Introduction to Herbal Medicine 2
Different Types of Herbal Extracts..................................................................................... 3 Infusion: the herbal tea.................................................................................................... 3 Decoction: simmer herb for 10 min ................................................................................ 3 Tincture: usually 1:5 ratio by maceration ....................................................................... 3 Fluid extract: used to be 1:1 by percolation.................................................................... 3 Liquid extract: 1:2 by percolation................................................................................... 3 Glycerol Extracts ............................................................................................................ 3 Standardisation of Liquid Extracts.................................................................................. 4 Dry Extracts .................................................................................................................... 6 Herbal Manfacturing........................................................................................................... 6 Good Manufacturing Practice ......................................................................................... 6 Fundamental Principles of Manufacturing...................................................................... 6 Maximizing Extraction of Active Constituents .............................................................. 8 Quality Control ................................................................................................................. 12 What are the issues of quality in botanical medicine? .................................................. 12 Quality Raw Materials Beginning with the Best .......................................................... 13 Trade, Organic or Wildcrafted raw materials ............................................................... 13 WHO “Guidelines on Good Agricultural and Collection Practices” of Herbs ............. 13 Thin Layer Chromatography(TLC) .............................................................................. 18 High Performance Liquid Chromatography (HPLC) ................................................... 18 Ultraviolet and visible spectroscopy (UV/VIS)........................................................... 20 Scientific testing to ensure safety and efficacy................................................................. 21 Coleus- how much forskolin? ....................................................................................... 22 Echinacea- increased potency ....................................................................................... 23 Buchu – not too much pulegone ................................................................................... 25 Turmeric – antioxidant spice ........................................................................................ 28 Olive Leaf Extract......................................................................................................... 29 Products in the Market Place ........................................................................................ 30 Pharmacologically Active Dosages.................................................................................. 33 Traditional Dosage........................................................................................................ 33 Dosages from reliable text books.................................................................................. 34 Scientific Dosage .......................................................................................................... 34 Liquid Extract equivalent.............................................................................................. 34 Dosages on product labels ............................................................................................ 34 Selling Herbal Medicines From a General Practice.......................................................... 35 Complementary Medicine In Australia............................................................................. 36 Herbal Medicine in Australia........................................................................................ 42 How to work with a alternative and complementary therapist ......................................... 45 Herbal Medicine in Australia........................................................................................ 45 Safety and Effectiveness of Herbal Medicine............................................................... 45 Why do so few consumers of herbal medicines disclose their use to their GP?........... 46 Referral Patterns............................................................................................................ 46 How to Locate a Responsible Herbalist........................................................................ 48 Establishing a Working Relationship............................................................................ 49
Write a Referral Letter .................................................................................................. 49 A Model for Co-operation ............................................................................................ 49 A Positive Outcome: Better Patient Care...................................................................... 50 References..................................................................................................................... 50 Prescribed Texts................................................................................................................ 51 Recommended Texts......................................................................................................... 51 Glossary of Herbal Terms ................................................................................................. 52
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Different Types of Herbal Extracts
Infusion: the herbal tea For soft plant parts such as leaves and flowers Let it steep for 10 min under lid (to contain aromatic oils) Decoction: simmer herb for 10 min for harder plant parts such as roots and barks Tincture: usually 1:5 ratio by maceration 200 mg herb is used to make 1 litre of 1:5 tincture Soak herb for 2-3 weeks, decant and press Fluid extract: used to be 1:1 by percolation Involves a concentration step (removing most of the alcohol and water) Liquid extract: 1:2 by percolation Strongest extract one can make without concentration step to maximise extraction Conversion table 1 mL of a 1:2 herbal extract equals 500 mg of dried herb. 1 mL of a 1:5 herbal extract equals 200 mg of dried herb. 1 mL of a 1:1 herbal extract equals 1000 mg of dried herb. Liquid extracts are mostly made from dried plant material simply because it is easier and generally produces a more potent extract. Some herbs however, are more active when given as fresh plant tinctures, for example, cleavers and chickweed, but for most herbs the large amounts of water in fresh plant tinctures make the dosage necessary far too high. Glycerol Extracts Eg. Marshmallow commonly made as a glycerol extract. Glycerol makes for a thick, sweet extract, which is suitable for cough mixtures and other indications where the consitency and taste is inportant eg. When treating children. Actions • demulcent • • vulnerary diuretic
