Herbal Drugs: clinical perspectiveDr. Bhavesh NayakPrincipalShree Swaminarayan Sanskar Pharmacy College

Definition: Herbal Drug /Herbal Medicine:The WHO has defined traditional medicine (including herbal drugs) as comprising therapeutic practices that have been in existence, often for hundred of years, before the development and spread of modern medicine and are still in use today.Traditional medicine is the synthesis of therapeutic experience of generations of practicing physicians of indigenous system of medicine. Traditional preparations comprise medicinal plants, minerals and organic matter etc. Herbal drugs constitute only those traditional medicines which primarily use medicinal plant preparations for therapy. The earliest recorded evidence of their use in Indian, Chinese, Egyptian, Greek, Roman and Syrian texts dates back to about 5000 years.

Classification of Herbal DrugsOrganized drugs.Unorganized drugs.Also classified on the basis of Therapeutic use, chemical constituents and indigenous method of preparationOn the basis of Traditional system of medicinePhytopharmaceuticalNutraceutical (Nutritionally or Medicinally enhanced foods with health benefits)

Why Herbal medicine?Herbal medicine are being used by about 80% of the world population primarily in the developing countries for primary health care. They have stood the test of time for their safety, efficacy, cultural acceptability and lesser side effect.The chemical constituents present in herbs are part of physiological functions of living flora and hence they are believed to have better compatibility with human body.

Ancient literature also mentions herbal for age related diseases namely memory loss, osteoporosis, diabetic wounds, immune and liver disorders for which no modern medicine or only palliative therapy is available.Herbal drugs are made from renewable resources of raw materials by ecofriendly processes and will bring economic prosperity to the population growing these raw material.

In rural areas, there are additional cultural factors that encourage the use of botanicals, such as the environment and culture, a man earth relationship. People believe that where an area gives rise to a particular disease, it will also support plants that can be used to cure it (Winslow and Kroll, 1998).In India vast sections of the rural population have no assess to modern medicine (Mudur, 1997). Hundred of primary health centers which are intended to serve rural areas, lack staffs, diagnostic facilities, and adequate supplies of drugs. The rural population is heavily dependent on traditional medical systems (Mudur, 1995).

Natural (plant) products are perceived to be healthier than manufactured medicine (Gesler, 1992). Report of adverse effect of conventional medications are found in the nonprofessional reports at a much higher rate than reports of herbal toxicities

Status of Herbal Medicine in IndiaIndia has a rich tradition of herbal medicine as evident from Ayurveda, which could not have flourished for two thousand years without any scientific basis. Ayurveda which literally means knowledge (Veda) of life (Ayur) had its beginning in Atharvaveda (Circa 1500-1000 BC). Charak Samhita and Sushruta Samhita are the two most famous treatises of Ayurveda several other were compiled over the centuries such as Bela Samhita, Kashyap Samhita, Agnivesh Tantra, Vagbhatas Ashtang hridaya (600), Madhava Nidan(700 AD).Vegetable products dominated Indian Meteria Medica which made extensive use of bark, leaves, flower, fruit, root, tubers and juices.

Charak, Sushruta and Vagbhata described 700 herbal drugs with their properties and clinical effects. Based on clinical effects 50 categories of drug have been described such as appetizers, digestive stimulant, laxatives, anti-diarrhea, anti-haemorrhoid, anti-emetic, anti-pyretic, anti-inflammatory, anti-pruritic, anti-asthmatic, antiepileptic, anti-helminthic, haemoptietic, haemostatic, analgesis, sedative, promoter of life (Rasyana), promoter of strength, complexion, voice, semen and sperm, breast milk secretion, fracture and wound healing, destroyer of kidney stones etc (Lele, 1999).

Ayurvedic drugs which are understood in termsof todays molecular pharmacology:Sarpagangha (Rauwolfia serpentina) Reserpine uniquely prevent pre-synaptc neuronal vesicular uptake of biogenic amines (dopamine, serotonin and nor-epinephrine).Mainmool (Coleus forskoli Briq) Forskolin directly stimulates adenylate cyclase and cyclic AMP, with inotropic and Lusitropic effect on heart muscle.Sallaki (Boswellia serrata) Boswelic acid inhibits 5-lipooxygenase and leukotreine B4 resulting in anti-inflammatory and anti-complement effect.Shirish (Albizzia lebek) prevents mast cell degranulation, similar to sodium cromoglycate.Aturagupta (Mucona pruriens) contains L-DOPAAshwagandha (Withania somnifera) GABA-A receptor agonist.Katuka (Picrorhiza kurua) anti-oxidant action equal to a tocopherol, effect on glutathion metabolism in liver and brain

Drugs like Asparagus racemousus, Tinospora codifolia and Ocimum sanctum antagonise the effect of stress (Dhuri et al., 2000). Emblica officinalis L., Curcuma longaL., Mangifera indica L., Momordica charantia L., Santalum album L., Swertia chirata Buch-Ham, Winthania somnifera (L.) have well defined antioxidant properties and justify their use in traditional medicine in the past as well as the present.Use of the herbal medicine in jaundice, presumably viral hepatitis, has been known in India science the Vedic times. About 170 phyto-constituents isolated from 110 plants have been reported so far to possess liver protective activities. It is estimated that about 6000 commercial herbal formulations are sold world over as hepatoproctective drugs.

