A Comprehensive Review of Integrative Pharmacology-based Investigation: A Paradigm Shift in Traditional Chinese Medicine

Overview

Journal Acta Pharm Sin B

Publisher Elsevier

Specialty Pharmacology

Date 2021 Jul 5

PMID 34221858

Citations 45

Authors

Haiyu Xu

Yanqiong Zhang

Ping Wang

Junhong Zhang

Hong Chen

Luoqi Zhang

Xia Du

Chunhui Zhao

Dan Wu

Feng Liu

Hongjun Yang

Changxiao Liu

Affiliations

Soon will be listed here.

Abstract

Over the past decade, traditional Chinese medicine (TCM) has widely embraced systems biology and its various data integration approaches to promote its modernization. Thus, integrative pharmacology-based traditional Chinese medicine (TCMIP) was proposed as a paradigm shift in TCM. This review focuses on the presentation of this novel concept and the main research contents, methodologies and applications of TCMIP. First, TCMIP is an interdisciplinary science that can establish qualitative and quantitative pharmacokinetics-pharmacodynamics (PK-PD) correlations through the integration of knowledge from multiple disciplines and techniques and from different PK-PD processes . Then, the main research contents of TCMIP are introduced as follows: chemical and ADME/PK profiles of TCM formulas; confirming the three forms of active substances and the three action modes; establishing the qualitative PK-PD correlation; and building the quantitative PK-PD correlations, etc. After that, we summarize the existing data resources, computational models and experimental methods of TCMIP and highlight the urgent establishment of mathematical modeling and experimental methods. Finally, we further discuss the applications of TCMIP for the improvement of TCM quality control, clarification of the molecular mechanisms underlying the actions of TCMs and discovery of potential new drugs, especially TCM-related combination drug discovery.

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References

Patridge E, Gareiss P, Kinch M, Hoyer D . An analysis of FDA-approved drugs: natural products and their derivatives. Drug Discov Today. 2015; 21(2):204-7. DOI: 10.1016/j.drudis.2015.01.009. View

Szklarczyk D, Santos A, von Mering C, Jensen L, Bork P, Kuhn M . STITCH 5: augmenting protein-chemical interaction networks with tissue and affinity data. Nucleic Acids Res. 2015; 44(D1):D380-4. PMC: 4702904. DOI: 10.1093/nar/gkv1277. View

Haiyu X, Yang S, Yanqiong Z, Qiang J, Defeng L, Yi Z . Identification of key active constituents of Buchang Naoxintong capsules with therapeutic effects against ischemic stroke by using an integrative pharmacology-based approach. Mol Biosyst. 2015; 12(1):233-45. DOI: 10.1039/c5mb00460h. View

Li C, Chen H, Liu W, Rui W . Multi-fingerprint profiling combined with chemometric methods for investigating the quality of Astragalus polysaccharides. Int J Biol Macromol. 2018; 123:766-774. DOI: 10.1016/j.ijbiomac.2018.11.037. View

Huang Z, Fan X, Wang Y, Liang Q, Tong X, Bai Y . A new method to evaluate the dose-effect relationship of a TCM formula Gegen Qinlian Decoction: "Focus" mode of integrated biomarkers. Acta Pharmacol Sin. 2017; 38(8):1141-1149. PMC: 5547551. DOI: 10.1038/aps.2016.165. View

Salwinski L, Miller C, Smith A, Pettit F, Bowie J, Eisenberg D . The Database of Interacting Proteins: 2004 update. Nucleic Acids Res. 2003; 32(Database issue):D449-51. PMC: 308820. DOI: 10.1093/nar/gkh086. View

Blatti C, Sinha S . Characterizing gene sets using discriminative random walks with restart on heterogeneous biological networks. Bioinformatics. 2016; 32(14):2167-75. PMC: 4937193. DOI: 10.1093/bioinformatics/btw151. View

Jiao Q, Wang R, Jiang Y, Liu B . Study on the interaction between active components from traditional Chinese medicine and plasma proteins. Chem Cent J. 2018; 12(1):48. PMC: 5935606. DOI: 10.1186/s13065-018-0417-2. View

An X, Bao Q, Di S, Zhao Y, Zhao S, Zhang H . The interaction between the gut Microbiota and herbal medicines. Biomed Pharmacother. 2019; 118:109252. DOI: 10.1016/j.biopha.2019.109252. View

10.

