Anti-Inflammatory and Neuroprotective Effects of a Novel Water-Soluble Formulation of Coenzyme-Q10 and Ashwagandha Root Extract in a Paraquat-Induced Rat Model of Parkinson’s Disease

Introduction: Parkinson's disease (PD) is characterized by progressive loss of dopaminergic neurons in the substantia nigra resulting in impaired movement coordination. There is no cure, and current therapies only provide symptomatic relief and have adverse side effects over long-term use. There are several biochemical mechanisms implicated in PD, which include oxidative stress, inflammation, and impaired autophagy. Previous studies have shown that a combination of two nutraceuticals, Ubisol-Q10 and ethanolic Ashwagandha root extract was more effective than each used alone at reducing neurodegeneration in a paraquat-induced rat model of PD by targeting the biochemical mechanisms all at once. In previous research, the oral doses of Ubisol-Q10 were low; however, the doses of ethanolic Ashwagandha used were unrealistically high because the extract's hydrophobicity causes poor bioavailability. The current study aims to determine the neuroprotective effects of Ubisol-Q10 and a novel water-soluble formulation of Ashwagandha extract (WS-ASH) on a Paraquat-injected rat model of PD. Methods: WS-ASH was prepared using a methodology analogous to that used for creating Ubisol-Q10. To test the efficacy of Ubisol-Q10, WS-ASH, and a combination Tonic solution, premortem gross- and fine-motor tests were conducted on a PD rat model, followed by immunofluorescent staining of biomarkers for inflammation, neurotrophic factors, oxidative stress, senescence, autophagy, and synaptic health. Results: This WS-ASH had significant neuroprotective effects at lower doses. The combination of WS-ASH and Ubisol-Q10 (Tonic) provided a better neuroprotective effect. Importantly, Tonic treatment improved gross- and fine-motor skills of a paraquat-injected rat model of PD compared to the untreated group. Furthermore, the combined treatment led to decreased oxidative stress, decreased inflammation, resumption of autophagy, induced the production of pro-survival neurotrophic factors, and increased synapse-specific protein. Conclusion: The results indicate that this combined formulation has potential for an effective therapy for PD patients.