed to induce such effects when administered in isolation. Current data provide evidence of both anxiolytic- and antidepressant-like effect of whole extract of Zem, with relatively higher concentrations required to achieve antidepressant-like effect. Of all alkaloids assessed, only mesembrine contributed significantly to the anxiolytic-like effects of Zem. No alkaloid alone could be pinpointed as a contributor to the antidepressant-like activity observed for higher concentration Zem. This may be due to synergistic effects of the alkaloids or may be due to other components not tested here. Current data warrants further investigation into mechanisms of action, as well as potential synergy, of ST alkaloids in suitable mammalian in vivo models." @default.
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• W4386385220 date "2024-01-01" @default.
• W4386385220 modified "2023-09-27" @default.
• W4386385220 title "Sceletium tortuosum-derived mesembrine significantly contributes to the anxiolytic effect of Zembrin®, but its anti-depressant effect may require synergy of multiple plant constituents" @default.
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• W4386385220 doi "https://doi.org/10.1016/j.jep.2023.117113" @default.
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