Costunolide and Parthenolide Ameliorate MPP+ Induced Apoptosis in the Cellular Parkinson’s Disease Model

Abstract

Monoamine oxidase B (MAO-B) is an enzyme that metabolizes several chemicals, including dopamine. MAO-B inhibitors are used in the treatment of Parkinson’s Disease (PD), and the inhibition of this enzyme reduces dopamine turnover and oxidative stress. The absence of dopamine results in PD pathogenesis originating from decreased Acetylcholinesterase (AChE) activity and elevated oxidative stress. Here, we performed a molecular docking analysis for the potential use of costunolide and parthenolide terpenoids as potential MAO-B inhibitors in the treatment of PD. Neuroprotective properties of plant-originated costunolide and parthenolide terpenoids were investigated in a cellular PD model that was developed by using MPP+ toxicity. We investigated neuroprotection mechanisms through the analysis of oxidative stress parameters, acetylcholinesterase activity and apoptotic cell death ratios. Our results showed that 100 µg/mL and 50 µg/mL of costunolide, and 50 µg/mL of parthenolide applied to the cellular disease model ameliorated the cytotoxicity caused by MPP+ exposure. We found that acetylcholinesterase activity assays exhibited that terpenoids could ameliorate and restore the enzyme activity as in negative control levels. The oxidative stress parameter analyses revealed that terpenoid application could enhance antioxidant levels and decrease oxidative stress in the cultures. In conclusion, we reported that these two terpenoid molecules could be used in the development of efficient treatment strategies for PD patients.

Deciphering the Mysterious Relationship between the Cross-Pathogenetic Mechanisms of Neurodegenerative and Oncological Diseases

“…In a model of transgenic APP/PS1 mice, parthenolide significantly improved memory performance in the Morris water maze test, perhaps due to its antioxidant properties and ability to reduce neuroinflammation by blocking the AKT/MAPK/NF-κB signaling pathway [239]. Moreover, in the work of Arslan et al [240], the ability of costunolide and parthenolide to inhibit the activity of the enzyme monoamine oxidase B was considered a possible mechanism of neuroprotective activity in a cellular model of Parkinson's disease.…”