Soluble guanylate cyclase (sGC) is a type of lyase enzyme with profoundly increasing importance in treatments of cardiovascular and
neurodegenerative disorders. Modulation of sGC activity demonstrated beneficial effects against Parkinson's disease by reducing
glutamate excitotoxicity. It is of interest to evaluate the pharmacological activity of Momordica charantia phytoconstituent (DGalacturonic
acid) and ODQ with catalytic domain of sGC enzyme, using Autodock version 4.2 programs. Docking results revealed
the binding ability of ODQ at the allosteric sites of sGC. D-galacturonic acid also shows binding interaction at the same allosteric sites
in the catalytic domain of sGC like ODQ. Results show that both the ligands have efficient binding to THR 474 amino acid residue of
beta 1 subunit of the enzyme. The drug likeliness score further implies the suitability of D-Galacturonic acid as a drug-like molecule.
The binding property of ODQ and D-Galacturonic acid with the catalytic domain help to inhibit sGC activity having pharmacological
effects. Moreover, ODQ interaction with heme site of sGC is already known while its interaction with the catalytic domain is shown in
this report.
Recent researches have suggested 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ), a soluble guanylate cyclase inhibitor may attenuate motor impairments in Parkinson's disease (PD). The antiparkinsonian activity of ODQ were studied on motor abnormalities induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to provide a better understanding of this drug group. The objective of the present study is to evaluate the effect of ODQ on behavioral parameters such as Beam walk test, Adhesive removal test and to assess the biochemical changes due to ODQ against MPTP induced PD mice model. Eighteen C57BL/6J male mice were included in the study, divided into three groups of 6 each. Group A mice were treated with vehicle (Normal saline). Group B mice were subjected to MPTP sub acute protocol. Group C mice were treated with MPTP as according to sub acute protocol and administered with ODQ subcutaneous injection after final MPTP dose. Behavioral tests like Beam walk test, Adhesive removal test, along with Biochemical correlation were done using standard methods. Narrow beam walk and adhesive removal behavior were significantly reversed, and Superoxide dismutase (SOD) levels were enhanced in ODQ treated group compared to MPTP intoxicated mice group. Soluble guanylate cyclase inhibitor ODQ, could be a potential treatment for maintaining the balance of antioxidant and oxidant biochemical environment during oxidative stress which may be helpful for treating PD, targeting one or more factors of its multiple etiological factors.
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