Bioactive compounds with antidepressant potential in rodents: A narrative review

Abstract

Plant bioactive compounds are a potential source to alleviate depression symptoms and management of this disorder. Depression is a multifactorial mental health disorder that significantly impairs an individual's social functioning and is commonly associated with persistent stress, maladaptive coping mechanisms, and an unhealthy lifestyle. Several hypotheses, such as neurotransmitter modulation, oxidative damage, neuroinflammation, hyperactivity of the Hypothalamic-pituitary-adrenal (HPA) axis, etc., have been suggested to elucidate the pathophysiology of depression. On these hypotheses, many synthetic antidepressants have been discovered to cure depression. These agents are therapeutically effective in reducing symptoms of depression but are associated with various side effects. Therefore, medicinal plant-based therapy has achieved considerable attention as these agents have negligible side effects. The present review consolidates findings on 90 phytoconstituents, identified through a comprehensive literature survey spanning the past 33 years, utilizing search terms related to bioactive compounds with demonstrated antidepressant activity. Based on the analysis, ConBr emerged as the most potent compound, exhibiting efficacy at doses of 0.1–50 μg/site i.c.v. In addition, Ursolic acid, Forskolin, Dehydrozingerone, Hesperidin, Montamine, and Ascorbic acid were also identified as bioactive phytomolecules with notable antidepressant potential. Moreover, possible mechanisms of action of the antidepressant effects have also been mentioned in this review. The findings of this review suggest that most bioactive compounds alleviate depression by influencing the synaptic regulation of crucial neurotransmitters like serotonin, noradrenaline, and dopamine, inhibiting the activity of monoamine oxidase-A (MAO-A), modulating the hypothalamic-pituitary-adrenal axis, reinforcing the anti-oxidant defense system, and reducing inflammatory mediators. The multi-faceted pathways through which these bioactive compounds alleviate depression highlight their potential as a novel source for developing antidepressants. However, further research might be needed to understand the detailed mechanisms of action for many of these herbal bioactive compounds before clinical studies.