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

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概要

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• Saw palmetto extract (SPE), used widely for the treatment of benign prostatic hyperplasia (BPH) has been shown to bind α_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 (α_1-adrenergic, muscarinic and 1,4-DHP) receptors. The fatty acids inhibited specific [^3H] prazosin binding in rat brain in a concentration-dependent manner with IC_<50> values of 23.8 to 136μg/ml, and specific (+)-[^3H]PN 200-110 binding with IC_<50> values of 24.5 to 79.5μg/ml. Also, lauric acid, oleic acid, myristic acid and linoleic acid inhibited specific [^3H]N-methylscopolamine ([^3H]NMS) binding in rat brain with IC_<50> values of 56.4 to 169μg/ml. Palmitic acid had no effect on specific [^3H]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 [^3H]prazosin, [^3H]NMS and (+)-[^3H]PN 200-110. The results suggest that lauric acid and oleic acid bind noncompetitively to α_1-adrenergic, muscarinic and 1,4-DHP calcium channel antagonist receptors. We developed a novel and convenient method of determining 5α-reductase activity using LC/MS. With this method, SPE was shown to inhibit 5α-reductase activity in rat liver with an IC_<50> of 101μg/ml. Similarly, all the fatty acids except palmitic acid inhibited 5α-reductase activity, with IC_<50> values of 42.1 to 67.6μg/ml. In conclusion, lauric acid, oleic acid, myristic acid, and linoleic acid, major constituents of SPE, exerted binding activities of α_1-adrenergic, muscarinic and 1,4-DHP receptors and inhibited 5α-reductase activity.

• 2009-04-01

著者

• Ito Yoshihiko

  Department of Molecular Science and Technology, Doshisha University

• 山田 幸子

  日本大学医学部生化学分野

• 山田 愼一

  トーアエイヨー株式会社

• Oyunzul Luvsandorj

  Department Of Pharmacokinetics And Pharmacodynamics And Global Center Of Excellence (coe) Program Sc

• Oyunzul Luvsandorj

  静岡県立大学 グローバルcoeプログラム

• ABE Masayuki

  Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, S

• OKI-FUJINO Tomomi

  Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, S

• YAMADA Shizuo

  Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, S

• Yamada Shizuo

  Departments Of Pharmacokinetics And Pharmacodynamics Pharmacognosy And Global Center Of Excellence (

• Oki-fujino Tomomi

  Department Of Pharmacokinetics And Pharmacodynamics And Global Center Of Excellence (coe) Program Sc

• Yamada S

  School Of Pharmaceutical Sciences And Coe21 University Of Shizuoka

• Yamada Shizuo

  Department Of Pharmacokinetics And Pharmacodynamics And Global Center Of Excellence (coe) And Clinic

• Yamada S

  Department Of Biopharmacy University Of Shizuoka School Of Pharmaceutical Sciences

• Ito Yoshihiko

  Dep. Of Pharmacokinetics And Pharmacodynamics And Global Center Of Excellence (coe) Program School O

• Abe Masayuki

  Departments Of Pharmacokinetics And Pharmacodynamics Pharmacognosy And Global Center Of Excellence (

• Yamada Shizuo

  Department Of Pharmacokinetics And Pharmacodynamics And Global Coe Program School Of Pharmaceutical

• Yamada Shizuo

  Department Of Biophamacy School Of Pharmaceutical Sciences University Of Shizuoka

• Abe Masayuki

  Drug Formulation Research Laboratories Pharmaceutical Research Center Kyowa Hakko Kogyo Co.. Ltd.

• Ito Yoshihiko

  Department Of Mathematics Faculty Of Education Kumamoto University

• Abe Masayuki

  Department Of Electrical Engineering Faculty Of Engineering Science Osaka University

• Abe Masayuki

  Department Of Applied Biological Chemistry Faculty Of Agriculture Tohoku University

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