WHAT CONSTITUTES AN HERBAL CLINICAL RESEARCHDoctrine of Signatures:The Doctrine of Signatures- the idea that the shape, colour and other features of a plant may suggest its medicinal purpose.For example, they noted the red and puffy bladder-shaped covering of Physalis alkekengi fruit, and experimented with various parts of the plant in treating kidney and bladder disorders.walnuts were good for curing head conditions because "they have the perfect signatures of the head".the general impression today is that there is no scientific evidence that plant shapes and colours help in the discovery of medical uses of plants (Bennett, 2007). But the idea cannot be discarded.

Zoopharmacognosy Animal Self-MedicationThe term zoopharmacognosy to describe the phenomenon whereby animals self-medicate, by selecting and using plants, soils, and insects to treat and prevent disease (Gerber, 1998).The term literally means animal drug knowledge, coined from zoo ("animal"), pharma ("drug"), and gnosy ("knowledge").In East Africa, pregnant elephants self-medicate by chewing the leaves of a tree (Family:Boraginaceae) that induces labor. Incidentally, Kenyan women also use this tree for the same purpose (Linden, 2002).

herbalism developed from necessity, trial-and-error, and serendipity, rather than from phased trials as we know them today. Still the term herbal clinical trials is not a misnomer since a certain amount of human experimentation must have taken place at some stage in the long history of herbal medicineopium, mandrake, tea, coffee, volatile oil (sandalwood oil, rose oil), fruit juice, salt solution, Herbs and spices stand out as herbal remedies that have a long history of application in TM

Herbal Clinical Research at a GlanceGeneral purpose: The general purpose of an herbal clinical trial is to generate safety and efficacy data needed to guide the use of an herbal medicine.ApprovalThe trial can only take place when the respective national regulatory authority is satisfied with the quality of data provided on:The safety and efficacy of the drug.The necessity for the trial.How the trial is to be carried out that is: a detailed study protocol.The capability of investigators/ sponsor.

Principles of pharmacodynamics to herbal drugs:Principles of pharmacodynamics to herbal drugs invariably lead one of the following three scenarios:Herbal drugs whose efficacies have been demonstrated -their active principles are known and their doses are more-or-less established.Herbal drugs whose efficacies are probable, but have not been clearly demonstrated - their active agents may be used to standardize them.Herbal drugs with uncertain efficacies, but a long history of traditional usage such drugs can be used for treating common disorders, but should be used exactly as in the traditional practice.

Methodologies of herbal clinical studies:Administration of the drug to selected subjects.Collection of data on the subjects conditions, such as: measurements of vital signs, concentration of the drug in the blood or other fluids, whether the patient's health improved or not, and so on.The data collected are subjected to statistical analysis.

TRADITIONAL HERBAL REMEDIES IN THE CONTEXT OF PHASED CLINICAL TRIALSPhase I: First trial of an herbal remedy or formulation is carried out with a small number of healthy volunteers or patients suffering from the disease for which the remedy is intended.The main purpose is to observe tolerance to the remedyTo get an indication of the dose that might be used safely in subsequent studies.

Phase II: Although phase II studies are often preferably designed as randomized, doubleblind,controlled studies, using for control groups either an existing alternative treatment or a placebo; such is uncommon with long standing herbal remedies. The dosage schedules established in phase II studies are used for the phase III study.

Phase III: A phase III trial of an herbal drug involves a large patient group studied at several centres using a randomized double-blind design.To validate preliminary evidence of efficacy obtained in phase II. As in the case of conventional drugs,herbal phase III trials are conducted under conditions that are as close as possible to the anticipated conditions of normal use.

Phase IV: Phase IV studies are desired for an herbal remedy, they may be performed after the dosage form is made fully available for general use. The main purpose of such studies is to detect toxicities and idiosyncrasies that may occur so rarely that they are not detected earlier.

Double-blinded and well-designed clinical trials have also been conducted with Argyowardhani in viral hepatitis. Mucuna pruriens in Parkinsons disease.Phyllanthus amarus in hepatitis Tinospora cordifolia in obstructive jaundice

Global status of Herbal Clinical Research:In 2002 the US National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (NIH) began funding clinical trials into the efficacy of herbal medicine (Herbal Medicine-NIH-NCCAM, 2011). In a survey conducted in 2010, 356 of 1000 herbal products available in Europe and North America had published trial results on "pharmacological activities and therapeutic applications" (Cravotto et al., 2010).

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