Parkinson’s disease (PD) is characterized by progressive neurodegeneration in the substantia nigra (SN) region resulting in loss of movement coordination. Current therapies only provide symptomatic relief, and there is no agent to halt the progression of PD. Previously, Ubisol-Q10, a water-soluble formulation of coenzyme-Q10, and ethanolic root extract of ashwagandha (ASH) have been shown to inhibit PD pathology in rodent models when used alone. Here, we evaluated the neuroprotective efficacy of oral administration of ASH and Ubisol-Q10 alone and in combination in a paraquat-induced PD rat model. The combined treatment resulted in better-preserved neuron morphology compared to Ubsiol-Q10 or ASH alone. The combination treatment enhanced activation of pro-survival astroglia and inhibited pro-inflammatory microglia. While anti-oxidative effects were seen with both agents, Ubisol-Q10 activated autophagy, whereas ashwagandha showed a better anti-inflammatory response. Thus, the combined treatment caused inhibition of oxidative stress, autophagy activation, inhibition of pro-inflammatory microglia, and activation of pro-survival astroglia. Consequently, paraquat (PQ)-treated rats given the combination treatment in drinking water did not show motor impairment. Based on these interesting observations, the combined treatment containing two well-tolerated natural compounds could be a more effective strategy to halt the progression of PD.

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