The number of patients seeking alternate and herbal therapy is growing exponentially. Herbal medicines are the synthesis of therapeutic experiences of generations of practicing physicians of indigenous systems of medicine for over hundreds of years. Herbal medicines are now in great demand in the developing world for primary health care not because they are inexpensive but also for better cultural acceptability, better compatibility with the human body and minimal side effects.
However, recent findings indicate that all herbal medicines may not be safe as severe consequences are reported for some herbal drugs. Most herbal products on the market today have not been subjected to drug approval process to demonstrate their safety and effectiveness.
Thousand years of traditional use can provide us with valuable guidelines to the selection, preparation and application of herbal formulation. To be accepted as viable alternative to modern medicine, the same vigorous method of scientific and clinical validation must be applied to prove the safety and effectiveness of a therapeutically product.
Studies on chemical ecology can identify materials of potential benefit to humanity, either in terms of agriculture or pharmaceutical development. The current view of many ecologists is that, although secondary metabolites may not have been produced mainly for the defence of the organism, a large subset of them are maintained because they do improve the fitness of the produce to survive.
Acceptance of this idea makes it clear that secondary metabolites are characterised by a high degree of biological activity. This worldwide botanical cornucopia includes many reliable medicines. The World Health Organization (WHO) records the fact that 80% of the world population still relies on Herbal medicines.
Because of commercial orientation and the increasing demand for natural products, a paucity of well-qualified and trained personnel in herbal industries and the lack of harmonised regulations in various countries, the quality of the herbal products available in the market are unreliable and sometimes misleading.
Therefore, it is essential that the information provided to healthcare professionals and consumers be unbiased, accurate, trusted and guarantees optimum quality, safety and efficacy.
To prove the efficacy of the herbal drugs, good clinical research is needed but to produce the results carrying sufficient statistical weight is expensive and laborious and the cost of undertaking research studies may not be justified commercially.
It is difficult to patent herbs and the size of the market is not comparable with most patentable conventional drugs. Being a mixture of complex chemicals, the herbs as a whole will have different properties from that of any single constituent acting alone.
The action of the latter will not predict the effect of the former, particularly if the experimental evidence is based on work done on laboratory animals. The strategy for deriving a single molecule as a therapeutic product is fairly well known.
Each country has its own strategy for product development, since the window of opportunity in herbal medicine is very large, but difficulties abound, not least that herbal products are generally kept as a trade secret, and knowledge of useful herbs is not always shared, something that has to happen if HMPs are to be viewed seriously as important in healthcare globally.
A well-accepted product development strategy should be introduced, so that new HMPs can be developed and evaluated. Herbal extracts are complex mixtures, so high sensitivity and miniaturised assays are required, together with innovative technologies, for example immunochemical and enzymatic methods coupled with online chemoanalytical systems, high-performance liquid chromatography (HPLC)-based assays used directly for a wide range of mechanism-based and cellular assays. The most fruitful approach has been suggested to be a combination of pure compounds, fractions and extracts and a differential use thereof, depending on the target and the screening format.
Limitations of traditional experience in developing HMPs
Although many conventional drugs or their precursors are derived from plants, there is a basic difference between administering a pure chemical substance and the same chemical in a plant matrix. Herbal products represent a number of unique problems in quality control because of the nature of herbal ingredients present therein.
The constituents responsible for the claimed therapeutic effects are often unknown and the complex composition of drugs that are used in the form of whole plant, plant parts or the extracts obtained there from raises unique standardisation problems.
Another limitation concerns safety. Not all HMPs have firm roots in traditional practices, and this may well be an underestimated issue. When traditional source plants are extracted in a non-traditional way (e.g. by resorting to a non-polar solvent such as hexane), the question arises whether this non-traditional extract is just as safe as the traditional one.
Moreover, the administration form also differs based on the application pattern, e.g. most of the Unani and Ayurvedic preparations of the Indian systems of medicine are used in traditional medicine by mixing the same with different solvents or adjuvants called ‘Anupan’ such as milk, honey, etc. While exploring those, the same drug may be used with other anupan which does not comply with the traditional concepts, and so the chances of adverse reaction, or less activity than the original HMP cannot be overlooked.
Establishing the quality of herbal product
Definition and characterisation of the material is necessary prior to the assessment of the relevance of available efficacy and safety data. It is also important that the material used and available commercially should be consistent with the evaluated material, because any significant change in quality would trigger the need for a re-evaluation of the relevance of the safety and efficacy data.
There is a general, worldwide consensus on how to control the quality of herbal medicinal products, although considerable effort is necessary to guarantee a constant and adequate quality. Specifications and analysis of the preparations of multi-component drugs involve complicated factors and use of herbal materials of good quality, along with proper control of the manufacturing processes, are prerequisites for quality control.
Scientific monographs especially by World Health Organization, for example, offer a valuable and updated overview on published scientific literature, which may be used in support of the demonstration of the safety and efficacy of a botanical product in a bibliographical application.
