A chemical family-based strategy for uncovering hidden bioactive molecules and multicomponent interactions in herbal medicines

Two concepts involving natural products were proposed and demonstrated in this paper. (1) Natural product libraries (e.g. herbal extract) are not perfect for bioactivity screening because of the vast complexity of compound compositions, and thus a library reconstruction procedure is necessary before screening. (2) The traditional mode of “screening single compound” could be improved to “screening single compound, drug combination and multicomponent interaction” due to the fact that herbal medicines work by integrative effects of multi-components rather than single effective constituents. Based on the two concepts, we established a novel strategy aiming to make screening easier and deeper. Using thrombin as the model enzyme, we firstly uncovered the minor lead compounds, potential drug combinations and multicomponent interactions in an herbal medicine of Dan-Qi pair, showing a significant advantage over previous methods. This strategy was expected to be a new and promising mode for investigation of herbal medicines.

• Publication year

  2016

• Venue

  Scientific Reports

• Publication date

  2016-03-30

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1038/srep23840PMID 27025397PMCID 4812296
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Analysis and improved characterization of minor antioxidants from leaves of Malus doumeri using a combination of major constituents' knockout with high-performance liquid chromatography-diode array detector-quadrupole time-of-flight tandem mass spectrometry.

  2015cited by this paper
• Virtual screening for high affinity guests for synthetic supramolecular receptors

  2015cited by this paper
• A strategy for screening of high-quality enzyme inhibitors from herbal medicines based on ultrafiltration LC-MS and in silico molecular docking.

  2015cited by this paper
• Rational hopping of a peptidic scaffold into non-peptidic scaffolds: structurally novel potent proteasome inhibitors derived from a natural product, belactosin A.

  2014cited by this paper
• Identification of new synthetic PDE-5 inhibitors analogues found as minor components in a dietary supplement.

  2014cited by this paper
• Bioactive Equivalence of Combinatorial Components Identified in Screening of an Herbal Medicine

  2014cited by this paper
• Virtual screening and optimization of Type II inhibitors of JAK2 from a natural product library.

  2014influential reference
• Magnetic ligand fishing combination with high-performance liquid chromatography-diode array detector-mass spectrometry to screen and characterize cyclooxygenase-2 inhibitors from green tea.

  2014cited by this paper
• Screening for selective inhibitors of xanthine oxidase from Flos Chrysanthemum using ultrafiltration LC-MS combined with enzyme channel blocking.

  2014cited by this paper
• The traditional medical uses and cytotoxic activities of sixty-one Egyptian plants: discovery of an active cardiac glycoside from Urginea maritima.

  2013cited by this paper
• Antithrombin Effect of Polyphenol‐Rich Extracts from Black Chokeberry and Grape Seeds

  2013cited by this paper
• An in vitro Study on the DNA Damaging Effects of Phytochemicals Partially Isolated from an Extract of Glinus lotoides

  2013cited by this paper
• The anti-diabetic effects and pharmacokinetic profiles of berberine in mice treated with Jiao-Tai-Wan and its compatibility.

  2013cited by this paper
• Quantitative purity-activity relationships of natural products: the case of anti-tuberculosis active triterpenes from Oplopanax horridus.

  2013cited by this paper
• Tanshinones: Sources, Pharmacokinetics and Anti-Cancer Activities

  2012cited by this paper
• A System-Level Investigation into the Mechanisms of Chinese Traditional Medicine: Compound Danshen Formula for Cardiovascular Disease Treatment

  2012cited by this paper
• ATP-Directed Capture of Bioactive Herbal-Based Medicine on Human tRNA Synthetase

  2012cited by this paper
• Peroxidase-mimic bismuth-gold nanoparticles for determining the activity of thrombin and drug screening.

  2012cited by this paper
• Enhanced chromatographic fingerprinting of herb materials by multi-wavelength selection and chemometrics.

  2012cited by this paper
• Marine natural products.

  2012cited by this paper
• Compatibility art of traditional Chinese medicine: from the perspective of herb pairs.

  2012cited by this paper
• Natural products as sources of new drugs over the 30 years from 1981 to 2010.

  2012cited by this paper
• Searching for the main anti-bacterial components in artificial Calculus bovis using UPLC and microcalorimetry coupled with multi-linear regression analysis.

  2011cited by this paper
• Isolation and identification of degradation products of salvianolic acid A by NMR and LC-MS.

  2011cited by this paper
• Ruggedness and robustness of conversion factors in method of simultaneous determination of multi-components with single reference standard.

  2011cited by this paper
• [Drug discovery and natural products: end of era or an endless frontier?].

  2011cited by this paper
• Chemoselective enrichment for natural products discovery.

  2011cited by this paper
• Privileged scaffolds for library design and drug discovery.

  2010influential reference
• Drug combination studies and their synergy quantification using the Chou-Talalay method.

  2010cited by this paper
• Application of the combination index (CI)-isobologram equation to study the toxicological interactions of lipid regulators in two aquatic bioluminescent organisms.

  2010cited by this paper
• Interaction study of two diterpenes, cryptotanshinone and dihydrotanshinone, to human acetylcholinesterase and butyrylcholinesterase by molecular docking and kinetic analysis.

  2010cited by this paper
• Identification of natural product fonsecin B as a stabilizing ligand of c-myc G-quadruplex DNA by high-throughput virtual screening.

  2010cited by this paper
• Traditional medicine-inspired approaches to drug discovery: can Ayurveda show the way forward?

  2009cited by this paper
• A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity.

  2009cited by this paper
• Drug Discovery and Natural Products: End of an Era or an Endless Frontier?

