Acute/Subchronic Oral Toxicity of Brucea javanica Seeds with Hypoglycemic Activity

Abstract

Brucea javanica (L.) Merr (Simaroubaceae) seeds are used as antidiabetic folk medicine. This study examined acute and sub-chronic toxicity of seed extracts with hypoglycemic activity. Dried powdered seeds were extracted using different polarity solvents: methanolic solution, n-hexane, chloroform and n-butanol. These extracts were orally administered to mice with blood glucose levels determined. The median lethal doses (LD₅₀), biochemical and histological profiles of liver and kidney of mice were assessed. Methanolic and butanolic extracts reduced blood glucose levels of mice at 32 mg/kg with no mortality, unlike inactive hydrophobic extract. The LD₅₀ values of methanolic and butanolic extracts were 281.71 and 438.43 mg/kg respectively. The butanolic extract exhibited a similar activity as methanolic sample but had a lower level of acute toxicity. The inactive hydrophilic and toxic hydrophobic constituents of butanolic extract were removed via aqueous residual and hydrophobic solvent partitioning during extraction. Histology examination and blood tests of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, urea, billirubin and creatinine indicated that the butanolic extract did not induce liver and kidney toxicity upon 9-week consumption. Butanolic extract contained blood glucose lowering quassinoids bruceine D (10.3 %) and E (0.4 %). It is safe for treatment of diabetes mellitus in extract form.