FUNDAMENTALS OF PHYTOTHERAPY 

Characteristics and Status of Herbal Medicines

Preliminary Remarks

• Herbal medicine is a scientifically recognized complementary and alternative treatment method  with proven efficacy. 
• In North America, herbal remedies are considered dietary supplements by law and are considered safe unless proven otherwise. Manufacturing standards are not as stringent as required for pharmaceutical drugs. While only a few “structure and function” claims (such as “benefits digestion”) can be made by manufacturers, many work around that limitation by making extensive use of “third-party” advertising in magazines and through company representatives. 
• In Germany, herbal remedies are defined as medicinal products by German Drug Law. 
• German legislators regard herbs and herbal remedies as medicinal products with specific pharmaceutical characteristics. Together with homeopathic and anthroposophic medicines, herbal medicines are classified as drugs of a special system of therapeutics. 
• According to German law, every physician must be knowledgeable about herbal medicine. North American physicians are not required to have this training, and few classes are offered in herbs or natural medicine in medical school. 
• The public interest in alternative therapies for general health maintenance and supportive treatment of chronic diseases has increased tremendously.

Distinctions Between the Different Types of Therapeutic Preparations

• Herbal products: One of the main distinguishing features of herbal preparations is their complex chemical composition. 
• Chemical or synthetic drugs: Chemically defined drugs in general contain precisely definable quantities of usually one particular active ingredient and also accompanying substances.
• Homeopathic remedies: Homeopathic products are prepared according to special formulation techniques and are prescribed according to the principles introduced by Samuel Hahnemann in the early nineteenth century. His “Law of Similars” states that the remedy prescribed, in a more or less highly diluted form, to cure a given condition or disease should be a substance that induces similar symptoms in healthy individuals when given in much higher amounts.
• Anthroposophic remedies: Anthroposophic remedies are prepared according to the ideas and teachings of Rudolf Steiner.

Definitions

Ø Herbal medicine: A time-honored system of healing practiced in every culture in the world. Science has modernized the system using analytical and pharmaceutical testing. The science-based practice of herbal medicine is now called phytomedicine Or phytotherapy, which is a system of therapeutics in which diseases and disorders are treated with medicinal plants and preparations made from them using scientific principles.

Ø Medicinal herbs: Medicinal products whose active ingredients consist exclusively

Ø of medicinal plants and preparations made from them. Using modern chemical and pharmaceutical methods, a number of popular herbal remedies are nowadays “standardized” to provide consistent levels of proven identified active compounds.

Ø Phytochemistry: The study of plant chemistry, including the identification, isolation, analysis, and characterization of plant constituents, and determination of the chemical structures of plant constituents.

Ø Pharmaceutical biology: The field of research concerned with the extraction and development of biogenic drugs from plants and other living organisms as well as the processing and application of these drugs.

Ø Phytopharmacology: The study of the uptake, distribution, and effect of herbal preparations and of their elimination from the body.

Ø Active principles: Substances or substance groups definable by chemical analysis that essentially contribute to the therapeutic action of a medicinal herbal preparation.

Ø Active ingredients of medicinal herbal preparations: Plant ingredients in their natural states and preparations made from them.

Ø Minor constituents: Substances that have an indirect or slight effect on the therapeutic action of an herbal drug.

Ø Single-herb herbal preparation: Herbal medicinal preparation from one medicinal plant.

Ø Target constituents: Herbal drug preparation constituents definable by chemical analysis that are used as parameters of in-process quality control and may contribute to a characteristic pharmaceutical property.

Ø Species, genus, family: Taxonomic terms classifying a plant. A genus may include one or more species, and a family may include one or more genera.

Research on Herbal Remedies: State of the Art

Ø Remarkable advances in phytotherapeutic research have been made within the past 15 years.

