Apilarnil exerts neuroprotective effects and alleviates motor dysfunction by rebalancing M1/M2 microglia polarization, regulating miR-155 and miR-124 expression in a rotenone-induced Parkinson's disease rat model.

Microglial activation contributes to the neuropathology of Parkinson's disease (PD). Inhibiting M1 while simultaneously boosting M2 microglia activation may therefore be a potential treatment for PD. Apilarnil (API) is a bee product produced from drone larvae. Recent research has demonstrated the protective effects of API on multiple body systems. Nevertheless, its impact on PD or the microglial M1/M2 pathway has not yet been investigated. Thus, we intended to evaluate the dose-dependent effects of API in rotenone (ROT)-induced PD rat model and explore the role of M1/M2 in mediating its effect. Seventy-two Wistar rats were equally grouped as; control, API, ROT, and groups in which API (200, 400, and 800 mg/kg, p.o.) was given simultaneously with ROT (2 mg/kg, s.c.) for 28 days. The high dose of API (800 mg/kg) showed enhanced motor function, higher expression of tyrosine hydroxylase and dopamine levels, less dopamine turnover and α-synuclein expression, and a better histopathological picture when compared to the ROT group and the lower two doses. API's high dose exerted its neuroprotective effects through abridging the M1 microglial activity, illustrated in the reduced expression of miR-155, Iba-1, CD36, CXCL10, and other pro-inflammatory markers' levels. Inversely, API high dose enhanced M2 microglial activity, witnessed in the elevated expression of miR-124, CD206, Ym1, Fizz1, arginase-1, and other anti-inflammatory indices, in comparison to the diseased group. To conclude, our study revealed a novel neuroprotective impact for API against experimentally induced PD, where the high dose showed the highest protection via rebalancing M1/M2 polarization.