INTRODUCTION: Parkinson's disease, a neurodegenerative disorder, affects millions globally, with age, genetics, and environmental conditions increasing risk. Global burden could reach 12 million by 2050. To observe the effect of Celastrus paniculatus in rotenone-induced Parkinsonism in zebrafish model. METHOD: The fishes were divided into four groups and the experiment was carried out for 21days. Group I- Control
Group II- Rotenone induced (5 µg/L) dissolved in 0.1% DMSO
Group III - Aqueous extract of Celastrus paniculatus (CP) (20 µg/L) and Group IV - Rot + CP. After 21 days zebrafish was sacrificed and the brain was isolated for further analysis. The neurobehavioral studies were done using open field test, novel tank test and light and dark test, and the cognitive behavior using T-maze and customized fish maze. The antioxidant, neurotransmitter, mitochondrial assay and mRNA expressions were seen. RESULT: The rotenone has shown an increased freezing bout, decreased exploration of the tank and average speed has demonstrated motor impairment and also memory impairment was exhibited. There was elevated cortisol and LPO and reduced antioxidant status. The neurotransmitters changes and mitochondrial dysfunction were also observed. The study showed increased in α-synuclein and decreased in DJ1 and LRRK2 expressions. In the present study, the aqueous extract of CP has cognitive dysfunctions and improves memory. CP has also shown amelioration against the production of ROS, mitochondrial dysfunctions and DNA damages caused by rotenone. CONCLUSION: CP is known for its medicinal and pharmacological properties. CP has also shown to improve the cognitive dysfunction caused by rotenone and have showed an improvement in effect.