Study On The Toxicity Of Veratrum Nigrum L. And The Incompatibility Mechanisms Of Veratrum And Ginseng Based On Chemical Substances And Metabonomics

Veratrum nigrum L. is a uncommon Traditional Chinese Medicine, of which thealkaloids are the most toxic ingredients. This research was guided by property study ofTCM and incompatibility theory, and aimed to revealing the toxic mechanisms ofVeratrum and incompatibility mechanisms of Veratrum and ginseng. We applied themodern analytical instruments in order to research the chemical substances of Veratrum,and ingredients going into blood. On the basis of comprehensive evaluation of thechemical substances of Veratrum, the influences on organism metabolism environmentswere studied based on metabonomics for the elucidation of the toxicity of Veratrum. At thesame time, the herbal drug serum on the liver and kidney cells was studied by serumpharmacology, which provide examples for the toxicity evaluation of Veratrum bymetabonomics. This paper will provide directions to medication safety of Veratrum, andalso illustrate samples for study the interactions of the complex TCM system by usingmetabolomics as a powerful tool. Detailed research contents are shown as follows:1. Study on chemical substances of VeratrumWe identified the chemicals of Veratrum by using UPLC-Q-TOF/MS, and analyzed threegroups of isomers in it. The conditions are: Chromatogram: Agilent Eclipse Plus C18（2.1mm×100mm，1.8μm）column; Mobile phase:ACN-0.1%Formic Acid; Columntemperature:40℃; Flow:0.35mL/min; Ms: EI Ion source; Positive mode: MS range:m/z100-1100; CE4000V; Gas folw:11L/min; Gas temperature:350℃; Pressure:50Psig;Fragmentation Voltage:150;We identified32chemicals in the17min, from which we found3groups of isomers at m/z414,674,412. Finally we determined these isomers and speculated itspossible fragment way by MS/MS.We treated mice with extracts of Veratrum ig and obtained the blood. Based on theidentification above, we analyzed the chemicals in the blood with UPLC-Q-TOF/MScomparing to the chemicals of Veratrum. Eventually,11prototype steroidals wereidentified.2. Study on toxicity of Veratrum based on metabolomics and serum pharmacologyThis research studied the urine of SD rats of Veratrum group by the application of~1H NMR. To screen the potential toxic biomarkers, we collected urine samples in differenttime for analysis the changing ways of endogenous metabolites. Through the study on theurine samples collected in the rats of7days by metabolomics, we discussed the toxic characteristics and provided basis for further studying. Moreover, the paper applied serumpharmacology to the toxic study on Veratrum and illustrated the toxicity of Veratrum incell molecular level, which clarified the toxicity of Veratrum for liver and kidney.3. Preliminary research on the incompatibility mechanisms of veratrum and ginsengThe research investigated the change of chemicals after the combination of two drugsand analyzed the toxic chemicals mechanism based the study on chemical substances. Also,we combined experiments in vivo and vitro to investigate interaction laws of theconflicting combination, and we aim at providing theory basis for clinical drugs using.