Indications • gastrointestinal ulceration
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• • •
colitis respiratory irritation and inflammation urinary tract infection
Standardisation of Liquid Extracts There are essentially two different types of liquid extracts: standardised and nonstandardised. Non-standardized These extracts are known as tinctures, liquid extracts or fluid extracts. The solvent is usually a mixture of ethanol and water, but may also include glycerol and other solvents. Ethanol and water are considered the most effective solvents. The drug-solvent ratio varies from 1:1, 1:2, 1:5 or weaker. As the level of active constituents in the raw material varies from batch to batch, the level in the finished product will also vary. Quality control, however, can still be applied by using HPLC to identify the level of active constituents or marker compounds, although these levels may not be stated on the label. Three types of standardised extracts 1. Marker compound standardised extracts 2. Active compound standardised extracts 3. Biological standardisation Marker Compount Standardized Extracts Full-spectrum standardized extracts contain a pre-determined level of a marker compound. They are known as ‘full-spectrum’ because they still contain the full spectrum of constituents as found in the raw material. They are ‘standardized’ by varying the herbsolvent ratio in order to reach a particular level of a marker compound in the final product. The levels of the marker compounds are verified by HPLC. The drug:solvent ratio for these extracts will vary from batch to batch depending on the level of the marker compound in the raw herb. One batch may be a 1:1 another 1:2. Examples of full-spectrum standardized extracts include kava extracts, standardized to not less than 20.0 mg/mL kavapyrones, licorice extracts, containing not less than 30.0 mg/mL glycyrrhizinic acid, and hypericum extracts, containing not less than 0.7 mg/mL total hypericins. Sometimes extracts are referred to as full-spectrum standardisation which means that they have the same ratio of all the constituents in the final product as found in the crude herb. However, due to GMP manufacturing, the process from raw material to finished product is constant and reproducible and the manufacturer can guarantee that a certain constituent in a particular extract will never fall below a certain level. In the case of Ginkgo, the German company who first developed the extract used solvents to single out certain constituents such as the Ginkgo flavone glycosides and terpenes. This company’s levels of constituents subsequently became the industry standard, and all companies manufacturing standardised Ginkgo extracts must now also standardise to the Michael Thomsen 4
same level although they may use a different method of extraction. 98% of the plant material is discarded, only 2% is included in the final extract. Of the 2%, 24% are ginkgo flavonoe glycosides, 6% are terpenes, the rest (70%) consist of a variety of unidentified plant compounds. When using standardized extracts, it would be helpful if the marker compound was also the active compound. However, this is not always the case. For example, hypericum was previously standardized to the level of hypericin. Then some manufacturers believe that hyperforin is the most active anti-depressant compound and began to standardise to this compound. Now we know that hyperforin is actually the compound also most responsible for the adverse drug interaction of St. John’s wort, so in fact it is best to have a reasonable level of hypericin but a low level of hyperforin in the extract as this will still be efficacious while minimising the adverse reactions. In fact, the whole extract (many constituents) is the active in St John’s wort, not just one or two constituents. It is therefore essential to use a full-spectrum standardized extract of St. John’s wort in order to ensure that all active constituents are included in the final product. A ‘full-spectrum’ standardized extract is extracted to achieve a minimal amount of a certain marker compound, but not at the expense of other constituents. Active Compound Standardized Extracts ‘True’ standardized extracts are standardized to one or more constituents by using special solvents to single out those specific constituents. They are often standardized at the expense of other constituents, either because they are harmful or because they are considered inert or less active and must be removed in order to concentrate the active constituents. The silymarin concentrated extract is an example of an extract where a single group of constituents has been concentrated at the expense of other constituents. However, in the case of silymarin, it is necessary to do this as very high doses of silymarin is needed to treat actual liver damage. Such high doses of silymarin are hard to achieve with a normal St Mary's thistle extract. For many other liver conditions, however, a normal 1:1 liquid extract is preferable. Biological standardisation Illustrated by chaste tree (Vitex agnus-castus) the key herb for female complaints: PMS and mastalgia seem to be partly related to latent hyperprolactaemia. Dopamine acts as a prolactin inhibitor. Activation of the dopamine receptor by either dopamine, or compounds in vitex which are molecularly related to dopamine, may inhibit prolactin secretion and help reduce symptoms. The ability of a compound, or a herbal extract, to bind with the dopamine receptor can be measured and this would provide a way to determine the level of activity of a vitex extract. When Vitex extracts on the German market were tested, only 2 out of 9 liquid extracts showed significant dopaminergic activity. There was a 100-fold difference in the dopaminergic activity between the extract tested. Although all of these extract were supposedly manufactured to the standard of the German pharmacopoeia, it is clear that not all extraction methods produces equally active
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preparations. Biological standardisation for vitex could be determined as a certain level of dopamine receptor activity. Dry Extracts Liquid extracts can be spray or freeze dried into dry extracts and used in tablets and capsules. That a standardized extract is described as a 50:1 means that 50 kg of dried herb was used to make 1 kg dried extract. Highly concentrated dry extracts may be 50:1, 70:1 or 25:1. Full spectrum standardised dry extracts are typically 5:1.
