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

Abstract In different cell systems, the lipido-sterolic extract of Serenoa repens (LSESr, Permixon ® ) inhibits both type 1 and type 2 5α-reductase activity (5αR1 and 5αR2). 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 5αR1 or 5αR2 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 (5αR2) and pH 7.4 (5αR1) with 1 or 3 nM 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 5αR1 and 5αR2 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 5αR1 or 5αR2 inhibition has been found. Long unsaturated chains (oleic and linolenic) were active (IC 50 =4±2 and 13±3 μg/ml, respectively) on 5αR1 but to a much lesser extent (IC 50 >100 and 35±21 μg/ml, respectively) on 5αR2. Palmitic and stearic acids were inactive on the two isoforms. Lauric acid was active on 5αR1 (IC 50 =17±3 μg/ml) and 5αR2 (IC 50 =19±9 μg/ml). The inhibitory activity of myristic acid was evaluated on 5αR2 only and found active on this isoform (IC 50 =4±2 μg/ml). The dual inhibitory activity of LSESr on 5α-reductase type 1 and type 2 can be attributed to its high content in free fatty acids.