Celastrol fractionated from Celastrus paniculatus improves rotenone-induced SH-SY5Y cell death. Our study confirmed that Celastrol is a potential neuroprotective agent by preventing ROS generation, MMP reduction. Administration of Celastrol may slow down the rapid neuronal death as Celastrol having more antioxidant activity. As the total synthesis of Celastrol is difficult, cost addictive Industries might use this plant as a resource for rapid synthesis for further use.