Herbal Manfacturing
Good Manufacturing Practice It is rapidly becoming a requirement to produce herbal products under the Pharmaceutical code of Good Manufacturing Practice (cGMP) as prescribed by the TGA. Fundamental Principles of Manufacturing The most fundamental concept is that different herbs require different methods. The most common extraction methods are listed below: • • • • • • Maceration Cold Percolation Temperature controlled percolation Dual-process percolation CO2 extraction Specific solvent extraction
Maceration Maceration simply refers to soaking the cut and milled herb in a suitable solvent (the solvent is known as the ‘menstruum’, often a combination of water, ethanol or glycerol) for a specified time after which the herb is drained and pressed. This method is mainly used for extraction of water-soluble constituents. The cough soothing mucilage in marshmallow is thus well extracted in a combination of water and glycerol. For most other constituents, maceration is an inefficient extraction method, often only extracting less than 70% of active constituents. The drug-solvent ratio is also only about 1:5 or weaker. Cold Percolations Percolation involves packing the cut, milled and wetted herb in tall, cylindrical percolators. After a suitable maceration period, extra solvent is added above and allowed
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to seep through the percolator. A simple, one-process percolation is fairly efficient, extracting upwards of 90% of active constituents and giving a maximum drug-solvent ratio of 1:2 (whereby 1 kg herb produces 2 liters of extract). An example where cold percolation is suitable is the extraction of Echinacea spp., the immune-enhancing alkylamides are temperature unstable. For most herbs, however, it would be like making a cup of tea with cold water!
Temperature Controlled Percolation Most herbs are better extracted at varying temperatures above room temperature. The effects of various temperatures is illustrated below: Solidago virgaurea
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Figure 1
Figure 2
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Figure 1 illustrates a HPTLC of an extract of Solidago virgaurea (golden rod) extracted in 50% ethanol at 0°C, 25°C and 55°C respectively. Figure 2 illustrates the same extracts analysed by HPLC. It is clear from Figure 1 that the intensity of the coloured bands increases as the temperature increases. Figure 2 shows that the total solids in golden rod are extracted twice as well in 55°C as they are at at 0°C. Dual-Process Percolation For some herbs, where research has identified several different active principles, some of which are water soluble and some of which are water insoluble, a dual-process method may be appropriate. Research has indicated that the immunomodulatory properties of ethanolic Echinacea extracts are mainly due to alkylamides, and polyphenols such as chicoric acid. Due to the oil-like character of the non-polar alkylamides, the first extraction uses a high alcohol menstruum. This extraction should take place at low temperature due to the heat sensitivity of the alkylamides. To maximise the extraction of the polar, or water soluble polyphenols (including chicoric acid), the second extraction is performed using a lower alcohol menstruum and a higher temperature. The two extracts are combined to yield a superior, broad spectrum, highly potent Echinacea extract. Carbon Dioxide Extraction Hypercritical carbon dioxide extraction is a relatively new process used in plant extraction. Under pressure, carbon dioxide gas turns into liquid. This liquid CO2 can be used as an inert ‘liquid solvent’. CO2 extraction is used in the extraction of essential oils and high volume extractions, such as hops for beer brewing. Specific Solvent Extraction The first standardized Ginkgo biloba extract, Egb761, was produced by the German company Schwabe GMBH of Karlsruhe. Egb761 contains 24% flavone glycosides (quercetin, kaempferol, isorhamnetin) and 6% terpene lactones (ginkgolides, bilobalide), various organic acids, and other constituents. Egb761 is manufactured using special solvents during a multi-step extraction and subsequent purification process. The end result is a highly concentrated extract (50:1), with a consistent level of certain active compounds and a maximum level of undesirable compounds (ginkgolic acids). There are now many other ginkgo extracts in the market place, but until their individual clinical efficacy has been verified, it can not be assumed that they will have the same beneficial effects as the original, and clinically tested, special extract of Ginkgo biloba, Egb761. Maximizing Extraction of Active Constituents Although several pharmacopoeias, including the German, British and American pharmacopoeias, prescribe certain manufacturing methods, it is recommended that companies investigate certain variables involved in botanical extraction. The following investigative analysis illustrates how a company may determine the optimal manufacturing method. Eleutheroside E is one of the active constituents in Eleutherococcus senticosus (formerly known as Siberian ginseng, now eleuthero).
