Curcumin's Antidepressant Mechanisms in Animal Models

Curcumin, the primary polyphenolic compound of Curcuma longa, exerts antidepressant-like effects in a range of animal paradigms by targeting multiple neurobiological systems. In rodent models of chronic stress, olfactory bulbectomy and inflammatory challenge, curcumin mitigates behavioural despair, anhedonia and anxiety‐like responses. Mechanistically, it attenuates neuroinflammation by downregulating proinflammatory cytokines such as interleukin-1β and tumour necrosis factor-α, and by inhibiting p38 mitogen-activated protein kinase signalling. Concurrently, curcumin activates antioxidant defences via the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, reducing markers of oxidative stress and restoring levels of catalase and glutathione. It also promotes neuroplasticity through upregulation of brain-derived neurotrophic factor (BDNF), enhancement of synaptic proteins (PSD-95, synaptophysin) and preservation of dendritic architecture in the hippocampus and prefrontal cortex. Furthermore, curcumin influences monoaminergic systems by modulating the release and reuptake of serotonin, dopamine and noradrenaline, and by inhibiting monoamine oxidase activity. Its poor bioavailability has been addressed in preclinical studies through co-administration of adjuvants such as piperine, leading to potentiation of its neuroprotective and antidepressant properties. Collectively, these findings underline curcumin’s pleiotropic actions on inflammatory, oxidative and neurochemical pathways that underpin its efficacy in alleviating depression-like states in animal models.

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Curcumin's Antidepressant Mechanisms in Animal Models publication trend

The graph below shows the total number of articles in curcumin's antidepressant mechanisms in animal models across all publications each year (not limited to Nature Index journals).

Technical terms

Brain-derived neurotrophic factor (BDNF): a protein promoting neuron survival, growth and synaptic plasticity.

Nrf2-ARE pathway: a cellular defence mechanism where Nrf2 induces antioxidant gene expression via the antioxidant response element (ARE).

Chronic unpredictable mild stress (CUMS): an animal model inducing depression-like behaviours through varied mild stressors over weeks.

Interleukin-1β (IL-1β): a proinflammatory cytokine implicated in neuroinflammation and depression pathophysiology.

p38 MAPK: a signalling kinase activated by stress and inflammation, leading to apoptosis and cytokine production.

References

1. Polyphenols as novel interventions for depression: Exploring the efficacy, mechanisms of action, and implications for future research. Neuroscience & Biobehavioral Reviews (2023).
2. Suppression of Neuroinflammatory and Apoptotic Signaling Cascade by Curcumin Alone and in Combination with Piperine in Rat Model of Olfactory Bulbectomy Induced Depression. PLOS ONE (2013).
3. Curcumin Attenuates Chronic Unpredictable Mild Stress‐Induced Depressive‐Like Behaviors via Restoring Changes in Oxidative Stress and the Activation of Nrf2 Signaling Pathway in Rats. Oxidative Medicine and Cellular Longevity (2020).
4. Neuroprotective Effects of Curcumin on IL-1β-Induced Neuronal Apoptosis and Depression-Like Behaviors Caused by Chronic Stress in Rats. Frontiers in Cellular Neuroscience (2019).
5. Curcumin in Depression: Potential Mechanisms of Action and Current Evidence—A Narrative Review. Frontiers in Psychiatry (2020).