Evaluation des propriétes anxiolytiques de l'extrait aqueux des écorces du tronc de Bridelia micranta (Hochst) Bail.( Euphorbiaceae) chez les souris

Abstract

Anxiety disorders are the most common psychiatric disorders affecting nearly 21  population over lifetime. These disorders lead to high morbidity and health costs and constitute a real public health problem because they reduce work and life expectancy. Conventional treatments are not always appropriate andor have many side effects. Hence, traditional medicine is heavily used. Bridelia micrantha (Euphorbiaceae) is a plant traditionally used in Cameroon to treat many neurological diseases, including anxiety and epilepsy. The aim of the present study was to assess the anxiolytic properties of the aqueous extract of Bridelia micrantha stem bark on transient and chronic anxiety mice models. Transient anxiety behavior in mice was assessed by stress-induced hyperthermia (SIH), elevated plus maze (EPM), open field, and hole board tests. In tests of chronic anxiety induced by chronic immobilization stress (CIS), maternal separation (MS), or chronic ingestion of nicotine, behavioral parameters of animals were assessed by the EPM, open field or hole board test. At the end of the experimental period in chronic anxiety tests (CIS and MS), serotonin and corticosterone activity was determined in plasma by ELISA. The oxidative status of brain sample was assessed after chronic nicotine ingestion (p.o, 1.5 mgkg) by colorimetric analyzes. In each test, mice were generally randomized into 6 animals per group. Normal, negative and positive controls, and three test groups. The limits of the use of the plant extract were evaluated in an acute and sub-chronic toxicity study. In the stress-induced hyperthermia test, both plant extract (76, 152 and 305 mg/kg) and phenobarbital (20mg/kg) significantly (p0.001) decreased rectal temperature of mice compared to control mice. In EPM, plant extract (76, 152 and 305 mg/kg) as well as diazepam (3 mg/kg) significantly (p0.001) increased the number of entries, percentage of number of entries, time spent and percentage of time spent in open arms of the elevated plus maze compared to control mice. Percentage number of entries in the open arms of the elevated plus maze was 53,61  and 73,89  in mice receiving plant extract at 152 and 305 mgkg respectively, compared to control mice. Bicuculline and flumazenil significantly inhibited the anxiolytic effects induced by plant extract at 152 and 305 mg/ kg. In the open field test, the results showed a significant (p0.001) increase of the number of crossing, the number of grooming and time spent in the center of open field in mice treated with plant extract at all doses and diazepam (0.3 mg/kg). The number of crossing increased from 17.33  0.55 in control mice to 30.50  0.56; 42.50  3.18 and 52.17  2.90 in those treated with plant extract at 76, 152 and 305 mgkg respectively. In the hole board test, plant extract significantly (p0.001) decreased the latency time of the first headdipping, the number of rearing, and significantly increased the number of headdippings. The assessment of behavioral parameters of mice after induction of chronic anxiety also showed that the plant extract would have anxiolytic properties. Compared to the negative control, a decrease (p0.001) in corticosterone activity and an increase (p0.001) in serotonin in plasma were observed. Plasma corticosterone significantly decreased of 21.68  and of 43.62  at 152 and 305 mgkg respectively of plant extract compared to the negative control. Stress induced by chronic nicotine ingestion (p.o) resulted in decrease brain SOD and catalase activity, reduced glutathione levels and increase malondialdehyde (MDA) levels. These parameters were improved by the plant extract at all doses, suggesting that this extract would have antioxidant properties. The LD50 of the plant extract was estimated to be greater than 5000 mg/kg, suggesting a relatively low toxicity. In the sub-chronic toxicity study, the extract induced a significant decrease (p0.01) in ALAT and ASAT activity, total cholesterol, triglycerides and LDL-cholesterol levels; HDL-cholesterol levels were significantly increased. The results of this study showed that the aqueous extract of Bridelia micrantha exerts its anxiolytic effects by interfering with neurotransmission systems (GABA, serotonin, and corticosterone) and through its antioxidant properties. These results justify the empirical use of this plant for the management of nervous system disorders such as anxiety.