Ø The worldwide interest in herbal drug research is steadily increasing.

o   Collaboration between universities, the dietary supplement and herbal industry, and the pharmaceutical industry is essential to promote the success of this research. In North America, government funding of human studies on the efficacy and safety of herbal preparations is just beginning.

o   Comparable to research on chemically defined drugs, research on herbal preparations is also carried out using molecular biological, pharmacological, and clinical techniques of investigation.

o   The findings of herbal research are published in recognized medical journals such as JAMA, the British Medical Journal, and Arzneimittelforschung

o   Researchers are developing high-quality standardized extracts with proven efficacy.

o   Both basic research and clinical studies have repeatedly shown that wholedrug complexes are superior with respect to range of action and tolerability to isolated chemical constituents.

From the Plant to the Remedy

Origins of Medicinal Plants for the Manufacture of Herbal Products

Ø  Wild harvested herbs

–      Half of all medicinal plants on the market and two-thirds of all plant species are harvested from the wild.

–     For economic reasons, wild harvested herbs are preferably used in the cases of certain slow-growing plants and of plants of which there is a naturally abundant supply.

Ø  Cultivated herbs

–   Cultivated herbs are used when the natural supply is not sufficient to meet demand or if a herb required for medicinal purposes is a protected plant species, such as purple coneflower, Echinacea purpurea, and goldenseal, Hydrastis canadensis

–       Advantages of controlled farming

·       Uniform seed material, optimal growing conditions and harvesting times

·       Reduced risk of mistaken identity or adulteration

·       Reduction of impurities, microbial contamination, and residues from pesticides and heavy metals (especially in plants imported from developing countries)

–       Organic farming: Ensures the maintenance of natural growing conditions and is environmentally friendly.

Ø  Cultivation of special crops

–    Mainly used to enrich and optimize the primary constituents of medicinal plants. A way of standardizing active constituent levels.

–      Reduces the number and quantity of undesirable substances in the plants.

–      Enhances the resistance of the plants to atmospheric influences, diseases, and pests.

Quality Assurance

Ø  Homogeneous starting materials

–   Homogeneity is achieved by optimization and wide-scale standardization of growing conditions (e. g., in cultures), and asexual propagation 

Note : The concentrations of constituents in a given plant (e. g., ginseng or arnica) tend to vary according to location of origin, season of harvesting, and age.

Ø  Standardized preparation process

–      Manufacturers use exact specifications for analyzing parent substances— meaning the herbs and their parts used—and herbal extracts made from them, using solvents such as ethanol. Specifications for assaying the content of target or primary constituents are just as exact and are designed to ensure that the chemical composition of the herbal extracts remains consistent from batch to batch.

–    Standardization ensures that the quality of medicinal plants and extracts made from them are reproducible and consistent.

–    Minimum concentrations of active principles in raw (unprocessed) herbs are specified in sources such as the German and European Pharmacopeias and, lately, the US Pharmacopeia.

Note : Insofar as the manufacturers of phytomedicines use different methods of processing, the final products may vary greatly with respect to the type and/ or concentration of their ingredients. This is especially true of liquid tinctures of all kinds, including glycerites, and herb products that contain powdered herbs.

Ø  Chemical standardization: Many manufacturers today sell products that contain standardized extract powders in capsule and tablet form, and the levels of identified active constituents vary much less in these products.

Ø Quality is ensured through good harvesting, drying, processing, and storage practices of both herbs and preparations (see also section on storage):

–      Good harvesting practice takes into account the growth phase (time of year) and best time of day to harvest a given plant.

–     The drying process should be performed at a suitable temperature, without overheating, and under appropriate lighting conditions.

–  The plant material should be cut, cleaned, and stored without direct light exposure at an appropriate temperature in accordance with the rules of good professional practice. Herbal preparations such as liquids, capsules, or tablets should be stored away from heat and direct sunlight, preferably in glass containers that exclude oxygen.

Ø In-process controls: The manufacturer should monitor each step of the process of converting raw materials into finished medicinal products by applying the appropriate analytical tests.

