Vinpocetine and Lactobacillus Attenuated Rotenone-Induced Parkinson's Disease and Restored Dopamine Synthesis in Rats through Modulation of Oxidative Stress, Neuroinflammation, and Lewy Bodies Inclusion.

Abstract

Parkinson's disease (PD) is the main neurodegenerative disorder affecting motor activity, there are different pathophysiological pathways contributing to its development including oxidative stress, neuroinflammation, Lewy's bodies accumulation, and impaired autophagy. Vinpocetine is an herbal extract with antioxidant and anti-inflammatory activities that may counteract pathophysiologic neurodegeneration pathways. Moreover, Lactobacillus is a probiotic that can modulate the gut-brain axis and provide the body with the needed precursors of antioxidants and anti-inflammatory mediators. In the current study PD was induced experimentally in Sprague Dawley rats with rotenone (2.5 mg/kg, i.p, daily) for 60 days, vinpocetine; Vinpo (20 mg/kg, orally, daily) and Lactobacillus; Lacto (2.7 × 10⁸ CFU/ml, orally, daily) were applied as protective treatment. Vinpocetine and Lactobacillus treatment significantly ameliorated motor function by increasing distance traveled and rearing frequency in the open field test with a concomitant increase in falling time from both the accelerating rotarod and the wire screen test. Moreover, vinpocetine and Lactobacillus treatment upregulates tyrosine hydroxylase expression (the rate-limiting enzyme in dopamine synthesis), leading to enhanced dopamine synthesis and improved dopaminergic function with regression of histopathological hallmarks. Antioxidant GSH levels were significantly increased after vinpocetine and Lactobacillus treatment with a significant decrease in MDA content in brain homogenates. Furthermore, vinpocetine and Lactobacillus treatment significantly decreased striatal inflammatory markers; nitrite, IL-1β and TNF-α. Proteinopathies were regressed with a substantial decrease in striatal α-synuclein and tau content. In conclusion, vinpocetine and Lactobacillus treatment reduced rotenone neurotoxicity with improved dopamine release and motor activity with correction of oxidative burden, neuro-inflammation, and proteinopathy.