Fajemiroye James O, Galdino Pablinny M, Florentino Iziara F, Da Rocha Fabio F, Ghedini Paulo C, Polepally Prabhakar R, Zjawiony Jordan K, Costa Elson A
Department of Physiological Sciences, Federal University of Goiás, Goiânia-GO, Brazil
Department of Physiological Sciences, Federal University of Goiás, Goiânia-GO, Brazil.
J Psychopharmacol. 2014 Oct;28(10):923-34. doi: 10.1177/0269881114536789. Epub 2014 Jun 11.
Our study sought to evaluate the anxiolytic and antidepressant activities of oleanolic acid as well as the neural mechanisms involved. Animal models such as barbiturate sleep-induction, light-dark box, elevated plus maze, forced swimming test, tail suspension test and open field test were conducted. Male Albino Swiss mice were treated orally with vehicle 10 mL/kg, fluoxetine 20 mg/kg, imipramine 15 mg/kg, diazepam 1 mg/kg or oleanolic acid 5-40 mg/kg. Pretreatment (intraperitoneal) of animals with pentylenetetrazole (PTZ) 20 mg/kg, 1-(2-methoxyphenyl)-4-[4- (2-phthalimido) butyl]piperazine hydrobromide (NAN-190) 0.5 mg/kg, p-chlorophenylalanine methyl ester (PCPA) 100 mg/kg or α-methyl-p-tyrosine (AMPT) 100 mg/kg, WAY100635 (WAY) 0.3 mg/kg, prazosin (PRAZ) 1 mg/kg, yohimbine 2 mg/kg as well as monoamine oxidase assay and hippocampal brain-derived neurotrophic factor (BDNF) quantification were carried out. Oleanolic acid potentiated the hypnotic effect of barbiturate and demonstrated an anxiolytic effect in both the light-dark box and elevated plus maze. This effect was not reversed by PTZ. Acute and/or chronic oral treatment of mice with oleanolic acid (5-20 mg/kg) elicited an antidepressant effect in the forced swimming test and the tail suspension test without interfering with the locomotor activity. The antidepressant effect of oleanolic acid was attenuated by NAN-190, AMPT, PCPA, WAY and PRAZ. Although monoamine oxidase activity remained unaltered by oleanolic acid, chronic administration of oleanolic acid augmented hippocampal BDNF level. These findings demonstrate multiple mechanisms of the anxiolytic and antidepressant effect of oleanolic acid.
我们的研究旨在评估齐墩果酸的抗焦虑和抗抑郁活性以及相关的神经机制。进行了诸如巴比妥酸盐诱导睡眠、明暗箱、高架十字迷宫、强迫游泳试验、悬尾试验和旷场试验等动物模型实验。将雄性白化瑞士小鼠分别口服给予10 mL/kg的溶媒、20 mg/kg的氟西汀、15 mg/kg的丙咪嗪、1 mg/kg的地西泮或5 - 40 mg/kg的齐墩果酸。对动物进行腹腔注射预处理，分别给予20 mg/kg的戊四氮（PTZ）、0.5 mg/kg的1-(2-甲氧基苯基)-4-[4-(2-邻苯二甲酰亚胺)丁基]哌嗪氢溴酸盐（NAN-190）、100 mg/kg的对氯苯丙氨酸甲酯（PCPA）或100 mg/kg的α-甲基对酪氨酸（AMPT）、0.3 mg/kg的WAY100635（WAY）、1 mg/kg的哌唑嗪（PRAZ）、2 mg/kg的育亨宾，同时进行单胺氧化酶测定和海马脑源性神经营养因子（BDNF）定量分析。齐墩果酸增强了巴比妥酸盐的催眠作用，并在明暗箱和高架十字迷宫中均显示出抗焦虑作用。该作用未被PTZ逆转。用齐墩果酸（5 - 20 mg/kg）对小鼠进行急性和/或慢性口服治疗，在强迫游泳试验和悬尾试验中产生了抗抑郁作用，且不影响运动活性。齐墩果酸的抗抑郁作用被NAN-190、AMPT、PCPA、WAY和PRAZ减弱。尽管齐墩果酸未改变单胺氧化酶活性，但长期给予齐墩果酸可提高海马BDNF水平。这些发现证明了齐墩果酸抗焦虑和抗抑郁作用的多种机制。
