A STUDY OF THE PHARMACOLOGICAL EFFECTS OF METHANOL EXTRACT OF RIPE AND UNRIPE PLANTAIN (Musa paradisiaca) ON THE ISOLATED GUINEA-PIG ILEUM

CHAPTER ONE

INTRODUCTION

1.1 Background to the Study

1.1.1 Natural products and drug discovery

Natural products, whether pure compounds or standardised plant extracts, offer many opportunities for drug discovery because of the chemical diversity they contain. Traditional medicine remains in wide use. The World Health Organization (WHO) reports that 170 of its member states acknowledge the use of traditional and complementary medicine, and that it contributes to health care in many regions (WHO, 2013, 2019). Herbal medicine has a long history of human interaction with the environment, and plants used traditionally contain a wide range of substances that can treat chronic and infectious diseases.

Adverse effects and microbial resistance to synthetic drugs have renewed interest in plant-derived alternatives. Many plants have been reported to show anticancer, antimicrobial, antioxidant, antidiarrhoeal, analgesic and wound-healing activity. Communities often claim benefits from particular herbal products, but such claims require scientific verification. Clinical trials are needed to confirm the efficacy of a bioactive compound. They examine pharmacokinetics, bioavailability, efficacy, safety and drug interactions, and they are planned to protect participants while answering specific research questions about immediate and long-term effects. The usual route from plant to medicine runs through extraction, pharmacological screening, isolation and characterisation of the active compounds, toxicological evaluation and clinical evaluation.

1.1.2 Plantain (Musa paradisiaca)

Musa paradisiaca (plantain) is a large herbaceous plant of the family Musaceae, grown widely in tropical and subtropical regions. Reviews of its traditional uses report that the unripe fruit is used in diarrhoea, dysentery and intestinal lesions, among other conditions (Imam & Akter, 2011; Mahadeva Rao, Khamsah Suryati, Mohaslinda, & Rosmawati, 2014). Ajijolakewu et al. (2021) reviewed the ethnomedicinal, antimicrobial and phytochemical properties of plantain and concluded that its extensive traditional use has a scientific basis in several areas. They noted that data on antiviral activity and in vivo studies remain limited, and that toxicity studies suggest general safety and tolerance.

1.1.3 Pharmacologically active components of unripe plantain

Phytochemical reviews report that the fruit contains minerals and a range of bioactive constituents (Imam & Akter, 2011; Mahadeva Rao et al., 2014). Ajijolakewu et al. (2021) link much of its activity to phytosterols such as stigmasterol and β-sitosterol and to triterpenes. The unripe fruit has traditionally been associated with three groups of components relevant to gut function.

Phenolic amines. Earlier phytochemical work identified dopamine, 5-hydroxytryptamine (5-HT, serotonin), noradrenaline and tyramine in plantain, with dopamine concentrated mainly in the skin and low in the pulp. These amines arise by a recognised biosynthetic route. Tyrosine is converted to tyramine, then to dopamine and finally to noradrenaline. 5-HT is derived from tryptophan, as in other organisms. 5-HT is of particular interest in this study because it influences gut function. It can reduce gastric acid secretion and stimulate intestinal smooth muscle, and it is a classic spasmogen in isolated intestinal preparations.

Tannins. Unripe plantain contains tannins, which give it its astringent property. Astringency results from the formation of tannin–protein complexes that reduce secretions in the mouth and gut. Most of the tannin in unripe fruit is reported to be leucoanthocyanidin, which is thought to condense into inactive high-molecular-weight tannin polymers as the fruit ripens. Ripening may therefore change both the amount and the activity of tannins.

Phytin (phytate). Phytin is a calcium–magnesium salt of phytic acid. It can bind calcium and reduce its absorption.

Because the levels of these constituents change with ripening, ripe and unripe pulp may differ in pharmacological activity. Comparing their extracts is therefore a reasonable way to test the traditional preference for unripe fruit in diarrhoea.

1.2 Economic and Medicinal Uses of Musa paradisiaca

Plantain has been associated with antispasmodic action and with the management of diarrhoea. Its other reported pharmacological activities have led to its use in many conditions in addition to its role as a food (Mahadeva Rao et al., 2014; Ajijolakewu et al., 2021). Medicinal uses vary from place to place.

Traditional preparations have been criticised for lacking standardised dosage and for failing to relate quantities to age or body weight. WHO's traditional medicine strategy likewise stresses safety, quality and evidence of efficacy (WHO, 2013). Even so, traditional medicine has contributed compounds to modern pharmacy and continues to meet the health needs of people, especially in developing countries.

