Synergistic effect of carboxymethyl chitosan and phloroglucinol against rotenone induced Parkinson's disease in zebrafish model.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder that impairs motor function in humans. This research explores the combined neuroprotective effects of carboxymethyl chitosan (CMC) and phloroglucinol (PGL) in a zebrafish (ZF) model of PD induced by rotenone (ROT). The structural features of the CMC-PGL conjugate were analysed using UV-visible, Fourier Transform Infrared (FT-IR), and fluorescence spectroscopy. The phenolic content of conjugated sample was estimated and confirmed the conjugation of CMC with PGL. The LD50 of CMC-PGL was determined as 8 μg/mL in ZF embryo (ZFE). In vivo experiments revealed that ROT exposure decreased locomotor activity, while CMC-PGL 4 mg/L treated ZF exhibits improved was confirmed by the ToxTrac analysis. Behavioural parameters improvements were also seen in Novel tank test (NTT) and light/dark tests with CMC-PGL 4 mg/L (LD) and CMC-PGL 8 mg/L (HD) treated ZF. RP- HPLC showed the significant (P < 0.0001) restoration of dopamine (DA) levels post-treatment. Histological analysis showed ROT-induced brain damage in ZF, including necrosis, cytoplasmic vacuolisation, and neuronal degeneration, whereas in the CMC-PGL 4 mg/L showed a decrease in neuronal loss and vacuolisation. These findings suggest that CMC-PGL conjugates may hold promise as therapeutic agents for managing neurodegeneration (ND) associated with PD.