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Figure 3: Eleutheroside E
R1 R2 O R3 R4 R5 R6
R1 OCH3 R2 O-β-D-Glc R3 OCH3 R4 OCH3 R5 O-β-D-Glc R6 OCH3
O
The active constituents in eleuthero are known as eleutherosides. The eleutherosides are actually a diverse group of quite different compounds and include: • • • • Lignans : Eleutherosides D & E (syringaresinols) and B4 (sesamin) Phenylpropane derivatives including Eleutheroside B (syringin), caffeic acid and chlorogenic acid Coumarins including Eleutheroside B1 & Isofraxidin Sterins including Eleutheroside A (daucosterin)
Eleutheroside E and chlorogenic acid, which are known to be significant contributors to the adaptogenic and immune enhancing activities of eleuthero, are often chosen as marker compounds. The effects of the ethanol percentage, milled particle size, intermediate maceration and temperature influence the extraction of these compounds. Ideal Alcohol Percentage Figure 4 The curves in Figure 4 illustrates that eleutheroside E is best extract in 30-50% ethanol, whereas the chlorogenic acid is best extracted in 40-60%, for both batches of raw material tested. It also illustrates the quality differences between the batches.
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mg/mL 1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 0 10
Effectivity of extraction in correlation to ethanol concentration
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Elutheroside E, raw material A Elutheroside E, raw material B
Chlorogenic acid, raw material A Chlorogenic acid, raw material B
Figure 5 illustrates that when overlaying and normalizing the curves, both compounds follow the same curve (except below 40%). It can be concluded that the maximum extraction of both compounds takes place at 40-60% ethanol.
Normalised extraction curves of elutheroside E and chlorogenic acid
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Elutheroside E
Chlorogenic acid
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Ideal Particle Size When milling the dried herb material, it is important to choose the ideal particle size. A larger surface area increases the extraction, however, if milled too finely it may block the percolator. Figure 6 illustrates the effects of various mesh sizes. 62% of the cut herb is still larger than 2 mm after use of a 6 mm mesh. Using a 2 mm mesh turns more than 50% of the herb into a useless powder, whereas a 3 mm mesh produces herb material 90% smaller than 2 mm, 41% less than1-2 mm, and 32% less than 0.5mm (powder).
Particle composition of herb after different milling grades
100% 90% 100% 100% 74% 49% 14%
60% 40%
22% 38%
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Figure 7
Correlation between particle size and achievable percolation rate for 50 g root
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m at er ia < l 2. 0 m m < 1. 0 m m < 0. 5 m m
al l
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Using a 6mm mesh, the solvent would run too fast through the percolator and extract too little of the active constituents. A 2 mm mesh produces a raw material that is Michael Thomsen 11
52%
80%
99%
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100%
Elutheroside E Maximum flow
impractically slow to extract. The 3 mm mesh, for that particular hammer mill, ensures that a high level of active constituents are extracted at a moderate flow rate. Intermediate Maceration The British (BP 80) and German (DAB 8) pharmacopoeias recommend that the milled herb is macerated in the percolator for 24 hrs before percolation is commenced. When testing for total solids and eleutheroside E by HPLC, however, no difference was found between macerating for 12 or for 24 hrs. Macerating for under four hours significantly decreased the extraction of active constituents. Figure 8
Time for intermediate maceration in correlation to elutheroside E and total solids.
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Elutheroside E (mg/mL)
Total solids (mg/ 10uL)
Ideal Temperature The initial test did not find any advantage in using higher than room temperature. However, if the cut and soaked herb is covered with menstruum (solvent), increasing the temperature increased extraction of active constituents. The ideal temperature was found to be 50°.
