Inhibition of type 1 and type 2 5alpha-reductase activity by free fatty acids, active ingredients of Permixon
- PMID: 12477490
- DOI: 10.1016/s0960-0760(02)00187-5
Inhibition of type 1 and type 2 5alpha-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 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.
Similar articles
-
Pharmacologically relevant receptor binding characteristics and 5alpha-reductase inhibitory activity of free Fatty acids contained in saw palmetto extract.Biol Pharm Bull. 2009 Apr;32(4):646-50. doi: 10.1248/bpb.32.646. Biol Pharm Bull. 2009. PMID: 19336899
-
Effects of long-term treatment with Serenoa repens (Permixon) on the concentrations and regional distribution of androgens and epidermal growth factor in benign prostatic hyperplasia.Prostate. 1998 Oct 1;37(2):77-83. doi: 10.1002/(sici)1097-0045(19981001)37:2<77::aid-pros3>3.0.co;2-i. Prostate. 1998. PMID: 9759701
-
Enzyme assay for 5alpha-reductase type 2 activity in the presence of 5alpha-reductase type 1 activity in rat testis.J Steroid Biochem Mol Biol. 2000 Dec 1;75(1):75-82. doi: 10.1016/s0960-0760(00)00139-4. J Steroid Biochem Mol Biol. 2000. PMID: 11179911
-
Type 1 and type 2 5alpha-reductase expression in the development and progression of prostate cancer.Eur Urol. 2008 Feb;53(2):244-52. doi: 10.1016/j.eururo.2007.10.052. Epub 2007 Nov 5. Eur Urol. 2008. PMID: 18006217 Review.
-
Serenoa repens (Permixon). A review of its pharmacology and therapeutic efficacy in benign prostatic hyperplasia.Drugs Aging. 1996 Nov;9(5):379-95. doi: 10.2165/00002512-199609050-00008. Drugs Aging. 1996. PMID: 8922564 Review.
Cited by 17 articles
-
Use of saw palmetto (Serenoa repens) extract for benign prostatic hyperplasia.Food Sci Biotechnol. 2019 Apr 17;28(6):1599-1606. doi: 10.1007/s10068-019-00605-9. eCollection 2019 Dec. Food Sci Biotechnol. 2019. PMID: 31807332 Free PMC article. Review.
-
Beneficial effects of pumpkin seed oil as a topical hair growth promoting agent in a mice model.Avicenna J Phytomed. 2019 Nov-Dec;9(6):499-504. doi: 10.22038/AJP.2019.13463. Avicenna J Phytomed. 2019. PMID: 31763209 Free PMC article.
-
Hypothesis on Serenoa repens (Bartram) small extract inhibition of prostatic 5α-reductase through an in silico approach on 5β-reductase x-ray structure.PeerJ. 2016 Nov 22;4:e2698. doi: 10.7717/peerj.2698. eCollection 2016. PeerJ. 2016. PMID: 27904805 Free PMC article.
-
Effect of Saw Palmetto Supplements on Androgen-Sensitive LNCaP Human Prostate Cancer Cell Number and Syrian Hamster Flank Organ Growth.Evid Based Complement Alternat Med. 2016;2016:8135135. doi: 10.1155/2016/8135135. Epub 2016 May 4. Evid Based Complement Alternat Med. 2016. PMID: 27272436 Free PMC article.
-
Identification of a new plant extract for androgenic alopecia treatment using a non-radioactive human hair dermal papilla cell-based assay.BMC Complement Altern Med. 2016 Jan 21;16:18. doi: 10.1186/s12906-016-1004-5. BMC Complement Altern Med. 2016. PMID: 26796631 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
-
Full Text Sources
-
Other Literature Sources