Mifunctional Cembranoids for Therapy of Parkinson’s Disease

Objective/Rationale:
Although considerable achievements have been made in the understanding of pathophysiology of Parkinson’s disease (PD), there are still limited effective approaches available for PD treatment. Thus, there are strong needs for exploring new therapeutics and approaches for PD patients. The objectives of this project are to characterize therapeutic effect of beta-cembrane, a tobacco cembranoids extract, and to understand its underlying mechanisms in the treatment of Parkinson’s disease.

Project Description:
The therapeutic strategy proposed in this application is to use a multifunctional compound, beta-cembrane, to treat 6-hydroxydopamine (6-OHDA)-induced PD in a pre-clinical model. The models will be treated with various doses of beta-cembrane (6mg/kg, 12mg/kg) and an equal volume of vehicles or saline by intraperitoneal injection. The treatment will start at one hour after toxin injection into the brain every two days over the following three weeks. The outcome of PD in the model will be evaluated by the rotation testing and forelimb placing testing. The level of related biomarkers like VCAM-1, ICAM-1, p-Akt, ROS, dopamine, degenerating neurons and infiltration of inflammatory cells will also be detected in different brain areas.

Relevance to Diagnosis/Treatment of Parkinson’s disease:
This study is expected to provide a novel effective therapy for PD and will guide our future studies of using beta-cembrane to treat PD in humans. The success of the project will have immediate impact on therapy of Parkinson’s disease, and explore novel use of tobacco for medical purpose.

Anticipated Outcome:
Upon completion of this project, we expect that beta-cembrane will have a therapeutic effect on a PD pre-clinical model. Beta-cembrane significantly protects the model against 6-OHDA-induced symptoms of Parkinson’s disease, and the loss of dopaminergic neurons and inflammation.