Chapter 6 Pharmacological activities of natural products
As indicated in Chapter 2, a valid scheme for the study of medicinal plants and their products, and one which emphasizes pharmaceutical use, can be based on pharmacological action. The scheme can be extended to include numerous plants which, although eliciting a pharmacological response, are not, for varied reasons, used as drugs. In the latter category would be placed hundreds of alkaloid- and glycoside-containing plants.
Some major pharmacological groupings involve drugs which act on the nervous systems, heart and blood vessels, lungs, gastrointestinal tract, kidneys, liver, reproductive organs, skin and mucous membranes. Other categories include hormones, vitamins and chemotherapeutic drugs used for the treatment of infections and malignant diseases. Some plants (e.g. Papaver, ipecacuanha and liquorice) contain a range of compounds with differing pharmacological properties. Oliver-Bever’s classical review (J. Ethnopharmacol., 1983, 7, 1) on West African plants which act on the nervous system well illustrates the problems of constructing a purely pharmacological classification for herbal materials. A system based on clinical usage may be more straightforward for the throughly studied allopathic drugs used in Western medicine but difficulties can arise for plants used in traditional medicine because of the often numerous conditions for which any one drug may be employed. However, this is a very active area of research and the situation for a particular drug becomes clearer as the chemical nature of the active constituents together with their pharmacological properties are elucidated.
The nervous system coordinates and regulates the various voluntary and involuntary activities of the body and is conveniently considered under two headings—the central nervous system (CNS) and the autonomic nervous system. The two are interlinked and some drugs which affect the CNS may also produce reactions associated with the autonomic system. In the case of others which act via the autonomic system it is sometimes more convenient to classify them under other headings appropriate to the organs involved; thus, those producing vasoconstriction or vasodilation may appear under the consideration of the circulatory and respiratory systems.
The central nervous system comprises the brain (cerebrum, cerebellum, medulla oblongata) and the spinal cord. It coordinates the voluntary activities of the body and exhibits numerous interactions within the system together with linkages to the autonomic system. Drugs involved with the CNS can be broadly classified according to whether they have a general stimulatory or depressant action with further subdivision regarding specific actions such as anticonvulsant and psychopharmacological activities. Some of the most useful natural drugs of the group are the narcotic (opioid) analgesics; a number of herbal drugs are popular sedatives and others such as the hallucinogenic drugs have important sociological implications. See Table 6.1 for a summary of drugs acting on the central nervous system.
Table 6.1 Drugs acting on the central nervous system.
| Drugs affecting mental activity | |
| Lysergic acid diethylamide | Hallucinogenic. Prepared by partial synthesis from ergot alkaloids or by artificial culture |
| Mescaline | Hallucinogenic. Obtained from peyote cactus |
| Cannabis | Hallucinogenic. Active constituents contained in the resin of Cannabis sativa |
| Purine bases (e.g. caffeine, theophylline, theobromine) | Stimulate mental activity; constituents of beverages—coffee, tea, cocoa, kola, maté |
| Cocaine | One of the earliest drugs used as a mental stimulant. Produces addiction. Contained in the leaves of Erythroxylum coca |
| Ginkgo biloba | Improves short term memory |
| Ginseng | Improves mental concentration particularly in the elderly |
| Galanthamine | Promising Amaryllidaceous alkaloid for treatment of Alzheimer’s disease |
| Hops | Sedative, often combined with other herbs |
| Hypericum | Popular herbal remedy for relief of mild–moderate depression |
| Passiflora | Treatment of insomnia often in combination |
| Sage | Revived interest in its use for counteracting memory loss |
| St John’s wort | Antidepressant, may adversely react with some mainstream drugs |
| Reserpine | Depresses mental activity. Used in psychiatric treatment. Obtained from Rauwolfia spp. |
| Yohimbine | Similar action to reserpine but its antiadrenaline reactions and effect on heart muscle render it of no clinical use. Found in various species of the Apocynaceae |
| Valerian | Sedative and hypnotic; aids sleeplessness and improves sleep quality |
| Analeptic drugs (stimulants of the CNS in addition to the mental stimulants indicated above) | |
