Oleanolic acid acrylate elicits antidepressant-like effect mediated by 5-HT 1A receptor
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2015-07
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The development of new drugs for the treatment of depression is strategic to achieving clinical
needs of patients. This study evaluates antidepressant-like effect and neural mechanisms of four
oleanolic acid derivatives i.e. acrylate (D1), methacrylate (D2), methyl fumarate (D3) and ethyl
fumarate (D4). All derivatives were obtained by simple one-step esterification of oleanolic acid prior
to pharmacological screening in the forced swimming (FS) and open field (OF) tests. Pharmacological
tools like α-methyl-p-tyrosine (AMPT, catecholamine depletor), p-chlorophenylalanine (serotonin
depletor), prazosin (PRAZ, selective α1-receptor antagonist), WAY-100635 (selective serotonin
5-HT 1A receptor antagonist) as well as monoamine oxidase (MAO) and functional binding assays
were conducted to investigate possible neural mechanisms. In the FS test, D1 showed the most
promising antidepressant-like effect without eliciting locomotor incoordination. Unlike group of
mice pretreated with AMPT 100 mg/kg, PCPA 100 mg/kg or PRAZ 1 mg/kg, the effect of D1 was
attenuated by WAY-100635 0.3 mg/kg pretreatment. D1 demonstrated moderate inhibition of MAO-A
(IC 50 = 48.848 ± 1.935 μM), potency (pEC 50 = 6.1 ± 0.1) and intrinsic activity (E max = 26 ± 2.0%) on
5-HT 1A receptor. In conclusion, our findings showed antidepressant-like effect of D1 and possible
involvement of 5-HT 1A receptor.
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FAJEMIROYE, James O. et al. Oleanolic acid acrylate elicits antidepressant-like effect mediated by 5-HT1A receptor. Scientific Reports, Berlim, v. 2015, n. 11582, p. 1-12, July 2015.