In-silico profiling of phenolic acids for gallstone prevention: a basis for in-vitro studies in high physical activity and rapid weight loss
DOI:
https://doi.org/10.47197/retos.v68.116454Keywords:
ADMET, bile acid metabolism, gallstone disease, molecular docking, phenolic acids, physical activity, rapid weight loss, sports medicine, sinapic acidAbstract
Background: Cholelithiasis is increasingly seen in individuals with rapid weight loss or high physical stress, such as athletes. Existing therapies like ursodeoxycholic acid have limited efficacy, prompting interest in safer natural options.
Aim: To assess the anti-cholelithiatic potential of selected phenolic acids via molecular docking and pharmacokinetic profiling.
Methodology: Molecular docking, ADMET analysis, and molecular dynamics simulations were performed for sinapic, p-coumaric, caffeic, and ferulic acids, focusing on targets involved in cholesterol and bile acid regulation (LXR, FXR, PPAR-γ, NPC1L1). Tools used included AutoDock 4.2, SwissADME, and GROMACS 2019.4.
Results: Sinapic acid showed the strongest binding with LXR (-6.65 kcal/mol), suggesting enhanced cholesterol efflux, while p-coumaric acid showed significant interaction with FXR (-4.86 kcal/mol), implicating a role in bile acid regulation. Both compounds exhibited stable binding and favourable pharmacokinetics with low toxicity.
Conclusion: Sinapic and p-coumaric acids appear promising for gallstone prevention, particularly in active individuals or those with rapid weight loss, warranting further in-vitro, in-vivo, and clinical studies.
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