title: A strategy for the identification of combinatorial bioactive compounds contributing to the holistic effect of herbal medicines.
abstract: It has been well claimed that herbal medicines (HMs) elicit effects via a multi-compounds and multi-targets synergistic mode. However, it lacks appropriate strategies to uncover the combinatory compounds that take effect together and contribute to a certain pharmacological effect of an herb as a whole, which represents a major bottleneck in providing sound evidence in supporting the clinic benefits of HMs. Here, we proposed a strategy to the identification of combinatory compounds contributing to the anti-inflammatory activity of Cardiotonic Pill (CP). The strategy proposed herein contains four core steps, including the identification of bioequivalent combinatorial compounds, chemical family classification-based combinatorial screen, interactive mode evaluation, and activity contribution index assay. Using this strategy, we have successfully identified six compounds in combination responsible for the anti-inflammatory effect of CP, whose anti-inflammatory activities were found comparable to that of the whole CP. Additionally, these six compounds take effect via an additive mode but little synergism. This study, together with our recent work in the identification of bioactive equivalent compounds combination, provides a widely applicable strategy to the identification of combinatory compounds responsible for a certain pharmacological activity of HMs.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Long
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Haiping
authors.initials: H
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology; D001685:Biological Factors / Q000737:chemistry* / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000494:pharmacology*; D029001:Herbal Medicine / Q000379:methods; D051379:Mice; D010946:Plants, Medicinal / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D001685:Biological Factors; D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal