Parkinson’s Disease is a common neurodegenerative disease with environmental factors that contribute to its pathophysiology. Rotenone is a universally used insecticide that has been shown to exacerbate PD. This study aimed to test whether piperlongumine (PL) and piperlonguminine (PM) can mitigate rotenone-caused neurodegeneration at both a cellular and molecular level. The protection of each alkaloid was evaluated by comparing the chemical and rotenone to rotenone alone, with glutathione used as a positive control. Treatments were tested by measuring cell viability through an MTT assay, cell cytotoxicity/necrosis through an LDH assay, cell morphology through computer-assisted image analysis, and apoptosis through a caspase assay. The results indicated that PL, at micromolar concentrations, was most effective at increasing cell viability (23.0%, p<0.05) against rotenone’s damage. Computer-assisted image analysis revealed that this chemical also most significantly increased cell count by 86.5% (p<0.005), cell density by 93.3% (p<0.005), and cell area by 141% (p<0.005), and reduced roundness by 64.3% (p<0.005), respectively. PM, while not as effective as PL in the aforementioned tests, was greatest at reducing cell cytotoxicity by 478% (p<0.005) and downregulating caspase activity by 41.2% (p<0.05). All of these results demonstrate that PL and PM are able to provide strong protection against rotenone-induced neurodegeneration. Therefore, the two chemicals have the potential to be novel treatments against pesticide-induced Parkinson’s disease.

Piperlongumine and Piperlonguminine Mitigate Rotenone Induced Neurotoxicity: Implications For Parkinson’s Disease Treatment

ACS Spring Meeting 2021

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