Herbal drugs/ Pharmaceuticals

Problems and Prognosis

Dr. P. Pushpangadan
Director, National Botanical Research Institute
Lucknow, India
Growing popularity
5 trillion $ 2020
2005
62 billion $
Business standard, 2005
ccessible
ffordable
ssured safety
About 70% Indian population (60-70
crore) depends on alternative system
of medicine.
WHO
Herbal drugs are
cheaper than generic
drugs !!??
Herbal drugs
have been
used in India
for more than
4000 years.
Allopathy or Modern Medicine
Glamorized discipline
Pursued by most (influenced and so called
Literate) in India and, in western countries
Backed by technological advances -
investigations
Based on sound scientific reasoning
experimental evidence; not anecdotal
Thus, Modern Medicine is an evidence-
based, techno-savvy science that seems to
provide ultimate care to sick patients
Allopathy or Modern Medicine
But????
The treatment is often symptomatic, costly,
out of reach of most in developing countries
Except for infective pathologies, we do not
have much to offer except palliation
Treatment of Chronic Lifestyle Disorders like
neurodegenerative disorders is often very
disappointing and limited by adverse events
It treats the Disease (symptomatic) and not
the patient as a whole (Holistic approach)
Therapeutic Objective
The ultimate goal of every physician is to
CURE the disease.
Has Allopathy achieved this goal for all
ailments? No;
Except for infective pathologies, we do not
achieve CURE
Most often the treatment is Symptomatic and
Palliative.
Effective & Safe Medicine
Drug Discovery problems
It is notoriously inefficient
One in a hundred thousand or more compounds will
enter the market as a drug
Pharma majors have NO interest in higher plants
extracts for screening for biological activity
In NAPRALERT ethnomedical reports for 14,300
species (5.2% of all plant species) are there;
But 58% of these species have never been examined
biologically or chemically
Of these 74% are used in a manner which parallels
their ethnomedical use
Traditional medicine
Modern science Modern medicine
Golden triangle
Thus making cheaper affordable and safe medicine
Mashelkar 2005
Compound

Plant Species

Acetyl digoxin

Digitalis lanata

Ajmalicine

Catharanthus roseus, Rauwolfia sp.

Ajmmaline

Rauvolfia serpentina

Andrographolide

Andrographis paniculata

Artemissine

Artemisia annua

Asiaticoside

Centella asiatica

Berberine

Berberis spp.

Caffeine

Camellia sinensis

Caffeine

Camellia sinensis

Cocaine

Erythroxylum cocoa

Codeine

Papaver spp.

Codiene

Papaver somniferum

Colchicine

Colchicum autumnale, Gloriosa superba

Curcumin

Curcuma longa

Digitoxin, Digoxin, Digitoxigenin

Digitalis spp.

Emetine

Cephaelis ipecacuanha

Ephedrine

Ephedra gerardiana

Ergometrine, Ergotamine, Ergotoxin

Claviceps purpurea on Rye plants

Glycyrrhizin, Glycyrrhizinic acid

Glycyrrhiza glabra

Hesperidin

Citrus spp. Mentha spp.

Examples of some important plant derived drugs
Contd..
Hyoscine

Duboisia spp.

Hyoscyamine

Datura spp, Hyscyamus spp.

L-Dopa

Mucuna pruriens

Menthol

Mentha spp.

Morphine

Papaver spp.

Papain

Carica papaya

Podophyliotoxin

Podophyllum emodi

Quinine, Quinidine

Cinchona spp.

Reserpine & Deserpidine

Rauvolfia serpentina,

Rutin

Eucalyptus spp, Fagopyrum spp, Sophora japonica

Scopolamin

Datura sp.

Sennosides A&B

Cassia angustifolia, C. acutifolia

Silymarin

Silybum marianum

Strychnine

Strychnos nux-vomica

Taxol

Taxus baccata

Thymol

Thymus vulgaris

Vinblastine, Vincristine

Catharanthus roseus

Xanthotoxin

Ammi majus, Heracleum candicans

Chemical Intermediates



Citral

Lemon grass

Diosgenin

Dioscorea spp. Costus spp.

