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A STUDY OF THE PHARMACOLOGICAL EFFECTS OF METHANOL EXTRACT OF RIPE AND UNRIPE PLANTAIN

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CHAPTER ONE

INTRODUCTION

1.1       Background to Study

Natural products, such as plants extract, either as pure compounds or as standardized extracts, provide unlimited opportunities for new drug discoveries because of the unmatched availability of chemical diversity. According to the World Health Organization (WHO), more than 80% of the world’s population relies on traditional medicine for their primary healthcare needs. The use of herbal medicines in Asia represents a long history of human interactions with the environment. Plants used for traditional medicine contain a wide range of substances that can be used to treat chronic as well as infectious diseases. Due to the development of adverse effects and microbial resistance to the chemically synthesized drugs, men turned to ethnopharmacognosy. They found literally thousands of phytochemicals from plants as safe and broadly effective alternatives with less adverse effect. Many beneficial biological activity such as anticancer, antimicrobial, antioxidant, antidiarrheal, analgesic and wound healing activity were reported. In many cases the people claim the good benefit of certain natural or herbal products. However, clinical trials are necessary to demonstrate the effectiveness of a bioactive compound to verify this traditional claim. Clinical trials directed towards understanding the pharmacokinetics, bioavailability, efficacy, safety and drug interactions of newly developed bioactive compounds and their formulations (extracts) require a careful evaluation. Clinical trials are carefully planned to safeguard the health of the participants as well as answer specific research questions by evaluating for both immediate and long-term side effects and their outcomes are measured before the drug is widely applied to patients. According to the World Health Organization (WHO), nearly 20,000 medicinal plants exist in

91 countries including 12 mega biodiversity countries. The premier steps to utilize the biologically active compound from plant resources are extraction, pharmacological screening, isolation and characterization of bioactive compound, toxicological evaluation and clinical evaluation. [1]

Musa paradisiaca is a rich source of calcium, phosphorus, iron and some other trace elements

  1. PHARMACOLOGICALLY ACTIVE COMPONENTS (UNRIPE)

The known pharmacologically active components of plantain, and the unripe type specifically can be classified into;

(i)                Phenolic amines

(ii)             Tamin

(iii)           Phytin.

Simmonds, (1968), reported the presence of phenolic substances in plantain. The most abundant was 3, 4 – dihydroxyethylamine (dopamine). Through dopamine is abundant in the skin of plantain, the level is insignificant in the pulp (Anderson et al, 1978). Other substances were later discovered, of which 5-Ht is the most abundant. Others include noradrenaline and tyramine.

Not much have been reported about changes in the levels these pharmacologically active substances at ripening, but 5 – HT seems fairly constant in the pulp of the fruit and increases in the skin when ripe (Simmonds, 1966).

Bucley (1966), gave the biosynthetic pathway for phenolic amine synthesis in plantain thus

BIOSYNTHETIC PATHWAY FOR PHENOLIC AMINE SYNTH ESIS IN PLANTAIN.

The pathway starts from tyrosine, which is converted to tyramine, then to dopamine, and finally to noradrenaline in plantain pulp or skin.

5-Hydroxytryptamine (5-HT) is the most abundant pharmacologically active substance present in the plantain pulp. It inhibits gastric acid secretion and stimulates smooth muscles of the intestine (Simmonds, 1966; smith et al; 1960). Simmonds, 1966, reported the usefulness of this in combating coeliac disease.

The synthetic pathway for 5-HT has not been fully elucidated, however, it is presumed to be similar to the pathway in many other animals. Tryptophan is the precursor, and it is excreted as 5-hydroxy-indoleacetic acid in mammals, after eating plantain (Simmonds, 1966).

(II)     TANNIN

Tannin occurs in unripe plantain (Goldstein, 1963).

Tannin is responsible for the astringent property of plantain. Astringency has been defined as the formation of tannin-protein complex in the mouth and intestine. Astringent activity leads to various buccal, gastric and intestinal secretion arrest by tannin acid-containing vegetable products (Butherworths, 1978).

In unripe plantain the bulk of tanniins is Leucoanthocyanidin which is present as a monomeric falvo – 3, 4- diol or as oligomers and is believed to condense to inactive high tannin polymers at ripening. Polymerization leads to decreased solubility of high molecule tannins in methandic solvents (Goldstein et al; 1963).

Probable site of polymerization to give an inactive condensed tannin as seen in ripe plantain (Simmonds, 1966).

Othe4r phenolic substances present in banana include histidine, Leucodelphinidin, Eugenol, elemicin

Baggosan (1932), reported the presence of phytin in plantain. Phytin is a calcium-magnesium salt of phytic acid has been shown to interfere with the absorption of calcium either by precipitation or by converting it to a form which is not readily absorbed from the intestine. (Anon, 1945). Inositol is a basic sugar alcohol called myoinositol and is present in the form of phosphatidly inositol (Phytic acid) in the extracellular compartment of higher plant tissues (Lehninger, 19677).

