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. 2025 Dec 6;63(1):264.
doi: 10.1007/s12035-025-05434-y.

Chamomile Modulates Glucose Metabolism and Neuro-inflammation to Alleviate Stress-Induced Depression in Mice

Affiliations

Chamomile Modulates Glucose Metabolism and Neuro-inflammation to Alleviate Stress-Induced Depression in Mice

Shauryabrota Dalui et al. Mol Neurobiol. .

Abstract

Depression, a common psychiatric condition, is frequently associated with chronic stress. This research investigates the therapeutic benefit of chamomile (Matricaria chamomilla) against restraint stress (RS)-induced behavioral and neurobiological alterations in male mice. Animals were categorized into control, RS, and RS + chamomile (Cm) groups. Behavioral evaluation (open field, rotarod, catalepsy, memory test), histopathology, integrity of the blood-brain barrier, and gene expression profiling were done. In silico ProTox analysis confirmed the non-toxicity of chamomile compounds, including chamazulene, which also complies with Lipinski's Rule of Five, indicating drug-like properties. Molecular docking identified robust interactions between chamazulene and prominent stress-related and other relevant targets like IFN-γ, IL-6, caspase-3, BDNF, and GLUT-1. RS exposure interfered with locomotor activity, evoked neuroinflammation, apoptosis, and compromised neuronal-glial function. Treatment with chamomile greatly enhanced locomotor function and posture, decreased catalepsy latency test, and normalized neuronal architecture. Immunofluorescence staining and transcriptional analysis indicated that chamomile suppressed pro-inflammatory cytokines (IFN-γ, IL-6), the apoptotic marker Caspase-3, and increased neurotrophic and neuronal markers (BDNF, NeuN, GFAP) and glycolytic enzymes (GLUT-1, HK-1, LDHA). These results indicate that chamomile has neuroprotective actions by regulating RS-induced inflammation, apoptosis, and metabolic dysfunction. Although no remarkable effects were seen on body or brain-to-body weight ratio, chamomile exhibited powerful behavioral and molecular effects. Overall, the results highlight chamomile, particularly its active constituent chamazulene, as a promising candidate for alleviating restraint stress. However, further clinical validation is required to establish its therapeutic potential in neuropsychiatric disorders.

Keywords: Matricaria chamomilla; Cerebral cortex; Depression; Glucose metabolism; Neuroinflammation; Restraint stress.

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Conflict of interest statement

Declarations. Ethics Approval and Consent to Participate: All in vivo experiments involving animals were conducted in accordance with the Indian Protection of Animals law and were performed under the supervision of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA). Competing interests: The authors declare no competing interests. Informed Consent: Not applicable.

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