Anti-depressant and anxiolytic potential of Acacia hydaspica R. Parker aerial parts extract: Modulation of brain antioxidant enzyme status

Abstract

Background: Oxidative stress may link to psychiatric disorders, and is being regarded as a plausible mechanism that can affect the regulation of these illnesses. The present study was undertaken to investigate the antidepressant and anxiolytic potential of A. hydaspica R. parkers. Brain oxidative stress enzyme levels were analyzed to correlate depression and stress with brain antioxidant status.

Methods: Antidepressant and anxiolytic effect of methanol extract of A. hydaspica and its derived soluble fractions [n-hexane (AHH), ethyl-acetate (AHE), chloroform (AHC), n-butanol (AHB) and remaining aqueous fraction (AHA)] was investigated by using three behavioral models; the Forced swimming test, Tail suspension test and Elevated plus-maze test (EPM). Chronic unpredictable mild stress (CMS) was employed to induce stress in rats. AHM and AHE (200 mg/kg, p.o), fluoxetine (5 mg/kg, i.p) and diazepam (DZM) (1 mg/kg, p.o) were administered during the 7 day stress exposure period, and rats were assessed for antidepressant and anxiolytic behavioral despair paradigms. Antioxidant enzymes and oxidative stress markers were measured in brain tissue of depressed rats. Phytochemical analysis was done by GCMS experimentation.

Results: AHM and AHE (acute dose) significantly (p < 0.0001) reduced the immobility time and ameliorated climbing behavior as compared to the control in FST and TST, and similar to fluoxetine. AHM and AHE showed significant (p < 0.0001) anxiolytic potential in EPM, and comparable to DZM (1 mg/kg b.w., i.p). Significant decrease in antioxidant enzyme levels and increase in MDA, H₂O₂ and NO level were observed in stressed rats. AHM and AHE (for 7 days/CMS) significantly improved behavior in FST, TST and EPMT. Treatment also improved antioxidant enzyme level and controlled the oxidative stress markers in brain tissues. GCMS analysis indicated the presence of 10 different chemical constituents in A. hydaspica.

Conclusion: The present study revealed that A. hydaspica exerts an antidepressant and anxiolytic effect by improving brain antioxidant status. The observed activities might be due to the presence of diverse phytochemicals.

Keywords: Brain antioxidants; Depression; Force swimming test; GCMS; Immobility time; Phytochemicals.

Fig. 1

Flow chart describing the extraction procedure for fractionation of A. hydaspica

Fig. 2

GC Chromatogram of A. hydaspica crude methanol extract (AHM)

Fig. 3

Effect of acute and repeated dose of A. hydaspica extract/fraction (200 mg/kg b.w, p.o) and fluoxetine (10 mg/kg b.w, i.p.) on behavioral pattern in forced swing test in rats. a Effect acute dose on swimming and climbing behavior, b Effect repeated doses of AHM, AHE and fluoxetine on swimming and climbing behavior. Data presented as mean ± SEM (n = 6). Asterisks ***, * indicate significant (p < 0.001 and p < 0.05 respectively) difference from respective control. Data analyzed by one way ANOVA followed by Tukey’s multiple comparison tests

Fig. 4

Effects of the acute and repeated dose of AHM and AHE in the elevated plus-maze test on the percentage of the time spent in the open arms (a), the number of open-arm entries (b) and the number of crossing (c) in depressed rats. Values are means + SEM (n = 6). Data analyzed by one way ANOVA followed by Tukey’s multiple comparison tests