Antidepressant-like effects of the aqueous macerate of the bulb of Gladiolus dalenii Van Geel (Iridaceae) in a rat model of epilepsy-associated depression

Abstract

Background: In Cameroonian traditional medicine various extracts of Gladiolus dalenii Van Geel (Iridaceae) have been used as a cure for various ailments that include headaches, digestive problems, muscle and joint aches, and some central nervous system disorders such as epilepsy, schizophrenia and mood disorders. Owning to this background, the aim of the study was to investigate whether an aqueous macerate of the bulb of Gladiolus dalenii has any antidepressant activity focusing specifically on depression-like behaviours associated with epilepsy.

Method: We used the combined administration of atropine and pilocarpine to rats as our animal model of epilepsy. The forced swim test and spontaneous locomotor activity in the open field test were the two tools used to assess the presence of depression-like behaviour in epileptic and control animals. The following depression-related parameters were determined: plasma ACTH, plasma corticosterone, adrenal gland weight and hippocampal levels of brain-derived neurotrophic factor (BDNF). The effects of Gladiolus dalenii were compared to that of fluoxetine.

Results: Our results showed that we had a valid animal model of epilepsy-induced depression as all 3 measures of construct, predictive and face validity were satisfied. The data indicated that Gladiolus dalenii significantly reduced the immobility times in the forced swim test and the locomotor activity as assessed in the open field. A similar pattern was observed when the HPA axis parameters were analysed. Gladiolus dalenii significantly reduced the levels of ACTH, corticosterone, but not the adrenal gland weight. Gladiolus dalenii significantly increased the level of BDNF in the hippocampus. In all parameters measured the effects of Gladiolus dalenii were significantly greater than those of fluoxetine.

Conclusion: The results show that Gladiolus dalenii has antidepressant-like properties similar to those of fluoxetine in epilepsy-associated depressive states. The antidepressant activity of Gladiolus dalenii is likely to be mediated by restoring the activity of the HPA axis and increasing the levels of BDNF in the hippocampus.

Figure 1

Immobility times of animals in 5 minutes Porsolt swim test that were just handled and that displayed temporal lobe epilepsy (TLE). TLE was induced by injecting rats intraperitoneally (i.p.) with pilocarpine (350 mg/kg). Thirty minutes prior to the pilocarpine injection, the animals were treated with atropine (1 mg/ kg, i.p.) to reduce peripheral pilocarpine effects. Results are the mean ± SEM of n = 5 rats per group. ** p < 0.01, significantly different from handling group (Mann Whitney U test).

Figure 2

Immobility times of animals in 5 minutes Porsolt swim test that displayed temporal lobe epilepsy (TLE) and treated with saline, GD and Fluoxetine every day for seven days. TLE was induced by injecting rats intraperitoneally (i.p.) with pilocarpine (350 mg/kg). Thirty minutes prior to the pilocarpine injection, the animals were treated with atropine (1 mg/ kg, i.p.) to reduce peripheral pilocarpine effects. Results are the mean ± SEM of n = 5 rats per group. ** p < 0.01, significantly different from saline group (ANOVA followed by Neuman-Keuls test). *** p < 0.001 significantly different from saline group (ANOVA followed by Neuman-Keuls test). ### p < 0.001 significantly different from G. dalenii treated group (ANOVA followed by Neuman-Keuls test). GD: G. dalenii: aqueous macerate of the bulb of Gladiolus dalenii.

Figure 3

The plasma concentration of ACTH and corticosterone of rats that were treated with saline, GD and fluoxetine every day for seven days, displayed temporal lobe epilepsy (TLE). TLE was induced by injecting rats intraperitoneally (i.p.) with pilocarpine (350 mg/kg). Thirty minutes prior to the pilocarpine injection, the animals were treated with atropine (1 mg/ kg, i.p.) to reduce peripheral pilocarpine effects. a) The plasma concentration of ACTH; b) The plasma concentration of corticosterone. Results are the mean ± SEM of n = 4 rats per group. * p < 0.05, significantly different from saline group respectively (Kruskal-Wallis followed by Mann Whitney U test). GD: G. dalenii: aqueous macerate of the bulb of Gladiolus dalenii.

Figure 4

Adrenal glands weight of animals that displayed temporal lobe epilepsy (TLE) and treated with saline, G.dalenii and fluoxetine every day for seven days. TLE was induced by injecting rats intraperitoneally (i.p.) with pilocarpine (350 mg/kg). Thirty minutes prior to the pilocarpine injection, the animals were treated with atropine (1 mg/ kg, i.p.) to reduce peripheral pilocarpine effects. Results are the mean ± SEM of n = 5 rats per group. GD: G. dalenii: aqueous macerate of the bulb of Gladiolus dalenii.

Figure 5

The concentration of BDNF in the hippocampus of rats that were handled and displayed temporal lobe epilepsy (TLE). TLE was induced by injecting rats intraperitoneally (i.p.) with pilocarpine (350 mg/kg). Thirty minutes prior to the pilocarpine injection, the animals were treated with atropine (1 mg/ kg, i.p.) to reduce peripheral pilocarpine effects. Results are the mean ± SEM of n = 4 rats per group. *** p < 0.001, Significantly different from Handled group respectively (Student’s t-test).

Figure 6

The concentration of BDNF in the hippocampus of rats that were treated with saline, GD and fluoxetine, displayed temporal lobe epilepsy (TLE). TLE was induced by injecting rats intraperitoneally (i.p.) with pilocarpine (350 mg/kg). Thirty minutes prior to the pilocarpine injection, the animals were treated with atropine (1 mg/ kg, i.p.) to reduce peripheral pilocarpine effects. Results are the mean ± SEM of n = 4 rats per group. * p < 0.05 and *** p < 0.001, significantly different from saline group respectively (ANOVA followed by Neuman-Keuls test). ### p < 0.001, significantly different from G. dalenii treated group respectively (ANOVA followed by Neuman-Keuls test). GD: G. dalenii: aqueous macerate of the bulb of Gladiolus dalenii.