| Picrotoxin | Analeptic previously used in the treatment of barbiturate poisoning. Obtained from berries of Anamirta cocculus |
| Lobeline | Obtained from Lobelia inflata |
| Strychnine | Weak analeptic; toxic doses produce spinal convulsions. Obtained from the seeds of Strychnos spp. |
| Camphor | Weak analeptic. Obtained from Cinnamomum camphora and by synthesis |
| Central depressants of motor function | |
| Tropane alkaloids (e.g. hyoscine, atropine, etc.) | Formerly the only drugs effective in the alleviation of the symptoms of Parkinson’s disease. Used in treatment of travel sickness and delirium tremens |
| Gelsemium root | Rarely employed clinically owing to high toxicity. Galenical preparations occasionally used as antispasmodics |
| Analgesic drugs | |
| Morphine | Effective for relief of severe pain. Depressant action on the cough and respiratory centres. The principal alkaloid of opium |
| Codeine | Although less active than morphine it is a much safer drug for the relief of mild pain and for use as a cough suppressant |
The autonomic nervous system supplies the smooth muscle tissues and glands of the body. Its function is complex, involving ganglia situated outside the spinal cord; it is composed of two divisions, the sympathetic (thoracolumbar or adrenergic) division, which arises from the thoracic and lumbar regions; and the parasympathetic (craniosacral or cholinergic) division, originating in the brain and in the sacral region. In general, an increase in activity of the sympathetic system gears the body for immediate action (fight and flight), whereas stimulation of the parasympathetic or vagal system produces effects more associated with those occurring during sleep and with energy conservation. Two important neurotransmitter substances of the autonomic nervous system are acetylcholine and noradrenaline and its derivatives; hence, other substances which either mimic or antagonize the action of either of these will produce a marked physiological response. Drugs acting on the autonomic nervous system are summarized in Table 6.2.
Table 6.2 Drugs acting on the autonomic nervous system.
| Acetylcholine-like drugs | |
| Pilocarpine | From leaves of Pilocarpus microphyllus |
| Arecoline | From seeds of Areca catechu |
| Muscarine | From Amanita spp. and other fungi |
| Physostigmine | A cholinesterase inhibitor from seeds of Physostigma venenosum |
| Antagonists of acetylcholine | |
| Tropane ester alkaloids (e.g. hyoscine, atropine) | From a number of Solanaceae (e.g. Duboisia, Atropa, Datura etc.) They have widespread uses involving their gastrointestinal, bronchial, genito-urinary and ophthalmic effects in addition to the CNS activity (q.v.) |
| Neuromuscular blocking agents (e.g. tubocurarine) | From leaves and stems of Chondodrendon tomentosum |
| Ganglion blocking agents (e.g. tubocurarine in large doses) (not clinically important) | |
| Adrenaline-like drugs | |
| Ephedrine | From stems of Ephedra spp.; mainly synthetic |
| Antagonists of adrenaline | |
| Ergot alkaloids (e.g. ergotamine) | From sclerotia of Claviceps spp. |
| Noradrenaline depletion | |
| Reserpine | Has antihypertensive effect resulting from dilation of heart and circulatory vessels |
| Ophthalmic preparations | |
| The eye, being under the control of the autonomic nervous system, is affected by some of the drugs mentioned above; these include atropine, hyoscine, physostigmine and pilocarpine | |
In developed countries, coronary and associated circulatory diseases now constitute the principal cause of human mortality. Not surprisingly, therefore, this is an area of intensive research, not entirely devoted to treatment, but also to the prevention of these diseases. With increased public awareness of the importance of the latter, healthier living focused on diet, supplementary food factors, exercise, etc. has taken on a more important role, not least in the mind of the commercial world where health food stores now supply many dietary supplements and medicinal plant products which overlap the traditional pharmaceutical range.
Many factors affect the complex regulation of the heart and the large group of drugs which is known to possess cardiovascular activity is not confined to action on the heart muscle itself. Thus those drugs possessing antiarrhythmic, antihypertensive, antihyperlipidaemic, vasoconstrictor, vasodilator, blood anticoagulant, and platelet aggregation activities must also be considered in this group. As with other important areas, there is an active search in the plant kingdom for compounds which may also serve as lead compounds for the semi-synthesis of new drugs. For some therapeutic groups, the lack of simple reliable screening techniques is a problem.
