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

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.