Herbal drugs/ Pharmaceuticals Problems and Prognosis

Dr. P. Pushpangadan Director, National Botanical Research Institute Lucknow, India

5 trillion $

2020

62 billion $

2005

Growing popularity
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 evidencebased, 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

Golden triangle
Traditional medicine

Modern medicine

Modern science

Thus making cheaper affordable and safe medicine Mashelkar 2005

Examples of some important plant derived drugs

Compound Acetyl digoxin Ajmalicine Ajmmaline Andrographolide Artemissine Asiaticoside Berberine Caffeine Caffeine Cocaine Codeine Codiene Colchicine Curcumin Digitoxin, Digoxin, Digitoxigenin Emetine Ephedrine Ergometrine, Ergotamine, Ergotoxin Glycyrrhizin, Glycyrrhizinic acid Hesperidin Plant Species Digitalis lanata Catharanthus roseus, Rauwolfia sp. Rauvolfia serpentina Andrographis paniculata Artemisia annua Centella asiatica Berberis spp. Camellia sinensis Camellia sinensis Erythroxylum cocoa Papaver spp. Papaver somniferum Colchicum autumnale, Gloriosa superba Curcuma longa Digitalis spp. Cephaelis ipecacuanha Ephedra gerardiana Claviceps purpurea on Rye plants Glycyrrhiza glabra Citrus spp. Mentha spp.

Contd..

Examples of some important plant derived drugs (Contd..)

Hyoscine Hyoscyamine L-Dopa Menthol Morphine Papain Podophyliotoxin Quinine, Quinidine Reserpine & Deserpidine Rutin Scopolamin Sennosides A&B Silymarin Strychnine Taxol Thymol Vinblastine, Vincristine Xanthotoxin Chemical Intermediates Citral Diosgenin Phytosterols (Stigmasterol & Sitosterol) Solasodine Hypercin, Hyperforin Duboisia spp. Datura spp, Hyscyamus spp. Mucuna pruriens Mentha spp. Papaver spp. Carica papaya Podophyllum emodi Cinchona spp. Rauvolfia serpentina, Eucalyptus spp, Fagopyrum spp, Sophora japonica Datura sp. Cassia angustifolia, C. acutifolia Silybum marianum Strychnos nux-vomica Taxus baccata Thymus vulgaris Catharanthus roseus Ammi majus, Heracleum candicans Lemon grass Dioscorea spp. Costus spp. Soya & Calabar Beans Solanum Hypericum perforatum

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 19th 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 Related species

Traditional formulation

Identification, authentication Collection

Extraction
Biological screening

Clinical trial
Effective 1. Analytical standard 2. Safety 3. Modernise Technology 4. New Dosage Forms Pharmacokinetics/Pharmacodynamics Pilot Plant Production

Active Bioassay Linked Fractionation Active Compound(s) Characterisation Pure Compound, Standardised Extracts
1. Pharmacology 2. Toxicity 3. Clinical Pharmacology

Clinical Trials Commercial Production Marketing

Bio-availability

Registration

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

Multiple Targets Need A Combo

Pain, Cartilage Inflammation Oxidative stress Osteoporosis Anabolic CNS Immunomodulator Antistress Bioavailability Lubricant

Plant A Plant B Plant C Plant D Plant E Plant F Plant G Plant H

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

Final Product

Global Market

Traditional Approach

Selection of potential plants

IPR

Clinical studies

Toxicity stuides

Extraction and fractionation

Drug Discovery

Activity guided isolation of active copounds

Standardization of the formulation(s)

Formulation and Doasge studies

Pharmacological studies