title: Screening of minor bioactive compounds from herbal medicines by in silico docking and the trace peak exposure methods.
abstract: Screening of high potent enzyme inhibitors from herbal medicines is always lacking of efficiency due to the complexity of chemicals. The constituents responsible for the holistic effect may be trace-level chemicals, but these chemicals were covered by highly abundant compositions. To challenge this bottleneck, a strategy for screening minor bioactive compounds was proposed. It generally included four steps, (1) preliminarily find the enzyme binders by ultrafiltration; (2) optimise and predict the potential inhibitors by docking analysis; (3) selectively identify and prepare trace compounds by segment and exposure approach; (4) validate the activity and summarize the structure-activity relationship. As a case study, α-glucosidase (AGH) and Ginkgo biloba extract were used as the experimental materials. By comprehensive screening, 11 trace flavones were screened out and identified as strong AGH inhibitors. Among them, AGH inhibitory activities of syringetin and sciadopitysin were reported for the first time. Their IC50 values were 36.80 and 8.29μM, respectively, which were lower than that of a positive control acarbose. In addition, the AGH inhibitory activities of the flavonoids could be ranked, based on a decreased order, as biflavone, flavone, flavone glycoside, flavone biglycoside. The strategy is expected to be practical and useful for screening bioactive molecules from herbal medicines, especially for the minor compounds, which will definitely accelerate the discovery of new drug candidates.
authors: State Key Laboratory of Natural Medicines (China Pharmaceutical University), Nanjing 210009, China.
authors: Bin
authors: B
authors: Wu
authors: State Key Laboratory of Natural Medicines (China Pharmaceutical University), Nanjing 210009, China.
authors: Hui-Peng
authors: HP
authors: Song
authors: State Key Laboratory of Natural Medicines (China Pharmaceutical University), Nanjing 210009, China.
authors: Xu
authors: X
authors: Zhou
authors: State Key Laboratory of Natural Medicines (China Pharmaceutical University), Nanjing 210009, China.
authors: Xin-Guang
authors: XG
authors: Liu
authors: State Key Laboratory of Natural Medicines (China Pharmaceutical University), Nanjing 210009, China.
authors: Wen
authors: W
authors: Gao
authors: State Key Laboratory of Natural Medicines (China Pharmaceutical University), Nanjing 210009, China.
authors: Xin
authors: X
authors: Dong
authors: State Key Laboratory of Natural Medicines (China Pharmaceutical University), Nanjing 210009, China.
authors: Hui-Jun
authors: HJ
authors: Li
authors: State Key Laboratory of Natural Medicines (China Pharmaceutical University), Nanjing 210009, China. Electronic address: liping2004@126.com.
authors: Ping
authors: P
authors: Li
authors: State Key Laboratory of Natural Medicines (China Pharmaceutical University), Nanjing 210009, China. Electronic address: 104yang104@163.com.
authors: Hua
authors: H
authors: Yang
mesh_terms: D044946:Biflavonoids / Q000032:analysis*; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000032:analysis; D005419:Flavonoids / Q000032:analysis*; D020441:Ginkgo biloba / Q000737:chemistry; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry; D006027:Glycosides / Q000032:analysis*; D062105:Molecular Docking Simulation; D010936:Plant Extracts / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014462:Ultrafiltration / Q000379:methods; D000520:alpha-Glucosidases / Q000737:chemistry
chemical_list: D044946:Biflavonoids; D004791:Enzyme Inhibitors; D005419:Flavonoids; D065089:Glycoside Hydrolase Inhibitors; D006027:Glycosides; D010936:Plant Extracts; C546494:syringetin; C086243:sciadopitysin; D000520:alpha-Glucosidases
keywords: Docking; Ginkgo; LC-QTOF MS; Minor bioactive compounds; Trace peak exposure; Ultrafiltration