Centella asiatica in Stress-Induced Depression: Multitarget Modulation of Neuroendocrine, Inflammatory, Redox, and Neuroplastic Pathways

Onny Ziasti  Fricillia; Victoria Yulita F; Muh. Deni Kurniawan; Shindy puspita Kurniawan; Difatya Mula  Hardianto

doi:10.30872/jtpc.v10i1.372

Authors

Onny Ziasti Fricillia Department of Clinical Pharmacy, Study Program of Pharmacy, Faculty of Pharmacy, Universitas Mulawarman, Samarinda, Indonesia Author
Victoria Yulita F Department of Clinical Pharmacy, Study Program of Pharmacy, Faculty of Pharmacy, Universitas Mulawarman, Samarinda, Indonesia Author
Muh. Deni Kurniawan Study Program of Pharmacy, Faculty of Pharmacy, Universitas Mulawarman, Samarinda, Indonesia Author https://orcid.org/0000-0002-9888-8743
Shindy puspita Kurniawan Study Program of Pharmacy, Faculty of Pharmacy, Universitas Mulawarman, Samarinda, Indonesia Author https://orcid.org/0000-0002-9888-8743
Difatya Mula Hardianto Study Program of Pharmacy, Faculty of Pharmacy, Universitas Mulawarman, Samarinda, Indonesia Author https://orcid.org/0000-0002-9888-8743

DOI:

https://doi.org/10.30872/jtpc.v10i1.372

Keywords:

oxidative stress, Centella asiatica, stress induced depression, HPA axis, neuroplasticity

Abstract

Chronic stress is a major etiological factor in depression and is characterized by dysregulation of the hypothalamic pituitary adrenal axis, neuroinflammation, oxidative imbalance, and impaired neuroplasticity. Centella asiatica has gained attention as a potential natural neuromodulator; however, its mechanistic role in stress induced depression has not been comprehensively synthesized. This narrative review integrates preclinical and selected clinical evidence published between 2016 and 2026 to evaluate the antidepressant related mechanisms of Centella asiatica and its principal triterpenoids. Across validated stress models, administration of Centella asiatica consistently attenuated HPA axis hyperactivity, restored hippocampal brain derived neurotrophic factor signaling, suppressed NF kappa B mediated neuroinflammation, enhanced endogenous antioxidant defenses, and reduced ferroptosis associated neuronal injury. These molecular and cellular adaptations were accompanied by reproducible improvements in depressive like behaviors and preservation of hippocampal structural integrity. Emerging evidence also suggests involvement of the microbiota gut brain axis. Overall, the findings support a multitarget neuromodulatory profile consistent with contemporary multifactorial models of depression. Well designed biomarker driven clinical trials are warranted to confirm translational relevance and therapeutic potential in human populations.

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