title: Identification of effective combinatorial markers for quality standardization of herbal medicines.
abstract: Quality standardization of herbal medicines (HMs) is an important task with great challenges. Selection of abundant compounds as markers is currently a major approach for the quality control of HMs; however, such marker compounds are irrelevant to the bioactivities in many cases. Taking Lycoridis Radiatae Bulbus (LRB) as an example, we proposed a universal strategy to identify the effective combinatorial markers (ECMs) that are representative of the bioactivities of HMs, and took them as chemical markers for quality standardization. Fingerprinting and quantification were employed to find out the common components in various batches of medicines. The contribution of each common compound to the overall bioactivity was determined through fingerprint-bioactivity modeling, which based on the absolute quantification of each compound and the acetylcholinesterase (AChE) inhibitory activity of LRB. Two most effective compounds, ungerimine and galanthamine, were therefore proposed as ECMs. Interestingly, these two compounds could synergistically inhibit AChE. This approach demonstrated its strong advantage of the bioactivity relevant quality assessment when compared with conventional methods. And the success of applying this ECMs-based method to the quality assessment of unknown LRB samples proved that our approach was reliable and reproducible. In conclusion, this approach is not only useful for the bioactivity relevant quality control of HMs but also helpful for the discovery of ECMs as new drug candidates.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zi-Qi
authors.initials: ZQ
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: De-Fang
authors.initials: DF
authors.lastname: Song
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ruo-Qian
authors.initials: RQ
authors.lastname: Li
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: Lian-Wen
authors.initials: LW
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Gui-Zhong
authors.initials: GZ
authors.lastname: Xin
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ding-Qian
authors.initials: DQ
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hui-Peng
authors.initials: HP
authors.lastname: Song
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: hhp_770505@126.com.
authors.forename: Haiping
authors.initials: H
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: liping2004@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000032:analysis*; D004365:Drugs, Chinese Herbal / Q000032:analysis / Q000737:chemistry; D029001:Herbal Medicine / Q000592:standards*; D006801:Humans; D013058:Mass Spectrometry; D010946:Plants, Medicinal / Q000737:chemistry*; D011786:Quality Control
chemical_list: D002800:Cholinesterase Inhibitors; D004365:Drugs, Chinese Herbal; D000110:Acetylcholinesterase
keywords: Alkaloids; Drug discovery; Effective combinatorial markers; Lycoridis Radiatae Bulbus; Quality control; Synergistic effects