The Potential of Herbal Products for Nutraceutical and Pharmaceutical Development.

Presented at the International Business Communications (IBC) Fifth Annual Conference,
"Functional Foods 1998", Copthorne Tara Hotel, London
7th-8th September 1998

 by Dr John A. Wilkinson, Middlesex University, UK



Discovery of new medicines from plants
New trends in the use of herbal products
Leading European phytopharmaceuticals
New, emerging herbal products:
* Reishi mushrooms
* Vitex agnus-castus
Quality of herbal products
Herbs as foods or medicines?
Herbs of greatest interest
Implications for the future


Humans have used plant materials since prehistoric times and in some countries such as China documentary evidence shows that herbal medicines have been used for at least 7000 years. In Europe there is a rich history in the use of herbal medicines and these have been well documented in medieval herbals such as Culpeper's and Gerard's materia medica. Interest in herbal medicines however began to decline in the 1700's when the reductionist approach to science began to dominate. Plants were extracted and pure isolated compounds were produced and eventually synthesised. This eventually led to the development of the pharmaceutical industry where the synthetic approach to drug design still dominates today. Despite these technological advances herbal medicine in Europe especially in the UK has still survived. With the increasing consumer interest in natural products and the desire for complementary medicine, herbal medicine is now thriving with a market of over $5 billion in Europe in 1996. In realisation of the interest in herbal medicines and the need for training in this area, Middlesex University established the first BSc degree in Herbal Medicine in 1994 and now has over 180 undergraduates training to become medical herbalists. This unique course enables students to learn phytochemistry, pharmacology pharmacy, physiology, clinical sciences and many other medical and science subjects. Many of these graduates will find excellent employment opportunities in the herbal as well as the nutraceutical industries.

Herbal medicines have great potential in the emerging nutraceutical industry in that these materials are often considered foods as well as medicines and are used in preventative and curative treatments throughout the world. Although there is a large amount of anecdotal evidence supporting the use of herbal medicines, the scientific studies to support these claims is in its infancy in many cases. One of the problems is that the scientific work that has been carried out is often published in obscure journals or by groups that do not specialise in herbal medicines but are interested in the subject peripherally. For example, the work may come from research groups that are looking for drug leads from plants rather that the use of the plant itself. Often this kind of research can highlight the fact that a particular plant may contain active constituents but it usually does not prove that the herbal medicine will be effective clinically or clarify its potential as a nutraceutical.

Discovery of new medicines from plants - Nutraceutical use vs. Drug development

Little work was carried out by the pharmaceutical industry during 1950 -1980's; however during the 1980s - 1990's massive growth has occurred. This has resulted from new developments in the area of combinatorial chemistry, new advances in the analysis and assaying of plant materials and a heightened awareness of the potential plant materials as drug leads by conservationists.

New plant drug development programmes are traditionally performed by either random screening or an ethnobotanical approach, a method based on the historical medicinal /food use of the plant. One reason why there has been resurgence in this area is that conservationists have argued that by finding new drug leads from the rainforest, the value of the rainforests to society is proven and that this would prevent these areas being cut down for unsustainable timber use. However Tropical forests have produced only 47 major pharmaceutical drugs of world - wide importance. It is estimated that 328 potential drugs of major importance may still be hidden somewhere. These 328 drugs would be worth $147 billion. It is thought that 125,000 flowering plant species are of pharmacological relevance in the tropical forests. It takes 50,000 to one million screening tests to discover ONE profitable drug. (Balick and Memdelsohn) Conservationists are asking: Is it worth saving the forests for this amount rather than cutting them down? However if we search for new herbal medicines rather than new active compounds for drug leads, then potentially at least 125,000 herbal medicines are to be discovered from the rainforests alone.

Even in developed countries there is huge potential for the development of nutraceuticals and pharmaceuticals from herbal materials. For example the UK herbal materia medica contains around 300 species whereas the Chinese herbal materia medica contains around 7000 species. There is therefore plenty of opportunities for future developments including specific morphological plant products, i.e. use of the fruit rather than the leaf or root, which often have different phytochemical profiles and therefore different therapeutic potential.

New trends in the use of herbal products

* 1960's - 1980's mainly driven by traditional folklore usage and consumers were hippy/alternative medicine advocates.
In the 1990s the market is driven by a combination of folklore, scientific research and media hype.