In a review (over 390 refs) E. L. Ghisalberti et al. (see Further Reading) have listed some 447 species from 109 families having cardiovascular activity, together with a compilation of over 700 secondary plant metabolites having such activity.
A considerable number of plants scattered throughout the plant kingdom contain C23 or C24 steroidal glycosides which exert a slowing and strengthening effect on the failing heart. In Western medicine it is the glycosides of various Digitalis species that are extensively employed. The pharmacological effectiveness of the cardioactive glycosides is dependent on both the aglycones and the sugar attachments; the inherent activity resides in the aglycones, but the sugars render the compounds more soluble and increase the power of fixation of the glycosides to the heart muscle.
The overall action of the digitalis glycosides is complicated by the number of different effects produced, and their exact mode of action on myocardial muscle in relation to current views on cardiac muscle physiology is still an area of investigation. Digitalis probably acts in competition with K+ ions for specific receptor enzyme (ATPase) sites in the cell membranes of cardiac muscle and is particularly successful during the depolarization phase of the muscle when there is an influx of Na+ ions. The clinical effect in cases of congestive heart failure is to increase the force of myocardial contraction (the positive inotropic effect) resulting in a complete emptying of the ventricles. As a result of depression of conduction in the bundle of His, the atrioventricular conduction time is increased, resulting in an extended P–R interval on the electrocardiogram. Arising from their vagus effects, the digitalis glycosides are also used to control supraventricular (atrial) cardiac arrhythmias. The diuretic action of digitalis, important in the treatment of dropsy, arises from the improved circulatory effect. However, following the introduction of safer diuretics in the 1950s, diuretic therapy for heart failure has become much more important and in some cases can replace digitalis treatment.
Among the many other plant genera containing cardioactive glycosides related to those of Digitalis, and used similarly, are Strophanthus, Convallaria, Nerium, Thevetia and Erysimum. For a full account of these drugs see Chapter 23.
As mentioned above, the cardiac glycosides can be used to control supraventricular (atrial) cardiac arrhythmias. There are a number of other drugs such as the alkaloid quinidine (obtained from various cinchona barks, q.v.) which act on both supraventricular and ventricular arrhythmias. Quinidine is official in most pharmacopoeias as its salts and finds prophylactic use in recurrent paroxysmal dysrhythmias such as atrial fibrillation or flutter. Its therapeutic use for the attempted conversion of atrial fibrillation to sinus rhythm has now been largely replaced by electrical cardioversion.
Other drugs in this category include hawthorn and motherwort.
The control of hypertension is an important element in the management of cardiovascular disorders. Primary hypertension, as distinct from other special forms which usually require hospitalization, represents about 90% of all cases ranging from mild conditions with the occasional rise in blood pressure to those with severe unrelieved high pressure. Of the hypotensive plant drugs rauwolfia and its principal alkaloid reserpine together with Veratrum extracts were recognized in allopathic medicine in the early 1950s. A number of plants regularly employed by Western herbal practitioners include mistletoe, Crataegus, Yarrow, Tilia and Fagopyrum. In fact, a large number of other herbal drugs, used to treat various conditions, have also been shown to possess antihypertensive activity. In Ayurvedic medicine Piper betle, Jasminum sabac, Cardiospermum halicacabum and Tribulus terrestris, used in the treatment of hypertension, have been shown to exhibit a high angiotensin converting enzyme inhibition suggesting a possible mechanism of action for these drugs (B. Somanadhan et al., J. Ethnopharmacology, 1999, 65, 103).
In the circulatory system thrombi may be caused on the arterial side as a result of the adhesion of blood platelets to one another and to the walls of the vessels. This platelet aggregation is triggered by the platelet activating factor which is released from activated basophils. PAF from the rabbit was characterized in the 1970s as a 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine. A number of prostaglandins and thromboxanes are also involved in the aggregation mechanism and thromboxane A2 which is synthesized from arachidonic acid (q.v), is particularly potent. In undamaged vessels thromboxane A2 is possibly balanced by a prostaglandin e.g. prostacyclin of the arterial intima which has deaggregation properties.
