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Thursday, December 11, 2008              

Researchers unveil local herbs for hastening childbirth

Nigerian researchers have verified folklore uses of two local plants, Umbrella tree and Lizard's tail, in hastening childbirth. CHUKWUMA MUANYA reports.

UNTIL now, several drugs are used to hasten or facilitate childbirth, especially by stimulating contractions of the uterus, but not without unpleasant side effects and complications.

However, stem bark of local herbs, Musanga cecropioides and the leaves of Monechma ciliatum have been shown to have oxytocic effect. Oxytocic means stimulates uterine contractions as per the action of the hormone oxytocin.

Commonly called African corkwood or Umbrella tree in English and parasolier (for its resemblance to a parasol) or bois bouchon (corkwood) in French, Musanga cecropioides belongs to the plant family Cecropiaceae.

In Nigeria it is known by different names by the various ethnic nationalities. It is obonia in Abua, obe in Bokyi, oghohen in Edo, ototo uno (the inflorescence, or fruit), lino dm, idim (stream alluding to sap from the stem and roots) in Efik, egimamfuk in Ejagham, egum-amfuk in Ejagham-Etung, uboniboni in Engenni, uru in Igbo (Arochukwu), ulu (Awka), nru (Onitsha), nr (Owerri), uru (Umuakpo), may be heard as nr, a nasalisation not shown in the standard orthography, bny in Ijaw (Nembe), fnfn in Ijo-Izon (Kolokuma), egbesu in Ishekiri, gbw Izon (Oporoma), taku Mungaka, mkpenga in Olulumo-Okuni; hovb in Urhobo, ufogho in Yekhee, ga or agbw (grab the hook) in Yoruba.

Popularly called Lizard's tail, Monechma ciliatum belongs to the plant family Acanthaceae. The Dagbani in Ghana call it hunglade. In Nigeria, it is fisawa, kumudoi, alkama gidan tururuwa, damfark'ami (loosely applied to weeds of fallows), fidda hakukuwa, kan-bunsuruu (ram's head), or wtsyar-kadangaree (lizard's tail) in Hausa. It is called nabla by Manding-Bambara tribe in Senegal.

Nigerian researchers found that the water extract of Musanga cecropioides produced a dose-related increase in the force of uterine contraction. The drug was observed to potentiate the uterine contractile activity of the extract while pre-treating the tissue with either atropine or salbutamol before administering the water extract showed the inhibitory effects of the drugs on the activity of the extract. The inhibition effect showed by atropine suggests the probable stimulation of the muscarinic receptors of the uterus by the extract. Between doses of one to four gram/kilogram (g/kg), the water extract of Musanga cecropioides were observed to be well tolerated in mice as no obvious signs of toxicity were observed on the animals.

Atropine is a tropane alkaloid extracted from deadly nightshade (Atropa belladonna), jimsonweed (Datura stramonium), mandrake (Mandragora officinarum) and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects. Atropine is a core medicine in the World Health Organisation's (WHO's) "Essential Drugs List", which is a list of minimum medical needs for a basic health care system.

Salbutamol (INN) or albuterol (USAN) is used for relief in conditions such as asthma and chronic obstructive pulmonary disease.

The study: "Oxytocic effects of the water extract of Musanga cecropioides R. Brown (Moraceae) stem bark", was published in African Journal of Biotechnology B. A. Ayinde and D. N. Onwukaeme of the Department of Pharmacognosy and Z. A. M. Nworgu of the Department of Pharmacology, Faculty of Pharmacy, University of Benin, Edo State.

Musanga cecropioides is a very rapidly growing tree to 20 metre tall with an umbrella-shaped crown - hence the English and French names. Trunk straight cylindrical and up to two metres in girth with stilt roots to three metres above ground level and spreading branches.

Musanga cecropioides is found mostly in the tropical forests of Africa stretching from Guinea to Congo. Traditionally, the plant is used to induce labour, reduce elevated blood pressure and also to reduce high blood sugar. In some parts of Edo and Delta states of Nigeria, the plant is used as anthelmintic (or antihelminthics are drugs that expel parasitic worms (helminths) from the body, by either stunning or killing them) and antidysentric (drug used to stop dysentery).

