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Pharmacological and Toxicological Activities of the Methanolic Root Extract of Cnestis Ferruginea

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Pharmacological and Toxicological Activities of the Methanolic Root Extract of Cnestis Ferruginea CHAPTER 1 INTRODUCTION 1 1.0 INTRODUCTION 1.1 Background of Study Herbal medicines are an important part of the culture and traditions of African people. Today, most of the population in urban Nigeria, as well as rural communities, rely on herbal medicines for their health care needs. Epidemiological data suggest that lower incidences of certain chronic diseases such as atherosclerosis, arthritis, diabetes, acquired immune deficiency syndrome (AIDS) mediated by the human immunovirus, asthma, neoplasia, neurodegenerative and cardiovascular diseases are associated with frequent intake of fruits and vegetables (Ames et al., 1993; Chu et al., 2002). Various factors influence the use of traditional medicine by 80% of developing nation‘s population which include; accessibility, confidence in treatment, convenience, cost of treatment, socioeconomic status, education and adverse effects of orthodox medicine. As a consequence, there is an increasing trend, worldwide, to integrate traditional medicine with primary health care. Renewed interest in traditional pharmacopoeias has meant that researchers are concerned not only with determining the scientific rationale for the plant‘s usage, but also with the discovery of novel compounds of pharmaceutical value. Instead of relying on trial and error, as in random screening procedures, traditional knowledge helps scientists to target plants that may be medicinally useful (Cox and Balick, 1994). Already an estimated 122 drugs from 94 plant species have been discovered through ethnobotanical leads (Fabricant and Farnsworth, 2001). The prescription and use of traditional medicine in Nigeria is currently not regulated, with the result that there is always the danger of misadministration, especially of toxic plants. The potential genotoxic effects that follow prolonged use of some of the more popular herbal remedies, are also cause for alarm. People who use traditional remedies may not understand the scientific rationale behind their medicines, but they know from personal experience that some medicinal plants can be highly effective if used in certain amounts (doses). Since we have a better understanding today of how the body functions, we are thus in a better position to understand the healing powers of plants and their potential as multi-functional chemical entities for treating complicated health conditions. 2 The positive contribution of plants to medicine, however, has not been without side effects at normal doses, or toxic effects at toxic doses. Although, the literature has documented several toxicity resulting from the use of herbs on many occasions, still the potential toxicity of herbs has not been recognized by the general public or by professional groups of traditional medicine practitioners (Jou-fang, 1994; O‘Hara et al., 1998). Cnestis ferruginea Vahl ex DC (Connaraceae) is a short ornamental shrub, sometimes a climber, which is about 2.5 meters high and is usually covered by dense, brown velvety hairs (Hutchinson and Dalziel, 1958; Nielson, 1965). The plant abounds throughout West Tropical Africa particularly in Gambia, Sierra Leone, Liberia, Ivory Coast, Ghana and Nigeria. In Africa, forty- one species of Cnestis have been recorded (Olugbade et al., 1982). The plant is widely employed in the treatment of various ailments in traditional medicine throughout West Africa. The bitter fruit is used to clean teeth in Sierra Leone and in Nigeria (Burkill, 1985). In West Africa, healers use this plant for various infantile illness (Olugbade et al., 1982). The extract of the fruit is used to treat sore throat as a tonic, and boiled fruits or fresh fruits crushed with rum or palm wine (a sweet alcoholic sap obtained from palm trees used as a common beverage) are usually taken systemically but may also be applied topically for the treatment of snake bite in Nigeria and Ghana (Dalziel, 1955). In Ivory Coast, the roots and leaves are employed in the treatment of dysmenorrhoea, epilepsy, mental illnesses (Garon et al., 2007), whereas in Nigeria the leaves are employed as a laxative. A decoction of the bark is used in treating infected gum and a decoction of various parts of the plant is also believed to assist weak children to walk (Dalziel, 1955). The aqueous extract of the roots (Malcolm and Sofowora, 1969) and the methanolic extract of the root, stem and leaves of C. ferruginea (Bakye-Yiadom and Konning, 1975) were shown to have antimicrobial properties. This study was undertaken to investigate the toxicity profile, and pharmacologic effects of the methanolic root extract of C.ferruginea with a view to isolating and characterizing the active constituents responsible for these effects. 