For the secondary prevention of cerebrovascular or cardiovascular disease, aspirin, which irreversibly acetylates the platelet enzyme cyclo-oxygenase has been employed at dosages of 300 mg daily with useful results. A large number of plants have been screened for anti-PAF activity. One of the first natural products so identified was the neolignan kadsurenone obtained from Piper futokadsura, a plant long used in Chinese traditional medicine for allergy treatments. Other plants of traditional medicine reported to have anti-PAF activity include species of Forsythia, Arctium, Centipeda, Tussilago, Pyrola, Populus and Peucedanum. The active constituents include lignans, sesquiterpenes, coumarins, pyrocatechol and salicyl alcohol.
Extracts of the maidenhair tree, Ginkgo biloba have proved especially interesting and are commercially available in Europe for the treatment of various circulatory disorders.
Certain fish oils (e.g. cod-liver, halibut-liver) once employed solely for their vitamin contents together with ‘oily fish’ body oils have recently received a resurgence in popularity as dietary supplements. One favourable response is that they decrease the ability of platelets to aggregate by virtue of their high eicosapentaenoic acid content; this acid tends to favour the biosynthesis of thromboxane A3, a weaker stimulator of platelet aggregation than thromboxane A2.
These drugs are essentially either vasoconstrictor or vasodilator substances but their action may originate in a variety of ways (direct, central, peripheral or reflex). Some of the drugs (e.g. ergot, bronchodilators, diuretics), which are particularly useful in relation to specific systems, are classified elsewhere.
Table 6.3 Drugs acting on blood vessels.
| Peripheral vasoconstrictor drugs | |
| Ergotamine (tartrate) from Claviceps purpurea | Produces a direct constrictor effect in vascular smooth muscle; the reversal of the dilation of cranial vessels leads to its use at the onset of classical migraine attack |
| Ergotoxine | Similar to ergotamine |
| Ephedrine (synthetic and from Ephedra spp.) | Prolonged action on blood pressure—see also ‘Autonomic Nervous System’ |
| Nicotine | Vasoconstrictor effects arise from its action on sympathetic ganglia, and by it promoting release of vasopressin and adrenaline |
| Central vasoconstrictor drugs | |
| Most of the drugs (e.g. picrotoxin) which stimulate the central nervous system also stimulate the vasomotor centre in the medulla, producing a rise in blood pressure. Although at one time used as respiratory stimulants, these drugs have been largely replaced by mechanical devices for artificial ventilation of the lungs | |
| Vasodilator drugs | |
| Papaverine (an opium alkaloid) | Acts directly on the blood vessels by causing relaxation of smooth muscle. An intravenous injection used for the treatment of pulmonary arterial embolism |
| Xanthine derivatives (caffeine, theobromine, theophylline) | As papaverine; they also have a central vasoconstrictor action counteracting the peripheral effect. Also diuretic |
| Ergotamine | Adrenaline antagonist—see ‘Autonomic Nervous System’ |
| Reserpine | Vasodilatation is produced by a peripheral and central action (q.v.) |
| Veratrum alkaloids (from Veratrum spp.) | Bradycardia and peripheral vasodilatation by sensitization of cardiac, aortic and carotid sinus baroreceptors |
These compounds inhibit the clotting mechanism of the blood and are of value in arterial thrombosis; they have no effect on platelet aggregation. One group of active drugs constitutes the 4-hydroxy-coumarins which act by antagonizing the effects of vitamin K (see Chapter 31). Warfarin sodium is one of the most widely used drugs. Plants used in herbal medicine which contain coumarin derivatives and possess anti-vitamin K activity include Melilotus officinalis, Galium aparine and Lavandula officinalis.
Other anticoagulants are heparin, which is given by injection, and hirudin, produced by the leech; hirudin, a polypeptide of 65 amino acids, can also be obtained from genetically modified Saccharomyces.
In recent years much prominence has been given to the association of high levels of blood cholesterol and plasma triglycerides with atherosclerosis and ischaemic heart disease. Treatment of hyperlipidaemia is preferably dietary accompanied by other natural regimens. Drug therapy is reserved for the more intractable conditions. Natural products having a beneficial action include nicotinic acid (Chapter 31) and those fish oils containing high quantities of ω-3-marine triglycerides. The latter involve eicosapentaenoic acid and docasahexaenoic acid which, when counting from the methyl end, possess the first double bond at C-3 (see Chapter 19).
