Thyroid Factor

The Natural Thyroid Diet

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L In Nigeria the juice of the leaves of A. schweinfurthi Bak. is used in the treatment of guinea worm infestation and in Ghana it is used for the treatment of vitiligo (Dalziel, 1937, p. 476). In India extracts of A. barbadensis are considered a tonic in small doses and a purgative, emmenagogue and anthelmintic in larger doses. The dried juice is cathartic and is used to relieve constipation. The pulp is used to reduce or prevent menstruation (Chopra etal., 1956, p. 13).

C The juice of the leaves contains anthraquinone derivatives (emodin, aloin, barbaloin, isobarbaloin and resins (Chopra et al., 1956, p. 13; Shah and Mody, 1967). Whole leaves, the rind and the pulp contain oxidases, catalases and sugars.

P A. barbadensis powder has been widely used as a purgative and was found to have a beneficial effect in the healing of thermal burns and of radiation therapy (Singh etal., 1973). When given in doses of 60 mg/kg intragastrically to female rabbits this powder increased not only the fertility rate but also the litter size of the animals (Sharma etal., 1972).

Aloe compound was reported to be very useful in cases of disturbed menstrual function and functional sterility (Bhaduri et al., 1968; Garg et al., 1970). This was confirmed by Gupta (1972), who found in 250 cases of sterility that Aloe powder improved fertility in 85% of the cases and that menstrual functions improved in 44.6% of them. However, when plants were tested for interceptive action, it was found that a 50% ethanol extract of the leaves, in contrast to all other extracts tested, had a strong interceptive action when given in high doses (100-200 mg/kg) on Days 1-7 post coitum (Casey, 1960; Gupta etal., 1971).

Plants with an action on lactation

Plants with latex, such as Euphorbia hirta and other Euphorbia spp., and Alstonia scholaris, often have the folkloric reputation of acting as galactogogues. These properties are still reported by reviewers today. Although the constituents and pharmacological properties of these plants have been studied in more detail in the last few years, a scientific confirmation of their galactogogue action has not been reported.

It has long been known that prolactin, the lactation stimulating hormone of the anterior pituitary can increase lactation. There is, however, often a certain reluctance nowadays to manipulate the hypothalamus-pituitary axis because of the other pharmacological effects produced.

Sarcostemma viminale R.Br. ASCLEPIADACEAE

L In some South African tribes this plant is used as a galactogogue for both women and cows (Watt and Breyer-Brandwijk, 1962). C The stems contain 2% of a mixture of five pregnane glycosides. One of two recently reported genins contains a dihydroacetone group like Cortisol but has different stereochemistry at C-14andC-17(Schauber al., 1968; Stockel et al., 1969). P Not only does this plant seem to act via the adrenal-pituitary axis but convulsions similar to those produced by strychnine, which result in paralysis and death, have been observed in cattle (sheep) after they have eaten the plant (Steyn, 1937). Therefore this plant should not be considered for human or veterinary applications!

Vitex agnus castus L.c. VERBENACEAE

C The fruit contains an essential oil, cineol, flavonoids and the glycoside aucubin and its hydroxybenzoic ester agnuside. These melanin-forming glycosides are unstable and polymerize to form black pigments when exposed to the air (Steinegger and Hansel, 1968, p. 497; Paris and Moyse, 1971, Vol. Ill, p. 255). P V. agnus castus has been reported to have a luteinizing action as a result of inhibition of the gonadotrophic action of the posterior lobe of the pituitary. Extracts of the fruits have been on the market for the treatment of dysmenorrhoea and as a galactogogue (Steinegger and Hansel, 1968, p. 497).

Other Verbenaceae like Verbena officinalis are also said to have galactogogue properties. The active principle is aucubin (a glycoside of a lactonic monoterpene). It has weak parasympathomimetic properties and causes contraction of the smooth muscle of the uterus (Steinegger and Hansel, 1968, pp. 497-8). In mammals V. officinalis produces a strong and prolonged milk secretion. The twigs, leaves and flowers yield verbenalin (Mcllroy, 1951, p. 110).

Ipomoea mauritiana Jacq. syn. (/. digitata of F.T.A.) CONVOLVULACEAE

L In Nigeria the whole root is used as a purgative and a galactogogue (Dalziel, 1937, p. 438). The same uses are mentioned for the very closely related I. digitata L. syn. (I. paniculata R.Br.) in India, which is also claimed to be an aphrodisiac (Chopra et al., 1956, p. 142).