Available literature reports revealed the scientifically established uterotonic (increasing the tone of uterine muscle) effects of the leaf in rats, the hypotensive (lowers blood pressure) effects of the water extracts of the leaf and stem bark as well as antihyperglycaemic (has high blood sugar reducing effect) activities of the leaf extract in laboratory animals.

Also, researchers have reported the isolation of antioxidants (substances that stops or reverses cell damage)- isovitexin, vitexin, cholorogenic acid, catechin and procyanidins from the leaf.

According to the authors, the compounds are responsible for the hypotensive effect of the leaf extract via inhibition of angiotensin converting enzyme. Angiotensin causes blood vessels to constrict and drives blood pressure up.

Phytochemical studies reported the presence of kalaic acid (a new type of secondary metabolite- saponin) in the stem bark and some other triterpenoid acids in the leaves, stem bark and the root wood.

Monechma ciliatum is an annual herb to about one metre high of savanna and disturbed wastelands, throughout West Africa, and occurring widely in tropical Africa. The plant is not grazed in Senegal and, indeed, it is often considered by herdsmen and cultivators to be toxic to stock. In Nigeria the dried leaves are powdered and burnt as an inhalation for head colds. In Sudan the dried seeds are used as a scent-preparation.

Phytochemical and pharmacological studies on Monechma ciliatum published in Phytotherapy research by Mary O. Uguru of the Department of Pharmacology and Clinical Pharmacy, University of Jos, Plateau State and F. Evans of the Department of Pharmacognosy, School of Pharmacy, University of London, United Kingdom found the leaves of Monechma ciliatum to contain alkaloids, glycosides, proteins, tannins and saponins. The hot methanol extract (HME) of the leaves, previously found to have potent oxytocic effect in various species was fractionated in various solvents and the fractions analysed chemically and also assayed on the rat uterus in an attempt to identify the chemical constituents present and in particular the oxytocic principle. Positive reaction with ninhydrin spray suggests that the oxytocic constituent is an amino acidic derivative.

The University of Benin researchers examined the probable effect of the water extract of the stem bark of Musanga cecropioides on rat uterus in the presence of standard antagonists like salbutamol and atropine and a uterine stimulant like oxytocin.

The stem bark was observed to contain saponins, tannins, flavonoids with no traces of alkaloids, anthraquinones and cyanogenetic glycosides.

Both oxytocin and the water extract of Musanga cecropioides stem bark induced a dose-related increase in force of contraction of the rat-isolated uterus. Addition of varying concentrations of oxytocin to the tissue elicited a dose-dependent uterine contraction. While 0.02 International Unit (i.u) produced a force of contraction of 1.45 0.22 g, maximum contraction was obtained with the administration of 0.16 i.u., which produced a force of 1.9 0.08 g although the variations in the responses to each concentration were observed not to be significantly different. While 12.5 mg of the extract elicited a mean force of contraction of 1.10 0.15 g, administration of 1600 mg produced a corresponding maximum uterine force of contraction equivalent to 2.53 0.6 g.

The variations in the force of contractions were observed to be significant after administration of 800 mg of the extract. The uterine contractile effect produced by 400 mg of the water extract was observed to be similar to that produced by 0.16 i.u.oxytocin.

Simultaneous administration of oxytocin and the water extract produced uterine force of contractions significantly higher than either oxytocin or water extract alone.

Administration of atropine did not evoke any effect on the activity of the uterus but significantly inhibited the contractile activity of the water extract in a competitive and dose-dependent manner. Pre-treating the tissue with 1 mg atropine decreased the uterine contraction of 1.22 0.25 g elicited by the 25 mg of the water extract to .19 0.01 g. Administration of 2 mg of atropine completely inhibited the contraction induced by the same concentration of the extract. Contractions induced by 100 and 400 mg of the extract were also significantly inhibited by 2 mg atropine.

