Zhou Peng, Hua Fang
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, People's Republic of China.
Pharmacy School, Anhui Xinhua University, Hefei 230088, China.
Acta Pharm. 2019 Nov 1;70(1):111-119. doi: 10.2478/acph-2019-0056. Print 2020 Mar 1.
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 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.
本研究旨在通过计算预测白藜芦醇、塞来昔布、来氟米特与人血清白蛋白（HSA）之间的分子相互作用，然后采用超滤技术研究白藜芦醇与塞来昔布或来氟米特联合使用时的血浆蛋白结合情况。使用分子操作环境（MOE，2008.10）软件包来探究药物与HSA之间的分子相互作用。采用分子对接来预测白藜芦醇与其他药物之间的相互作用，然后使用超滤技术验证对接结果。在实验中，将白藜芦醇与塞来昔布或来氟米特的混合物添加到大鼠血浆中，以测定血浆蛋白结合率。分子对接结果表明，白藜芦醇主要通过氢键和π-π堆积与HSA相互作用，而塞来昔布和来氟米特仅通过氢键结合。即使在高测试剂量下，塞来昔布或来氟米特也不影响白藜芦醇的血浆蛋白结合，因此表明所研究的组合在药理学上具有适用性。
