Analgesic and toxic effects of venenum bufonis and its constituent compound cinobufagin: A comparative study

In this study, we aimed to compare the analgesic and toxic effects of Venenum Bufonis (VB) with those of cinobufagin (CBG), a monomer isolated from VB, to provide the experimental basis for further research and development of VB.After intragastric administration, the analgesic activities of VB and CBG were compared using the hot plate test and acetic acid-induced writhing test. Their side effects were also compared using hepatotoxicity, acute toxicity, cytotoxicity, and hemolytic toxicity tests, as well as by evaluating their effects on rat heart rate.In the hot plate test, both drugs prolonged paw withdrawal latency; however, CBG-treated mice exhibited significantly longer latency than VB-treated mice. In the acetic acid-induced writhing test, both drugs inhibited mouse writhing; however, the inhibitory effects of CBG were stronger. In addition, VB significantly increased serum aspartate aminotransferase (AST) levels, whereas CBG did not these levels. The LD50 of VB and CBG was 36.25 and 4.78 mg/kg, respectively. Both drugs increased the heart rate with CBG exhibiting stronger effects. Moreover, results showed that the cytotoxicity of CBG was more dose-dependent than that of VB. Both VB and CBG showed low hemolytic toxicity.Both VB and CBG exhibited analgesic effects and low hemolytic toxicity; however, the latter showed stronger analgesic activity and less hepatotoxicity. Additionally, both VB and CBG increased the heart rate; however, CBG had stronger effects and higher acute toxicity.