Salbutamol was observed to show remarkable inhibition of uterine contraction elicited by both the oxytocin and water extract. While the contractile effect of 0.16 i.u. oxytocin was reduced by 63 per cent, administration of 2 g salbutamol before 25 mg/ml of the water extract produced no contraction. This inhibition was sustained with administration of 100 mg/ml of the extract. Also, 2 g of the drug almost completely inhibited the uterine contractile effect of 400 mg/ml of the water extract.

The water extract was well tolerated by the animals as no signs of acute toxic effects like restlessness, dizziness, excitation, food or water avoidance were observed after the administering the extract between one to four g/kg.

Another study, "Oxytocic and oestrogenic effects of Monechma ciliatum methanol extract in vivo and in vitro in rodents," by M. O. Uguru, F. K. Okwuasaba, M. M. Ekwenchi and V. E. Uguru of the Department of Pharmacology, University of Jos, Plateau State, tested various solvent extracts of the leaves of Monechma ciliatum for oxytocic properties on uterine preparations in vivo and in vitro. The methanol extract (HME) contracted the non-pregnant uterus of the rat, guinea pig and mouse as well as preparations obtained from guinea pigs on days six to seven and 11-12 of pregnancy. The rat pregnant uterus was not affected by the extract. Oral administration of HME to rats on days 15, 16 and 17 of pregnancy had no abortifacient (induces abortion) effect compared with oxytocin. However, laparotomy (a large incision made into the abdomen) on day 23 revealed fetal death in utero. The extract was also found to have oestrogenic activity based on parameters such as uterine weight ratio, premature vaginal opening and degree of vaginal cornification (conversion of cells to hard tissue). Oestrogen is a female sex hormone that controls the reproductive cycle and prepares the body for pregnancy.

The University of Jos researchers in another study, "Uterotonic properties of the methanol extract of Monechma ciliatum" compared the oxytocic activity of the hot methanol extract (HME) of the leaves of Monechma ciliatum with other uterine stimulants like ergometrine, oxytocin, 5-hydroxytryptamine (5-HT) or serotonin, acetylcholine (ACh) and prostaglandins (PGs) E2 and F2 a (PGE2aand PGF2a) in the presence of some antagonists in an attempt to explain the mechanism of action of the extract.

Ergometrine, also known as ergonovine is one of the primary ergot and morning glory alkaloids Ergometrine has a medical use in obstetrics to facilitate delivery of the placenta and to prevent bleeding after childbirth by causing smooth muscle tissue in the blood vessel walls to narrow, thereby reducing blood flow. It is usually combined with oxytocin (syntocinon) as syntometrine. 5-hydroxytryptamine is an important neurotransmitter made by neurons in the central nervous system. Acetylcholine (often abbreviated ACh) is a neurotransmitter in both the peripheral nervous system (PNS) and central nervous system (CNS) in many organisms including humans. A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring. They are mediators and have a variety of strong physiological effects, although they are technically hormones, they are rarely classified as such.

The effects of the reference drugs on uteri isolated from rats pretreated with HME for two weeks were also observed. Atropine blocked the effect of ACh and partially blocked those of HME, while L-366-948 blocked only the effect of oxytocin. Indomethacin inhibited the effects of HME as well as all the other drugs, except the PGs and ACh. D-600 blocked the effect of all the drugs including HME. Methysergide antagonised only the effect of 5-HT and partially blocked ergometrine. Prolonged treatment altered the uterine musculature and the activity profile of the reference drugs. These results suggest that the HME may be acting by more than one mechanism to contract the uterus and explains the mechanism of the anti-implantation activity of the plant.

The researchers wrote: "The water extract was well tolerated by the animals as no signs of acute toxic effects like restlessness. This work has established the oxytocic effects of the dizziness, excitation, food or water avoidance were water extract of Musanga cecropioides stem bark. The fact that observed after the administering the extract between one to four the contractile effect was dose-related showed the gram/kilogram (g/kg) potency of the stem bark in contracting the uterus. In literature, the water extract of the leaf has been reported to evoke uterine contraction in rats.

