Researchers Affirm Efficacy of Bitter Kola in Respiratory Diseases

Used as folklore remedies for the treatment of ailments such as liver disorders, hepatitis, diarrhoea, laryngitis, bronchitis and gonorrhoea, BEN UKWUOMA writes on the promising use of Bitter kola in the management of respiratory problems.

NIGERIAN researchers have described as promising the use of Bitter kola in the management of respiratory problems, particularly asthma, raising hopes of a possible formulation of the extracts or active constituents as medicines.

Though there are various orthodox drugs for the treatment of respiratory tract diseases in the country, the search for cost effective local herbal remedies have always excited researchers.

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In fact, the seeds of Bitter kola also called Garcinia kola (GK) which forms a major part of the herbal preparation used in traditional African medicine practice for the treatment of various respiratory tract diseases, including asthma have attracted scientific scrutiny in the last decade.

In a report published recently in The Internet Journal of Pulmonary Medicine. 2009:Volume 11 Number 1, the researchers: A.K. Okojie ,I. Ebomoyi,C.N. Ekhator,O. Emeri,J. Okosun, G. Onyesu, O. Uhuonrenren, and J. Atima from the Department of Physiology, University of Benin and Ambrose Alli University Ekpoma,in a holistic review decided to find out the physiological mechanism(s) underlying the use of GK for the treatment of asthma. Specifically they were interested in finding out the function(s) of its phytochemical contents and how they are beneficial in the treatment of asthma.

At the end, they said:”Garcinia kola appears to be very promising in the treatment and management of asthma, Our review showed that xanthone and flavonoid, which are its major phytochemical contents inhibit calcium influx and histamine release stimulated by IgE dependent ligands respectively.”

Used in folklore remedies for the treatment of ailment such as liver disorders, hepatitis, diarrhea, laryngitis, bronchitis and gonorrhoea, Garcinia kola belongs to the family Guittiferae and it is commonly called Orogbo in Yoruba language and Aki ilu in Igbo while the English name is bitter kola. Although valued because of its edible nut, the plant exhibits very potent pharmacological activities such as antioxidant, antibacterial, antiviral, antifungal and anti-inflammatory properties. The anti-oxidant property of GK is attributed to its very high content of ascorbic acid.

Phytochemistry of Gk has shown its content to include benxophenones, xanthones, biflavonoids, alkaloids, phenols, tannins and saponins.

It is usually found in the tropical rain forest region of West Africa. It prevails as a multi-purpose tree crop in the home gardens of southern Nigeria. It grows to a height of about 12 – 14m and produces reddish, yellowish or orange coloured fruit. Each fruit contains 2 to 4 yellow seeds and a sour tasting pulp. The seeds when chewed have a bitter astringent taste. The flowering of the plant occurs between December and January while the fruits mature between June and August.

Garcinia kola is highly valued because of its medicinal use. The seeds are chewed as an aphrodisiac or used to cure cough, dysentery, chest colds in herbal medicine.

The plant has also found usefulness in the treatment of stomach ache and gastritis. In fact, Professor Maurice Iwu, the chairman of INEC in a study carried out at the University of Nigeria Nsukka reported the use of the plant for the treatment of jaundice, high fever, and as purgative.

Some researchers have also reported that the administration of Gk seed extract caused an increase in testosterone production in Sprague-Dawley rates which is thought to be due to its antioxidant properties. Also, studies have confirmed the spermatogenic and tissue enhancing effect of GK extract in male Wistar rats.

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They showed that Gk extract exhibits a dilatory effect on the alveolar ducts, alveolar sacs and alveoli thereby improves respiratory activities, which may be due to its antioxidant properties in Swiss albino mice.

Gk has been shown to inhibit smooth muscle activity. It relaxes the smooth muscles of the uterus and the intestine. Although, Gk lacks caffeine, its alkaloid and biflavonoids fractions are said to relax the smooth muscles. Gk has a bronchodilatory effect.

The seeds are used in the treatment of bronchitis and throat infections. They are also used to prevent and relieve colic, cure head or chest colds and relieve cough. Also, the plant is used for the treatment of liver disorders and as a chewing stick.

Historically, plants have provided a source of inspiration for novel drug compounds, as plant derived medicines have made large contributions to human health and well being. The seeds of Garcinia kola (Gk) forms a major part of the herbal preparation used in traditional African medicine practice for the treatment of various respiratory tract diseases including asthma.

Asthma is a very common chronic disease involving the respiration system. Episodic or chronic wheezing, cough, and feeling of tightness in the chest as a result of bronchoconstriction characterize it. The fundamental cause is still unknown despite intensive research. However, three abnormalities are present: airway obstruction that is at least partially reversible, airway inflammation, and airway hyper responsiveness to a variety of stimuli. A link to allergy has long been recognized, and plasma IgE levels are often elevated.

Public attention in the developed world has recently focused on asthma because of its rapidly increasing prevalence, affecting up to one in four urban children.

The disease is caused by a complex interaction of environmental and genetic factors that researchers do not yet fully understand.

Environmental tobacco smoke, especially maternal cigarette smoking, is associated with high risk of asthma prevalence and asthma morbidity, wheeze, and respiratory infections.

The fundamental problem in asthma appears to be immunological. In immunologic model, asthma is a disease mediated by reaginic (IgE) antibodies bound to mast cells in the airway mucosa. On reexposure to an antigen, antigen-antibody interaction on the surface of mast cells triggers both the release of mediators stored in the cells granules and the synthesis and release of other mediators. The agents responsible for the early reaction mediating bronchoconstriction including histamine, tryptase and other neural proteases, leukotrienes C4 and D4, and prostaglandin causes muscle contraction and vascular leakage. The mechanisms underlying bronchial reactivity, such as ozone exposure, allergen inhalation, and infection with respiratory viruses also cause airway inflammation. In humans, the increase in bronchial reactivity induced by ozone is associated with an increase in the number of polymorphonuclear leukocytes found in fluid obtained by bronchial lavage or from bronchial mucosa biopsies. The increase in reactivity due to allergen inhalation is associated with an increase in both eosinophils and polymorphonuclear leukocytes in bronchial lavage fluid. Whatever the mechanisms responsible for bronchial hyperreactivity, bronchoconstriction itself seems to result not simply from the direct effect of the released mediators but also from their activation of neural or humoral pathways.

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The researchers reviewed actions of all the major phytochemical component particularly Xanthone, Flavonoids and phenol. They confirmed that Xanthone potentiates its anti-asthmatic activity by dependently inhibiting the Ca2+ influx induced by either noreprinephrine or high K+, suggesting that xanthone might act as a blocker of both receptor-operated and voltage-dependent Ca2+ channels.

Furthermore, they review reported that xanthone causes increase in the level of intracellular cyclic adenosine 3′, 5′-monophosphate (cAMP) but not cyclic guanosine 3′, 5′-monophosphate (cGMP) content. They reported that xanthone showed inhibitory effects on cAMP phosphodiesterase. Intracellular levels of cAMP can be increased by _-adrenoceptor agonist, which increase the rate of its synthesis by adenyl cyclase (AC) or by phosphodiesterase (PDE) inhibitors such as xanthone, which slow the rate of its degradation.

On Flavonoids, the report stated it works by inhibiting platelet-activating factor (PAF), phospholipase A2 (PLA2) and phosphodiesterase (PDE).

Flavonoids protect against allergies, inflammation, free radicals and platelet aggregation. These observations support the importance of Gk in traditional medicine for the treatment of various conditions.

Flavonoids have been shown to exhibit a predilection to inhibit histamine release stimulated by IgE-dependent ligands Copper a transitional metal; most effectively block the inhibitory activity of flavonoids, possibly through a chelation mechanism. Zinc deficiencies can lead to excess copper levels, since zinc and copper compete for absorption. Also, a high intake of vitamin C and zinc decrease the absorption of copper.

Intake of Gk will therefore reduce the inhibition of antihistamine activity of flavonoids by copper which is as a result of its high content of vitamin C and zinc. Some studies noted that naturally occurring plant flavonoids affect a variety of cell activation phenomena including the secretion of histamine from human basophils. They also showed that flavonoids inhibit the degranulation of mast cells. Degranulation of mast cells would release not only histamine, but all the mediators of the allergy response.

The review reported that flavonoids exhibited anti-spasmodic and anti-inflammatory properties induced by acetylcholine, histamine, noradrenaline and barium chloride in four different smooth muscles. In addition, flavonoids are said to inhibit antigen-induced release of histamine from mast cells, basophils and also inhibit contractions induced by histamine, acetylcholine and PGEÂÂÂ2. It was noted that this effect was concentration dependent.

Flavonoids are said to inhibit phospholipids metabolism and 5- lipoxygenase (5-LO). Leukotrienes are derived from arachidonic acid through 5-LO and the nucleophilic attack to produce peptidoleukotrienes. These 5-LO products mediate constriction of airway smooth muscles, leukocyte chemotaxis and vascular permeability . Therefore inhibiting 5-LO can attenuate leukotriene production.

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The presence of phenol in GK further indicated that it could act as anti-inflammatory, antioxidant and immune enhancers. Phenols have been responsible in having the ability to block specific enzymes that cause inflammation. They also modify the prostaglandin pathways and thereby protect platelet from clumping.

From this review, the following could be the underlying physiological mechanisms by which Garcinia kola may be beneficial in the treatment of asthma:

Inhibition of Ca2+ influx by acting as a blocker of both receptor-operated and voltage-dependent Ca2+ channels. Increasing the intracellular levels of cAMP by inhibiting the effects of phosphodiesterase.

Inhibition of histamine release stimulated by IgE dependent ligands. Inhibition of platelet-activating factor and platelet aggregation. Its high vitamin C and zinc content. Inhibition of 5-lipoxygenase (5-LO) pathway, thereby attenuating leukotriene production.

“Garcinia kola appears to be very promising in the treatment and management of asthma. There is therefore the need to further examine its various phytochemical contents on respiratory smooth muscle, with a view to possibly formulating its extracts or active constituents as medicines.”.


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