Pharmacologically Relevant Receptor Binding Characteristics and 5α-Reductase Inhibitory Activity of Free Fatty Acids Contained in Saw Palmetto Extract

Saw palmetto extract (SPE), used widely for the treatment of benign prostatic hyperplasia (BPH) has been shown to bind alpha(1)-adrenergic, muscarinic and 1,4-dihydropyridine (1,4-DHP) calcium channel antagonist receptors. Major constituents of SPE are lauric acid, oleic acid, myristic acid, palmitic acid and linoleic acid. The aim of this study was to investigate binding affinities of these fatty acids for pharmacologically relevant (alpha(1)-adrenergic, musearinic and 1,4-DHP) receptors. The fatty acids inhibited specific [H-3]prazosin binding in rat brain in a concentration-dependent manner with IC50 values of 23.8 to 136 mu g/ml, and Specific (+)-[(3)Hi]PN 200-110 binding with IC50 values of 24.5 to 79.5 mu g/ml. Also, lauric acid, oleic acid, myristic acid and linoleic acid inhibited specific [H-3]N-methylscopolamine ([H-3]NMS) binding in rat brain with IC50 values of 56.4 to 169 mu g/ml. Palmitic acid had no effect on specific [H-3]NMS binding. The affinity of oleic acid, myristic acid and linoleic acid for each receptor was greater than the affinity of SPE. Scatchard analysis revealed that oleic acid and lauric acid caused a significant decrease in the maximal number of binding sites (B-max) for [H-3]prazosin, [H-3]NMS and (+)-[H-3]PN 200-110. The results suggest that lauric acid and oleic acid bind noncompetitively to alpha(1)-adrenergic, muscarinic and 1,4-DHP calcium channel antagonist receptors. We developed a novel and convenient method of determining 5 alpha-reductase activity using LC/MS. With this method, SPE was shown to inhibit 5a-reductase activity in rat liver with an IC50 of 101 mu g/ml. Similarly, all the fatty acids except palmitic acid inhibited 5a-reductase activity, with IC50 values of 42.1 to 67.6 mu g/ml. In conclusion, lauric acid, oleic acid, myristic acid, and linoleic acid, major constituents of SPE, exerted binding activities of alpha(1)-adrenergic, muscarinic and 1,4-DHP receptors and inhibited 5 alpha-reductase activity.