The suggested beneficial properties of garlic (Allium sativum) for the treatment of various cardiovascular conditions remain a subject of extensive investigation. With reference to hyperlipidaemic patients, the majority of published data supports the hypothesis that garlic lowers serum total cholesterol and improves the lipid profile. There is a tendency towards reduction of low-density lipoprotein and an increase in high-density lipoprotein giving a more favourable HDL:LDL ratio. Similar hypocholesterolaemic properties have been demonstrated for globe artichoke. A reduction in the serum levels of total cholesterol, low-density lipoprotein cholesterol together with a lowered atherogenic index was observed with mild hypercholesterolic patients after a three-month course of psyllium seeds (K. Sagawa et al., Biol. Pharm. Bull., 1998, 21, 184).
The gastrointestinal tract can be divided into three regions—the upper (mouth, stomach and upper portion of the duodenum), the middle (lower half of the duodenum to the ileocolic sphincter) and the lower (caecum, colon and rectum). It is the upper and the lower portions that are most susceptible to disorder and are consequently associated with the greatest number of drugs for their treatment (see Table 6.4).
Table 6.4 Drugs acting on the gastrointestinal tract.
| Bitters At one time these were extensively used in liquid medicaments to stimulate appetite. The bitter constituents stimulate the gustatory nerves in the mouth and give rise to an increase in the psychic secretion of gastric juice. Extracts of the following drugs have been so employed: gentian, quassia, calumba, cinchona (or quinine), nux vomica (or strychnine). Considerable recent research has involved the investigation of a number of these bitter compounds for other possible uses, e.g. the bitters of the Simaroubaceae as antitumour and antimalarial agents | |
| Anticholinergic drugs In this capacity hyoscine and hyoscyamine help disturbances caused by gastric mobility and muscle spasm particularly with some ulcer patients | |
| Emetics Ipecacuanha preparations, on oral administration, have a delayed emetic action produced by irritation of the mucous membranes (see ‘Expectorants’). Picrotoxin stimulates the vomiting centre through its general effect on the central nervous system | |
| Antiemetics Ginger has received scientific approval for the prevention of the symptoms of travel sickness. Cannabis affords sickness relief to patients undergoing chemotherapy | |
| Carminatives These are aromatic substances which assist the eructation reflex; their mode of action is obscure. Dill oil is used for the relief of flatulence, especially in babies. Other plants or oils used as carminatives include caraway, fennel, peppermint, thyme, nutmeg, calamus, pimento, ginger, clove, cinnamon, chamomile, matricaria. Chalk is used as an antacid and charcoal as an adsorbent | |
| Ulcer therapy Derivatives of glycyrrhetinic acid (a triterpenoid of liquorice root) prove effective in the treatment of peptic ulcer. Deglycyrrhizinized liquorice has also been employed. Other antiulcer agents include alginic acid, marshmallow and comfrey | |
| Demulcents These soothe and protect the alimentary tract and overlap with some materials used in ulcertherapy. Iceland moss, orris and elm bark may be included here | |
| Laxatives and purgatives Purgatives may be classed according to their mode of action | |
| Agar, psyllium and ispaghula | Hydrophilic colloids which function as bulk-producing laxatives |
| Bran | An indigestible vegetable fibre which absorbs water and provides bulk |
| Senna (leaves and fruit) | Contains anthraquinone derivatives which are hydrolysed in the bowel to stimulate Auerbach’s plexus in the wall |
| Cascara, rhubarb, aloes | As senna |
| Castor oil | Contains glycerides which on hydrolysis yield riconoleic acid, irritant to the small bowel |
| Podophyllum resin, jalap resin, colocynth | Drastic purgatives, now little used for this purpose. They were often prescribed with belladonna to reduce griping |
| Rectal and colonic drugs Arachis oil, esculin, hamamelis, pilewort and balsam of Peru are examples of this group; they include those used in suppositories | |
| Antidiarrhoeal drugs Morphine and codeine act by increasing the smooth muscle tone of the bowel and by reducing its mobility. Commonly prescribed with kaolin | |
A large number of drugs of plant origin are to be found in this group. As infections of the respiratory tract are amongst the most common of illnesses, it is not surprising that there are numerous proprietary preparations for their treatment (Table 6.5).