C The roots of the Indian species contain 1.3% of fixed oil (glycerides of oleic, palmitic, linoleic and linolenic acids). In addition /3-sitosterol and a heteroside, paniculatin, which is soluble in water and thermostable, have been isolated (Matin et al., 1969).

P The heteroside of the Indian species acts as a stimulant of the smooth muscles of the myocardium, bronchi and bowel and is also oxytocic; when it is given intraperitone-ally, the LD50 in mice is 867.4 mg/kg (Mishra and Datta, 1962; Matin et al., 1969).

Kigelia africana (Lam.) Benth. syn. (K. pinnata (Jacq.) DC., (K. aethiopica Decne, K. abyssinica Rich., AT. elliotii Sprague, etc.) (16 synonyms!) BIGNONIACEAE Sausage tree

L In South Africa the fruits are used as a dressing for ulcers or to increase the flow of milk in lactating women (Watt and Breyer-Brandwijk, 1962). In Ghana the fruit and roots are boiled together with the 'tassels' of plantain flowers as a 'women's remedy' (Dalziel, 1937). In Northern Nigeria the fruit is used in some districts as a purgative, whereas in other regions it is used to treat dysentery (Dalziel, 1937, p. 443). In Cape Verde the fruit is rubbed on the breast of young girls to enhance their development. The fruit also has many superstitious uses. In Kenya a decoction of bark and leaves is drunk as an abortifacient. The fruit is commonly added to beer and claimed to be an aphrodisiac (Kokwaro, 1981). The unripe fruit is said to be very toxic.

C From the fruits and leaves El Sayyad (1981) isolated and identified the flavonoids 6-hydroxyluteolin-7-0-glucoside, luteolin-7-O-glucoside, luteolin and quercitin. From the roots Govindachari et al. (1971) have obtained dihydro-isocoumarins, lapachol and sterols and Alamelu and Bhuwan (1974) have reported the presence of iridoid glycosides.

Other plants growing in Nigeria that are reported to act as galactogogues are Allopliyllus africanus Beauv. (Sapindaceae) (the leaves are also used to treat piles) and Alternanthera repens (L.) Link. (Amaranthaceae) (the leaves of which are also used as an abortifacient). The presence of flavonoids and the absence of steroids, terpenes, alkaloids, saponosides, tannins, quinones and cyanogenetic glucosides has been reported for the bark of the Congolese specimen of Allophyllus africanus (Bouquet, 1972). The chemistry of Alternanthera appears not to have been studied.

Trigonella foenum graecum L. (Fabaceae) is considered a galactogogue in the Sudan (Ayoub and Svendsen, 1981).

Indirect stimulation of lactation has also been obtained with dried thyroid gland or thyroxine via the pituitary gland (Robinson, 1947; Naish, 1954).

Jasminum sambac (L.) Ait. c. OLEACEAE

The flowers are used in India to stop the secretion of milk in women in the puerperal state after childbirth (in cases of threatened abscess) by applying them unmoistened to the breasts. The roots areclaimed to beemmenagogic(Chopra«a/., 1956,p. 144).

C An iridoid glycoside as well as jasminin, quercetrin, isoquercetrin, rutin, quercetin-3-dirhamnoglycoside, kaempferol-3-rhamnoglycoside, mannitol, a-amyrin, ¡3-sitosterol and sucrose have been reported to be present in the leaves of this plant (Ross et al., 1982). The flowers contain an essential oil.

(c) Male sex hormones (androgens)

The main androgen is testosterone. It is secreted by the interstitial cells of the testis under the influence of luteinizing hormone and is required for spermatogenesis. In fact both androgen secretion and spermatogenesis are controlled by the hypothalamic-pituitary axis. In the liver a large proportion of the testosterone is degradated into androsterone and etiocholanone. These two substances and testosterone glucoronide are eliminated by the kidneys. The androgens are also secreted from the adrenal cortex and the ovaries. They cause retention of water and of nitrogen, sodium, calcium, chloride, sulphate and phosphorus ions and also increase protein metabolism (Burgen and Mitchell, 1972; Lechat etal., 1978).

