Benzoic-D5 acid as D2 receptor agonist in the treatment of rotenone induced Parkinson’s disease in mice

Abstract

Parkinson's disease is a progressive neurological disorder that affects movement. It is caused by the degeneration of dopamine-producing neurons in the brain. There is no cure for Parkinson's disease, but there are treatments available that can help manage the symptoms. Medications such as levodopa, dopamine agonists and Amantadine (Amd) can help to increase dopamine levels in the brain. Sodium benzoate (Benzoic-D5) is used as preservative in foods due to its antimicrobial potential. Benzoic-D5 showed a pivotal role in ameliorating the symptoms of Parkinson’s disease (PkD) in animal model. The current study is designed to probe the anti-Parkinson potential of Benzoic-D5 in the rotenone (ROT)-induced PkD mice. Behavioral studies showed improvement in sensory-motor functions, and neuromuscular strength in wire hanging test, grip strength, vertical rod test, and swim test. Evaluation of biochemical markers suggested increase in catalase (CAT) and superoxide dismutase (SOD), but decreases in the malondialdehyde (MDA) activity. Dopamine, dihydroxyphenyl acetic acid (DOPAC), and homovanillic acid (HVA) levels were improved in Benzoic-D5-treated animals. Moreover, there were down regulation of pro-inflammatory markers like TNF-α, NF-Kβ, and up regulation of anti-inflammatory IL-4 in the RT-PCR analysis. In molecular docking Benzoic-D5 showed strong binding affinity with an active site of Dopamine D2 receptor. Afterwards, ADMET analysis points to the selected drug’s acceptable properties. Conclusively, in vivo, and in silico studies propose that Benzoic-D5 possesses potentials to ameliorate symptoms of PkD. Binding energy data of Benzoic-D5 (-6.2), shows promising results compared to ROT (-6.0), and Amd (5.8).

Keywords

• Sodium Benzoate
• Dopamine
• Sensory-motor functions
• Behavioral modulation