title: Exploring the interaction between Salvia miltiorrhiza and human serum albumin: Insights from herb-drug interaction reports, computational analysis and experimental studies.
abstract: Human serum albumin (HSA) binding is one of important pharmacokinetic properties of drug, which is closely related to in vivo distribution and may ultimately influence its clinical efficacy. Compared to conventional drug, limited information on this transportation process is available for medicinal herbs, which significantly hampers our understanding on their pharmacological effects, particularly when herbs and drug are co-administrated as polytherapy to the ailment. Several lines of evidence suggest the existence of Salvia miltiorrhiza-Warfarin interaction. Since Warfarin is highly HSA bound in the plasma with selectivity to site I, it is critical to evaluate the possibility of HSA-related herb-drug interaction. Herein an integrated approach was employed to analyze the binding of chemicals identified in S. miltiorrhiza to HSA. Molecular docking simulations revealed filtering criteria for HSA site I compounds that include docking score and key molecular determinants for binding. For eight representative ingredients from the herb, their affinity and specificity to HSA site I was measured and confirmed fluorometrically, which helps to improve the knowledge of interaction mechanisms between this herb and HSA. Our results indicated that several compounds in S. miltiorrhiza were capable of decreasing the binding constant of Warfarin to HSA site I significantly, which may increase free drug concentration in vivo, contributing to the herb-drug interaction observed clinically. Furthermore, the significance of HSA mediated herb-drug interactions was further implied by manual mining on the published literatures on S. miltiorrhiza.
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Science, Zhejiang University, Hangzhou, Zhejiang, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Shao
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Science, Zhejiang University, Hangzhou, Zhejiang, PR China. Electronic address: ai_ni@zju.edu.cn.
authors.forename: Ni
authors.initials: N
authors.lastname: Ai
authors.affiliation: Department of Pharmacy, The 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, PR China. Electronic address: xudonghang@zju.edu.cn.
authors.forename: Donghang
authors.initials: D
authors.lastname: Xu
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Science, Zhejiang University, Hangzhou, Zhejiang, PR China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Fan
mesh_terms: D000925:Anticoagulants / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D041743:Herb-Drug Interactions; D006801:Humans; D062105:Molecular Docking Simulation; D011485:Protein Binding; D027561:Salvia miltiorrhiza / Q000737:chemistry / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism*; D014859:Warfarin / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D004365:Drugs, Chinese Herbal; D012709:Serum Albumin; D014859:Warfarin
keywords: Docking; Fluorescence; Herb–drug interactions; Human serum albumin; Salvia miltiorrhiza; Warfarin