Testosterone can only be administered by injection as it is absorbed by the digestive mucous membranes and immediately inactivated by the liver when given perorally. Dissolving testosterone in oil and making chemical substitutions in the molecule can to a certain extent slow down the hepatic catabolism.

Exogenous oestrogen produces an anti-testosterone effect, mainly owing to its action on the hypothalamus and pituitary (Lechat et al., 1978, pp. 548-51). The need to administer the hormone parenterally explains the dearth of published reports and indications in folkloric medicine of the use of plant androgens. Aphrodisiacs seem to be the main indication mentioned. The use of a leaf decoction of Lonchocarpus cyanescens for the treatment of venereal disease and semen insufficiency has, however, been reported (Ainslie, 1937).

Apart from being given in replacement therapy when normal secretions are reduced or absent, androgens are used to stimulate anabolic activity, encouraging protein anabolism, in the treatment of osteoporosis and sometimes to inhibit the growth of breast carcinoma. For their use as anabolic agents the difficulty lies in obtaining compounds with high anabolic and low androgenic activity, as in female patients there is the danger of masculinization (Burgen and Mitchell, 1972). A West African plant used in the treatment of osteoporosis is Cissus quadrangularis (see Chapter 3).

II Thyroid hormones

The thyroid gland plays an important part in the organism as it stimulates metabolic activity and also controls growth. The two hormones secreted by the gland are thyroxine and triiodotyronine, and they are present in a proportion of 50:1; they are both iodine-containing amino acids and are synthesized in the gland itself, which takes up iodine from the blood (Burgen and Mitchell, 1972).

Hypoactivity of the thyroid gland causes myxoedema and a 20-30% decrease in basal metabolism. Lack of iodine is often the basis of this insufficiency and treatment is usually effected by administration of thyroxine or thyrotrophin (anterior pituitary hormone) or of components rich in organic or inorganic iodine, for example algae like Fucus vesiculosis L., which contains 0.03-0.1% iodine (Chesney and Webster, 1928; Steinegger and Hansel, 1968). Hyperactivity of the thyroid function, e.g. in patients with Basedow's disease, can be inhibited by drugs which inhibit the uptake of iodine by the gland. Thiocyanates inhibit this uptake and have a weak inhibitory action on iodide binding (Burgen and Mitchell, 1972, p. 148). Temporary treatment is obtained with iodine as it causes retention of thyroxine in the gland and so it is not released into the blood. (This effect is used in preparing hyperthyroid patients for thyroidectomy.) Other drugs which inhibit, by substrate competition, the peroxidase enzyme which releases iodine from circulating iodides and, in addition, inhibit the enzymes responsible for iodination of tyrosine and coupling of the iodinated derivatives are imidazoles and thiouracils (Turner and Richens, 1978, p. 168; Kagihara, 1980).

Other substances which reduce hyperactivity are extracts of Brassica oleraceae L. and other Brassica spp. as had already been observed in 1928. In 1949 an active 'goitrogenic' principle was isolated from the turnip, B. napa; it was called goitrine and was found to be a glucoside of l,5-vinyl-2-thio-oxazolidone (Astwood et al., 1949). Subsequently it was shown that the seeds, roots and aerial parts of many Brassica spp. contain progoitrine. Through hydrolysis by enzymes such as myrosinase, a common enzyme in the Cruciferae, but also under the influence of bacteria present in the digestive tracts of animals, progoitrine liberates the isothiocyanate of 2-hydroxy-3-butenyl. Cyclization of this leads to the active principle, goitrine (Virtanen, 1961). The mechanism of action of goitrine is believed to be based on its intervention in the biosynthesis of thyroxine and not on the accumulation of iodine in the thyroid gland (Murti et al., 1964).

Diverse polyphenols are also capable of fixing iodine and of removing this element from the thyroid gland. The goitrogenic effect of Glycine soya is thought to be related to the presence of phytoagglutinins, which prevent normal intestinal absorption of thyroxine. Other plants which contain phenols of the flavonoid type such as quercetin, rutin and catechin also have an action on the thyroid gland (Steinegger and Hansel, 1968).

An indirect inhibitory effect on thyroid secretion by Lithospermum ruderale and L. officinale (not in W. Africa) has been reported (Train et al., 1941; Kemper and Loeser, 1957); they act via the thyrotrophic (and also gonadotrophic) hormone of the pituitary gland.

