Abstract
Atorvastatin, an HMG-CoA reductase inhibitor, has been employed in the current study with animal models. In vitro models comprised of theimally induced Bovine serum albumin denaturation and egg albumin denaturation along with membrane stabilization assay while in vivo study involves founaldehyde induced arthritis. Paw swelling, arthritic score and body weight was evaluated for a period of 10 days after induction with formaldehyde. Histological analysis of ankle joint was also performed on 10th day. Molecular docking was done by targeting BSA (PDB id 4JK4), Histamine H1 receptor (PDB id 3RZE) and Prostaglandin E2 (PDB id 5YWY) to explore binding interactions of atorvastatin with BSA, Histamine H1 receptor and Prostaglandin E2. Atorvastatin revealed protein denaturation inhibition and stabilization of RBC membrane in a concentration dependent manner, with maximal effect at the concentration of 6400 mu g/ml. Likewise, at the dose of 40mg/kg maximum attenuation of paw edema was being observed. Significant reduction in arthritic indices with body weight increment was observed in atorvastatin and standard drug treated groups. Histological investigation unveiled no substantive structural alterations in ankle joints of treated rats in comparison to arthritic control group. Molecular docking analysis of atorvastatin with the selected three targets revealed that the drug displayed strong binding interactions with BSA, Histamine H1 receptor and PGE2. Thus it can be concluded on the basis of aforementioned results that atorvastatin provided significant protection against arthritis by multiple mechanism and should be considered for further phaimacological evaluation to point out the exact mechanism of action.