The Toxicity Study Of Veratrum Nigrum L Combined With Salvia Miltiorrhiza Bge Based On Drug Interactions

Veratrum nigrum L and Salvia miltiorrhiza Bge are chosen for current study, Ultra-performance liquid chromatography coupled with time-of-fight mass spectrometry (UPLC-Q-TOF MS) is used to analyze the change of the material composition of the compatibility, exploring the relation between contents variation of chemical constituents and acute toxicity experiments, finally, dig out the regularity of toxic alkaloids which is related to the acute toxicity. On the other hand, investigated the effects of Veratrum nigrum combined with Salvia miltiorrhiza on the activity of CYP450informs, and the metabolic regularity of Veratrum toxic alkaloids. The in vivo and in vitro experiments, showed the possible mechanism of changes in toxicity from the drug interaction level.Conclusion:Fixed dosage of Veratrum nigrum as LD50, the acute toxicity experiments of Veratrum nigrum combined with Salvia miltiorrhiza with different ratio contains the two designs of1:1compatibility and uniform design experiment, so it is suitable for research toxicity variation the Veratrum nigrum compatibility with Salvia. From the acute toxicity experiments, we can get that compatibility ratio of1:1is toxicity cut-off point, when the ratio greater than1:1, compatibility is more toxic than the Veratrum nigrum single decoction group, showing the contrary increased toxicity. When the ratio less than or equal tol:1, compatibility doesn’t show any toxicity. Meanwhile, components analysis showed that the dissolution trends of some alkaloids are same with toxic change trend, such as verdine、 pseudojervine、germidine and so on, and these alkaloids may be the main chemical markers of Veratrum nigrum combined with Salvia miltiorrhiza in specific ratio. Reveals a small amount of Salvia miltiorrhiza is able to increase alkaloids’dissolution, it is maybe one of the possible mechanisms of Veratrum nigrum combined with Salvia miltiorrhizaThe group of Veratrum nigrum、Salvia miltiorrhiza single-agent and the compatibility of the two drugs can inhibit the activity of CYP1A2,CYP2C9,CYP2C19, CYP2B6strongly, At the same time, pharmacokinetic parameters show the metabolic rate of veretramine, jervine, pseudojervine, and germinalinine slow down in Salvia miltiorrhiza treated rats, area under curve (AUC) increase; this may cause Veratrum alkaloids accumulate in the body, resulting increased toxicity. Figure26, table24, reference72...