Quality Control
In the wider community, herbal medicine is often regarded as ‘second best’ to allopathic medicine. This is in part because, until relatively recently, herbal medicine has been empirically rather than scientifically verifiable. Additionally, the extreme variations in the quality of herbal products have been too great to guarantee efficacy. Contemporary herbal manufacturers must rectify this, by providing herbal products, which are of consistent quality and efficacy. What are the issues of quality in botanical medicine? • quality raw materials Michael Thomsen 12
• • • •
good laboratory practice good manufacturing practice standardized manufacturing principles pharmacologically active dosages
Quality Raw Materials Beginning with the Best It is absolutely vital that the raw materials are thoroughly checked. It is not uncommon for a manufacturer to receive cut herb containing stones, packing material and other extraneous materials. It is also important to ensure the material is not contaminated with plant parts other than the specified part used. Trade, Organic or Wildcrafted raw materials Botanical extract companies must support sustainable agricultural methods. To ensure authenticity, they must, wherever possible, work directly with suppliers of quality organic herbs. Organic growers should be certified by a Government or trustworthy organic certification organizations. It is also vital that only wildcrafted herbs which have been harvested in an ecologically sensitive way are used. The companies must further guarantee that all raw materials and finished products are free of pesticide and herbicide residues and other contaminants such as heavy metals. WHO “Guidelines on Good Agricultural and Collection Practices” of Herbs By Mathias Schmidt, Michael Thomsen and Georges Betti Quality, efficacy and safety are parameters that are required for all medicines. These are particularly important to herbal preparations as they gain popularity. The past decade has witnessed significant worldwide growth in the use of medicinal herbs as teas and dietary supplements. Due to the increasing knowledge of both the traditional and scientifically documented benefits of herbs, consumers are now more likely to consider herbal remedies as a viable alternative to conventional medicines. The World Health Organization (WHO) estimates the total world market for medicinal botanicals to be about $60 billion.1 According to data cited in a report of the Secretariats of the Convention on Biological Diversity (CDB), sales of herbs in the United States increased from $1.6 billion in 1994 to $5.4 billion in 2000. In recent decades, the tremendous growth of the herbal sector has revealed the need for improved quality control in cultivation and collection of herbal raw material. Consistent and reproducible quality of herbal raw materials used for medicinal purposes is paramount for clinical efficacy, and for the reproducibility of beneficial effects as observed in clinical studies. Furthermore, numerous safety issues are dependant on consistent composition of botanical ingredients. Ideally, raw material for the production of herbal medicines will come from a traceable and reproducible source. In reality, the trading habits co-evolving with the growth of the market frequently obscure the origin of the plant material and facilitate adulterations, which, especially in case of adverse events, have already damaged the reputation of otherwise relatively safe plants.
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In February 2004 the WHO released “WHO guidelines on good agricultural and collection practices (GACP) for medicinal plants,” [ref #1] which addresses quality issues in the production of herbal raw material. It covers recommendations that range from the selection of appropriate seed material and cultivation sites to the avoidance of contaminations in post-harvesting handling, training and working conditions of personnel, and general rules for handling and construction of tools and facilities. Some of the major issues and their practical implications are briefly discussed below. Selection of appropriate plant/seed material Though seemingly trivial, the selection of the correct species for cultivation is still of major concern. The replacement of species with seeds from species that are closely or less closely related plants is a common feature in modern plant trading, even though the required species is frequently defined in pharmacopeias, monographs or other scientific literature. For example, large tracts of the world market of licorice root (Glycyrrhiza glabra) do not consist of batches of the species as defined in European pharmacopoeia (Ph. Eur.) and United States Pharmacopeia (USP), but from G. uralensis, such as permitted by the Japanese pharmacopeia. The mixture of species of various origins, partly from uncontrolled and destructive wild harvesting, is frequently sold as G. glabra. Another example is devil’s claw (Harpagophytum procumbens) secondary tuber from Namibia, where replacements of the root with material collected from H. zeyheri from Angola is increasingly observed. In addition to the replacement of entire species, the question of chemotypes and cultivars must also be addressed. For instance, common thyme (Thymus vulgaris L., Lamiaceae) herb can be obtained that is rich in the phytochemicals thymol, geraniol, linalool, αterpineaol, trans-thujanol, 1,8-cineol or carvachrol. Current trading practices