Long-term systemic toxicity of shikonin derivatives in Wistar rats.

Abstract Context: Although the antitumor, immunomodulatory activities, and other effects of shikonin have been studied for decades, its systemic toxicity in vivo remains unclear. Objective: To estimate the long-term systemic toxicity of shikonin derivatives (ShD) in a rat model. Materials and methods: The roots of Arnebia euchroma (Royle) Johnst. (Boraginaceae) were extracted in ethanol, passed through a molecular sieve, and dried. A microemulsion solution in water was subsequently prepared. Adult Wistar rats were treated with ShD by gavage at concentrations of 200, 400, and 800 mg/kg per day for 90 days or 180 days. Hematological and biochemical examinations were performed, and the vital organs were subjected to pathological analyses. Results: We did not observe hematological or non-hematological toxicity of ShD at a dose as high as 800 mg/kg per day for 6 months. Discussion and conclusion: Our findings may offer some beneficial information for the practical application and research of Arnebia euchroma. We demonstrated in an animal model that ShD may be safe for usage.