Antidepressive and anxiolytic effects of a combination of Saffron and Chamomile in rats and their relationship with serotonin using methods

Abstract

Objective: To explore the potential of combining natural herbs like chamomile and saffron for the management of anxiety and depression.

Methods: A rodent model of Major Depressive Disorder (MDD) and anxiety, secondary to streptozotocin-induced diabetes mellitus was made. A total of 6 rat groups were chosen; healthy and diseased controls; and diseased test groups of fluoxetine, saffron, chamomile, and combined saffron and chamomile treated (n = 6/group). Activity by forced swim test (FST), elevated plus maze test (EPMT), and correlations with biochemical markers like serum glucose, tryptophan, C-reactive protein (CRP), brain derived neurotrophic factor (BDNF) and 5-hydrox-ytryptamine 2C receptor (5HT2CR) expression, were assessed at the end of the 3rd week of the treatment. A one-way analysis of variance with a post-hoc Tukey's test was applied.

Results: The combined herbal treatment group showed significantly better (P <0.05) than all other groups in terms of anti-hyperglycemic effect. All treatments improved the CRP levels; however, the combination group was also significantly better than fluoxetine and the individual herb groups. Only the herb groups showed efficacy in the FST with added benefits of the combination group over the healthy controls and similar trends in the EPMT. However, expression of 5HT2CR was repressed while BDNF was elevated through treatment.

Conclusion: This study shows that in comparison to treatment with a SSRI, and individual herbs, the combination of chamomile and saffron showed overall improved outcomes.

Keywords: chamomile; crocus; depression; diabetes mellitus.

Figure 1. Effects of treatments on EPMT parameters

A: EPMT latency and time spent in open arms in seconds; B: EPMT number of entries in the open arms for all the groups. The animals were divided into six groups (n = 6): healthy control (standard chow and water), disease control (diabetic without treatment), positive control (diabetic with Fluoxetine 5 mg·kg^-1·d^-1), saffron group (diabetic with saffron 10 mg·kg^-1·d^-1), chamomile group (diabetic with chamomile 30 mg·kg^-1·d^-1), and combination group (diabetic with saffron 5 mg·kg^-1·d^-1 and chamomile 15 mg·kg^-1·d^-1). All treatments were administered via oral gavage, with decoctions prepared fresh daily. After three weeks of treatment duration, analysis performed. EPMT: elevated plus maze test; ANOVA: analysis of variance. The bar values in average and error bars are standard deviation. ANOVA followed by Tukey's test revealed statistically significant differences (P < 0.05), denoted by the following legends: ^aindicates comparison with the diseased control group, ^bindicates comparison with the fluoxetine group, and ^c indicates comparison with the combination of saffron and + chamomile group.

Figure 2. 5HT2C receptor expression in the cortex and hippocampus

The animals were divided into six groups (n = 6): healthy control (standard chow and water), disease control (diabetic without treatment), positive control (diabetic with Fluoxetine 5 mg·kg^-1·d^-1), saffron group (diabetic with saffron 10 mg·kg^-1·d^-1), chamomile group (diabetic with chamomile 30 mg·kg^-1·d^-1), and combination group (diabetic with saffron 5 mg·kg^-1·d^-1 and chamomile 15 mg·kg^-1·d^-1). All treatments were administered via oral gavage, with decoctions prepared fresh daily. After three weeks of treatment duration, analysis performed. 5HT2C: 5-hydroxytryptamine 2C; ANOVA: analysis of variance. The bar values in average and error bars are standard deviation. ANOVA followed by Tukey's test revealed statistically significant differences (P < 0.05), denoted by the following legends: ^aindicates comparison with the diseased control group, ^b indicates comparison with the fluoxetine group, and ^c indicates comparison with the combination of saffron and + chamomile group.

Figure 3. BDNF expression in the cortex and hippocampus

The animals were divided into six groups (n = 6): healthy control (standard chow and water), disease control (diabetic without treatment), positive control (diabetic with Fluoxetine 5 mg·kg^-1·d^-1), saffron group (diabetic with saffron 10 mg·kg^-1·d^-1), chamomile group (diabetic with chamomile 30 mg·kg^-1·d^-1), and combination group (diabetic with saffron 5 mg·kg^-1·d^-1 and chamomile 15 mg·kg^-1·d^-1). All treatments were administered via oral gavage, with decoctions prepared fresh daily. After three weeks of treatment duration, analysis performed. BDNF: brain-derived neurotrophic factor; The bar values in average and error bars are standard deviation. ANOVA followed by Tukey's test revealed statistically significant differences (P < 0.05), denoted by the following legends: ^aindicates comparison with the diseased control group, ^bindicates comparison with the fluoxetine group, and ^cindicates comparison with the combination of saffron and + chamomile group.