often do not allow for a distinction between the thyme raw materials of various different origins, which very likely will have varying chemical profiles, and therefore, produce variations in the reproducibility of effects in pharmacological and clinical studies. Finally, commercial orders for raw material of a given plant are often conducted using the local plant name or the English common names. These names are frequently not unique, and are in some cases confusing or misleading. For example, the Siberian/Chinese adaptogenic plant eleuthero (Eleutherococcus senticosus, Araliaceae) is frequently collected using the Chinese plant name, referring to physical attributes of the plant (fivefingered leaves, fleshy root), ci wu jia. This description not only may refer to completely unrelated plants, as was observed in a case report of a misplacement or substitution of eleuthero with the potentially toxic roots of Chinese silk vine (Periploca sepium Bunge, Asclepiadaceae)2, but it also obscures the fact that the genus Eleutherococcus (also referred to by its formerly accepted genus name Acanthopanax) contains dozens of botanical species, e.g., A. koreanus. While in the case of Eleutherococcus this does not appear to have a significant impact on the safety of the herb, there is nonetheless the question of reproducibility and reliability of clinical effects. The WHO guideline addresses this problem by stating the need for a proper botanical identification not only of the plant material, but also of the seeds used for cultivation. In GAP conform cultivation, the Latin binominal name and the definition of the Michael Thomsen 14
subspecies/cultivar/chemotype (where applicable) must be laid down in the farmer’s documentation. The same documentation applies to plants issued from wild-harvesting, where the botanical identification should be even stricter than for plants grown under the controlled conditions associated with commercial cultivation, in order to take the local phytochemical variability into account. Selection of a suitable cultivation site and appropriate cultivation methods As trivial as it may sound, the ecological and climatic conditions found on the cultivation site must meet the needs of the cultivated plant. Factors such as local rainfall, irrigation, water and soil quality and local climate have an important impact on plant quality. Too often, a decision to cultivate medicinal plants on a given site is made, not based on the specific requirements of the plant, but on the availability of the agricultural surface. In recent years, cultivations of St. John’s wort (Hypericum perforatum L., Clusiaceae) in Poland were affected with phytosanitary problems (red ring-root), as the genus Hypericum naturally thrives in dryer climates. Similarly, the inappropriate plantation of kava (Piper methysticum Forst., Piperaceae) on former sugar cane fields on Fiji led to viral infections which destroyed large parts of some local kava cultivars. Consequently, a poor choice of a cultivation site may affect not only the local harvest, but, in extreme cases, can have a global impact on biodiversity. The WHO guideline provides recommendations for the choice of an appropriate cultivation site. It also points to the exclusion of sites with possible industrial contaminations with heavy metals, pesticides or herbicides, and radioactive contaminations. In practice this means that soil samples must be collected and analyzed. Wherever possible, suggests WHO, organic growing techniques should be employed, thus avoiding the use of herbicides or pesticides. In addition, the impact of the growing of herbs on local biodiversity must be respected. Harvesting and processing conditions Harvesting time and methods are in close relation to phytochemical parameters. For example, St. John’s wort (SJW) was traditionally collected in the flowering season with fully developed flowers – a season when the content of hyperforin is relatively low. SJW harvested towards the end of the flowering season, with fruit formation more or less pronounced, leads to batches with considerably higher hyperforin content. As this compound is now suspect as a major contributing factor in the much publicized herb-drug interactions documented with the use of SJW3-6, techniques that limit the hyperforin content in the SJW raw materials and preparations are currently being discussed. The simplest and most logical approach to achieve this goal is by choosing an appropriate harvesting time. Another practical example is artichoke (Cynara scolymus, Asteraceae) where the leaves are collected in the preparation of choleretic (bile producing) and cholesterol-lowering herbal preparations. The harvesting time greatly affects the phytochemical composition and quality of artichoke leaves. The harvest of leaves as a by-product of vegetable production (i.e., the pre-flowering heads) leads to herbal products of lesser quality (albeit
