Acta Pharm. 70 (2020) 111-119


full paper

Short communication


Prediction of drug-drug plasma protein binding interactions of resveratrol in combination with celecoxib and leflunomide by molecular docking combined with an ultrafiltration technique


1 Department of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine Research, Institute of Integrated Traditional Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Key Laboratory of Chinese Herbal Compound Formula in Anhui Province, Hefei 230012, China

2 Pharmacy School, Anhui Xinhua University, Hefei 230088, China

3 Natural Products Laboratory, International Joint Lab of Tea Chemistry and Health Effects, State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei 230036, China

Accepted March 20, 2019

Published online April 8, 2019


The present study is aimed at computational prediction of the molecular interactions between resveratrol, celecoxib, leflunomide and human serum albumin (HSA) and then investigates the plasma protein binding of resveratrol combined with celecoxib or leflunomide by an ultrafiltration technique. Molecular operating environment (MOE, 2008.10) software package was used to explore molecular interactions between the drugs and HSA. Molecular docking was adopted to predict the interactions between resveratrol and other drugs and then the ultrafiltration technique was used to verify the docking results. In in vitro experiments, a mixture of resveratrol and celecoxib or leflunomide was added to rat plasma for determination of the plasma protein binding rate. Molecular docking results have shown that resveratrol interacts with HSA mainly through hydrogen bond and π-π stacking, while celecoxib and leflunomide bind only with the hydrogen bond. Celecoxib or leflunomide, even at high tested doses, did not affect the plasma protein binding of resveratrol, thus suggesting pharmacological suitability of the investigated combinations.


Keywords: resveratrol, celecoxib, leflunomide, molecular docking, plasma protein binding, ultrafiltration