Evaluation Of Anti-Cholelithiatic Activity Of Phenolic Acids: In-Silico And In-Vitro Approach
Abstract
Worldwide, cholelithiasis, or gallstone disease, is a prevalent gastrointestinal disease. It is marked by biliary colic in the bile ducts and is linked to a high rate of morbidity and death. Gallstone disease has a complicated pathogenesis.Cholecystectomy(removal of gall bladder ) is the only treatment for cholelithiasis. The aim of this study is to evaluate the potential of phenolic acid (vanillic acid) and safe alternative for gallstone dissolution. In this research, we employed computational modeling techniques (in-silico) using ligand -protein approach to predict the interactions between phenolic acids and key biomolecular targets implicated in cholelithiasis formation. The In-silico and In-vitro methods are used to evaluate phenolic acids for anti-cholelithiatic activity. Docking were performed with several receptors such as Vascular endothelial growth factor receptor 2 (VEGFR-2),Tumour Necrosis Factor alpha(TNFα), Peroxisome proliferator-activated receptor gamma (PPARγ), Interleukin-6 (IL-6), and Hydroxymethy lglutaryl-CoA (HMG CoA) and phenolic acids such as chlorogenic acid,coumaric acid,Caffeic acid ,Ferulic acid and Vanillic acid .Based on high binding affinity from In-silico method,In-vitro study was performed.For In-vitro anti-cholelithiatic method,cholesterol human gall stone were collected along with human bile from the hospital.The treatment was performed between standard drug Ursodeoxycholic acid (UDCA) 2mg/ml and test drug (Vanillic acid-2mg/ml,7mg/ml) which was incubated for 4 weeks. Weight of gall stone and the amount of cholesterol release in the bile before and after treatment were evaluated.The results of the In-silico show that vanillic acid has high binding affinity when compared to other phenolic acids .From In vitro study , the vanillic acid exert decrease in the weight of cholesterol gall stone and increase in the amount of cholesterol released from gall stone.Vanillic acid also shows morphological alterations in gallstone. The present study provides an overview of the pharmacological and clinical potential of the phenolic acids (Vanillic acid).Further ,In-vivo studies should be carried for understanding the mechanism or pathway behind vanillic acid over anti-cholelithiatic activity.
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