A strategy for screening active lead compounds and functional compound combinations from herbal medicines based on pharmacophore filtering and knockout/knockin chromatography.
Screening and deciphering active natural products of herbal medicines are of great importance for modern drug discovery. In this study, a novel strategy was proposed to rapidly filter ineffective compounds and target the most potential leads. The aim is to answer the key question of what components are responsible for the holistic bioactivity of an herbal product. To support the strategy, the pharmacophore-guided knockout/knockin chromatography was established for the first time. The greatest advantage of this method is that any interesting components could be automatically fished or knocked out. The method validation shows that the herbal extract was accurately reconstructed according to the experimental design. By combining with bioactivity assays, we demonstrated that "functional compound combination (FCC)", which is the core and indispensable effective part, could be discovered from an herbal medicine and suitable as marker compounds for quality control. The applicable objects of the strategy include single herbs, herbal formulas and commercially herbal preparations. As an illustrative case study, the strategy was successfully applied to simultaneously determine active leads and the FCC in Dan-Qi formula which shows excellent free radical scavenging activity. The potential mechanisms of compounds in Dan-Qi formula reacting with three different free radicals were systematically reported for the first time. This strategy was expected to unveil the mystery of herbal medicines and inspire a natural product-based drug discovery.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Hui-Peng
HP
Song
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Si-Qi
SQ
Wu
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Lian-Wen
LW
Qi
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Fang
F
Long
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Li-Feng
LF
Jiang
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Ke
K
Liu
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Hao
H
Zeng
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Zhi-Meng
ZM
Xu
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: liping2004@126.com.
Ping
P
Li
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: 104yang104@163.com.
Hua
H
Yang
D002845:Chromatography / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D055808:Drug Discovery / Q000379:methods; D016166:Free Radical Scavengers / Q000737:chemistry; D029001:Herbal Medicine; D057166:High-Throughput Screening Assays; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry; D028321:Plant Preparations / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry*; D011786:Quality Control; D015203:Reproducibility of Results
D016166:Free Radical Scavengers; D010936:Plant Extracts; D028321:Plant Preparations
Herbal medicine; High-throughput screening; Knockout/knockin chromatography; Lead compound; QTOF mass; Quality control