Acute and sub-chronic toxicity studies of 5-methylcoumarin-4-β-glucoside isolated from <i>Vernonia glaberrima</i> in Wistar rats

Abstract

5-methylcoumarin-4-β-glucoside is a natural product isolated from Vernonia glaberrima – a plant used in African traditional medicine for the treatment of cancer and skin diseases. This compound possesses significant in-vitro antiproliferative potentials against colon cancer cell lines. However, safety assessment in several laboratory animals is required before commencing the in-vivo anticancer evaluation of the compound. This study is designed to evaluate the safety of 5-methylcoumarin-4-β-glucoside using 28 days sub-chronic toxicity model in Wistar rats. Acute toxicity study was carried out at a single oral dose of 10 mg/kg, 100 mg/kg and 1000 mg/kg body weight (phase 1) for 24 hours, and 1600 mg/kg, 2900 mg/kg, and 5000 mg/kg body weight (phase 2). Sub-chronic toxicity was conducted by oral administration of distilled water, 1%hydroxypropyl cellulose in distilled water as controls, and graded doses of 10 mg/kg, 50 mg/kg, and 100 mg/kg body weight of 5-methylcoumarin-4β-glucoside freshly prepared in 1% hydroxypropyl cellulose as vehicle to five groups of six rats each for 28 days. The result indicates that 5-methylcoumarin-4β-glucoside at a dose of 100 mg/kg body weight is non-toxic as serological indices like liver and kidney functioning test, serum lipid profile, oxidative stress markers and hematological indices remained in the normal range after the 28 days sub-chronic administration of the compound. Moreover, the histopathology findings revealed no alteration in the normal tissue architecture. Overall, the findings in Wistar rats corroborate the initial findings in mice. Conclusively, the compound 5-methylcoumarin-4β-glucoside is safe at the prescribed doses for further preclinical in vivo investigations.