Emerging Role of Natural Products and Dietary Supplements in Major Depressive Disorder: Therapeutic and Mechanistic Insights
Ankit Kumar Yadav, Bikash Kumar Sah, Faiz Ahmad, Vishal Jamwal, Sanjeev Kumar SahuIntroduction:
Major Depressive Disorder (MDD) is the fourth highest cause of morbidity and mortality in the world, and its prevalence has grown significantly during the COVID-19 pandemic. The pathophysiology of the disorder is multifactorial, involving genetic, environmental, cellular, and molecular factors. Traditional pharmacotherapies are characterized by delayed action, inadequate response, and side effects, thus prompting studies of complementary or additional treatments. The review aims to provide a comprehensive evaluation of the therapeutic potential of natural products and dietary supplements in MDD, clarify their mechanism of action, and identify new and integrative approaches to treatment.
Methods:
A systematic search was conducted through July 2025 across various databases, including PubMed, Google Scholar, Web of Science, repositories of traditional integrated resources, local dissertations, and monographs. The key terms included major depressive disorder with a combination of phytomedicine, natural products, dietary supplements, phytoconstituents, therapeutic potential, and mechanisms of action.
Results:
The use of natural products and dietary supplements has emerged as a potential means to effectively treat MDD due to their ability to regulate dysregulated biochemical processes and mechanisms.
Discussion:
Natural compounds such as polyphenols, alkaloids, terpenoids, and essential fatty acids use a variety of cellular and molecular pathways to have an antidepressant effect, including augmenting neurotransmitter levels, modulating the hypothalamic-pituitary-adrenal axis, reducing neuroinflammation, and inhibiting oxidative damage. Dietary supplements also contribute to mood regulation by supporting neuronal integrity, modulating the gut–brain axis, and maintaining immune homeostasis. The overall evidence suggests that natural interventions can be used to supplement traditional pharmacotherapy and enhance treatment success.
Conclusion:
The review provides a framework for the cellular and molecular pathways underlying the antidepressant effects of various natural compounds and dietary supplements, therefore establishing a foundation for future investigation and clinical use.