Rev Pharmacog Olemiss Padma Venkat

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    ReversePharmacognosy: A Novel Strategy toStandardise ISM Drugs

    Dr.Dr. PadmaPadma VenkatVenkat

    Joint Director & Head

    Centre for Pharmacognosy & PharmaceuticsFoundation for Revitalisation of Local Health

    Traditions (FRLHT) , [email protected]

    8th Annual Oxford-International Conference on the Science of Botanicals, Apr 6-9, 2009

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    Why-Novel Strategy? What is Reverse Pharmacognosy?

    How do it?

    FRLHTs Approach

    Presentation

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    Why A New Strategy?

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    ISM & Western Biomedicine are

    TWO DIFFERENT KNOWLEDGE-SYSTEMS

    THAT HAVE EVOLVEDINDEPENDENTLY

    .TWO DIFFERENT WAYS OFKNOWING

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    Current QS of ISM Drugs

    Parameters & Standards are

    Non-contextual to the culturefrom which it evolved

    Do not reflect safety &efficacy; but at best identity,

    purity

    While Traditionally identity,safety and efficacy were anintegral part of Drug Property( Dravya guna )

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    Bacoside A (2.5 - 3 % ), Bacoside B andother bacosides, Hersaponin, Betulicacid, Monnierin, Alkaloids - Brahmine(0.01-0.02 %) and Herpestine;Flavonoids; Saponin, D-mannitol,Nicotine, Saponins-Monierin .Sapogenins-Bacogenin A1-A4 . Bacosine

    Parallel Systems of Knowledge with no dialogue

    Rasa : Tikta Kasaya

    Guna : Laghu, Sara

    Virya: Sita

    Vipaka: MadhuraKarma: V Kara,

    rasayana, medhya..

    Varied Uses

    Fever, Anaemia,

    Inflammation, Diabetes,Psychiatric disorders

    Modern Ayurvedic

    ? ?

    Bacopa monnieri (Brahmi)

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    Our approach inStandardisation today

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    Some Phytomedicines

    that have failed

    in modern times

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    Non-Contextual Usage

    Acetone/Methanol extract

    Isolatedcompounds,

    Syntheticcompound,Large dose

    Practice

    Anxiolyticeffect

    Aqueouspreparation

    CalmingPiper methysticum

    Stroke,heartattack

    Weight loss,Energiser

    Dietarysupplement

    Under supervision,as a whole herb Asthma, Asthma,

    coldcold

    Ephedrasinica

    AdverseEffects

    Modern useRecommendationTraditionalUsePlant

    Hepato-toxicity

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    What is Reverse Pharmacognosy?

    Pharmacognosy guided byTraditional Knowledge

    Developing Contemporary Standardsbased on Traditional Advice,Parameters and tools

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    Factors Acknowledged by ISM

    Processing & Storage

    Collection

    Identity of Ingredients

    QualityStandards

    Diagnosis of theailment

    Administration of the Drug

    Constitution of Patient

    (What?)

    (When? Where from)

    (How? How long?)

    EfficacyWho to? How? How much? How long?

    (For What?....

    The Purpose)

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    Plant parts Season of collection

    Branches andleaves

    Rainy ( Varsha ) and Spring(Vasantha )

    Roots Summer ( Greeshma ) or

    Late winter ( Shishira )Bark, Rhizome,Sap

    Autumn ( Sharad )

    Heart wood Early winter ( Hemantha )

    Flowers and

    fruits

    As per Season

    Traditional Recommendations-General

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    Traditional Recommendations- Specific

    Should be used after

    storing for 1 year

    Vidanga

    (Embelia ribes)

    Storage

    Should be boiled in milk(Kshirapaka)

    Pippali (Piper longum)

    Processing

    Collection at nightHaridra(Curcuma longa)

    Collection

    Chitra tandula, KapaaliVidanga (Embelia ribes)IdentityRecommendationPlantFactor

    Abhava

    Pratinidhi DravyaConcept of

    Legitimate DrugSubstitution

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    Importance of Processing

