Top Banner

Click here to load reader

of 49

Content Overview of TCM TCM and systems biology Computer methods and databases of TCM

Mar 15, 2016

ReportDownload

Documents

Lecture 8 Bioinformatics of TCM Y.Z. Chen Department of Pharmacy National University of Singapore Tel: 65-6616-6877; Email: [email protected] ; Web: http://bidd.nus.edu.sg. Content Overview of TCM TCM and systems biology Computer methods and databases of TCM Bioinformatics and TCM. - PowerPoint PPT Presentation

  • Lecture 8 Bioinformatics of TCM

    Y.Z. Chen Department of PharmacyNational University of Singapore Tel: 65-6616-6877; Email: [email protected] ; Web: http://bidd.nus.edu.sg

    ContentOverview of TCM TCM and systems biologyComputer methods and databases of TCMBioinformatics and TCM

    Essential Bioinformatics and Biocomputing (LSM2104)

  • TCM History

    The history of TCM can be summarized by a list of important doctors and books.Unknown, Hungd nijng (/) (Yellow Emperor's Inner Canon) - Swn (/) and Lngsh (/). The earliest classic of TCM passed on to the present.Warring States Period (5th century BC to 221 BC): Silk manuscripts recording channels and collaterals, Zubi shiyi mai jiu jing (/) (Moxibustion Classic of the Eleven Channels of Legs and Arms), and Yinyang shiyi mai jiu jing (/) (Moxibustion Classic on the Eleven Yin and Yang Channels). The latter was part of a cache of texts found in Mawangdui in the 1970s.

  • TCM History

    Han Dynasty (206 BCAD 220) to Three Kingdoms Period (220 - 280 AD): Zhenjiu zhenzhong jing (/) (Classic of Moxibustion and Acupuncture Preserved in a Pillow) by Hu Tu (/).Shanghan zabing lun (/), which has since been split into two texts: the Shnghn ln (/) ("Treatise on Cold Damage [Disorders]" - focusing on febrile conditions attributed to "Cold") and the Jingui yaolue () ("Essentials of the Golden Cabinet" - focusing on "miscellaneous illnesses") by Zhng Zhngjng (/).Jn Dynasty (265-420): Zhnji jiy jng (/) (Systematic Classic of Acupuncture and Moxibustion) by Hungf M (/).

    Essential Bioinformatics and Biocomputing (LSM2104)

  • TCM History

    Tang Dynasty (618907)Beiji qianjin yaofang (/) (Emergency Formulas Worth a Thousand in Gold) and Qianjin yifang () (Supplement to the Formulas Worth a Thousand in Gold) by Sn Smio (/).Waitai miyao (/) (Arcane Essentials from the Imperial Library) by Wang Tao (/).Song Dynasty (960 1279):Tngrn shxu zhnji tjng (/) (Illustrated Manual of the Practice of Acupuncture and Moxibustion at (the Transmission) (and other) Acu-points, for use with the Bronze Figure) by Wng Wiy ().Yuan Dynasty (1271 to 1368): Shs jng fhu (/) (Exposition of the Fourteen Channels) by Hu Shu (/).

    Essential Bioinformatics and Biocomputing (LSM2104)

  • TCM History

    Ming Dynasty (1368 to 1644): golden age of acupuncture and moxibustion. Many famous doctors and books. To name only a few:Zhnji dquan (/) (A Complete Collection of Acupuncture and Moxibustion) by Xu Feng (/).Zhnji jyng fhu (/) (An Exemplary Collection of Acupuncture and Moxibustion and their Essentials) by Go W ().Zhnji dchng (/) (Compendium of Acupuncture and Moxibustion) by Yng Jzhu (/), completed in 1601.Bnco gngm (/) (Compendium of Materia Medica) by L Shzhn (/), the most complete and comprehensive pre-modern herbal book (completed in 1578).Wenyi lun (/), by Wu Youxing (1642).

    Essential Bioinformatics and Biocomputing (LSM2104)

  • TCM History

    Qing Dynasty (1644-1912):Yizong jinjian (/) (Golden Mirror of the Medical Tradition) compiled by Wu Qian (/) under imperial commission.Zhenjiu fengyuan (/) (The Source of Acupuncture and Moxibustion) by Li Xuechuan (/).Wenre lun (/), by Ye Tianshi (/).Wenbing tiaobian (/) (Systematized Identification of Warm-factor disorders) compiled by Wu Jutong () in 1798.

    Essential Bioinformatics and Biocomputing (LSM2104)

  • Classification of TCM herbs based on traditional therapeutic classes

    Essential Bioinformatics and Biocomputing (LSM2104)

  • Classification of TCM herbs based on traditional therapeutic classes

    Essential Bioinformatics and Biocomputing (LSM2104)

  • Classification of TCM herbs based on traditional therapeutic classes

    Essential Bioinformatics and Biocomputing (LSM2104)

  • Classification of TCM herbs in traditional therapeutic classes

    Essential Bioinformatics and Biocomputing (LSM2104)

  • Classification of TCM herbs based on traditional therapeutic classes

    Essential Bioinformatics and Biocomputing (LSM2104)

  • TCM Therapeutics

    Potentially novel therapeutic approachesExisting markets in certain countries and potential market in othersPharmacology & Therapeutics 2000, 86:191-198

    Essential Bioinformatics and Biocomputing (LSM2104)

  • TCM Therapeutics

    Need for standardization, validation, & further developmentMarkers for standardizationMolecular mechanismSafety and efficacy testsNew recipes, combination drug mimicsPharmacology & Therapeutics 2000, 86:191-198

    Essential Bioinformatics and Biocomputing (LSM2104)

  • TCM Therapeutics

    Multiple herb therapiesCollective synergistic actions, maintenance and balance.