Consumers have shifted to the middle classes and elderly who are looking for "natural medicines" and maintenance of health.

New Emergence of Phytopharmaceutical and Phytonutraceutical Products

Top selling herbs and growth rates
European sales $7 Billion in 1996

Asia 2.3 Billion
Japan 2.1 Billion
North America 1.5 Billion

Average growth rate world-wide is around 12 - 15 % (Institute of Medical Statistics)

Leading European Phytopharmaceuticals

Sales (Million US$)
Evening primrose

Main therapeutic categories for Herbal Products

Therapeutic area

J. Grunwald, Herbalgram p60, 1994

Specific example: Sales of St Johns Wort, Hypericum perforatum

Tablets sold
2.5 million
140 million

* Only 36 reported side effects in 5 years.
Increase in sales due to increase in research findings

New emerging herbal products that have potential as nutraceuticals

Reishi Mushrooms

Consist of Ganoderma lucidum and Shitake mushrooms

Used for over 2000 years by Japanese and Chinese

Known by the Chinese as "The Medicine of Kings"

Known for centuries as a cardiotonic herb

 The plants main active phytochemicals are: polysaccharides and triterpenoids

Ganodermic acid A
Ganodermic acid B
Ganodermic acid C
Ganodermic acid D

Researchers in China and Japan have demonstrated that the extract:

Inhibits platelet aggregation

Lowers blood pressure (6 month clinical trial : 47% of hypertensive patients lowered their blood pressure by 10 -19 mmHg, 10% by 20-29%)

LDL levels dropped by 68% of 90 patients following 4 months of ingesting Reishi

Historically the plant has been reported to relieve pain and inflammation in the joints.

The extract has been shown to have powerful anti inflammatory effects in vitro and in vivo.
(Journal of Chinese Medicine, 669 -674 1992).

The immune stimulating properties of the extract have been attributed to the polysaccharides.

 Ganodermic acids (oxygenated triterpenoids) present in the extract are implicated in platelet inhibition, lowering LDL and anti inflammatory processes

Vitex agnus castus

Common names: Chaste Berry Tree, Monks Pepper
Origin: Mediterranean Countries
Folklore: Reduces sexual desire in men; relieves menopausal symptoms and PMS in women. Has product license status in the UK
Early investigations assumed that Vitex contained progesterone like compounds

Herb acts at the pituitary gland

Release of follicle stimulating hormone (FSH) is blocked while the secretion of luteinising hormone (LH) and prolactin is stimulated

Net effect: shift in the balance in the production of oestrogen to progesterone is stimulated.

Evidence from clinical trials support a progesterogenic effect, but many were not randomised double blind trials. (Herbal Medicines 1994 Anderson and Phillipson)

In vitro work on the extract has demonstrated inhibition of prolactin secretion from rat pituitary cell cultures (Zeitschrift fur Phytotherapie 12, 77 - 82, 1991)

Flavonoids: flavanol (Kaempferol, quercetagetin) derivatives, casticin, isovitexin, isoorientin, luteolin 7 glucoside
Iridoids: Aucubin, agnuside


 At present it is not known which constituents contribute to the activity.

Some Iridoids are known to be bitter stimulants, anxiolytics and anti inflammatory.

The above flavonoids have anti-inflammatory activity, sedative and hepatoprotective properties. Keto steroids have been recently found.
There is also no published standard for quality control. 

Quality of herbal products for Nutraceutical Development

The quality of the herbal material used in nutraceutical products needs to take into account the following aspects of the plant material:

Macroscopic and microscopic properties

Its BOTANICAL name and family

Its geographical source

The method of drying and/or extraction (including solvents used etc.)

Consistent analytical data (TLC, HPLC etc.)

 Theoretically from a pharmacognostic point of view the above points need to be carried out in great detail, regardless of its final use, whether it is considered as a food or medicine, so that the quality of the product is known to a high degree. Once this is known then further work such as clinical trials and toxicity testing can be undertaken in the knowledge that the material being assessed is of consistent quality and therefore of consistent pharmacological activity.

NOTE: In the commercial world however the amount of data one needs will vary depending on what the regulatory requirements are.

Herbs as foods or medicines?

For example, if the herbal material has been previously licensed as a medicine, is on the Medical Control Agency's (MCA) general sales list and has a long history of use, the regulatory requirements are often fairly straightforward to meet if a similar product is to be developed as a nutraceutical. The Medical Control Agency will often accept data gleaned from the scientific literature rather than ask a company to start the research themselves again.

