title: Modulation of glucocorticoid, mineralocorticoid and androgen production in H295 cells by Trimesemine™, a mesembrine-rich Sceletium extract.
abstract: BACKGROUND
  Stress-related illnesses rate among the most prevalent non-fatal diseases globally. With the global trend for consumer bias towards natural medicine, the Sceletium plant has become more prominent in the field of natural products. Although potentially useful effects of Sceletium tortuosum on the central nervous system have been reported, limited data is available on effects of the plant in the peripheral compartment.
  
  
  OBJECTIVE
  The current study aimed to elucidate the effect(s) of a Sceletium extract (TRI) rich in mesembrine (1% of plant extract w/w), on adrenal steroid biosynthesis.
  
  
  METHODS
  Steroidogenesis was assessed basally and in response to stimuli (forskolin, angiotensin II, KCl), in human adrenocortical carcinoma cells (H295R). Steroid hormone levels were assessed using UPLC-MS/MS. UPLC-MS analyses of TRI identified major alkaloids Δ7-mesembrenone, mesembrenone and mesembrine.
  
  
  RESULTS
  Highest dose TRI treatment (1 mg/ml, 34.5 μM mesembrine) increased pregnenolone and decreased 16-hydroxyprogesterone levels (both P<0.00001) in forskolin-stimulated conditions only, suggesting CYP17 enzyme inhibition. This led to significant inhibition of forskolin-associated increases in cortisol levels at the highest dose (P<0.001) and basal cortisol levels across all doses (P<0.0001). Independently of forskolin, TRI inhibited androstenedione and testosterone production across all doses (both P<0.00001), suggesting inhibition of 3βHSD and 17βHSD respectively. TRI decreased both the angiotensin II- (P<0.05) and forskolin-induced (P<0.0001) increases in aldosterone production.
  
  
  CONCLUSIONS
  Our data suggest potentially beneficial effects of TRI in the context of stress and hypertension. These should be further investigated in a whole organism model, while the effects on the androgenic pathway should also be further elucidated.
authors.affiliation: Dept Biochemistry, Stellenbosch University, South Africa. Electronic address: acswart@sun.ac.za.
authors.forename: A C
authors.initials: AC
authors.lastname: Swart
authors.affiliation: Dept Physiological Sciences, Stellenbosch University, South Africa. Electronic address: csmith@sun.ac.za.
authors.forename: C
authors.initials: C
authors.lastname: Smith
mesh_terms: D000728:Androgens / Q000378:metabolism*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D035723:Mesembryanthemum / Q000737:chemistry*; D008901:Mineralocorticoids / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal
chemical_list: D000728:Androgens; D005938:Glucocorticoids; D026121:Indole Alkaloids; D008901:Mineralocorticoids; D010936:Plant Extracts; C011300:mesembrine
keywords: Adrenal steroidogenesis; Alkaloid; Anxiolytic; Cortisol; Cytochrome p450; Endocrine disrupting compound; Hypertension; Sceletium tortuosum; Stress