Biological activities of the shrub Salsola tuberculatiformis Botsch.: contraceptive or stress alleviator?
Plants belonging to the genus Salsola (Family: Chenopodiaceae) are common in the arid and semiarid regions of our planet with no less than 69 different Salsola species found in Namibia and the Republic of South Africa. This genus is used as a traditional medicine and aqueous extracts of Salsola have been used by Bushmen women as an oral contraceptive. Ingestion of the Namibian shrub Salsola tuberculatiformis Botsch. by pregnant Karakul sheep leads to prolonged gestation and fetal post-maturity and, as a result, the pelts of the new-born karakul lambs are worthless. This initiated an investigation into the active agents in the plant, using the terminal enzyme in adrenal corticosteroidogenesis, cytochrome P450-dependent 11beta-hydroxylase (P450c11), as a bioassay. Although the active fraction, S2, was extremely labile, partial structure determination suggested the presence of synephrine and a highly reactive aziridine. Therefore a more stable analogue, 2-(4-acetoxyphenyl)2-chloro-N-methylethylammonium-chloride (compound A), was synthesised, which, like the active plant extracts, inhibited adrenal steroidogenesis and acted as a contraceptive. In addition, compound A was stabilised by interaction with steroid-binding globulins in plasma thus enhancing biological activity in vivo. These findings provided explanations for the complex biological effects of the shrub as well as a new insight into the mode of action of chemically labile plant products in vivo.
Swart
Pieter
P
Department of Biochemistry, University of Stellenbosch, Stellenbosch, South Africa. pswart@sun.ac.za
Swart
Amanda C
AC
Louw
Ann
A
van der Merwe
Kirsten J
KJ
D000085:Acetates / Q000737:chemistry; D000818:Animals; D001688:Biological Products / Q000494:pharmacology*; D029748:Caryophyllaceae / Q000378:metabolism*; D003270:Contraceptive Agents / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry; D005021:Ethylamines / Q000737:chemistry; D005260:Female; D008954:Models, Biological; D008956:Models, Chemical; D018384:Oxidative Stress; D010936:Plant Extracts / Q000494:pharmacology*; D010940:Plant Proteins / Q000737:chemistry*; D011487:Protein Conformation; D051381:Rats; D013252:Steroid 11-beta-Hydroxylase / Q000737:chemistry*; D013256:Steroids / Q000737:chemistry; D014439:Tyramine / Q000031:analogs & derivatives
C104564:2-(4-acetoxyphenyl)-2-chloro-N-methylethylamine; D000085:Acetates; D001688:Biological Products; D003270:Contraceptive Agents; D005021:Ethylamines; D010936:Plant Extracts; D010940:Plant Proteins; D013256:Steroids; D003577:Cytochrome P-450 Enzyme System; D013252:Steroid 11-beta-Hydroxylase; D014439:Tyramine