IN SILICO PROBING OF ANTI-ARTHRITIC POTENTIAL OF TRADITIONALLY FERMENTED AYURVEDIC POLYHERBAL PRODUCT BALARISHTA REVEALS LUPEOL AND DESULPHOSINIGRIN AS EFFICIENT INTERACTING COMPONENTS WITH UREC
Keywords:
Ayurveda, Balarishta, Polyherbal fermentation, Urinary Tract Infection, Rheumatoid Arthritis, Proteus mirabilis, Urease proteins, Computational Pharmacology, Molecular dockingAbstract
Objective: To assess the anti-arthritic properties of Balarishta, an Ayurvedic fermented poly herbal product used to combat the immunological disorder, Rheumatoid Arthritis which is an autoimmune disease triggered by Proteus urinary tract infection through in silico analysis and assay of antimicrobial activity.
Methods: Antibacterial activity of Balarishta against Proteus mirabilis was assessed. Phytochemical analysis was performed by Gas Chromatography-Mass Spectroscopy. Urease interaction proteins were homology modeled based on template constraints and physicochemical parameters and stereo chemical nature of the proteins were analyzed. Rigid and flexible docking was done to study the hydrogen bond interaction patterns between active ingredients of Balarishta and urease interaction proteins.
Results: In Balarishta, 42 bioactive metabolites were identified by Gas Chromatography-Mass Spectroscopy analysis. These metabolites were checked for strong binding affinities against urease subunits and urease accessory proteins of Proteus mirabilis in silico. ureC subunit exhibited high binding to the compound desulphosinigrin (-10.5217 Kcal/mol) followed by lupeol (-10.0308 Kcal/mol) with conserved residue interaction ranging from amino acid residues 308 – 327. Further, lupeol when bound to ureC had 4 hydrogen bonds as compared to desulphosinigrin with 6 hydrogen bonds. Free energy calculations based on flexible docking showed that lupeol had significant binding affinity for ureC with -9.2 Kcal/mol rather than -6.0 Kcal/mol for desulphosinigrin. Both binding has residue conservation - Cys 319, His 320 and His 321. The results corroborated with in vitro antibacterial activity.
Conclusion: It is proposed that Balarishta would be efficient in arresting Rheumatoid Arthritis complicated urinary tract infections.
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