    Poison Proper Processing Drug

    Drug Improper Processing Poison

    Yogadapi visham teekshnam uttamam bheshajam bhavet, bheshajam chapi duryuktam teekshnam sampadyate visham

    (Cha. Su. 1.26)

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    Effect of Processing Rice- Uncooked- Very Heavy

    Cooked rice- Cooked with water-Comparatively light

    Kanji- Cooked with abundant water- light Puffed paddy-V.light

    The changes in property of rice with cooking (Cha. Su.28. 271)

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    Tea Picking Picking early Spring &

    summer

    Hand pick only the topthree leaves

    Put no pressure on theleaves in the basket

    Start processingpromptly

    Quality varies if long leaves arepicked as opposed

    to young leaf buds

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    We should be investing similarlyinto each of the TM plants to

    study their variations, potenciesand to state their USPs

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    We need RELEVANTParameters, Protocols &

    Standards that not only reflectQuality but also Safety &

    Efficacy

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    Inter-cultural approach1. Traditional recommendations?2. Logic behind the recommendations?

    3. Traditional quality parameters? How are theymeasured?

    4. How do we make them contemporary andapplicable to industry?

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    FRLHT, 74/2, Jarakhabande Kaval, Attur Post, via Yelahanka, Bangalore 560 064Tel: 080 28568017; www.frlht.org

    FRLHT

    Campus

    How do it?

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    TradeInformationHerbarium & RawDrug Collection

    Field Botanists Informatics

    Characterisation Pharmacology

    Pharmacognosy&

    Pharmaceutics

    TSM Experts

    Clinic

    ISM R&D

    Garden

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    Document Traditional Knowledge on Drugs

    (simple non-Instrumental measurements)

    Traditional&

    Modern Stdisn. Methods

    Physical, Chemical

    &

    Biological Markers

    Standard Drug

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    DocumentationFrom

    Texts

    &

    Traditions

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    TQS Informatics

    Softwareto store,retrieve

    andanalyse

    data

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    Develop Relevant Parameters,

    Methods and Standards Sensory Evaluation

    Morphology

    Microscopy Chemistry

    Molecular Markers

    Bioactivity

    Bio-chemical Standards

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    Uniqueness about HumanUniqueness about Humanperceptionperception

    All five sensesAll five senses --perceived &perceived & analysedanalysed by ONEby ONE

    instrumentinstrument --the Human Bodythe Human Body Cognition adds valueCognition adds value mental processor mental processor SensitivitySensitivity -- more sensitivemore sensitive

    Nose: 0.00025ppm; x1000 times better Nose: 0.00025ppm; x1000 times better Correlation specific to requirementCorrelation specific to requirement

    E.g., unripe & ripe mangoE.g., unripe & ripe mango --purposepurpose Measures characteristic differencesMeasures characteristic differences

    Subjectivity..reducedSubjectivity..reduced by training panelby training panel

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    Sensory Analysis

    An Important QC tool for ISM Drugs

    PROFILING BYTRAINED PANEL

    MODERNATTRIBUTES

    TRADITIONALATTRIBUTES

    TESTING AND STATISTICAL ANALYSIS

    SENSORY STANDARDSSENSORY STANDARDS

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    Bio-Chemical MarkersTrade, Distribution information

    Traditional Information & Botanical Authentication

    Bioassay/ Phytochemical/ Microscopy/ Mol Bio studies

    Identify unique profiles/chemical markers

    Relevant Quality Parameters/Tests/Markers

    Isolation/ Characterisation , Biological activity

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    Identity.?Correct Botanical Correlation

    Substitutes Adulterants

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    Etymological Analysis of AyurvedicSynonyms

    A. Pueraria tuberosaB. Palasha (Butea monosperma)

    Triparni : Three-leavedPalashparni : Leaves similar toPalasha

    White tubers of Pueraria tuberosa

    (Shuklakanda, Sitha )