Wang Z, Liu J, Cheng Y, Wang Y . Fangjiomics: in search of effective and safe combination therapies. J Clin Pharmacol. 2011; 51(8):1132-51. DOI: 10.1177/0091270010382913. View

11.

Chong J, Xia J . Using MetaboAnalyst 4.0 for Metabolomics Data Analysis, Interpretation, and Integration with Other Omics Data. Methods Mol Biol. 2020; 2104:337-360. DOI: 10.1007/978-1-0716-0239-3_17. View

12.

Zhao K, Li B, He D, Zhao C, Shi Z, Dong B . Chemical characteristic and bioactivity of hemicellulose-based polysaccharides isolated from Salvia miltiorrhiza. Int J Biol Macromol. 2020; 165(Pt B):2475-2483. DOI: 10.1016/j.ijbiomac.2020.10.113. View

13.

Rappaport N, Twik M, Plaschkes I, Nudel R, Iny Stein T, Levitt J . MalaCards: an amalgamated human disease compendium with diverse clinical and genetic annotation and structured search. Nucleic Acids Res. 2016; 45(D1):D877-D887. PMC: 5210521. DOI: 10.1093/nar/gkw1012. View

14.

Shen J, Mo X, Tang Y, Zhang L, Pang H, Qian Y . Analysis of herb-herb interaction when decocting together by using ultra-high-performance liquid chromatography-tandem mass spectrometry and fuzzy chemical identification strategy with poly-proportion design. J Chromatogr A. 2013; 1297:168-78. DOI: 10.1016/j.chroma.2013.05.001. View

15.

Tian J, Shi J, Zhang X, Wang Y . Herbal therapy: a new pathway for the treatment of Alzheimer's disease. Alzheimers Res Ther. 2010; 2(5):30. PMC: 2983439. DOI: 10.1186/alzrt54. View

16.

Chen Z, Quan L, Zhou H, Zhao Y, Chen P, Hu L . Screening of active fractions from Curcuma Longa Radix isolated by HPLC and GC-MS for promotion of blood circulation and relief of pain. J Ethnopharmacol. 2018; 234:68-75. DOI: 10.1016/j.jep.2018.09.035. View

17.

Wang P, Li K, Tao Y, Li D, Zhang Y, Xu H . TCM-ADMEpred: A novel strategy for poly-pharmacokinetics prediction of traditional Chinese medicine based on single constituent pharmacokinetics, structural similarity, and mathematical modeling. J Ethnopharmacol. 2019; 236:277-287. DOI: 10.1016/j.jep.2018.07.008. View

18.

Wang Y, Wang X, Wang J, Li B, Yu R, Hu Y . Tongmai Yangxin intervening in myocardial remodeling after PCI for coronary heart disease: study protocol for a double-blind, randomized controlled trial. Trials. 2020; 21(1):287. PMC: 7085139. DOI: 10.1186/s13063-020-4208-4. View

19.

Huang X, Zhang S, Ma Y, Yang H, He C, Tian R . Bioequivalence of two quetiapine extended release tablets in Chinese healthy volunteers under fasting and fed conditions and effects of food on pharmacokinetic profiles. Drug Des Devel Ther. 2019; 13:255-264. PMC: 6319427. DOI: 10.2147/DDDT.S182965. View

20.

LeCluyse E . Human hepatocyte culture systems for the in vitro evaluation of cytochrome P450 expression and regulation. Eur J Pharm Sci. 2001; 13(4):343-68. DOI: 10.1016/s0928-0987(01)00135-x. View