Safety Evaluation and Hepatoprotective Activity of the Aqueous Stem Bark Extract of Spathodea Campanulata

Spathodea campanulata, a widely used traditional African medicinal plant for skin diseases and stomach aches has not been scientifically assessed for toxicity and hepatoprotection. The aqueous extract of the stem bark of the plant Spathodea campanulata (SCE) was therefore evaluated for safety and potential hepatoprotective activity in rodents. The extract (1250, 2500, 5000 mg/kg, p.o) administered to rats and mice over a 24-hour period did not show any signs of toxicity or mortality, suggesting that the oral LD50 of the aqueous extract (in rats and mice) was beyond 5000 mg/kg. Daily administration (1250, 2500, 5000 mg/kg; p.o) of extract for 14 days did not cause any changes in behavior or alterations in haematological parameters of the animals. Serum biochemical analysis in rats showed a rise in alkaline phosphatase (ALP) (339.50±90.50 in the control to 582.5±28.50 U/L in the highest dose of 5000 mg/kg) and a decrease in Na+ concentration (147.3±1.856 mmol/L in the control to 135.0±1.00 in the 5000mg/kg dose), but no change in other parameters. These observations did not reflect in the histopathology of the liver and kidneys of treated animals. However, the diuretic test on the extract was positive. Urine output, Na+ and K+ concentration in urine were increased significantly by the administration of extract for seven days. In hepatoprotective studies, rats were pre-treated with 625 mg/kg , 1250 mg/kg, 2500 mg/kg p.o for 4 days before intoxication with carbon tetrachloride (CCl4) (1 ml/kg, 20 % in liquid paraffin, p.o) or mice and rats with 100 mg/kg, 300 mg/kg, 625 mg/kg for 4 days before intoxication with paracetamol or aflatoxin B1 (AFB1) respectively. Generally, the administration of these hepatotoxic agents caused an increase in liver weights which were prevented or restored by pre-treatment with extract in both rats and mice. The aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyl transpeptidase (GGT), bilirubin-induced by these hepatotoxic agents (CCl4, parcetamol and AFB1) were significantly reduced with SCE treatment. Additionally, administration of CCl4 daily for 5 days, followed by treatment with 100, 300, and 625 mg/kg p.o daily for 3days (curative) decreased profoundly the AST, ALT and GGT levels induced by CCl4. These results correlated well with the histopathological studies observed in the photomicrographs of liver for treated and control groups. Treatment with the extract decreased the extent of fatty liver and necrosis caused by the hepatotoxic agents. Lipid peroxidation measured as TBARS was elevated by CCl4 but this was reversed by treatment with the extract at all dose levels. Again, pretreatment with SCE (625 mg/kg) before hepatotoxicity by CCl4 or paracetamol restored the decrease in super oxide dismutase (SOD) and glutathione peroxidase (GPx) activity caused by the hepatotoxin. This decrease was more profound after paracetamol intoxication than it was after CCl4 intoxication. The extract (625 mg/kg) also showed strong enzyme inhibition when it reduced the total cytochrome P450 in both mice and rats when given for seven consecutive days. This decrease was also reflected in the presence of CCl4 and paracetamol. The preliminary phytochemistry which showed the presence of tannins, sterols and reducing sugars as well as the in vitro testing which gave positive results for reducing power and total phenolic content also support the activity of the plant extract in interference with hepatotoxicity. Collectively, the results indicate that the aqueous extract of Spathodea campanulata is fairly nontoxic and may exhibit hepatoprotective activity at lower doses by enhancing antioxidant protection in the cell and inhibiting total cytochrome P450 hence interfering with bioactivation of hepatotoxic agents.

Source: KNUST