    Mutual accentuation mutual enhancement mutual counteraction mutual suppression mutual antagonism mutual incompatibility

    Pharmacology & Therapeutics 2000, 86:191-198

  • TCM Therapeutics

    Multiple targets: therapeutic effectssymptom treatmenttoxicity modulationImmune regulation drug delivery energy metabolismharmonizationPharmacology & Therapeutics 2000, 86:191-198

    Essential Bioinformatics and Biocomputing (LSM2104)

  • TCM Therapeutics

    Essential Bioinformatics and Biocomputing (LSM2104)

  • TCM Therapeutics

    Essential Bioinformatics and Biocomputing (LSM2104)

  • Systems: the way for TCM to produce clinical effectsFact1: Weak effect of componentsFact2: Validated effect of TCM by clinical practiceInference: Interaction among componentsDirect Interaction(seldom)Indirect Interaction(often)TCM relatedBiological systemSystems are the targets of TCM function

    TCM function

    Essential Bioinformatics and Biocomputing (LSM2104)

  • Targeting systems: interpreting the mechanism of TCM functionDirect Interaction(seldom)Indirect Interaction(often)TCM relatedBiological systemMechanism of TCM function

    Essential Bioinformatics and Biocomputing (LSM2104)

  • Targeting systems: bridging biology and TCM theoryDirect Interaction(seldom)Indirect Interaction(often)TCM relatedBiological systemTCM functionTCM theory

    Essential Bioinformatics and Biocomputing (LSM2104)

  • Targeting systems: providing new cues for the treatment of complex diseaseDirect Interaction(seldom)Indirect Interaction(often)TCM relatedBiological systemTCM functionTCM theoryValidated clinical prescription

    Essential Bioinformatics and Biocomputing (LSM2104)

  • Targeting systems: providing new resource for drug developmentDirect Interaction(seldom)Indirect Interaction(often)TCM relatedBiological systemTCM functionTCM theoryValidated clinical prescription Impact based molecular target selection Remote interruption of systems Complex drugs

    Essential Bioinformatics and Biocomputing (LSM2104)

  • A Proposed Platform for System-targeting TCM researchDatabaseTCMpathwaymoltargetsActivecompntsbiosystems

    Essential Bioinformatics and Biocomputing (LSM2104)

  • Biological Systems related with TCM Prescriptions that Promoting Blood Circulation and Removing Blood Stasis Map00590:prostaglandin and leukotriene metabolismMap00230: purine metablismMap00100: biosynthesis of steroidsMap00531: glycosaminoglycan degradationMap00010: glycolysis/gluconeogenesis

    Essential Bioinformatics and Biocomputing (LSM2104)

  • Galle Hardy, et. al.Urinary leukotriene E4 excretion is increased in type 1 diabetic patientsA quantification by liquid chromatographytandem mass spectrometry.Prostaglandins Other Lipid Mediat. 2005. 78(1-4):291-299 220 papers title inCNKI containing:promoting blood circulation and removing blood stasis+ diabetesBiological Systems related with TCM Prescriptions that Promoting Blood Circulation and Removing Blood Stasis

    Essential Bioinformatics and Biocomputing (LSM2104)

  • Computer Analysis of Molecular Mechanism of TCMY.Z. Chen and D.G. ZhiProteins 2001;43: 217 Traditional Medicine DatabaseHerbal Ingredient& ContentDatabase TherapeuticTarget Database Drug AdverseReactionTarget Database Drug AbsorptionDistributionMetabolismExcretion Database ComputerMatch-MakingSoftwareHerbalIngredientTherapeutic TargetToxicity TargetADME proteinCollective therapeutic and maintenance effectsToxicity / side effects and modulationDrug delivery and clearanceMatched TargetsMutual Enhancement ?Mutual Counteraction ?Maintenance or Balance ?Delivery or Clearance ?

  • Medicinal Herb Databases at BIDD

    Comparison with existing TCM databases:

    Formula: TCM-ID: 1000 TCHFL: 270Herb: TCM-ID: 1200 TCSHL: 520 TCMD: 1500Compound: TCM-ID: 9000 CNPD: 3000 TCMD: 6800

    TCM FormulaHerbHerbCompoundCompoundCompoundCompoundProteinProteinProteinProteinProteinProteinProteinProteinProteinProteinFunctionFunctionFunctionFunctionFunctionFunctionFunctionStructureStructureStructureStructureTCMDTCHF LibraryCNPDTCSH LibraryTCM-ID: Traditional Chinese Medicine - Information Database

    Only database providing integrated and comprehensive info about:TCM formula, constituent herbs, herbal ingredients, effect on proteinsMolecular structure Function at the formula, herb and compound levels

  • What bioinformatics can do in TCM1R4L from PDBPathway form KEGG

    Essential Bioinformatics and Biocomputing (LSM2104)

  • General ProteinLigand BindingLigand- Molecule that binds with a protein- DNA, drug lead compounds, etc.Protein active site(s)- Allosteric binding- Competitive bindingFunction of binding interaction- Natural and artificial

    Essential Bioinformatics and Biocomputing (LSM2104)

  • .Design of HIV-1 Protease Inhibitor

    Essential Bioinformatics and Biocomputing (LSM2104)

  • .Design of HIV-1 Protease Inhibito