Dopamine, a key factor of mitochondrial damage and neuronal toxicity on rotenone exposure and also parkinsonic motor dysfunction-Impact of asiaticoside with a probable vesicular involvement.

Persuasive evidence propose that the toxicity of dopamine in parkinsonism and the loss of dopaminergic neurons are the earliest events during the pathogenesis of Parkinson's disease (PD). In our earlier study, Asiaticoside (AS), a triterpenoid saponin isolated from Centella asiatica was shown to exert a neuroprotective effect against hemiparkinsonism, purportedly due to phosphoinositides (PI)-assisted cytodynamics and synaptic function. Here, we evaluate AS in the modulation of dopamine (DA), mitochondrial integrity and neurite variations in vitro and motor dysfunctions in vivo. PC12 cells challenged with rotenone-(ROT) (0.1 μM/mL) were exposed to AS and l-DOPA (10 mM and 20 μM/mL respectively). The protein expressions of Bax and Bcl-2 that regulate cell death were assessed following neurite length assays. Rats were distributed into 6 groups (6 rats/group): Sham, Vehicle controls, ROT-infused (6 μg/μl/kg), AS- treated (50 mg/kg/day), Drug control, and ROT + L-DOPA-treated (6 mg/kg/day) groups. At the end of the experimental period, the rats were sacrificed after performing motor behavioral analysis, and the striatum was dissected out. The contents of synaptic vesicular and cytosolic DA were analyzed. Further, the levels of striatal PI were also measured. ROT had caused significant reduction in the neurite outgrowth in the exposed PC12 cells while the tested concentrations of AS and l-DOPA can exert their protective effect on the stunted neurite growth. The levels of Bax, Bcl-2, and cytochrome c which were significantly disturbed by ROT, could also be affected by AS thereby suggesting its effect on neurons. AS treatment caused an improved motor performance, vesicular and cytosolic DA, and striatal PI. These pre-clinical findings force us to speculate that AS could be a potential drug candidate in combating ROT-induced variations that are possibly precipitated by varied vesicular trafficking of DA.