Inhibition of type 1 and type 2 5alpha-reductase activity by free fatty acids, active ingredients of Permixon

J Steroid Biochem Mol Biol. 2002 Oct;82(2-3):233-9. doi: 10.1016/s0960-0760(02)00187-5.

Abstract

In different cell systems, the lipido-sterolic extract of Serenoa repens (LSESr, Permixon inhibits both type 1 and type 2 5alpha-reductase activity (5alphaR1 and 5alphaR2). LSESr is mainly constituted of fatty acids (90+/-5%) essentially as free fatty acids (80%). Among these free fatty acids, the main components are oleic and lauric acids which represent 65% and linoleic and myristic acids 15%. To evaluate the inhibitory effect of the different components of LSESr on 5alphaR1 or 5alphaR2 activity, the corresponding type 1 and type 2 human genes have been cloned and expressed in the baculovirus-directed insect cell expression system Sf9. The cells were incubated at pH 5.5 (5alphaR2) and pH 7.4 (5alphaR1) with 1 or 3nM testosterone in presence or absence of various concentrations of LSESr or of its different components. Dihydrotestosterone formation was measured with an automatic system combining HPLC and an on-line radiodetector. The inhibition of 5alphaR1 and 5alphaR2 activity was only observed with free fatty acids: esterified fatty acids, alcohols as well as sterols assayed were inactive. A specificity of the fatty acids in 5alphaR1 or 5alphaR2 inhibition has been found. Long unsaturated chains (oleic and linolenic) were active (IC(50)=4+/-2 and 13+/-3 microg/ml, respectively) on 5alphaR1 but to a much lesser extent (IC(50)>100 and 35+/-21 microg/ml, respectively) on 5alphaR2. Palmitic and stearic acids were inactive on the two isoforms. Lauric acid was active on 5alphaR1 (IC(50)=17+/-3 microg/ml) and 5alphaR2 (IC(50)=19+/-9 microg/ml). The inhibitory activity of myristic acid was evaluated on 5alphaR2 only and found active on this isoform (IC(50)=4+/-2 microg/ml). The dual inhibitory activity of LSESr on 5alpha-reductase type 1 and type 2 can be attributed to its high content in free fatty acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / pharmacology*
  • Animals
  • Cell Line
  • Cholestenone 5 alpha-Reductase
  • Fatty Acids, Nonesterified / pharmacology*
  • Fatty Alcohols / pharmacology
  • Humans
  • Hypolipidemic Agents / pharmacology
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Oxidoreductases / antagonists & inhibitors*
  • Oxidoreductases / metabolism
  • Plant Extracts / pharmacology*
  • Serenoa
  • Sitosterols / pharmacology
  • Tocopherols / pharmacology

Substances

  • Androgen Antagonists
  • Fatty Acids, Nonesterified
  • Fatty Alcohols
  • Hypolipidemic Agents
  • Isoenzymes
  • Plant Extracts
  • Sitosterols
  • gamma-sitosterol
  • docosanol
  • Oxidoreductases
  • Cholestenone 5 alpha-Reductase
  • saw palmetto extract
  • Tocopherols