  2009cited by this paper
• Analysis of Chinese herbal medicines with holistic approaches and integrated evaluation models

  2008cited by this paper
• Natural products in drug discovery.

  2008cited by this paper
• Natural products as a screening resource.

  2007cited by this paper
• Traditional medicine: A culture in the balance

  2007cited by this paper
• High-throughput screening assays for the identification of chemical probes.

  2007cited by this paper
• An Overview of the Structure and Function of Thrombin

  2006cited by this paper
• Theoretical Basis, Experimental Design, and Computerized Simulation of Synergism and Antagonism in Drug Combination Studies

  2006cited by this paper
• High-throughput screening for enzyme inhibitors using frontal affinity chromatography with liquid chromatography and mass spectrometry.

  2005cited by this paper
• The evolving role of natural products in drug discovery

  2005cited by this paper
• Evaluation of Combination Chemotherapy

  2004cited by this paper
• Hydrophobic Collapse in Multidomain Protein Folding

  2004cited by this paper
• How fast is protein hydrophobic collapse?

  2003cited by this paper
• Small molecule affinity fingerprinting. A tool for enzyme family subclassification, target identification, and inhibitor design.

  2002cited by this paper
• Statistical molecular design, parallel synthesis, and biological evaluation of a library of thrombin inhibitors.

  2001cited by this paper
• Marine natural products.

  2000cited by this paper
• Initial hydrophobic collapse in the folding of barstar

  1995cited by this paper
• Structure of a retro-binding peptide inhibitor complexed with human alpha-thrombin.

  1995cited by this paper
• Effects of thrombin inhibition on the development of acute platelet-thrombus deposition during angioplasty in pigs. Heparin versus recombinant hirudin, a specific thrombin inhibitor.

  1989cited by this paper
• Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors.

  1984cited by this paper

• Bioactive compound combinations from Rhodiola tangutica alleviate pulmonary vascular remodeling in high-altitude pulmonary hypertension rats through the PI3K–AKT pathway

  2025cites this paper
• Alcohols as Alkyl Synthons Enabled by Photoredox-Catalyzed Deoxygenative Activation

  2024cites this paper
• Widely targeted metabolomics analysis reveals differences in volatile metabolites among four Angelica species

  2024cites this paper
• Discovery of effective combination from Renshen-Fuzi herbal pair against heart failure by spectrum-effect relationship analysis and zebrafish models.

  2023cites this paper
• Nanotechnology Involved in Treating Urinary Tract Infections: An Overview

  2023cites this paper
• The effects of Boswellia (Frankincense) gel and hydrocolloid dressing on healing of second- and third-degree pressure ulcers among hospitalized patients

  2021cites this paper
• Asiatic Acid Induces Mitochondrial Apoptosis via Inhibition of JAK2/STAT3 Signalling Pathway in Human Osteosarcoma.

  2021cites this paper
• Classification-based strategies to simplify complex traditional Chinese medicine (TCM) researches through liquid chromatography-mass spectrometry in the last decade (2011-2020): Theory, technical route and difficulty.

  2021cites this paper
• LC–MS-based multivariate statistical analysis for the screening of potential thrombin/factor Xa inhibitors from Radix Salvia Miltiorrhiza

  2020cites this paper
• Characterization of thrombin/factor Xa inhibitors in Rhizoma Chuanxiong through UPLC-MS-based multivariate statistical analysis

  2020cites this paper
• Herbal medicine and biotechnology for the benefit of human health

  2020cites this paper
• Quantitative fingerprint and quality control analysis of Compound Liquorice Tablet combined with antioxidant activities and chemometrics methods.

  2019cites this paper
• In vitro antiplasmodial, antitrypanosomal and antileishmanial activities of selected medicinal plants from Ugandan flora: Refocusing into multi-component potentials.

  2019cites this paper
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  2019cites this paper
• Mass Spectrometry-Sensitive Probes Coupled with Direct Analysis in Real Time for Simultaneous Sensing of Chemical and Biological Properties of Botanical Drugs.

  2019cites this paper
• Novel expression of CD11b in epithelial ovarian cancer: Potential therapeutic target.

  2018cites this paper
• A fast and accurate method for the identification of peroxidase inhibitors from Radix Salvia Miltiorrhizae by on-flow biochemical assay coupled with LC/Q-TOF-MS: comparison with ultrafiltration-based affinity selection

  2018cites this paper
• Bioactive fraction of Rhodiola algida against chronic hypoxia-induced pulmonary arterial hypertension and its anti-proliferation mechanism in rats.

  2018cites this paper
• Uncovering potential anti‐neuroinflammatory components of Modified Wuziyanzong Prescription through a target‐directed molecular docking fingerprint strategy

  2018cites this paper
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  2017cites this paper
• Chapter 1 – Traditional Chinese Medicine: Current State, Challenges, and Applications

  2017cites this paper
• Simultaneous determination of hydrophilic and lipophilic constituents in herbal medicines using directly-coupled reversed-phase and hydrophilic interaction liquid chromatography-tandem mass spectrometry

  2017cites this paper
• Specific point mutations in key redox enzymes are associated with chemoresistance in epithelial ovarian cancer

  2017cites this paper
• Label-free pharmacological profiling based on dynamic mass redistribution for characterization and authentication of hazardous natural products.

  2017cites this paper
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  2017cites this paper
• Comparative analysis of the main bioactive components of Xin-Sheng-Hua granule and its single herbs by ultrahigh performance liquid chromatography with tandem mass spectrometry.

  2016cites this paper
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  2016cites this paper