Biochanin A, a naturally occurring inhibitor of fatty acid amide hydrolase

L. Thors, J. J. Burston, B. J. Alter, M. K. McKinney, B. F. Cravatt, Ruth Alexandra Ross, Roger Guy Pertwee, R. W. Gereau, J. L. Wiley, C. J. Fowler

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background and purpose:

Inhibitors of fatty acid amide hydrolase (FAAH), the enzyme responsible for the metabolism of the endogenous cannabinoid (CB) receptor ligand anandamide (AEA), are effective in a number of animal models of pain. Here, we investigated a series of isoflavones with respect to their abilities to inhibit FAAH.

Experimental approach:

In vitro assays of FAAH activity and affinity for CB receptors were used to characterize key compounds. In vivo assays used were biochemical responses to formalin in anaesthetized mice and the 'tetrad' test for central CB receptor activation.

Key results:

Of the compounds tested, biochanin A was adjudged to be the most promising. Biochanin A inhibited the hydrolysis of 0.5 mu M AEA by mouse, rat and human FAAH with IC50 values of 1.8, 1.4 and 2.4 mu M respectively. The compound did not interact to any major extent with CB1 or CB2 receptors, nor with FAAH-2. In anaesthetized mice, URB597 (30 mu g i.pl.) and biochanin A (100 mu g i.pl.) both inhibited the spinal phosphorylation of extracellular signal-regulated kinase produced by the intraplantar injection of formalin. The effects of both compounds were significantly reduced by the CB1 receptor antagonist/inverse agonist AM251 (30 mu g i.pl.). Biochanin A (15 mg center dot kg-1 i.v.) did not increase brain AEA concentrations, but produced a modest potentiation of the effects of 10 mg center dot kg-1 i.v. AEA in the tetrad test.

Conclusions and implications:

It is concluded that biochanin A, in addition to its other biochemical properties, inhibits FAAH both in vitro and peripherally in vivo.

This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476-5381.2010.00831.x.

Original languageEnglish
Pages (from-to)549-560
Number of pages12
JournalBritish Journal of Pharmacology
Volume160
Issue number3
DOIs
Publication statusPublished - Jun 2010

Keywords

  • fatty acid amide hydrolase
  • pain
  • cannabinoid
  • isoflavones
  • biochanin A
  • anandamide
  • clover trifolium-pratense
  • vanilloid TRPV1 receptors
  • cannabinoid receptors
  • inflammatory pain
  • anesthetized rats
  • neuropathic pain
  • spinal neurons
  • PPAR-alpha
  • mice

Cite this

Thors, L., Burston, J. J., Alter, B. J., McKinney, M. K., Cravatt, B. F., Ross, R. A., ... Fowler, C. J. (2010). Biochanin A, a naturally occurring inhibitor of fatty acid amide hydrolase. British Journal of Pharmacology, 160(3), 549-560. https://doi.org/10.1111/j.1476-5381.2010.00716.x

Biochanin A, a naturally occurring inhibitor of fatty acid amide hydrolase. / Thors, L.; Burston, J. J.; Alter, B. J.; McKinney, M. K.; Cravatt, B. F.; Ross, Ruth Alexandra; Pertwee, Roger Guy; Gereau, R. W.; Wiley, J. L.; Fowler, C. J.

In: British Journal of Pharmacology, Vol. 160, No. 3, 06.2010, p. 549-560.

Research output: Contribution to journalArticle

Thors, L, Burston, JJ, Alter, BJ, McKinney, MK, Cravatt, BF, Ross, RA, Pertwee, RG, Gereau, RW, Wiley, JL & Fowler, CJ 2010, 'Biochanin A, a naturally occurring inhibitor of fatty acid amide hydrolase', British Journal of Pharmacology, vol. 160, no. 3, pp. 549-560. https://doi.org/10.1111/j.1476-5381.2010.00716.x
Thors, L. ; Burston, J. J. ; Alter, B. J. ; McKinney, M. K. ; Cravatt, B. F. ; Ross, Ruth Alexandra ; Pertwee, Roger Guy ; Gereau, R. W. ; Wiley, J. L. ; Fowler, C. J. / Biochanin A, a naturally occurring inhibitor of fatty acid amide hydrolase. In: British Journal of Pharmacology. 2010 ; Vol. 160, No. 3. pp. 549-560.
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AU - Burston, J. J.

AU - Alter, B. J.

AU - McKinney, M. K.

AU - Cravatt, B. F.

AU - Ross, Ruth Alexandra

AU - Pertwee, Roger Guy

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AU - Wiley, J. L.

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KW - clover trifolium-pratense

KW - vanilloid TRPV1 receptors

KW - cannabinoid receptors

KW - inflammatory pain

KW - anesthetized rats

KW - neuropathic pain

KW - spinal neurons

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