 If no claims are to be made on the product, then the herb may be considered as a food supplement rather than a medicine. Here the quality control issues again are similar but are also different! The lack of regulatory legislation puts the onus on the manufacturer/supplier to ensure that the product is not injurious to health, according to the Food Safety Act 1990. If the herbal material is well known then it maybe relatively straight forward to produce adequate safety data. If however, the company decides to introduce a herb from the Himalayas, which although has some supporting herbal folklore, is a species that is not found elsewhere in the world, then a very different scenario unfolds. The plant would be undefined and would need a full analytical and safety profile determining all the major constituents. If for example the plant contained a new class of alkaloids these would also need to be examined for safety, although it maybe possible to treat the plant extract as a whole, that is as a new chemical entity for assessment as a potential new medicine. At the end of the day, the quality control, safety and efficacy of herbal materials is very complex and each case needs to evaluated independently.

 Nutraceutical companies should not be put off by this as the sale of herbal materials continues to rise and reported side effects and toxic reactions are still small compared to synthetic drugs. In some countries the regulatory bodies are becoming more open minded to allowing herbal products to be developed as nutraceuticals or even "herbaceuticals".

Recently for example, the FDA has approved a clinical trial for the treatment of Psoriasis that consists of a Chinese herbal medicine that contains 12 different plants. Similarly, the FDA has approved the human evaluation of a cancer treatment based on a crude extract from Mistletoe. This would have been unheard of 5 years ago.

In the case of Vitex previously mentioned, if no published quality control methods are in place what is a nutraceutical company to do about this?
The answer comes down to using established general guide lines on the quality control of herbal materials developed by pharmacognosists and phytochemists and apply them to the case in hand, often in consultation with an academic laboratory. One would need to access the morphological characteristics of the material. Is the product dried or used fresh? If dried for how long and how. This is important as the amount of pharmacologically active compounds in the plant can change dramatically during the drying process. This change depends on the constituents found in the plant and also from any remaining enzyme activity, which can break down the phytochemicals in the plant and therefore change the phytochemical profile and subsequently the therapeutic profile of the plant.

"Me Too" Products verses "New Use" Products

The exact requirements also depend on the kind of product a company is planning to develop. If the product under development is a "Me Too" product then sticking to the traditional processes as laid down for example in the British Herbal Compendium, may be enough. If however the company is looking to develop "new use" products then the process is likely to be very different. If the company found that for example, Chamomile leaf is a potent anti cancer agent in vitro, and that the whole extract is needed for activity rather than a single active compound, the company would want to develop extraction processes and sources of the material which would maximise this activity. The company would therefore need to develop new quality standards, although supporting evidence on Chamomile could also be used to advantage. This plant has been previously well studied and therefore there is likely to be a fair body of knowledge on the phytochemicals found in the plant, the toxicology and also studies on the toxicology of the whole plant extract. Although there would be increased costs involved in these procedures they should be outweighed by the products novelty, which could turn out to be a market leader and therefore achieve far greater profits compared to a "Me To" product. Since the product is new the company could also protect the invention through process, use and formulation patents, which would increase the opportunities for raising finance to develop the product further. 

Herbs of immediate greatest potential

Future developments needed for product licences/efficacy studies:

Matricaria recutita
Precise effects of anti inflammatory terpenoids and flavonoids. Applications for topical/eczema

Zingiber officinalis
Confirm efficacy in motion sickness and nausea (including post-operative)

Bioactivity of constituents needs to be tied up properly. Clinical trials needed to confirm treatment/prevention of flu/colds

Ginkgo biloba
Establish if 24% flavonoids is the best dosage. Proper safety evaluation needs to be carried out. Potential for memory enhancement/Altzheimers disease.

Hypericum perforatum
Establish mode of action. Elucidate main actives and appropriate extract

Implications for the future - The Environmental Impact

With the increasing environmental pressures for industry to use "clean technology" and to utilise sustainable sources of materials for manufacturing processes, the use of crude plant extracts, if proved safe and efficacious must be encouraged. If the need for "greener" products continues to play an important role in our society, then in the future there may well be government legislation that insists on using herbal products rather than unsustainable synthetic products or highly purified natural products, which wastes raw materials and increases pollution. Companies that get involved now will become market leaders in a business that is likely to become much more important in the years to come.