"The oxytocin exhibited higher potency than the water extract, which may be attributed to the purity of drug while the extract in its crude and un-purified state contains different components, some of which may even have antagonistic effect. However, the contractile effect of 0.16 i.u. oxytocin was similar to the effect of 400 mg. The fact that the effects of oxytocin was augmented or potentiated by the presence of the extract suggests a probable synergism in the activities of the two. The extract may enhance the binding of oxytocin to the uterine tissues thereby causing a greater response or vice versa.

"The use of medicinal plants to facilitate labour may be due to stimulation of muscarinic receptors in the uterine tissue or through the synthesis and release by prostaglandins well known to be myometrial stimulants reported to mediate the activity of most drugs that stimulate uterine contraction. Although, this work could not establish the latter, the probable involvement of muscarinic receptors in the uterine contractile effect of the extract was supported by the significantly reduced contraction observed when the tissue was pre-treated with atropine before the water extract.

Atropine is a well-known antagonist of muscarinic receptors. Uterine contractile effects of the leaf extract of Musanga cecropioides, Agapanthus africanus and Monechma ciliatum were earlier reported to be significantly reduced in the presence of atropine.

"The uterine contractile effect of the water extract of Musanga cecropioides stem bark was completely inhibited by salbutamol. The drug reduced the uterine contractile effect of oxytocin by 63 per cent (result not shown), the inhibitory effect it showed on the extract was almost absolute. The higher inhibitory effect shown by salbutamol over atropine suggests probable higher concentration of salbutamol-sensitive receptors for the extract than atropine sensitive receptors. Salbutamol is known to be a 2 -receptor stimulating agent, which has been reported to elicit marked decrease in uterine contractility even in dysmenorrheic women.

"Pharmacological activities observed in plant extracts are due to the presence of various chemical constituents they possess. The observed uterine contractile effect of the water extract of Musanga cecropioides stem bark is invariably due to the constituents it contains.

"The fact that the mice used in the acute toxicity test did not show any signs of toxicity indicates that the constituents of the water extract are well tolerated in the animals. More work is being carried out to ascertain and isolate the constituent(s) that may be responsible for the oxytocic effect of the stem bark."

According to The Useful Plants of West Tropical Africa, Vol 1, by H.M. Burkill, the bark is intricately layered: light grey outer layer, then green, white, pink, white, all becoming brown on exposure. The outer part exudes a red-brown juice. In Ivory Coast this exudate is mixed with maize pap and is taken in the belief that it is a galactogogue (a substance which is used to increase the production of milk in humans and other animals). This belief is recorded again in Cameroun where women who have been taking it over a period of several days experience an increased milk-flow, and even those without child-at-breast. A number of substances are used in Zare to increase milk-flow, and some are known even to induce lactation in virgin animals and before puberty.

The sap of this plant has been investigated and found to contain an oestrogen and a galactogen with these properties. The treatment of dysmenorrhoea (a medical condition characterized by severe uterine pain during menstruation) in Ivory Coast may perhaps be explained by this presence. The plant is held to have some analgesic properties in Ivory Coast, and is administered for asthenia and loss of appetite, fumigation of bark and leaves mixed with leaves of Adenia lobata (Passifloraceae) is given to relieve asthenia in infants in which it acts as an expectorant (cough medficine) and dehydrant (a dehydrating substance).

In Gabon a bark-macerate is used as a gargle for toothache and as a decoction for pulmonary troubles, or to the same end a piece of bark is chewed. Also in Gabon a strip of the heated bark placed over the lumbar (lower backbone) region relieves lumbago (lower back pain). Root-bark is chewed in Sierra Leone with kola nuts as a cough-cure, and bark from callouses (a build up of dead skin and generally form on the heel, on the side of the big toe or on the ball of the foot) is tied onto wounds where it is supposed to effect a rapid healing (20) - sympathetic, may be, but perhaps with justification.

