Biochanin A

Biochanin A is a naturally occurring fatty acid amide hydrolase (FAAH) inhibitor, which inhibits FAAH with IC₅₀s of 1.8, 1.4 and 2.4 μM for mouse, rat, and human FAAH, respectively. IC50 & Target:IC50: 1.8 μM (mouse FAAH), 1.4 μM (rat FAAH), 2.4 μM (human FAAH)^[1] In Vitro: Biochanin A inhibits the hydrolysis of 0.5 μM AEA by mouse, rat and human FAAH with IC₅₀ s of 1.8, 1.4 and 2.4 μM respectively. FAAH is inhibited by Biochanin A with a pIC₅₀ value of 6.21±0.02, corresponding to an IC₅₀ value of 0.62 μM. Biochanin A produces significant inhibition of the URB597-sensitive tritium retention at high nanomolar-low micromolar concentrations. Experiments are run with human FAAH and 0.5 μM [³H]AEA with assay conditions giving these higher utilization rates, the activity is still inhibited by Biochanin A, Genistein, Formononetin and Daidzein in the low micromolar range (IC₅₀s of 6.0, 8.4, 12 and 30 μM, respectively)^[1]. In Vivo: Biochanin A is tested at doses of 30, 100 and 300 μg. The highest dose also reduced formalin-induced ERK phosphorylation in a manner antagonized by AM251. Thus, Biochanin A behaved like URB597 after local administration to the paw. In anaesthetized mice, URB597 (30 μg i.pl.) and Biochanin A (100 μg i.pl.) both inhibit the spinal phosphorylation of extracellular signal-regulated kinase produced by the intraplantar injection of formalin. The effects of both compounds are significantly reduced by the CB1 receptor antagonist/inverse agonist AM251 (30 μg i.pl.). Biochanin A (15 mg/k i.v.) does not increase brain AEA concentrations, but produces a modest potentiation of the effects of 10 mg/kg i.v. AEA in the tetrad test. Biochanin A (15 mg/kg i.v.) is without effects on its own, but significantly potentiates the effects of AEA (10 mg/kg i.v.)^[1].