In West Africa it is mainly Arachis hypogeae which provides the goitrogenic principle although some Capparidaceae and Carica papaya seeds are likely to have a similar effect.

Arachis hypogeae L. FAB ACE AE

Groundnut, peanut

(See also Chapter 2.) A goitrogenic and an oestrogenic factor have been isolated from the seeds of this species.

P The goitrogenic principle was found to be insoluble in oil and thermostable as it is retained in the oil-cake and in the roasted seeds (Greer and Astwood, 1948; Buxton et al., 1954; Busson, 1965; Adrian and Jacquot, 1968). If the normal diet of the rat is supplemented by 20% with the oil-cake, the weight of the thyroid gland is increased from 9 to 24 mg whilst its content of mineral iodine goes up from 5 to 20.5%. Addition of 1 g of water per day per animal completely re-establishes the thyroid metabolism. The goitrogenic factor is believed to be located in the chromogenic tegument of the nut. Arachoside and glycosides isolated from the nuts inhibit the formation of inorganic iodine and thyroxine and result in a major increase in the urinary secretion of iodine and phenols (Mudgal et al., 1957, 1958).

The oestrogenic factor is soluble in oil and is retained after refining. Introduction of refined peanut oil to form 10% of the food ration of immature mice increases uterine weight from 9.5 to 15.9 mg (refined olive oil produces an increase to 16.7 mg) (Booth et al., 1960). A substance antagonistic to aldosterone which modified sodium reabsorption and urinary secretion of sodium and potassium could also be detected in arachis oil; 0.05 ml of the oil largely antagonized the action of 10 /ng aldosterone (Kumar etal., 1962).

Kumar et al. (1962) noticed in earlier investigations that the effects of desoxycorti-costerone acetate on the urinary secretion of sodium and potassium ions in adrenalec-tomized animals were abolished when the 'deoxycortone' was dissolved in arachis oil. They therefore undertook a systematic investigation of the aldosterone-antagonistic action of various vegetable oils. Consistent and marked antagonism was seen only with arachis oil at all doses. The potent aldosterone antagonist is believed to be contained in the unsaponifiable portion of the oil (Kumar et al., 1962).

Manihot esculenta Crantz. syn. (Af. utilissima Pohl.) EUPHORBIACEAE

Cassava, manioc

L In West Africa this species occurs mainly as the bitter cassava (dark root) but a sweet variety is cultivated in the northern parts of West Africa. Cassava is a major foodplant which requires cooking as it contains a thiocyanate which is rendered inert by heat. Many varieties exist. The meal is called fitfu. Gari is a coarse powder obtained by dry methods of scraping, pounding, etc. A poultice, often used as a substitute for linseed meal, is put on burns, ulcers, etc. (Dalziel, 1937, pp. 150-4).

C Cassava is rich in starch and poor in nitrogen: there is 39% starch, 1.3% protein and 0.5% fat in Ghanaian cassava root after cooking. Linamarin is the source of the thiocyanate found in manioc meal.

P Antithyroid effects of cassava and the thiocyanate were observed in rats. In some areas of Zaire endemic goitre and cretinism was attributed to endogenous formation of thiocyanate resulting from ingestion of manioc; this aggravated iodine deficiency in these areas (Ermans, 1979). In Nigeria a degenerative ataxic neuropathy (polyneuritis of variable location) with deafness and bilateral optic atrophia in 320 patients could be traced to a chronic intoxication by hydrocyanic acid. The acid resulted from hydrolysis of cyanogenetic glycosides contained in manioc, which is a basic food in the country (Osuntokunei al., 1969,1970). Thus chronic intoxications can result from regular ingestion over long periods from boiled manioc. It had been observed that increasing thiocyanate in the blood of humans and rats aggravated the loss of iodine from the thyroid. Renal elimination of thiocyanate becomes apparent when the blood level exceeds 10-15 /¿g/ml, 'which was not adequate for prevention of thyroid anomalies' (Ermans, 1979; Ermans et al., 1980). Ermans et al. (1980) recommend, in endemic goitre studies, completion of the iodine level examination by determination of thiocyanate levels in the blood and urine and checking of the intake of manioc.

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