Bark-scrapings in Zare are added to fermenting sugar-cane sap to increase the potency. The sap, which tends to be tacky turns black on exposure and is used in Cameroun as ink. The bark is fibrous. Long strong fibres can be extracted amounting to 25-30 per cent by weight. They can be bleached and turned into a resistant paper, or made into twine. The aerial stilt roots and also the younger branches are noted for their capacity of yielding a large amount of potable sap. 'Half a bucketful' is said to be obtainable from a single tree overnight. It is colourless, odourless and of an insipid sweetish taste. This source of drinking water is of great importance to several tribes in Southeast Nigeria and West Cameroon for sometimes whole villages will depend upon it in dry seasons, and similarly in Zare.

Hunters and others break off stems to draw an impromptu drink, and even monkeys have learnt to do this. As a regular supply a renewed flow is obtained by recutting the cut surface and beating the severed limb. This evokes the Efik name uno idim, idim being 'a stream'. The Itung of Southeast Nigeria uses it for filming their earthenware pots. They and the Efik consider it medicinal for women.

In Congo sap from the larger roots is drunk as a blood-purifier, to clean the stomach, for blennorrhoea (mucous discharge, especially from the urethra or vagina), cough and chest affections, as a galactogogue, and commonly as a wash for persons with sleeping sickness, leprosy and fevers to relieve aches and pains, asthenia and rheumatism. The Kyama of Ivory Coast use the root-sap in topical embrocation (a lotion or liniment that relieves muscle or joint pain) for pulmonary congestion. Also in Ivory Coast ash from powdered roots mixed with palm oil into a paste is applied as a healing dressing to circumcision wounds.

The leaf and inflorescence buds are enclosed in a red stipular sheath, which may be 20 cm long. This attracts attention, in part, at least, on the Theory of Signatures, for treatment of gynaecological conditions. To hasten childbirth, the whole sheath boiled in soup is recorded used by the Asante as a powerful emmenagogue. Emmenagogues are herbs, which stimulate blood flow in the pelvic area and uterus; some stimulate menstruation. Women have used plants such as mugwort, parsley and ginger to prevent or terminate early pregnancy. Others use emmenagogues to stimulate menstrual flow when menstruation is absent for reasons other than pregnancy, such as hormonal disorders or conditions like oligomenorrhea (infrequent or light menses). The Igbo of Nigeria use the leaf, while the whole shoot is similarly used in Gabon and in Zare. The leaves enter a prescription in Ivory Coast to prepare a vaginal douche for painful menstruation and in Congo pulped buds are given to women for leucorrhoea and other vaginal affections. Leucorrhoea, commonly known as whites, refers to a whitish discharge from the female genitals. It is an abnormal disease condition of the reproductive organs of women.

The buds in Ivory Coast are crushed and boiled in water, which, after filtering, is taken by draught (a portion of liquid to be drunk, especially a dose of medicine) and by enema (the procedure of introducing liquids into the rectum and colon via the anus) for abdominal troubles. They are compounded in Sierra Leone with the bark of Uapaca guineensis (Euphorbiaceae), pepper (either a red chili or other pungent seed), salt and newly deposited soil from the top of a termite mound, and boiled up, the liquid after filtering is taken by mouth for swollen stomach and swellings in other parts of the body. The action is presumed to be diuretic (any drug that elevates the rate of urination and increases the excretion of water from bodies).

In Congo, the terminal bud is crushed whole and taken, often with sap added, to calm attacks of epilepsy and insanity, to treat blennorrhoea and heart-pains, sap expressed from the bud is an eardrop for earache and is applied topically for localised swellings. Hairs from the inside of the stipule are considered good in Congo for burns and healing sores. The catkins are cooked with groundnuts and are taken to facilitate childbirth in Gabon. The fruit is 10 to 13 cm long by five to six centimetres wide, yellowish green, succulent flesh with embedded seeds. The flesh is edible, though seemingly not much relished in the region. They are sought after by birds and bats, which ensures distribution of the small seeds.

The plant enters into magic. In Liberia pieces of bark are placed over a doorway as a protection against lightning. It is imprecated in a Yoruba incantation against heart disease. In Congo sap is used to wash newborn twins as a protection from evil spirits.

 
 

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