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Publications

Journal Article Review Epublish

PubMed: 40426956 DOI: 10.3390/biomedicines13051129

Neuroinflammation and Natural Antidepressants: Balancing Fire with Flora.

Biomedicines 13(5)

Authors: Ana Clara Figueiredo Godoy, Fernanda Fortes Frota, Larissa Parreira Araújo, Vitor E Valenti, Eliana de Souza Bastos Mazuqueli Pereira, Claudia Rucco P Detregiachi, Cristiano M Galhardi, Flávia Cristina Caracio, Rafael S A Haber, Lucas Fornari Laurindo, Masaru Tanaka, Sandra M Barbalho

Affiliations

  • Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil.
  • Autonomic Nervous System Center, School of Philosophy and Sciences, São Paulo State University, Marília 17525-900, SP, Brazil.
  • Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil.
  • School of Medicine, Faculdade de Medicina de Marília (FAMEMA), Marília 17519-030, SP, Brazil.
  • Danube Neuroscience Research Laboratory, HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Tisza Lajos krt. 113, H-6725 Szeged, Hungary.
  • Research Coordinator at UNIMAR Charity Hospital, Marília 17525-902, SP, Brazil.

Abstract

Background/Objectives: Major depressive disorder (MDD) is a major global health concern that is intimately linked to neuroinflammation, oxidative stress, mitochondrial dysfunction, and complicated metabolic abnormalities. Traditional antidepressants frequently fall short, highlighting the urgent need for new, safer, and more acceptable therapeutic techniques. Phytochemicals, i.e., natural antidepressants derived from plants, are emerging as powerful plant-based therapies capable of targeting many pathogenic pathways at the same time. Summary: This narrative review synthesizes evidence from preclinical and clinical studies on the efficacy of phytochemicals such as curcumin, polyphenols, flavonoids, and alkaloids in lowering depressed symptoms. Consistent data show that these substances have neuroprotective, anti-inflammatory, and antioxidant properties, altering neuroimmune interactions, reducing oxidative damage, and improving mitochondrial resilience. Particularly, polyphenols and flavonoids have great therapeutic potential because of their capacity to penetrate the blood-brain barrier, inhibit cytokine activity, and encourage neuroplasticity mediated by brain-derived neurotrophic factor (BDNF). Despite promising results, the heterogeneity in study designs, phytochemical formulations, and patient demographics highlights the importance of thorough, standardized clinical studies. Conclusions: This review identifies phytochemicals as compelling adjuvant or independent therapies in depression treatment, providing multimodal mechanisms and enhanced tolerability. Additional research into improved dosage, pharmacokinetics, long-term safety, and integrative therapy approaches is essential. Using phytotherapeutics could considerably improve holistic and customized depression care, encouraging new research routes in integrative neuroscience and clinical psychiatry.

MeSH

Depression, Antidepressive Agents, Brain-Derived Neurotrophic Factor, Tryptophan, Brain, Kynurenine, Oxidative Stress, Curcumin, Research, Therapeutics, Flavonoids, Fires, Polyphenols, Phytochemicals

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