Abstract
BACKGROUND: Vetiveria zizanioides (L.) is a traditional Indian medicinal plant belonging to the family Poaceae. Hydroalcoholic extract of Vetiveria zizanioides has been studied for its various pharmacological effects, but a systematic scientific study on its safety has not been done. OBJECTIVE: To study the toxic effects of single and repeated doses of hydroalcoholic extract of Vetiveria zizanioides root, and to establish the toxicity profile of hydroalcoholic extract using in silico toxicity prediction tools. METHODS: Acute and repeated dose toxicity studies were conducted following OECD guidelines 423 and 407, respectively. The acute toxicity study was carried out on female Sprague Dawley rats at 2000 and 5000 mg/kg doses, with effects monitored for 14 days. A repeated dose toxicity study was performed through daily dosing of the hydroalcoholic extract (ethanol: water, 1:1 v/v) of Vetiveria zizanioides extract for 28 days at doses of 250 mg/kg, 500 mg/kg, and 1000 mg/kg. At the end of the study, hematological parameters, biochemical parameters, kidney function, and histopathology were evaluated in all animals. Additionally, In silico toxicity prediction of the bioactive present in Vetiveria zizanioides root extract was performed using ProTox-II. Phytoconstituents of Vetiveria zizanioides roots were identified using GC-MS analysis. RESULTS: Single dose administration of Vetiveria zizanioides extract at 5000 mg/kg showed no toxicity or morbidity. Similarly, repeated doses of extract over 28 days did not significantly impact hematological and biochemical parameters. However, a significant increase in ALT (P < 0.05) was noted at the highest dose (1000 mg/kg) of the extract. Histopathological examinations of the liver at this dose revealed mild changes in hepatocytes compared to the control animals. The toxicity prediction revealed that all identified compounds of Vetiveria zizanioides hydroalcoholic extract were free from cytotoxicity and mutagenicity. More than 50 percent of the compounds were found to be class 5 (2000 < LD50 ≤ 5000). However, few compounds were found to be hepatotoxic at high doses. CONCLUSION: Vetiveria zizanioides extract may generally be safe, but long-term use at 1000 mg/kg in rats could pose a concern for liver toxicity. The results of the study indicate that Vetiveria zizanioides is safe for use up to 500 mg/kg in 28-day repeated dose toxicity study.