Ø Drug safety for herbal medicinal preparations

–  In Germany, herbal medicinal preparations are subject to essentially the same standards for toxicity, teratogenicity, and mutagenicity/carcinogenicity as chemically defined drugs. End user suppliers and storage specifications are described below.

–   The processed plant material must be tested for a wide variety of different pesticides. In North America, manufacturers of herbal products must follow good manufacturing practices based on regulations for food products regarding cleanliness and safety. The Food and Drug Administration (FDA) does not currently require manufacturers to test herbal medicines that are generally recognized as safe (GRAS) and have been used in food products before 1 January 1958 for toxicity in the same way as pharmaceutical drugs, since manufacturers are allowed to make only minimal “structure–function” claims for herbal preparations.

Note:  Plants collected in the wild, as well as plants raised in conventional (nonorganic) farms, may have high concentrations of pesticides and/or heavy metals.

Ø End user suppliers: Pharmacies, supermarkets, health food stores, web-based suppliers, or by direct order from certain suppliers.

Ø Storage

–      Store in a cool (not cold), dark place, out of the reach of children.

–      Discard after the expiration date.

–      Factors that can reduce the shelf life of herbal medicines:

·       Exposure to air (keep in airtight bottles)

·       Humidity

·       Heat

·       Light (leading to oxidation-related decomposition)

·       Fungal or bacterial contamination (leading to formation of poisonous metabolites)

·       Evaporation

Note: Plants infested with pests or mold must be destroyed.

–      In order to identify plants that are spoiled or infested, the plant material should be inspected for mold, altered or unpleasant odor, insects, and traces of insects (cobwebs, etc.).

–    The pharmacist should be able to furnish information on the shelf life of herbal medicines (e. g., teas and other herbal remedies prepared in the pharmacy).

–     Herbal preparations should be stored in containers that are airtight, waterproof, lightproof, and fragrance-free.

–      Storage temperature: 10 – 20 °C (50 – 68 °F).

Comparison of Efficacy

Ø It is virtually impossible to compare the efficacy of herbal remedies prepared by different manufacturers, even when they are derived from the same plant species, because different companies use different drying, processing, and manufacturing processes, and because plants from different populations vary in constituent levels.

Ø The therapeutic efficacy of herbal remedies with comparable concentrations of primary constituents but produced by different manufacturers may vary because of the differences in the content of minor constituents.

Ø In the future, individual pharmaceutical companies will be required to test the efficacy and tolerability of plant extracts prepared by different manufacturing processes.

Constituents and Active Principles

Primary and Secondary Metabolism

Ø A distinction is generally made between primary and secondary plant metabolism. The products of primary metabolism maintain the plant’s vital functions, whereas the products of secondary metabolism, as far as is currently known, are not essential for the plant’s immediate survival.

Ø Products of primary metabolism: Carbohydrates, fats and proteins are basic nutrients for humans and animals, but are rarely relevant as pharmacologically active substances. Nonetheless, they may have a positive or negative effect on the efficacy of the active principles in drugs.

Ø Products of secondary metabolism: Many secondary plant substances protect plants from feeding damage, act as storage or waste products, or ward off pests and diseases. Some are pharmacologically active.

Examples of Products of Primary Metabolism

Ø Pectins

–      Substance group: Carbohydrates.

–      Example: Apple pectin.

–      Structural properties: High-molecular weight compounds comprising sugarlike molecules.

–      Plant sources: Found in many kinds of fruit, especially when unripe.

–    Pharmacological properties: Pectins cannot be digested by endogenous intestinal juices and have a high water-binding capacity.

–      Indications: Diarrhea.

·    Pectins lower the pH of the bowel because they encourage growth of beneficial bacteria. This produces less favorable living conditions for the pathological bacteria that cause diarrhea (see p. 190, “Diarrhea”).

Ø Essential omega-3 and omega-6 fatty acids

–      Substance group: Fats.

