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Combined neuroprotective potential of Levodopa and Resveratrol to ameliorates cognitive impairments in rotenone-induced Parkinson's disease via targeting TLR mediated neuroinflammation
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  • Lin Liu,
  • Mangaiyarkarasi Rajkumar,
  • Boomi Pandi,
  • Anandharaj Jayaraman,
  • Jegatheeswaran Sonamuthu
Lin Liu
Second Hospital of Shanxi Medical University
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Mangaiyarkarasi Rajkumar
BioMe Live Analytical Centre
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Boomi Pandi
Alagappa University
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Anandharaj Jayaraman
BioMe Live Analytical Centre
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Jegatheeswaran Sonamuthu
BioMe Live Analytical Centre

Corresponding Author:[email protected]

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Abstract

Background and Aim By inducing oxidative stress and hindering mitochondrial activity, rotenone can cause neuronal death or cell apoptosis, which is the pathophysiological characteristic of PD. To investigate synergistic effects of levodopa (LD) and resveratrol (RES), a natural polyphenolic molecule, on rotenone-induced toxicity in PD-related cell lines and animal models. Methods The in vitro experiments were performed using the human neuroblastoma cells (SH-SY5Y) and PC-12 cell lines to investigate toxicity (MTT, LDH), cell apoptosis, ROS generation and mitochondrial membrane potential (MMP) assays. The expressions of neuroinflammatory factors (TLR-2 &TLR-4) and inflammatory cytokines was examined under qRT-PCR method. Animal behavioural analyses, neurochemical parameters and histopathological investigations were employed to study in vivo efficiency of drug molecules. Results The observed in vitro results exhibited that prepared formulation significantly inhibited ROS generation and mitochondrial malfunction. In additionally, developed formulations substantially improved motor function in a rotenone-induced SD rat model, as evidenced by rota-rod test and greater distances travelled during the spontaneous activity test. Subsequently, in vivo biochemical assays provided the evidences of LD/RES formulation effectively increased SOD activity and lowered MDA content. Conclusion Summary, our results show that the LD/RES formulation inhibits oxidative damage caused by rotenone by targeting neuroinflammation-related TLR-2 signalling pathway. Our research provided the way to an opportunity of using a combined LD/RES formulation as a neuroprotective medicinal agent in the treatment of Parkinson’s disease.