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cheaper) than the production of dedicated artichoke cultivations for medicinal purposes only. Conditions associated with processing raw materials, especially drying, frequently have a major impact on drug quality. Inadequate drying and storage leads to microbiological contaminations and changes in the phytochemical composition. Again, artichoke leaves are a practical example: the higher the drying temperature, the lower the content of caffeoyl quinic acids in the dried leaves; these acids (e.g. cynarine and derivatives) are associated with the leaves’s therapeutic effects. A major part of the WHO guidelines cover the various aspects of harvesting, storage and shipping. This section of the guidelines is essentially identical for cultivation and collection (wild harvesting or wildcrafting) of medicinal plants. In regard to harvesting times and post-harvesting processing, the guidelines refers to the specifications laid down in pharmacopeias, with respect of experience published in the scientific literature. Cross-contamination during storage must be avoided, and organically grown material must be stored separately from conventionally grown herbs (i.e., herbs not grown organically and not certified as organic by an appropriate third party organization, regardless of whether the conventionally grown herbs have been sprayed with pesticides or not, or grown in artificially fertilized soil or not). The documentation of the harvest must contain essential indications that allow the identification and assessment of the key steps. With the measures outlined in the GAP guidelines, the best possible harvest-to-harvest reproducibility and a full traceability of the herbal raw material should be guaranteed. Sustainability Many medicinal plants are as yet unavailable from controlled cultivation. TRAFFIC (a division of the World Wildlife Fund) estimates that almost 75 percent of all botanical species in trade continue to be sourced from the wild.7 [MF: KO, delete “(div…WWF)” One of the major goals of the WHO GACP guideline is to outline efficient, nondestructive, environmentally sound and sustainable procedures not only for cultivation, but also for controlled collection. In the case of wildcrafting, the guideline aims for the avoidance of negative impacts on plant population density and the maintenance of biodiversity. A major obstacle for sustainable collection projects is the overharvesting of medicinal plants in uncontrolled wildcrafting, as can be observed with many plants such as devil’s claw in Southern Africa. Intellectual property rights Almost hidden within the GACP guidelines is the issue of intellectual property rights for plants endemic to a certain region.. The brevity of the statement that “All intellectual property rights with regard to source materials must be respected” may seem to understate the importance of this topic for which the practical implications are still under discussion. The guidelinescall for a scientific botanical survey to outline the distribution and assess the abundance of the species to be cultivated.
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A practical solution for the question of intellectual property rights would be to organize GACP projects in the regions where the plant naturally occurs. With this access, several problems are solved simultaneously: • • • The plant grows in its natural habitat under conditions it is well adapted to. There is no problem with intellectual property rights, as the region the plant originates from immediately profits from the activities. GACP projects have a stabilizing impact on a regional economy, which is an important factor for the long-term sustainability of the cultivation.
Projects that ensure sustainability and quality in wildcrafting are not necessarily difficult to organize if addressed in a systematic manner. The authors are currently organizing projects that conform to GACP with a number of medicinal plants, with some success thus far. Georges Betti: Ethnobotanist, specialist in identification of chemotypes/cultivars and GAP conform sustainable cultivation respectively collection of herbal raw material. Medicinal & Aromatic Plants R&D, Les Algorithmes – Aristote A, 2000 Route des Lucioles, BP 29, F-06901 Sophia Antipolis. Dr. Mathias Schmidt: Pharmacist with experience in GAP projects, Specialized in quality issues of herbal medicine (analysis, pharmacovigilance, toxicology and clinical studies). Herbresearch Germany, Wartbergweg 15, D-86874 Mattisies. Schmidt@Herbresearch.de References: World Health Organization. WHO guidelines on good agricultural and collection practices (GACP) for medicinal plants. Geneva, Switzerland: World Health Organization; 2003. Available at: .
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Awang DVC. Siberian ginseng toxicity may be case of mistaken identity. Can. Med. Assc. J. 155(9): 1237 (1996).
Moore LB, Goodwin B., Jones SA, Wisely GB, Serabjit-Singh CJ, Wilson TM, Collins LJ, Kliewer SA. St. John’s wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc. Natl. Acad. Sci. U.S.A. 97(13): 7500-7502 (2000). Wentworth JM, Agostini M, Love J, Schwabe JW, Chatterjee VK. St. John’s wort, a herbal antidepressant, activates the steroid X receptor. J. Endocrinol. 166(3): R11-R16 (2000).
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Mai I, Bauer S, Johne A, Uehlecke B, Roots I. Effect of hypericum extracts with different hyperforin content on the pharmacokinetics of cyclosporin A. Herba Polonica 49(3/4): 79 (2003).
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Mueller S, Uehlecke B, Woehling H, Petzsch M, Majcher-Peszynska J, Hehl EM, Sievers H, Frank B, Riethling AK, Drewelow B. Effect of St. John’ wort dose and preparations on the pharmacokinetics of digoxin. Clin. Pharmacol. Ther. 75(6): 546-557.
Laird SA, Pierce AR. Promoting sustainable and ethical botanicals: Strategies to improve commercial raw material sourcing. New York: Rainforest Alliance, May 2002. Available at: