The Big Asthma Lie

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L The bitter roots were sold in Senegal as a remedy for remittent and 'bilious' fevers and also as an emmenagogue and cholagogue. In India, the plant was in the Indian Pharmaceutical Codex as a bitter tonic and the root as an antidysenteric. The plant has been called 'Indian quinine' (Dalziel, 1937).

C The roots contain palmatine and 2-3% of columbin (Beauquesne, 1938). Different bitter heterosides (picroretin = picroretinoside, tinosporide and cordifolin) and the glycosides giloin and giloinin have been reported to be present in T. cordifolia in India (Paris and Beauquesne, 1938; Paris and Moyse, 1963).

P The root can produce toxic effects: vomiting and depression of the respiratory centre. Columbin, in small doses, increases the secretion of the bile and of the glands of the stomach and intestines; at higher doses it produces fatty degeneration of the liver (Biberfeld, 1910). Toxicity trials on the total alkaloids have shown that 5 mg/kg are not toxic for guinea pigs whilst 100 mg/kg produce death within 20 min (without convulsions). In the chloralized dog, an injection into the internal saphenous vein of 10 mg of total alkaloids produces immediate hypotension followed by recovery to normal within minutes. In experimental hyperthermia in guinea pigs, the temperature is lowered in a more spectacular way than with quinine sulphate. Palmatine shows a stronger antipyretic effect than the total alkaloids and it lowers the blood pressure and depresses the CNS (frog and mammals). It paralyses the respiratory centre even more than morphine (Beauquesne, 1938; Paris and Beauquesne, 1938). It is supposed that the antipyretic effect is due, like that of berberine, to paralysis of the peripheral vessels and to the resulting heat dispersion, and not to its toxicity towards microorganisms (Kerharo and Adam, 1974, p. 556). T. cordifolia has also been found to have hypoglycaemic and diuretic effects (Namjoshi, 1955).

Khaya senegalensis (Desr.) Juss. syn. (Swietenia senegalensis Desr.) MELIACEAE Dry zone mahogany, Cail cedrat.

L In Nigeria, Senegal and Guinea the bark is used locally mainly as an antipyretic and tonic. Moreover, medicinal and veterinary uses of the bark as an anthelmintic (taenia), an emmenagogue (abortifacient) and as an emetic have also frequently been reported (Dalziel, 1937).

C The bark contains a bitter principle, first called 'calicedrin', which later proved to be a mixture of different components (Moyse-Mignon, 1942). On further investigation these were found to consist of several triterpenoids with a lactone or epoxide function and a furan ring. 6-Desoxy-3-destigloyl-swietenin and its acetates have been isolated from all parts of the plant. The bark, in addition, contains nimbosterol (/8-sitosterol), 7-diacetyl-7-oxo-gedunin, methyl angolensate, methyl-

6-hydroxyangolensate and 6-desoxy-3/3-destigloyl-12j3-diacetoxy-swietenin. In the rootbark, methyl-6-hydroxy-angolensate has been reported, and in the root, khayasine. In the heartwood, khayasine and derivatives, methyl-angolensate and

7-diacetyl-oxogedunin have been found. In the seeds, khivorine- and swietenine-derivatives have been found (Bevan et al., 1963, 1965; Adesogan et al., 1967; Adesogan, 1968; Adesogan and Taylor, 1968). Kerharo and Adam (1974) suggest the adoption of a new nomenclature based on a common nucleus, which can be named methyl-meliacate, more so as the composition varies in samples of different regions.

Similar bitter principles were found in K. ivorensis Chev. (K. klainei Pierre ex Pellegr., K. caudata Stapf ex Hutch. & Dalz.) (Adosogan & Taylor, 1970; Aspinal and Bhattacharjee, 1970). Further chemical investigation of stembark extracts of the two species by spectral, analytical and chromatographic methods led to identification of the sterols campestrol, stigmasterol and sitosterol and of the coumarins aesculetin and scopoletin. K. ivorensis was found to contain mainly scopoletin and scoparone and only traces of aesculetin and umbelliferone whilst in K. senegalensis scopoletin was the major coumarin next to aesculetin and only traces of scoparone were found. Scopoletin could also be isolated from the fruit (Adesina, 1983).

P Subcutaneous or intraperitoneal injections of calicedrin (0.05 g/kg) produce a distinct hypothermic effect (temperature reduction of 2-3°C) on experimental hyperthermia in guinea pigs (Moyse-Mignon, 1942; El Said et al., 1968). In dogs, calicedrin produces slight hypertension. An antibiotic action of an aqueous extract of the stems against Sarcina lutea and Staphylococcus aureus was reported, and in a dilution of 1:10000 calicedrin kills Paramecia within 20 min (Malcolm and Sofow-ora, 1969).

Crude hydroethanoJic extracts of the stembark of K. ivorensis and K. senegalensis caused depression, sedation and reduced locomotor activity in mice. The coumarins scopoletine and scoparone have recently been found to have antipyretic, analgesic and anticonvulsant activities (Adesina and Ette, 1982; Adesina, 1983; Ojewole, 1983b).

Andira inermis (Wright) DC. FABACEAE

Dog almond or wormback L The bark has been used in Northern Nigeria for trial by ordeal in the same way as

Erythrophleum. It is a dangerous poison in large doses, causing vomiting with drastic purgation, delirium and narcosis (Ainslie, 1937; Dalziel, 1937). In Senegal, the roots are used as an anthelmintic and in the treatment of mental diseases (Kerharo and Adam, 1974).

C The bark contains andirine, AT-methyltyrosine (y3-(p-hydroxyphenyl)-a-N-methylaminopropionic acid). Extraction of the heartwood produced an isoflavonoid as well as biochanine A (a trihydroxy-isoflavone), small amounts of fatty acids with long ramified chains and /3-sitosterol (Cocker et al., 1962, 1965). y-Aminobutyric acid was found in extracts of leaves and stems (Durand et al., 1962).

P The bark extracts are considered narcotic (Watt, 1967) and also have some insecti-cidal action (Heal and Rogers, 1950).

Nymphaea lotus L. syn. (N. liberiensis Chev. and other spp.) NYMPHAEACEAE

L A narcotic use of the rhizomes existed in ancient Egyptian and Mayan rituals (Oliver-Bever, 1961; Emboden, 1981). In West Africa, the rhizome is a food of scarcity. The seeds are used by the Hausas (Northern Nigeria) in eruptive fevers. In Sierra Leone, an eye lotion is prepared from the leaves, an infusion of stems and roots is used as an emollient and diuretic, and a decoction of the flowers as a narcotic and sedative. In the Ivory Coast a decoction of Nymphaea is taken for coughs and bronchitis (Oliver, 1960).

C A number of alkaloids have been recorded from the flowers and rhizomes of different Nymphaea spp. The chief alkaloids are nymphaeine, nymphaline, nupharine and a-and j8-nupharidine. Quercitin has been reported to be present in the leaves (Chopra et al., 1956; Hegnauer, 1962-68, Vol. V, p. 441). Delphaut and Balansard (1941) observed confusion concerning the reported constituents and their botanical origin. They studied 'nupharine' from N. alba L. (not growing in West Africa) and this was found to consist of nelombine, nupharidine, nymphaeine and a-nupharidine.

P The rhizomes of N. alba were tested on mice, eels and dogs, and in all cases there was a narcosis that terminated in somnolence (Delphaut and Balansard, 1941). Convulsions induced by strychnine could be counteracted by N. alba rhizomes, and these were characterized as antispasmodic and sedative by Delphaut and Balansard (1943). These workers found that nymphaeine is mainly localized in the rhizomes of N. lotus-, its minimum effective and lethal doses for frogs are 30 and 50 mg/kg, respectively, and in mice and pigeon 60 and 80 mg/kg, respectively; warm-blooded animals die from central respiratory paralysis. Nymphaline, found in the flowers, acts as a cardiac glycoside. Nupharine, also found in the flowers, produces paralysis of the cerebrum when administered to frogs, mice, rats, guinea pigs and pigeons; it acts also as a respiratory excitant and causes death by respiratory poisoning. Two un-named alkaloids found in the flowers and roots show sedative action in small doses (Chopra etal., 1956, p. 177). More recently the pharmacology of a number of Nymphaea alkaloids was studied by Dimitrov (1965), who reported sedative, spasmolytic and hypertensive properties. N. tuberosa is very active against Mycobacterium smegmatis (Su et al., 1975).

Anogeissus leiocarpus (DC.) Guill. & Perr. syn. (Conocarpus leiocarpus DC., A. schimperi Hochst. ex Hutch. & Dalz., A. leiocarpus var. Schimperi (Hochst. ex Hutch, and Dalz.) Aubrev.) COMBRETACEAE

L A decoction of the leaves is used in Nigeria for ablutions in the treatment of skin diseases and itch and is considered to be an antidiarrhoetic. The powdered bark is applied to wounds and ulcers and in some regions an infusion of the bark is given as a febrifuge and the bark or seeds as a vermifuge (mainly for tapeworm in horses and donkeys) (Dalziel, 1937). C The leaves, roots and bark contain 17% tannins. In the gum exuding from the trunk 20% uronic acids have been found. These produced, via hydrolysis, 12% (+)-xylose, 32% (—)-arabinose, 5% (+)-galactose, 2% (+)-mannose, 20% of oligosaccharides and traces of rhamnose, ribose and fucose (Aspinal and Christensen, 1961). The stembark of A. latifolia grown in India contains sitosterol, flavellagic acid, 3,3',4-tri-O-methyl ellagic acid, quercitin, myrecitin and procyanidin along with gallotannins, shikimic acid, quinic acid and free sugars. It also contains alanine and phenylalanine (Bhakuni etal., 1970). P A. leiocarpus appears to contain a non-toxic CNS depressant principle (Fong et al., 1972). The related A. latifolia Wall, has been found to have CNS depressant action to counteract an amphetamine hyperactivity test in mice (Bhakuni et al., 1969b).

Elaeocarpus sphaericus Schum. syn. (E. ganitrus Roxb.) TILIACEAE

L In traditional Indian medicine the fruits of the plants were used in mental diseases, epilepsy, hypertension, asthma and liver diseases (Bhattacharya et al., 1975b). The plant has been introduced in West Africa. C A fixed oil has been obtained from the seeds of E. serratus L. (Chopra et al. , 1956). P Bhattacharya et al. (1975b) noticed a prominent CNS-depressant effect of the water-soluble portion of the 90% ethanol extract of the fruit. The effect was characterized by potentiation of hexobarbitone hypnosis and morphine analgesia and by anticonvulsant and anti-amphetamine activities. In addition, cardiostimulant, smooth muscle relaxant and choleretic activities were reported. These effects were partly based on a direct musculotropic effect or were mediated through /3-adrenoreceptor stimulation (Bhattacharya etal., 1975b).

Passiflora foetida L. PASSIFLORACEAE

P. edulis Sims and related spp. Stinking passion flower L P. edulis and related spp. are cultivated in West Africa for their fruits. P. foetida has fruits which are edible when ripe, but before maturity the leaves and green fruit contain a cyanogenetic glucoside (Dalziel, 1937). A decoction of the leaves and roots is regarded in the Antilles as an emmenagogue and useful remedy in hysteria. The leaves were applied as a dressing for wounds (Sebire, 1899). In India, a decoction of the leaves is used in the treatment of biliousness and asthma (Chopra et al., 1956). C From the aerial parts of P. incarnata, Neu (1954, 1956) isolated indole derivatives and identified harmane. Traces of harmine and harmol were reported by Lutomsky and Wrocinski (1960) who, in addition, isolated flavonic derivatives by paper chromatography (Paris, 1963; Paris and Moyse, 1967, p. 458). P P. incamata was registered in the French Pharmacopoeia, 1937, for its sedative and antispasmodic properties. The extract of the plant shows antispasmodic activity on the rabbit intestine and is synergistic to papaverine and antagonistic to barium chloride and pilocarpine-induced effects. It decreases motility in mice and rats (Paris, 1963; Paris and Moyse, 1963).

Guiera senegalensis Gmell. COMBRETACEAE

L The dried pounded leaves are taken by women after childbirth to increase lactation and as a general tonic and blood restorer after any exhausting conditions. In Sokoto, the plant has the reputation of preventing leprosy and the leaves are applied externally for skin diseases. In Bornu, the roots are powdered, boiled and used as a remedy for diarrhoea and dysentery (Dalziel, 1937). Certain tribes in Senegal and Guinea use the leaves like those of certain species of Combretum for the treatment of colds, bronchitis and fever (Dalziel, 1937).

C For the first time, indole alkaloids (harmine and tetrahydroharmine) have been found in a member of the Combretaceae. They are present in the roots (Combier et al., 1977). The ash of roots and leaves is rich in mineral elements. Mucilage, gallic and catechuic tannins, flavonoids, amino acids and alkaloids (0.2% in the roots and 0.15% in the leaves) have also been reported (Koumare et al., 1968).

P Plants collected in Senegal and Mali showed a depressive action on the CNS. In addition, anti-inflammatory and antitussive actions (mainly of the leaves) were noted; an antidiarrhoeic effect was particularly spectacular in rats infected with parasites. Kerharo et al. (1948) report the spectacular effects of the treatment with G. senegalensis in an epidemic of choleriform diarrhoea with gallbladder infection in Upper Volta.

Alstonia boonei de Wild. syn. (A. congensis Chev. & Aubrev.) APOCYNACEAE Pattern wood, stool wood

L In Nigeria the bark of A. boonei, which is the most common variety of Alstonia in the country, is widely used as an antipyretic in the treatment of malaria, and sometimes, together with the leaves and roots, in external applications for rheumatic pains. Smearing the latex on Calabar swellings caused by filaria has also been recommended. In Ghana a decoction of the bark is given after childbirth to help the delivery of the placenta (Dalziel, 1937; Irvine, 1961).

C The bark of A. boonei contains echitamine (the main alkaloid), two echitamidine derivatives and a lactone boonein (Marini Bettolo et al., 1983). The yield of total alkaloids varies with the location: in Ghana, it is 0.38-0.56%; in Nigeria, 0.180.31%; in the Cameroons, 0.11% (Goodson and Henry, 1925; Monseur and van Bever, 1955). The triterpenes ¿8-amyrin and lupeol have been reported in the bark and ursolic acid has been found in the leaves of A. boonei (Kucera et al., 1972,1973). In the flowers of an Indian species, A. scholaris, a number of indole alkaloids have been reported, the major one being picrinine, which was found to possess a CNS depressant action in rats and mice (Dutta et al., 1976).

P The reputation of Alstonia spp. as antimalarial agents was such that A. scholaris and A. constricta bark had formerly been included in the British Pharmacopoeia, 1914. The antimalarial action could not be confirmed in many tests carried out by numerous authors on birds, monkeys and human beings (Henry, 1949, p. 720). It was noted, however, by some that the bark of A. scholaris produced a fall of temperature in human patients and while this lasted the patients appeared relatively free from symptoms (Chopra et al., 1938). This antipyretic action and the fact that these drugs were used in days when the diagnosis of malaria was not always accurate may account for doubtful results and earlier use (Henry, 1949, p. 720).

Echitamine was reported to lower carotid pressure and increase the renal output (Raymond-Hamet, 1934, 1941; Esdorn, 1961). More recently, Kucera et al. (1973) and Marquis (1975) observed that echitamine causes a fall of the blood pressure in hypertensive cats. Later, however, Marquis and Ojewole (1976) noticed that the hypotensive effect occurred only occasionally after a first intravenous injection of 6 mg/kg and thought that the diuretic action on saline-loaded dogs and cats may explain this hypotensive action. Ursolic acid, at first considered an inert compound, was found to act on the electrolytic balance. Doses of 3 mg produced a sodium retention equivalent to that of 3 /xg DOCA (desoxy-cortisone) and a considerably higher potassium retention in adrenalectomized rats (Wenzel and Koff, 1956; Marquis and Ojewole, 1976). These authors also reported that echitamine in particular potentiated the barbiturate sleeping time of mice and rats and enhanced the lethality of strychnine. Echitamine contracts the isolated toad rectus abdominis preparation and its action was enhanced by increasing concentrations of acetylcholine and reversed by physostigmine on the isolated rat hemi-diaphragm. This action could be an undesired side-effect in native malaria treatment with decoctions or infusions of the bark although the plant has been said to have a relatively low toxicity. The ineffectiveness of echitamine treatment against a strain of Plasmodium berghei was noted (Marquis and Ojewole, 1976).

The spasmolytic and hypotensive actions of echitamine have recently been confirmed by Ojewole (1983a). The alkaloid also blocked the neuromuscular transmission in various muscle-nerve preparations examined. The author was able to show that the depressor effect is unlikely to be mediated via a cholinergic mechanism or histamine Hj-receptor stimulation.

In Indian Alstonia spp. several alkaloids with a CNS action have been reported, thus picrinine was said to potentiate hexobarbitone hypnosis and morphine analgesia (Dutta etal., 1976), and alsto venine from A. venenata (not in West Africa) was in low doses a MAOI and in high doses a marked CNS stimulant. Venenatine, also from A. venenata, has, on the contrary, a reserpine-like action. It potentiates the hexobarbital sleeping time, antagonizes amphetamine toxicity, morphine analgesia and the anticonvulsant action of diphenylhydantoin, is synergistic with reserpine and can reduce the pressor response to tyramine but not to adrenaline (Bhattacharya et al., 1975a).

Waltheria indica L. syn. (W. americana L.) STERCULIACEAE

L In northern Nigeria and in Togo a decoction of the root is frequently given to children to strengthen their resistance against fever, etc., and the Hausas also recommend a root decoction to produce immunity. In Togo and also in India the root is used in a cough medicine, and in Senegal it is used for the healing of wounds. In Cayor (Senegal) it is sometimes used as an antiepileptic.

C An original analysis of the plant only revealed mucilage, tannins and sugars (Dalziel, 1937). Later, unidentified alkaloids were reported to be present in the leaves and root bark. Finally, three alkaloids were isolated from whole plants from the Ivory Coast. These were called adouetines x, y and z. These alkaloids are of a particular type, and were named 'basic peptides' by Goutarel. Of the four nitrogen atoms in the molecule only one is basic, the three others are present in peptide linkages (Pais et al., 1963).

P Pharmacological studies have been carried out with the amidosulphonate of adouetine z. The LD50 in mice is 52.5 mg/kg. The drug behaves as a sedative of the CNS and a stimulant of the medulla. In the dog it produces hypertension slows down the heartbeat (compensatory reflex?) and has a relaxing action on the smooth muscle fibres of the intestine (Blanpin et al., 1963).

Piper guineense Schum. & Thonn. syn. (P. leonense DC., P. famechonii DC.)

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