Phytosterols (Stigmasterol & Sitosterol)

Soya & Calabar Beans

Solasodine

Solanum

Hypercin, Hyperforin

Hypericum perforatum

Examples of some important plant derived drugs (Contd..)
Traditional medicine
Historical background
Earliest recorded use of a medicinal plant has
been mentioned in Rigveda
one mentioned in the modern texts is that of the
herb called Ma huang a species of Ephedra
used medicinally in China for over 5000 years
Cinchona was used by local south American
tribes long before before the isolation of quinine
for treating malaria
Source of aspirin (Salix officinalis) was used as
pain killer for long time before being identified
Traditional medicines
Middle of 19
th
century, 80% of all medicines
were herbal
Even today 25% of drugs are derived from
plant source
Most of these drugs came from traditional
lead, folk knowledge etc.
Some of these still could not substituted
despite the enormous advancement in
synthetic chemistry eg. Reserpine, taxol,
vincristine etc.
Revival of herbal medicine
widespread belief that green medicine is healthier
than synthetic products
leading to rapid spurt of demand for health products
like herbal tea, ginseng and such products of
traditional medicine
So rapid sale of herbal products are staggering 100
billion dollars a year.
After India and China, even the western world has
started working on herbals
NIH has set up CAM center and working on St.
Johns wort and Gingko biloba
Drug development based on traditional leads
Survey of traditional remedies
Choice of plant
Identification,
authentication
Collection
Traditional formulation
Clinical
trial
Related
species
Extraction
Biological
screening
Effective
1. Analytical
standard
2. Safety
3. Modernise
Technology
4. New Dosage
Forms
Active
Bioassay Linked Fractionation
Active Compound(s) Characterisation
Pure Compound, Standardised Extracts
Clinical Trials
Commercial
Production
Marketing
1. Pharmacology
2. Toxicity
3. Clinical Pharmacology

Bio-availability
Registration
Pharmacokinetics/Pharmacodynamics
Pilot Plant Production
Reverse pharmacology
What is required is Scientific evidence
Answer lies in providing scientific validation
for efficacy and safety
Screening based on ethnomedical and
ethnobotanical lead as chances of hitting the
target is more

System biology
The health triangle. The survival potential of all living systems, H, is expressed in the health
triangle, structured with lifes common denominator: Intelligence, Energy and Organization.
Synergy
Most of the effective phytomedicine in market are
as whole extracts of plants
Practitioners believe that synergistic interactions
between the components of individual or mixture
of herbs are a vital part of therapeutic efficacy
Mechanism of action of many phytomedicine is
still unknown and there are several instance
where total extract shows better activity than an
equalent dose of isolated compound
chemical and pharmacological evidence to
demonstrate conclusively the concept of
synergism
Multi-target approach
Combinations of herbs are normal and are
based on empirical observation and
reasoning based on a particular patient
these herbal combinations may not be
targeted to a particular organ (multi-targeted),
cell, tissue or any biochemical system,
making this synergy even more difficult to
identify
possibility of drug interactions and the
adverse reactions arising out of these have to
be checked before coming out with the drug
Plant A
Plant B
Plant C
Plant D
Plant E
Plant F
Plant G
Plant H

Pain,
Cartilage
Inflammation
Oxidative stress
Osteoporosis
Anabolic
CNS
Immunomodulator
Antistress
Bioavailability
Lubricant
Multiple Targets Need A Combo
Activity Matrix: Systems-Biology Approach
Pharmacovigilance
Any thing herbal is safe!!?????
Adverse drug reactions (ADR)
Drug-drug interactions
Herb-Drug interactions
Toxicity of the isolated ingredients
Traditional process (Shodhana)
Traditional Medicine: Threats
Poor positioning on a global level
Ignored by the global scientific community
Very little scientific research validations
Very little publications in peer-reviewed
science Journals
Deliberate negative propagandas
Traditional medicine: Future
Innovative, Effective and
Aggressive use of Emerging
Technologies without
Compromising the Basic
Principles will be the main key
towards the bright future
Pharmacological studies
Extraction and fractionation
Activity guided isolation of active copounds
Traditional Approach

Selection of potential plants
Formulation and Doasge studies

Toxicity stuides Standardization of the formulation(s)
Clinical studies
IPR
Final Product

Global Market

Drug Discovery