–      Examples: Alpha-linolenic acid and gamma-linolenic acid.

–      Plant sources: Flaxseed, rape seed, evening primrose seed, etc.

–      Structural properties: Fatty acids.

–   Pharmacological properties: Used in the synthesis of tissue hormones of the eicosanoid, prostaglandin, and thromboxane groups.

–      Indications: Symptoms and ailments involving inflammation.

Products of Secondary Metabolism

Ø Alkaloids

–      Examples: Atropine, caffeine, morphine, colchicine, nicotine, berberine.

–    Plant sources: Mainly in nightshades such as belladonna, bittersweet, and thornapple, but also in papaveraceous plants (opium poppy, greater celandine), the borage family (coltsfoot, comfrey), and the spea family (Crotalaria).

–      Structural properties: Alkaloids contain nitrogen have complex structures, and undergo alkaline reactions.

–  Pharmacological properties: Most alkaloids have a potent effect on the central nervous system, e. g., sympathomimetic or parasympatholytic effect.

–      Indications

·     Isolated alkaloids used in pure form (e. g., atropine) are highly potent drugs that are available by prescription only.

·      Chelidonine (celandine), berberine, caffeine, and theophylline are less potent alkaloids.

·   Pyrrolizidine alkaloids (present in members of the borage and aster family): Their significant toxicological features are hepatotoxicity and mutagenicity.

Ø Essential oils

–      Examples of individual essential oil components: Menthol, thymol, α-pinene, eugenol, chamazulene. Essential or volatile oils are highly complex mixtures of monoterpenes (containing 10 carbon atoms) and other types of compounds.

–      Plant sources: Found in a variety of plants, such as conifers, and members of the mint and parsley families.

–     Structural properties: Monoterpenes (e. g., menthol, thymol), sesquiterpenes (e. g., constituents of chamomile such as bisabolol), sesquiterpene lactones (parthenolide in feverfew), iridoid substances (gentopicrin in gentian root), and phenylpropane (e. g., chemicals in ginger root, eugenol).

–  Pharmacological properties: Essential oils are aromatic, highly volatile, fatsoluble substances that stimulate chemoreceptors. They are readily absorbed in the gastrointestinal tract and by the skin (e. g., when used in bath salts and liniments).

Ø Bitter substances

–      Examples: Gentianin, gentiopicrin, cynaropicrin.

–      Plant sources: Members of the Aster (artichoke, dandelion) and Gentian (gentian, centaury) families.

–      Structural properties: Mainly derivatives of terpenes and seco-iridoides.

–  Pharmacological properties: Bitter substances stimulate the reflex production of gastrointestinal secretions (especially saliva and gastric juices) via lingual taste buds.

–      Indications: For treatment of dyspeptic complaints; to stimulate appetite and improve digestion and assimilation of nutrients.

Ø Carotinoids

–      Examples: β-carotene, lycopene, lutein.

–      Plant sources: Colored fruit, leafy vegetables.

–      Structural properties: Tetraterpene derivatives.

–      Pharmacological properties: Antioxidants and immunomodulators; vitamin A precursors (β-carotene).

–      Indications: Inflammation, immunodeficiency, photodermatosis.

Ø Flavonoids

–      Examples: Rutin, silymarin, kaempferol, quercetin.

–      Plant sources: Found in a wide variety of plants.

–    Structural properties: Flavonoids have a molecular skeleton consisting of acetic acid units and a phenylpropane group. Their pharmacological properties are determined by those of their substituents.

–   Pharmacological properties: Flavonoids have a nonspecific protective effect on the capillaries, act as radical scavengers, and stabilize the cell membrane. They additionally have anticonvulsant and diuretic effects and increase the tolerance of cells to oxygen deficiency.

–      Indications: For treatment of varicose veins, inflammations, edema, dyspeptic complaints and liver disorders; to stimulate bile secretion.

Ø Tannins

–      Examples: Proanthocyanides; phenolcarboxylic acids such as chlorogenic acid, cynarin, and ursolic acid.

