HYPOTENSIVE ACTIVITY AND TOXICOLOGICAL PROFILE OF STEM BARK EXTRACT OF SYZYGIUM GUINEENSE (Willd, D.C. Myrtaceae) IN LABORATORY ANIMALS
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ABSTRACT
Hypertension of unknown cause is called essential or primary hypertension while hypertension of a known cause is called secondary hypertension. Hypertension is called a silent killer because it is usually asymptomatic. It is a global problem affecting 1 in 3 adults in the United States. It is preventable and treatable disease. Orthodox drugs for its management are expensive and have associated side effects. Alternative source with good efficacy and minimum toxicity from natural products are explored. Hypotensive activity and toxicological profile of methanolic stem bark extract of Syzygium guineense (Willd, D.C. Myrtaceae) were evaluated. It is a medicinal plant used in folk medicine to treat hypertension, diarrhoea and infection. Phytochemical analysis of the stem bark extract was carried out using standard procedures. Bioassy-guided fractionation and finger printing of the crude extract were carried out. Five fractions(SGF1-SGF5) were isolated. The oral and intraperitoneal acute toxicity studies were carried out in mice using Lorke‟s method with modification. Subchronic oral toxicity studies of the methanolic stem bark extract in male and female Wistar rats for 90 days. The assessment of the toxic effect was evaluated at 42 and 90 days respectively, on clinical observations, feed and water intake, body weight, heamatology, blood chemistry, urinalysis, gross necropsy, organ weight and histopathology. The in vivo assessment of hypotensive activity of extract and fractions were carried in anaesthesized normotensive cat. The in vitro investigations to assess the possible mechanisms of hypotensive action of the extract were carried out on isolated tissue experiments. These included: guinea pig atria, rabbit perfused heart, rabbit ileum and rat uterus. The oral median lethal dose of the methanolic stem bark extract of Syzygium guineense was greater than 5000mg/Kg body weight while the intraperitoneal median lethal dose was 2154.1mg/Kg. There was significant (p<0.05) increase in feed intake in extract- treated male and female rats when compared to the corresponding control. There was also significant increase in water intake in male and female rats treated with Syzygium guineense in a dosedependent manner in 90 days. The extract produced significant (p<0.05) increase in body weight of male and female rats. The relative organ body weight ratio values of extract-treated rats were not significantly different from those in the control groups. The haematological parameters and the biomarkers of liver function test and lipid profile were all normal in male and female rats when compared to the control. There xxix was also, no significant change in the serum levels of electrolytes, urea and creatinine in male and female rats. All the values were within normal range. The histopathology results revealed no significant changes in all the organs. Phytochemical tests revealed the presence of carbohydrates, alkaloids, saponins, tannins, phytosterols, anthranol glycosides, cardiac glycosides, phenols, terpenoids, and flavonoids. The extract and fraction F3 significantly (p<0.0001) reduced both systolic and diastolic blood pressure of anaesthetized normotensive cat. The extract significantly (P<0.05) reduced adrenaline induced rise in systolic and diastolic pressure in anaesthetized cat. Atropine competitively reversed the hypotensive effect of the extract towards basal rhythm obtained with normal saline. The extract produced significant (p<0.05) concentration-dependent decrease in height of contraction of guinea pig atria. The extract also produced a concentration-dependent decrease in contraction of perfused rabbit heart. Adrenaline alone increased the height of contraction of the heart muscles. In the presence of the methanolic stem bark extract of Syzygium guineense the height of the amplitude produced was markedly lower than that due to adrenaline alone. The extract abolished all the spontaneous contractions of the rat uterus. These results showed that methanolic extract Syzigium guineense is safe and possesses significant blood pressure lowering effect in anaesthetized normotensive cat thus justifying its folkloric use in the treatment of hypertension.
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