Protective Effect of Cordyceps militaris Extract Against Cigarette Smoke Extract Induced Neurodegeneration in Zebrafish Model.

Abstract

BACKGROUND AND OBJECTIVES: Neurodegenerative diseases are characterized by degeneration or progressive loss/death of neurons in specific areas of the brain, often worsened by cigarette smoke through oxidative stress and inflammation. Cordyceps militaris (C. militaris) exhibits antioxidant and anti-inflammatory properties, suggesting potential neuroprotective effects. This study evaluated the protective role of C. militaris hot water extract (CMWE) against cigarette smoke extract-induced neurodegeneration in zebrafish. METHODS: Neurodegeneration was induced in zebrafish using cigarette smoke extract, and CMWE was administered at 1 mg/L and 4 mg/L. Behavioral performance was assessed using Y-maze, inhibitory avoidance, and novel tank tests. LC-MS was employed to identify CMWE constituents, while antioxidant activity was evaluated by the DPPH assay. Histological analysis of the periventricular grey zone (PGZ) of the optic tectum was performed to assess neuronal integrity. RESULTS: Cigarette smoke exposure led to aimless exploration, impaired memory retention, and increased bottom-dwelling behavior. CMWE improved behavioral outcomes, with 4 mg/L showing greater efficacy than 1 mg/L. LC-MS revealed bioactive compounds including cordycepin, adenosine, ergothioneine, D-mannitol, and vitamins. The DPPH assay confirmed strong antioxidant activity. Histological evaluation showed reduced pyknotic neuronal density in CMWE-treated groups compared with diseased controls, indicating anti-inflammatory effects. CONCLUSIONS: CMWE mitigated cigarette smoke-induced behavioral and histological hallmarks of neurodegeneration in zebrafish, likely via synergistic antioxidant and anti-inflammatory mechanisms. These findings support the potential of C. militaris as a natural product-based therapeutic candidate for neurodegenerative disorders, warranting further studies on its individual constituents and mechanisms of action.