Documentation on traditional use
Documentation on traditional use may include:
- proper identification of the botanical used
- determination of parts used
- preparation process of the botanical ingredients
- formulation of the traditional product
- mode (route, schedule, and dose) of administration of the preparation
- indications of use of the botanical/preparation
- traditional geographical areas and populations in which such use occurred
- time span and extent of use of the botanical product
- contraindications and adverse effects that have been associated with use in humans and animals
Good agricultural practices
Good agricultural and collection practices for medicinal plants are only the first steps in quality assurance but play an important role in the protection of natural resources of medicinal plants for sustainable use.
GAP includes identification and authentication of cultivated medicinal plants, certification of seeds and other propagation materials, intensive care and management of cultivation, harvesting during the optimal season to ensure best quality of herbals and adequate knowledge of growers and producers on these aspects.
The quality of the herbal medicines may be affected based on the methods adopted in the cultivation and harvesting methods of herbs. Collection practices should ensure the long-term survival of wild populations and their associated habitats and management plans should provide a framework for setting sustainable harvest levels and describing appropriate practices that are suitable for each medicinal plant species and plant part used.
Macroscopical and microscopical evaluation
Organoleptic evaluation of herbal drugs is a primary means that includes evaluation parameters such as colour, size, odour and taste, and surface characteristics (texture and fracture). Macromorphological evaluation is different for different parts of crude drugs – e.g. for crude drugs from barks, they are nature of curvature, surface characteristics, fracture characteristics and characteristics of transverse surfaces. Similarly microscopical evaluation is still of great importance in evaluation of crude drugs and nowadays a range of techniques are applied.
Good manufacturing practices
Requirements and methods for quality control of finished herbal products, particularly for combining/mixing herbal products, are far more complex than for chemical drugs. Unlike conventional drugs, which are usually produced from synthetic materials by means of reproducible manufacturing techniques and procedures, herbal drugs are prepared from materials of natural origin obtained from various regions, varying climatic conditions and times of collection.
However, alterations to quality might also arise during the processing stage by which the HMP is produced, so good manufacturing practice (GMP) is one of the most important tools to ensure the quality of the manufactured herbal drugs.
Standardisation of chemical aspects using marker analysis
For standardisation and quality assurance purposes, three attributes, i.e. authentication, purity and assay are desirable. Authentication, as the name suggests, relates to proving that the material is true, that is, it corresponds to the claimed identity. Purity pertains to evaluating that there are no adulterants present in the plant material and it can be evaluated by classic pharmacognostic procedures such as microscopy, ash values and other tests, for example, extractive values.
The assay part of standardisation is chemical and biological profiling by which the chemical and biological effects could be assessed and effective doses are established. Safety for use could also be accessed through this parameter. Bioassay and Chemical studies are versatile and can be put to good use in standardisation, and are still the major technical approach used. Fingerprints can be generated for qualitative assessment.
As far as quantitative assessment is concerned, the concentrations of the secondary metabolites, which are considered to be the active constituents of herbal drugs, are studied and used to provide standardisation procedures. Marker analysis may help in different ways, for example to assess potency, anticipate the active constituents, and ensure the quality and consistency of botanical raw materials and finished products. They may also help in detecting the adulterants and monitoring decomposition, essential in the stability study of herbals and deciding the shelf-life of a product.
Safety of herbal products
Very few herbal drugs have been subjected to systematic toxicological and nutritional assessment, yet, because of their long history, customary preparation and use and absence of evidence of harm, they are generally regarded as safe to consume. This long ‘history of safe use’ of herbal drugs forms the benchmark for the comparative safety assessment of newer herbal products. Because the general public think that herbal remedies are 100% safe, they often take them without any medical advice and treat them like food.
Consequently, the occurrences of side-effects, toxicity and drug interaction are not documented. Phyto-pharmacovigilance is needed in every country, because there are differences between countries (and even regions within countries) in the occurrence of adverse drug reactions, and other drug-related problems and methods of data acquisition, handling and evaluation have to be developed, including the collection of consumer comments regarding non-prescription products.
Continual review and assessment of the safety of botanicals is needed, with an emphasis on surveillance of the use of these products to identify unknown hazards or risks and address them expeditiously. Herbal pharmacovigilance, however, is not a negative tool but a neutral one, especially when it identifies a new serious herbal health risk.
Pharmacovigilance can also be reassuring, however, by providing evidence that certain herbal health risks are absent or negligibly small. Thus, it can help to boost one of the major claimed features of phytotherapeuticals, namely their relative safety when compared with conventional pharmaceuticals. A
balance between scientific Scepticism of spiritual sensitivity should be taken into consideration while analyzing Herbal (Unani and Ayurvedic) drugs.While developing the systematic Pharmacovigilance, guidelines on the safety of Unani drugs for safe and effective use, meta – analysis, opinion of experts (authority), statement of credible person, perception through sense of mind, inferences based on clinical experiences, individual RCT, should be given due weightage.
Author is an Associate Professor, Regional Research Institute of Unani Medicine (RRIUM), University of Kashmir