Plantain is also an important food in coastal West Africa and in the Niger Delta. The pulp is energy-rich because of its carbohydrate content, mainly simple sugars. It is eaten roasted, boiled, fried, mashed into a paste or smoked for storage. Dried skins can be burned to produce ash rich in potash for soap making. Banana beer is made in parts of East Africa. The sap stains fabric, and the plant also provides fibre for ropes and brushes.

Recent reviews also support a possible role for green banana in gut health. Bomfim, Ferreira, Oliveira and Alfenas (2025) reviewed green banana biomass and reported that its consumption improves intestinal dysfunction in children, including persistent and acute diarrhoea. They proposed that the benefit arises from short-chain fatty acids produced by fermentation of its resistant starch, and they called for better clinical trials to clarify dosage and long-term effects.

1.3 Relevant Physiological and Pharmacological Concepts

1.3.1 Structure and innervation of the ileum

The ileum, like the rest of the small intestine, has four layers: the serosa, the muscular layer, the submucosa and the mucosa (Hall & Hall, 2021). The serosa is continuous with the mesentery. The muscular layer has an outer longitudinal and an inner circular coat, separated by the myenteric plexus. Stimulation of this plexus produces contraction and peristaltic waves along the gut. The submucosa contains connective tissue, blood and lymph vessels and the submucosal (Meissner's) plexus. The mucosa has finger-like villi that are specialised for digestion and absorption.

The gut is supplied by intrinsic and extrinsic nerves. The intrinsic supply consists of the myenteric and submucosal plexuses, and the extrinsic supply comes from the parasympathetic and sympathetic systems. Parasympathetic stimulation releases acetylcholine, which increases tone and motility. Sympathetic stimulation releases noradrenaline, which reduces them. Inhibitory purinergic and other non-adrenergic, non-cholinergic mechanisms also contribute to autonomic control of gut function (Hall & Hall, 2021). The motility of the ileum can therefore be altered by acting on either autonomic system.

1.3.2 Smooth muscle contraction

Intestinal smooth muscle contains actin and myosin. Contraction is triggered by calcium ions, and ATP is hydrolysed to ADP to supply energy. In smooth muscle, the sarcoplasmic reticulum is poorly developed, so much of the calcium that drives contraction enters from the extracellular fluid when the cell depolarises. Lack of available calcium therefore leads to muscle relaxation (Hall & Hall, 2021). This explains why drugs that interfere with calcium entry or handling can act as spasmolytics.

1.3.3 Spasmogens and spasmolytics

Spasmogens are agonists that increase smooth muscle contraction. They may act on receptors on the muscle membrane or on the nervous supply. Acetylcholine acts on muscarinic receptors. Histamine acts on histamine receptors on the muscle. 5-HT acts through both nerves and muscle, and classical work on the guinea-pig ileum distinguished neuronal and muscular 5-HT receptors, now described in terms of defined 5-HT receptor subtypes (Ritter et al., 2019). Nicotine acts indirectly by stimulating ganglia. Barium chloride and potassium chloride contract smooth muscle directly by depolarisation and calcium-dependent mechanisms.

Spasmolytics reduce smooth muscle contraction. Atropine and related drugs block muscarinic receptors and have been used where tone and motility are increased. Papaverine and xanthines act by phosphodiesterase inhibition and by effects on calcium-dependent contraction (Brunton, Knollmann, & Hilal-Dandan, 2018).

This background is useful because the actions of a plant extract can be compared with those of known spasmogens and spasmolytics. If the extract resembles or antagonises a particular agent, that comparison suggests how it may act.

1.4 Diarrhoea and Therapeutic Strategies

Diarrhoea is defined by WHO as the passage of three or more loose or liquid stools per day. In clinical research, it is commonly characterised by increased stool weight (above about 200 g per day) and excess loss of water and electrolytes (WHO, 2024). It may occur alone or with increased faecal loss of fat (steatorrhoea) or nitrogen (azotorrhoea). Loss occurs when the absorptive load exceeds absorptive capacity. This can result from increased load, for example heavy tube feeding with an osmotic effect, or from decreased absorption caused by mucosal or enzyme disturbances.

Causes include contaminated or decomposed food, bacterial or protozoal infection, nervous disorders of the gut and inflammation of the intestine or adjacent organs. Diarrhoea is a major cause of illness and death among young children in low-income settings, and it can lead to dehydration, exhaustion and loss of electrolytes, vitamins and nutrients. WHO recommends oral rehydration therapy and zinc supplementation as the core treatment for children (WHO, 2024). Therapeutic approaches also include the following.

1. Demulcents and protective agents (for example bismuth salts).
2. Adsorbents (for example activated charcoal and chalk mixtures).
3. Astringents (for example tannins).
4. Antimicrobials, when an infective cause is established.
5. Antispasmodics and opioids (for example atropine and opiates). These are generally inappropriate in infectious diarrhoea such as bacillary dysentery, where diarrhoea helps to clear the irritated gut of infected contents (Brunton et al., 2018).
6. Oral rehydration solution containing water, salt and sugar.