3 1.2 Statement of Problem Inflammation has long been known as a localized protective reaction of tissue to irritation, injury, or infection, characterized by pain, redness, swelling, and sometimes loss of function, but there has been a new realization about its role in a wide variety of diseases. These include; chronic arterial and venous disease (Ross, 1999), myocardial ischeamia (Entman, 1991), acute cerebral stroke and Alzheimer‘s chronic disease (Koistinaho and Koistinaho, 2005), arterial hypertension (Suematsu et al., 2002) and cancer (Li et al., 2005). Neuroinflammation is integral part of neurodegenerative diseases. A severe form of inflammation is observed in shock and multi-organ failure (Schmid-Schonbein and Hugli, 2005), a condition with one of the highest mortalities. The list of diseases associated with molecular markers of inflammation is large and growing. Today, inflammation has become the Holy Grail for studies of human disease. Anti-inflammatory treatments that have been shown to be effective in one disease may turn out to be effective in another, thereby opening a wider range of opportunities for intervention. Various classes of synthetic analgesic and anti-inflammatory drugs in use today are effective but not without adverse effects like gastrointestinal ulceration accompanied by anaemia from the resultant blood loss, fluid retention, bronchospasm and prolongation of bleeding time (Theophile et al., 2006). Therefore, it is necessary to search for new drugs with little or no side effects. Plant extracts can be an important source of natural and safer drugs for the treatment of pain, inflammation and psychiatric disorders. Depressive disorders, including major depression and dysthymia, are significant and disabling illnesses. It is estimated that one in five individuals is affected by a mood disorder in his or her lifetime. The World Health Organization estimated that major depression is the fourth most important cause worldwide of loss in disability-adjusted life years (DALY), and will be the second most important cause by 2020 (Murray and Lopez, 1997). Depression affects an estimated 121 million people worldwide. In spite of its prevalence and severe impact, the efficacy of currently available antidepressants is often inconsistent and many of them produce undesirable side effects. With a growing number of herbal medicines being introduced to psychiatric practice, many of them have been chosen as alternative therapies for the management of severe depression and dementia (Kessler et al., 2001; Thachil et al., 2007). 4 Thus, developing safe and effective agents from traditional herbs may provide us a good way to lessen the side effects as well as improve the efficacy. In many regions of the world where modern healthcare is not readily available or affordable, the public continues to rely on traditional medicines which are based on locally available natural resources and cultural knowledge. In a public health context, availability, accessibility, affordability, utility, quality, efficiency and equity have relevance in respective order in promotion of traditional medicine (Tan, 2008). The continuous surge in the popularity and patronage of herbal remedies, and the fact that reports of efficacy far outnumber those of toxicity, necessitate concern. This is mainly due to the adverse effects of potentially toxic constituents in plants (e.g. aristolochic acids, pyrrolizidine alkaloids, viscotoxins, saponins, benzophenanthrine alkaloids, lectins, diterpenes, cyanogenetic glycosides, and furonocoumarins (Fennell et al., 2004) which can be fatal. Based on these facts, it has been said that pharmacological and toxicological evaluations of medicinal plants are essential for drug development (Ibarrola et al., 2000; Ahmed et al., 2005). Different parts and preparations of Cnestis ferruginea Vahl ex DC (Connaraceae) have been reported to be used in traditional African medicine for the treatment of various conditions. These include painful and inflammatory conditions like periodontitis (powdered bark); headache (root-bark paste); bronchitis (decoction of leaves); eye defects (leaf sap); dysmenorrhoea (leaves or roots); all manner of pains (pulped plant); migraine; sinusitis (root sap or powder); toothache, mental illness (root); and conjunctivitis (fruit juice) (Burkill, 1985). The high treatment cost and incidences of adverse effects of most allopathic medicine used for pain, inflammation, depression, anxiety, dementia and convulsion, has necessitated the search for cheaper and safer sources of treatment for these ailments. Hence, Cnestis ferruginea could be a potential source of remedy for central nervous system disorders and inflammatory conditions. To the best of our knowledge no study has been carried out to investigate neither the pharmacological profile of the folkloric uses of this plant nor its
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