Combining vinpocetine or cocoa with levodopa, Coenzyme Q10 and vitamin B complex mitigates rotenone-induced Parkinson’s disease in rats: Impact on Nrf2/HO-1, NF-kB, AMPK/SIRT-1/Beclin-1, AKT/GSK-3β/CREB/BDNF and Apoptotic Pathways

Abstract

There are no curative treatments for Parkinson's disease (PD), and current treatments focus on symptomatic management. This study aimed to investigate the beneficial effects of combining L-DOPA/Carbidopa with essential cofactors (vitamin (VIT) B complex and coenzyme Q10 (CoQ10)), alone or in conjunction with vinpocetine (VIN) or cocoa, as a potential strategy to enhance neuroprotection in rotenone (RT)-induced PD rat model, highlighting mechanistic insights into their underlying neuroprotective mechanisms and focusing on addressing oxidative stress, inflammation, autophagy, and apoptosis. These combinations were tested on adult male Wistar rats allocated into six groups. Group I received saline (normal control), while groups II-VI were injected with RT for 19 days to induce PD. Group II received RT alone, group III received daily oral L-DOPA/Carbidopa, and groups IV-VI received L-DOPA/Carbidopa with VIT B complex and CoQ10, either alone (Group IV) or combined with cocoa (Group V) or VIN (Group VI). These treatments markedly improved RT-induced perturbations in locomotor and cognitive outcomes; neurotransmitters’ levels; oxidative stress (Nrf2/HO-1, MDA, INOS, SOD and TAC); inflammatory (NF-κB, TNF-α, IL-1β, GFAP and COX-2); neurotrophic (AKT/CREB/BDNF); apoptotic (BAX, caspase-3, AIF, and Bcl-2); and autophagic (AMPK/SIRT-1/Beclin-1) biomarkers; histopathological findings and tyrosine hydroxylase (TH) immunoexpression. Furthermore, the best outcomes were observed in cocoa and VIN combinations. These results indicated that combining L-DOPA with CoQ10 and VIT B complex in conjunction with either VIN or cocoa could provide a potential strategy for managing motor impairments and preventing neurodegeneration in PD. The interaction between key signaling pathways, including Nrf2/HO-1, NF-kB, AMPK/SIRT-1, and AKT/GSK-3β/CREB/BDNF, likely mediates this effect. However, further clinical validation is required to assess this approach's real-world applicability and therapeutic potential. • RT induced oxidative stress, inflammation, apoptosis and autophagic change. • L-DOPA with essential cofactors & VIN or cocoa offered a promising PD therapy. • Neuroprotection achieved by modulation of Nrf2/NF-kβ and AMPK/SIRT-1/AKT/GSK3β cues. • Treatments restored monoamine levels and enhanced locomotor and cognitive functions. • VIN or cocoa combinations improved behavior, biochemistry, histology, and immunology.