Acute toxicity of berberine and its correlation with the blood concentration in mice

The aim of this study was to investigate the LD₅₀ (median lethal dosage) of berberine (BBR) through three different routes of injection in mice: intravenous (IV) injection, intraperitoneal (IP) injection, and intragastric (IG) oral administration. The concentration of BBR in blood from their IG doses (10.4, 20.8, 41.6, and 83.2 g/kg) and the content relationship of BBR among different injections were analyzed by high-performance liquid chromatography (HPLC). The LD₅₀ of BBR from IV and IP injections is 9.0386 and 57.6103 mg/kg, respectively; but no LD₅₀ was found in the IG group. A significant difference in bioavailability was observed between the different routes. Furthermore, the concentration of BBR in the blood from different IG doses was also significantly different. However, we discovered an interesting phenomenon indicating that the absorption of BBR by oral administration has a limit, therefore, explaining the difficulty in obtaining an LD₅₀ of BBR for IG injection. From the analysis of BBR content in blood after various administrations, we hypothesized that not only does the concentration of BBR in blood contribute to its acute toxicity, but also the routes of administration may be an important facet that affects this toxicity evaluation.