–      Plant sources

·      Relatively high concentrations can be found in many parts of woody plants (e. g., oak bark) and in rose plants, blackberries, silverweed (goosewort), stag-horn, blackthorn, and tormentil.

·    Lower concentrations are present in many plant-based foods and beverages (black and green tea, bilberries [blueberries]).

–      Structural properties

·       Phenolcarboxylic acids are derived from caffeic acid, salicylic acid, and bile acid.

·       Condensed proanthocyanides consist of catechinic acids.

–      Pharmacological properties: Tannins irreversibly link protein chains and have astringent action on the skin and mucous membranes. Hence, they have anti-inflammatory, styptic, counterirritant, and weakly antibacterial effects and prevent the excess secretion of mucus.

–      Indications: External uses: for irritations of the skin and mucous membranes. Internal uses: for acute unspecific diarrhea.

Ø Glycosides

–      Examples: Cardiac glycosides, anthranoids, flavonol glycosides.

–      Plant sources: Found in many members of the plant kingdom.

–     Structural properties: Contain one or multiple sugar molecules as well as a nonsugar component that determines their pharmacological activity.

–      Pharmacological properties

·   Positively inotropic (cardiac glycosides); laxative (anthranoids); improve circulation (flavonol glycosides in ginkgo leaves).

·      Higher doses can induce severe side effects and, in some cases, poisoning (cardiac glycosides, anthranoids).

–      Indications: Cardiac failure, constipation; to improve the circulation.

Ø Phytosterins (phytosterols)

–      Examples: β-Sitosterol.

–      Plant sources: Pumpkin seed, nettle root, saw palmetto fruit.

–      Structural properties: Very similar to those of cholesterol.

–    Pharmacological properties: Phytosterols occupy cholesterol receptors and thus lower cholesterol levels. They also stabilize cell walls and inhibit the synthesis of mediators of inflammation.

–  Indications: To counteract elevated concentrations of lipids (antilipemic); for treatment of benign prostatic hyperplasia.

Ø Saponins

–      Examples: α-Hederine (ivy), diosgenin (wild yam), glycyrrhizic acid (licorice).

–      Plant sources: Widely distributed in plants such as ivy (leaf), licorice (rootstock), and horse chestnut.

–      Structural properties

·       Consist of a water-soluble sugar chain and a fat-soluble component (aglycone or genin).

·       Triterpene, steroid, and steroidal alkaline saponins are distinguished by their aglycone component.

–      Pharmacological properties: Saponins induce local tissue irritation and reflex expectoration, inhibit the growth of microorganisms, especially fungi, and have partial anti-inflammatory and antiedematous effects.

–      Indications: To emulsify watery and oily solutions and to promote the dissolution of substances that are not easily absorbed.

Note: Most saponins retain their hemolytic properties, even when highly diluted. Hence, they should not be used to treat injuries or inflammations of the digestive organs.

Ø Mucilage

–      Examples: Arabinolactans, glucans, lichenin.

–      Plant sources: Marshmallow root, Iceland moss, ribwort, linden flower.

–      Structural properties: Polysaccharides.

–    Pharmacological properties: Mucilaginous substances swell when added to water, forming viscous solutions or gels. Water-soluble mucilages are demulcent and reduce inflammation. Insoluble mucilages swell in the gastrointestinal tract and regulate the bowels.

–      Indications: To soothe irritated mucous membranes of the mouth, throat, and gastrointestinal tract; to alleviate dry cough and to regulate the bowels.

Ø Mustard oils

–      Examples: Sinalbin, glucobrassicin.

–      Plant sources: Black radish, mustard, great nasturium.

–      Structural properties: Steam-volatile, pungent compounds formed by organosulfuric acids.

–      Pharmacological properties: Mustard oils have antibacterial effects and induce hyperemia of the skin.

–      Indications: Used externally to increase the blood flow.