Table 6.5 Drugs acting on the nasal and respiratory systems.
| Aromatic inhalations | Benzoin, cineole, eucalyptus oil, menthol and peppermint, pumilo pine oil, balsam of Tolu, thymol, turpentine, menthol, eucalyptus |
| Bronchodilators and nasal decongestants | Ephedra, ephedrine, xanthines (theophylline) |
| Expectorants | Ipecacuanha (in subemetic doses), senega root, liquorice root, squill bulb, tolu balsam, pulmilio pine oil, lobelia, grindelia, angelica root and leaf, storax, cocillana, coltsfoot, sweet violet, bloodroot, balm of Gilead |
| Antiexpectorants | Codeine, atropine |
| Cough depressants | Morphine, codeine, noscapine, wild cherry |
| Demulcents | Marshmallow, verbascum, plantago, Iceland moss, honey |
The liver, the principal organ of metabolism and excretion, is subject to a number of diseases which may be classed as liver cirrhosis (cell destruction and increase in fibrous tissue), acute or chronic hepatitis (inflammatory disease) and hepatitis (non-inflammatory condition). The most common drug of plant origin used in Western medicine for its antihepatotoxic properties is Silybum marianum. In Indian and Oriental medicine many plants are so used. For a discussion of this field of current interest see Chapter 29.
A number of plant materials are to be found in this group; the examples given in Table 6.6 are confined to Western usage.
Table 6.6 Drugs acting on the urinary and reproductive systems.
| Diuretics | Xanthine derivatives as present in many beverages (tea, coffee, etc.) promote dilation of the renal medullary blood vessels. Digitalis glycosides improve the failing heart thereby increasing renal perfusion and glomerular filtration; hence, Withering’s original introduction of digitalis for the treatment of dropsy. There is also a small but finite effect on tubular reabsorption of sodium ions |
| Diuretics and urinary antiseptics | Buchu, boldo, horsetail, Java tea, bearberry, juniper, copaiba. These include drugs used for the treatment of cystitis and urethritis |
| Drugs acting on the uterus | Preparations of ergot were traditionally used in childbirth and then largely replaced by the isolated alkaloid ergometrine. Administered as its salts it has a direct stimulant action on the uterine muscle and reduces the incidence of postpartum haemorrhage. Ergotamine acts similarly but is not suitable for obstetric use because of its marked peripheral vasoconstrictor action |
| Black haw is a uterine tonic and sedative used for the prevention of miscarriage and for dysmenorrhoea after childbirth | |
| Hydrastis is employed for menorrhagia and other menstrual disorders | |
| Agnus castus has been traditionally employed for the treatment of menopausal disorders, premenstrual symptoms, dysmenorrhoea, etc. | |
| Oral contraceptives | Female, see ‘Steroids’. Male, gossypol (q.v.) |
| Numerous plants have been, and are being, tested for antifertility activity | |
| Male impotence | Papaverine (under careful medical supervision), yohimbine (erectile dysfunction) |
| Benign prostate hyperplasia (BPH) | A number of phytomedicinals are employed (often as admixtures) to treat the symptoms of BPH. Two metabolites associated with the condition are dihydrotestosterone and oestrogen which require two enzymes (5α-reductase and aromatase) for their synthesis in the body. It has been shown, for some of the drugs used, that they are inhibitors of these two enzymes. The following examples are well-established: Cucurbita pepo seeds (pumpkin), Epilobium angustifolium and other species, Prunus africana (Pygeum africanum) bark, Serenoa repens fruits (saw palmetto, sabal), Urtica dioica and U. urens root extracts |
In addition to acting as covering for the body, the skin performs a number of other physiological functions. Drugs affecting the skin may be of an emollient nature or they may act as absorbents, astringents, irritants or antiseptics (see Table 6.7). A number of substances are easily absorbed through the skin; this fact is utilized in transdermal medication but must also be borne in mind with respect to various poisons.