Phytic acid has been shown to produce a negative calcium balance by binding as non-ionizable complex thereby reducing absorption considerably (Anon, 1945).

1.4           ECONOMIC/MEDICINAL USES OF Musa paradisiaca

Musa paradisiaca have been associated with antispasmodic action and implicated in antidarrhoeal management. There are other myriad of pharmacological actions associated with plantain, hence its use in diverse conditions, in addition to being a source of food for man.

The medicinal uses of Musa paradisiaca. Vary from locality to locality.

The tradition applications and formulations have been severely criticised for lack of: standardization of its dosage regimen and specification of quantities related to the age or body weight. In spite of these setbacks, it has continued not only to provide modern medicine with a numbers of compounds, either useful in themselves or capable of improvement by chemical modification, but also has continued to meet the health care needs of the people, especially, in the developing countries.

Musa paradisiaca also makes a delicious meal. It is consumed in large quantity in the coastal regions of West Africa (William et al; 1980). Generally, the demand for plantain in Nigeria is relative low. However, it is one of the commonest food in the Niger Delta region (Oyenuga, 1968).

The pulp has high caborific value due to the high carbohydrate content. The pulp contains mainly simple sugars-fructose and glucose (Jay; 1970; Coursey; 1967).

The fruit is prepared by roasting; boiling; frying in oils; mashed into paste as fufu; or smoked for storage till when needed for use. The plantain skin when dried under the sun is a good materials to provide ash, rich in potash for soap making (Dalziel; 1936). The use of plantain for beer brewing has also recently been reported in some parts of Tanzania and Uganda.

The sap of plantain produces indelible stain in fabrics and can be stalk of the plant is pounded and smeared on the floor of native mud houses. Plantain also provides a good fibre for making ropes and brushes, from the peduncles.

1.5           RELEVANT PHYSIOLOGICAL & PHARMACOLOGICAL PROCESSES AND CONCEPTS.

The ileum like other parts of the small intestine consists of four histological layers. These are from outside, the serosa layer, the muscular layer, the submucosa, and the mucosa layer.

The serosa layer is a continuation of the mesentery and is tightly bound to the underlying muscle layer. The muscular layer consists of outer longitudinal layer and an inner circular layer. The tow muscular layers are separated at some points by the dysenteric nerve plexus. Stimulation of this plexus causes contraction of the muscular layers producing peristaltic wave along the entire gastrointestinal tract. The subnucosa consists of areolar tissue with blood and lymph vessels and the meissner’s nerve plexus. The mucosa consists of finger-like folds or villi which are modified for digestion and absorption of food substances.

COURTESY, VAN DAN BROUCHE & LEMLI, 1980)

The smooth muscle layer of ileum is innervated by post-ganglionic fibre located in the plexus which is derived from both the sympathetic and parasympathetic divisions of the post-ganglionic parasympathetic fibres with the liberation of cholinergic nero transmitter acetylcholine leads to increase in the motility and tone of the gut while stimulation of the sympathetic fibres causes moradrenaline release which causes a decrease in the tone and motility of the ileum.

An indept review of the gastro-intestinal physiological provides an insight into the general principles of intestinal motility which will help in laying a good foundation for a better understanding of interstinal motility both vivo and invitro. It will also help to appreciate the effects of drugs on the gastro-intestinal tract. Hence, sometime will be devoted to this topic.

The smooth muscle contains both actin and Myosin, the contractile proteins. Smooth muscle also contains tropomyosin but is is doubtful whether troponin or a tropomyosin-like substance exists in smooth muscle (Guyton, 1981). On stimulation of the muscle, there is an interaction between actin and Myosin, similar to that found in skeletal muscle. Furthermore, the contractile process is activated by calcium ions, and adenosine triphosphate (ATP) is reduced to adenosine diphosphate (ATP) to provide energy for the contrition.

The actual contractile process in skeletal and smooth muscles is activated by calcium ions. However, the source of calcium ions differ in smooth muscle bacuse the sarcoplasmic reticulum of skeletal muscle which is extensive and is the source of very nearly 100% of the contraction- inducing calcium ions. Due to the poor development of darcoplasmic reticulum in smooth muscle, most of the calcium ions used in contraction are obtained from extracellular fluid at the time of depolarization (Guyton, 1981). The lack of extracellular calcium or the intracellular blockade of calcium due to one factor or the other in smooth muscle results in muscle relaxation. Lack of calcium ion leaves the actin-nyosin fibres, cannot contractive state. The smooth muscle therefore, cannot contract (Hurwitz et al; 1972).

The gastro-intestinal tract is innervated by intrinsic and extrinsic nerves. The intrinsic innervation is the mycenteric and meissners plexuses. The extrinsic is the parasympathetic

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