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    Minutes

    5 10 15 20 25 30 35 40 45 50

    V o l t s

    0.00

    0.02

    0.04

    0.06

    0.08

    V o l t s

    0.00

    0.02

    0.04

    0.06

    0.08

    Detector A (254nm)maturewholewholemature001

    Detector A(254nm)immaturewholewholeimmature

    0

    20

    40

    60

    80

    2 . 7

    5 8

    . 8

    1 2

    . 4 1 4

    1 4

    . 7

    1 9

    . 1

    2 3

    . 1 7 1

    Average girth of tubers (in cm)

    R a

    t i o

    A / B

    Mature & Immature Tubers

    Ipomea mauritiana Jacq.

    HPLC

    Ratio of peaks Vs girth

    A

    B

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    Compounds of interest

    At least 3 compounds-identified that appear to berelated to maturity

    Isolation has been completed

    Characterisation is ongoingin collaboration with IISC

    Scopoletin and B-sitosterol

    seem to be present in bothmature & immature

    One compound, may be aplant sterol, significantly

    higher in mature

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    Mice model using colloidal Carbon

    ANIMAL STUDIES

    com paris ion of phagocytic activity of mature &imm ature tube rs of Ipom oea m auritiana

    00.020.040.060.08

    0.10.12

    C o n t r

    o l

    M a t u r

    e - 2 5 0 m

    g / k g

    M a t u r

    e - 5 0 0 m

    g / k g

    I m m a t u

    r e - 2 5 0 m

    g / k g

    I m m a t u

    r e - 5 0 0 m

    g / k g

    Group

    p h a g o c y t i c

    i n d e x

    Series1

    IMMUNOMODULATORY ACTIVITY OF VIDARI ISMORE THAN THAT IN CONTROL

    BIOACTIVITY OF MATURE IS MORE THAN THAT OFIMMATURE TUBERS

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    Day & Night collection of Curcuma longaL.

    Densitometric scans @ 254nm of C. longa

    Bioactivity of C. longa

    Effect of collection time on bioactivity of Curcuma longa (roots)

    0

    0.1

    0.2

    0.3

    0.4

    0.5

    4:00 17:00 21:00

    Time of collec t ion (hrs)

    L D 5 0 v a l u e

    ( m g / m

    l )

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    Milk Decoction

    Samples : water decoction, milk decoction& standard Piperine(0.5g)

    Bioactivity of water decoction &milk decoction

    Bioactivity of Piper longum preparations

    0

    1

    2

    3

    4

    5

    6

    Milk Decoction Water decoction

    Preparations

    E D

    5 0

    ( m g

    / m l )

    Bioactivity of Piper longum preparations

    0

    1

    2

    3

    4

    5

    6

    Milk Decoction Water decoction

    Preparations

    E D

    5 0

    ( m g

    / m l )

    Piperine Extracted

    Milk Decoction: 0.17%Water Decoction: 0.12%

    Piper longumL. (fruits)

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    In conclusion

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    Conclusion Reverse Pharmacognosy is a contextual

    strategy to develop relevant standards Trans-disciplinary and inter-cultural

    objective parameters, protocols andstandards need to be developed

    Research into TM principles, science andpractice in order to understand therecommendations

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    ConclusionWay forward

    Document TQS

    Select Top 100 traded drugs & their TQS

    R&D at 10 Research Partners

    Develop TK based objective methods & standardsthat not only reflect identity but activity as well,through modern tools

    Convert them to simple parameters & standardspossibly non-instrumental

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    Inter-cultural, Inter-disciplinary

    understanding Cost-effective QC Diagnostics for the

    industry Cost-effective Drugs for Consumers

    Challenges

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    Funds : MoEF, GoI, National Geographic Society, TATA Trusts

    Darshan Shankar

    Vd. GG Gangadharan

    Subrahmanya

    Shanthi

    Devaiah

    Chandrakala

    Al-Ameen College of Pharmacy, Bangalore

    Indian Institute of Science, Bangalore

    Acknowledgements

    Thank You!