Table 6.7 Drugs used on the skin and mucous membranes.
| Emollients and demulcents | These include a number of vehicles used in the preparation of ointments, creams, lotions, etc., and include fixed oils (e.g. olive, arachis, coconut, theobroma), fats (wool-fat, lard), waxes of animal origin (beeswax, spermaceti), gums (acacia, tragacanth) and mucilages (psyllium, elmbark) |
| Absorbents | Starch, alginates, charcoal |
| Astringents | Tannins (e.g. Tannic acid), krameria, catechu, galls, Aspidosperma, hamamelis, pomegranate rind, kinos |
| Counter-irritants | Camphor, turpentine, capsicum, aconite, methyl salicylate, mustard seed |
| Antiseptics | Tars, eucalyptus oil, thyme oil, eugenol, thymol, cajuput |
| Anti-inflammatory agents | Corticosteroids used locally, matricaria, arnica |
| Psoriasis and eczema treatment | Comfrey, allantoin, cadeoil, evening primrose oil, chrysarobin, Lithospermum, savin, myrrh, grindelia |
| Wound coverings | Type of wound covering (occlusive, non-occlusive, haemostatic) is important in the healing process. See alginates, cotton, etc. |
Many plants have been used in traditional systems of medicine for the oral treatment of diabetes and it is particularly important that Western practitioners be aware of any patients already taking such medication. Among the plants so used are karela fruit (Momordica charantia), cumin fruit, ginseng, Teucrium oliverianum, neem (Azadirachta indica), onion, Aloe spp., Job’s tears (Coix lachryma-jobi) and Galega officinalis. For a discussion of the current position on plant-derived oral hypoglycaemic substances see Chapter 29.
Two types of corticosteroidal hormone are the glucocorticoids, which regulate carbohydrate and protein metabolism and which also possess a strong anti-inflammatory action, and the mineralocorticoids, which influence the electrolyte and water balance of the body. The clinical indications for systemic treatment with these drugs are complex, but include use in replacement therapy, Addison’s disease, reduction of lymphatic tissues (leukaemias), suppression of lymphopoiesis (lymphomas) and as anti-inflammatory agents (a variety of conditions including rheumatoid arthritis, cerebral oedema and raised intracranial pressure).
These hormones are produced naturally in the adrenal cortex but a wide variety of semi-synthetic drugs of this type is commonly in use. These are synthesized using plant steroids as intermediates; diosgenin and hecogenin being the principal sources. To a lesser extent the steroidal alkaloids of the Solanaceae are employed. There is a large world demand for these compounds, particularly for the synthesis of oral contraceptives, and their distribution in nature and chemistry is considered in more detail in Chapter 23.
Aspirin, first synthesized in 1853 by Carl Gerhardt, is still one of the most widely-used mild analgesic and non-steroidal anti-inflammatory drugs (NSAID). It had its medicinal origin in the salicylates and glycosides of willow bark, long used for the treatment of rheumatic diseases, gout and painful conditions of all types.
In view of the universal requirement for NSAIDs very many plants have been utilized for the purpose in traditional medicine and in recent years considerable research effort has been expended on their investigation.
Enzymes have been used to detect anti-inflammatory activity of plants—galangin, a flavonoid of Alpinia officinarum (Zingiberaceae; galangal rhizome) was found to be a cyclo-oxygenase inhibitor. Lipoxygenase inhibitors are present in Spilanthes oleracea (a S. American plant of the Compositae used for the treatment of rheumatic disorders) and also in Echinacea purpurea root, also Compositae, which contains a range of compounds including isobutylamides.
In a review of plants exhibiting anti-inflammatory activity Handa et al. (1992) cite that species of 96 genera belonging to 56 families are ascribed such activity.
In addition to the wide range of plants involved there is a similar diversity in the chemical nature of the active constituents. Flavonoids constitute one group widely associated with anti-inflammatory activity and are exemplified in the BHP (1996) by the monographs on Balm of Gilead Bud, Cimicifuga Rhizome, Equisetum, Jamaica Dogwood, Marigold, Matricaria Flowers, Meadowsweet, Poke Root, Red Clover Flower and Willow Bark. In the case of an infusion of matricaria flowers (Chamomilla recutita, German chamomile), used for its anti-inflammatory action in the treatment of acute gastritis, it has been shown by the mouse-ear test that it is the flavonoids and not the volatile oils that are responsible for activity; however, for Calendula officinalis the terpenoids were found to be active constituents (see Anon., Pharm. J., 1992, 249, 474). With liquorice root (Glycyrrhiza glabra) both the triterpenoid saponin glycyrrhizin and the flavonoids have, among their other pharmacological actions, anti-inflammatory activity.
