Evaluating the Curative Potential of Vilangin for Parkinson’s Disease Treatment through in vitro and in silico Approach

Introduction

Parkinson’s Disease (PD) is due to gradual deterioration of the aging brain and motor functions. The rising prevalence of PD suggests the need for better therapies to slow down or halt its progression. Our Knowledge in the pathophysiology of PD has evolved over time, driven by advancements in preclinical models that mimic the disease and the refinement of specific clinical, genetic, and pathological traits. This led to the investigation of numerous objectives for disease management. Alzheimer’s disease and PD are two prominent neurological diseases for which there are lack of precise therapeutic strategies, and thus no cure. Hence, we need to explore new drugs until a definitive treatment strategy is attained. Vilangin, a dimeric form of embelin (a derivative of quinone), has recently received research attention owing to its chemical structure and functional activity. A preliminary investigation of this drug using an in vitro and in silico model is vital to validate its neuroprotective potential and efficacy.

Materials and Methods

Vilangin was synthesized from embelin by condensing formaldehyde in acetic acid. SHSY-5Y cells, a neuroblastoma cell line, were exposed to rotenone (400 nM) to develop an in vitro PD model and treated with vilangin (200 and 500 µg) to evaluate its potential to ameliorate rotenone toxicity. Cell viability, mitochondrial function, Reactive Oxygen Species (ROS) production, and membrane potential, and apoptosis were examined. In addition, Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was performed to analyze the expression of genes related to the antioxidant system (NRF2), apoptosis (ATF3), cell survival (NURR1), and neural transmission (DAT). Molecular Docking analysis was carried out between p53 (protein) and vilangin (ligand).

Results

The higher dose of vilangin (500 ug) had a significant protective effect; it attenuated the toxicity of rotenone to restore the SH-SY5Y cellular functions by reducing ROS and apoptosis, and improved cell viability and mitochondrial functions. Nrf2 and Nurr1 were upregulated and Atf3 and Dat were downregulated following vilangin treatment. The docking results showed good binding interactions between vilangin and p53; hence p53 could be a potential target of vilangin to manage PD complications.

Conclusion

Vilangin can be advocated as a potential antioxidant and anti-apoptotic agent to reduce PD-related complications such as Oxidative Stress (OS), ROS formation, mitochondrial dysfunction, and cell death.