The choice of treatment depends on the cause. This is why scientific evidence on a traditional remedy for diarrhoea, including whether its action is antispasmodic, is valuable.

1.5 Statement of the Problem

Unripe plantain is traditionally used to manage diarrhoea, and recent reviews support its role in gut health (Bomfim et al., 2025; Imam & Akter, 2011). Yet reviewers note that many reported activities still need proper scientific justification and that in vivo evidence is limited (Ajijolakewu et al., 2021; Mahadeva Rao et al., 2014). It is also unclear whether ripe and unripe pulp differ in their effects on intestinal motility. Traditional use favours the unripe fruit, but experimental comparison of the two is needed.

1.6 Aim of the Project

The aim of this project is to compare the pharmacological effects of methanol extracts of ripe and unripe plantain (Musa paradisiaca) on the motility of the isolated guinea-pig ileum, in an attempt to provide a scientific basis for the use of unripe plantain pulp in alleviating diarrhoea.

1.7 Objectives of the Study

The study aims:

1. to prepare methanol extracts of ripe and unripe plantain pulp;
2. to determine the effects of each extract on the motility of the isolated guinea-pig ileum;
3. to compare the effects of the ripe and unripe extracts; and
4. to relate the effects of the extracts to those of known spasmogens and spasmolytics in order to suggest a possible mechanism of action.

1.8 Research Hypotheses

H₀: Methanol extracts of ripe and unripe plantain have no significant effect on the motility of the isolated guinea-pig ileum, and the two extracts do not differ.
H₁: Methanol extracts of ripe and unripe plantain have significant effects on the motility of the isolated guinea-pig ileum, and the two extracts differ.

1.9 Significance of the Study

The study may provide experimental evidence for or against the traditional use of unripe plantain in diarrhoea. It may also indicate how the extract acts on intestinal smooth muscle and show whether ripening changes its activity. It adds to the literature on the pharmacology of Musa paradisiaca and supports efforts to base traditional medicine on evidence (WHO, 2013).

1.10 Scope and Limitations

The study is limited to methanol extracts of ripe and unripe plantain pulp and to their effects on the isolated guinea-pig ileum. Results from isolated tissue show effects in vitro and cannot be applied directly to the whole organism or to humans. They would need confirmation in vivo and in clinical studies. Animal experiments must also follow institutional ethical guidelines on the care and use of laboratory animals.

References

Ajijolakewu, K. A., Ayoola, A. S., Agbabiaka, T. O., Zakariyah, F. R., Ahmed, N. R., Oyedele, O. J., & Sani, A. (2021). A review of the ethnomedicinal, antimicrobial, and phytochemical properties of Musa paradisiaca (plantain). Bulletin of the National Research Centre, 45, Article 86. https://doi.org/10.1186/s42269-021-00549-3

Bomfim, N. da S., Ferreira, R. de S., Oliveira, J. S. e, & Alfenas, R. de C. G. (2025). Green banana biomass anti-obesogenic, anti-hyperlipidemic, antidiabetic, and intestinal function potential effects: A systematic review. Nutrition Reviews, 83(2), e290. https://doi.org/10.1093/nutrit/nuae040

Brunton, L. L., Knollmann, B. C., & Hilal-Dandan, R. (Eds.). (2018). Goodman & Gilman's the pharmacological basis of therapeutics (13th ed.). McGraw-Hill Education.

Hall, J. E., & Hall, M. E. (2021). Guyton and Hall textbook of medical physiology (14th ed.). Elsevier.

Imam, M. Z., & Akter, S. (2011). Musa paradisiaca L. and Musa sapientum L.: A phytochemical and pharmacological review. Journal of Applied Pharmaceutical Science, 1(5), 14–20.

Mahadeva Rao, U. S., Khamsah Suryati, M., Mohaslinda, M., & Rosmawati, M. A. (2014). Taxonomical, phytochemical and pharmacological reviews of Musa sapientum var. paradisiaca. Research Journal of Pharmacy and Technology, 7(11), 1356–1361.

Ritter, J. M., Flower, R. J., Henderson, G., Loke, Y. K., MacEwan, D., & Rang, H. P. (2019). Rang & Dale's pharmacology (9th ed.). Elsevier.

World Health Organization. (2013). WHO traditional medicine strategy: 2014–2023. WHO.

World Health Organization. (2019). WHO global report on traditional and complementary medicine 2019. WHO.

World Health Organization. (2024). Diarrhoeal disease [Fact sheet]. https://www.who.int/news-room/fact-sheets/detail/diarrhoeal-disease