| Summary: | Bee venom contains a number of pharmacologically active components, including enzymes and polypeptides such as phospholipase A<sub>2</sub> (PLA<sub>2</sub>) and melittin, which have been shown to exhibit therapeutic benefits, mainly via attenuation of inflammation, neurotoxicity, and nociception. The individual components of bee venom may manifest distinct biological actions and therapeutic potential. In this study, the potential mechanisms of action of PLA<sub>2</sub> and melittin, among different compounds purified from honey bee venom, were evaluated against Parkinson’s disease (PD). Notably, bee venom PLA<sub>2</sub> (bvPLA<sub>2</sub>), but not melittin, exhibited neuroprotective activity against PD in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP-induced behavioral deficits were also abolished after bvPLA<sub>2</sub> treatment, depending on the PLA<sub>2</sub> content. Further, bvPLA<sub>2</sub> administration activated regulatory T cells (Tregs) while inhibiting inflammatory T helper (Th) 1 and Th17 cells in the MPTP mouse model of PD. These results indicate that bvPLA<sub>2</sub>, but not melittin, protected against MPTP and alleviated inflammation in PD. Thus, bvPLA<sub>2</sub> is a promising and effective therapeutic agent in Parkinson’s disease.
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