Herbal drugs/ Pharmaceuticals – Problems and Prognosis

Dr. P. Pushpangadan

Director, National Botanical Research Institute

Lucknow, India

Growing popularity

5 trillion $ 20202020

2005200562 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 scienceModern 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 medicineHistorical 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. John’s wort and Gingko biloba

Drug development based on traditional leadsSurvey of traditional remedies

Choice of plant

Identification,authentication

CollectionTraditional formulation

Clinicaltrial

Related species

Extraction

Biologicalscreening

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

CommercialProduction

Marketing

1. Pharmacology2. Toxicity3. Clinical Pharmacology

Bio-availabilityRegistration

Pharmacokinetics/PharmacodynamicsPilot 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 life’s 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, CartilageInflammation Oxidative stress Osteoporosis Anabolic CNS ImmunomodulatorAntistressBioavailabilityLubricant

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