Colchicine, an alkaloid of Colchicum autumnale, is the classical drug for the treatment of acute attack of gout. It may act by reducing the inflammatory response caused by deposits of urate crystals in the joint and by reduction of phagocytosis of the crystals. Its use has been somewhat replaced by allopurinol (inhibition of xanthine oxidase) and by phenylbutazone. Guaiacum resin (q.v) is cited for the treatment of chronic rheumatic conditions and gout; it contains a mixture of lignans. The dried root of Harpagophytum procumbens (Devil’s claw) (Pedaliaceae), has recently received popular attention for the treatment of painful rheumatic conditions; iridoid glycosides, e.g. harpagoside, are the characteristic constituents. The juice of Ananas comosus, the pineapple (Bromeliaceae) contains a mixture of at least five proteolytic enzymes collectively called bromelin or bromelain. In Western medicine the enzyme has been introduced for its ability to dissolve fibrin in conditions of inflammatory oedema.
The action of ginkgolides (C20 terpenes from Ginkgo biloba) as potent antagonists of platelet activating factor has already been mentioned.
For natural products in this category, see Table 6.8.
Table 6.8 Drugs used for the treatment of infections.
| Antibiotics Many higher plants possess constituents having antibacterial properties; none has been utilized clinically, mainly because of high toxicity. Moulds and streptomyces are the principal sources; see Chapter 30 for a consideration of antibacterial and antiviral drugs | |
| Antimalarials Until the advent of the synthetic antimalarials, quinine, isolated from the bark of various Cinchona spp., constituted the most effective agent for the treatment of malaria; it is still used in Third World countries and is of some resurgent importance for combating malarial organisms resistant to other drugs. Artemisinin (Qinghaosa), an unusual sesquiterpene lactone, is the active constituent of an ancient Chinese drug derived from Artemisia annua. It is effective against chloroquine resistant strains of Plasmodium vivax and P. falciparum as well as against cerebral malaria; see Chapter 28 | |
| Amoebicides | |
| Emetine | An alkaloid of ipecacuanha root, used as its hydrochloride or bismuthiodide in the treatment of amoebic dysentery. Complete eradication of the chronic infection is difficult and combined therapy with other drugs is often necessary |
| Anthelminthics | |
| Extract of male fern | For tapeworm infections |
| Santonin | Possesses a powerful action in paralysing round-worms; although once extensively used its high toxicity has led to replacement by piperazine |
| Oil of Chenopodium | Like santonin; it has also been extensively used in hookworm disease but it gives variable results |
| Thymol | At one time much used in hookworm treatment |
The last 50 years has witnessed a vast search of the plant kingdom for phytochemicals with anticancer activity, and medicaments derived from Catharanthus, Taxus and Podophyllum are among the most effective in current usage. Originally, most research centred on plants of Western origin but since 1986 focus has shifted towards the investigation of tropical and subtropical species. The introduction of new techniques designed to eliminate ‘nuisance’ compounds (see Chapter 9) has accelerated the process of screening many hundreds of specimens. Clinical trials continue on a number of promising compounds. For a fuller discussion, see Chapter 27.
A large number of materials give rise to allergic conditions in sensitive individuals. Extracts containing specific allergies are available as diagnostic kits or for desensitization. Examples of plant allergens are grass, flower and tree pollens, dried plants and moulds (see Chapter 39).
Drugs affecting the immune system are termed immunomodulatory or adaptogenic. Some repress the system and are of value in, for example, preventing rejection of transplanted organs and others are stimulatory and can be used to help combat viral infections such as AIDS or assist in the treatment of cancer. Until relatively recently such herbal drugs were largely ignored by Western orthodox medicine, although they have always featured in traditional Chinese and Indian medicine in seeking to achieve homoestasis with regard tobodily functions. Now, however, ginseng leads the market in herbal sales in Europe and the US and Echinacea spp., used by native N. American Indians, ranks around fifth in the US herb market sales and is widely used in Europe, with 800 preparations being quoted as available in Germany. For immunomodulators of Chinese origin see L.-H. Zhang et al., Phytotherapy Research, 1995, 9, 315, and for Indian drugs see A. A. Mungantiwar et al., J. Ethnopharmacology, 1999, 65, 125.
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Wright CI, Van-Buren L, Kroner CI. Herbal medicines as diuretics: a review of the scientific evidence. Journal of Ethnopharmacology. 2007;114(1):1-31. (around 120 references)