Discussion On The Mechanism Of Ginseng And Licorice To Reduce The Toxicity Of Aconite Based On CYP450 Enzyme

Aconite is the root of Aconitum in the Ranunculaceae family.It has the effects of rejuvenating the sun,replenishing the fire and helping the yang,and relieving the wind and cold dampness,but it is more toxic,so it needs to be combined with other drugs to reduce its toxicity.Ginseng is a kind of qi-invigorating traditional Chinese medicine in clinical application,who comes from the perennial herb of Wujiake.Licorice is the root of leguminous plants and often used as a traditional Chinese medicine prescription.In animal experiments,firstly,we used mouse LD₅₀,rat blood biochemical detection and histopathological examination to investigate the attenuated effects of ginseng and licorice on aconite.Secondly,qPCR and Western blot were used to determine whether ginseng and licorice can alleviate the toxicity of aconite by regulating the expression of CYP450.In the cell experiments,the activity and toxicity of HepG2 and H9c2 cells were first determined by MTS and LDH,and the optimal concentration and time of administration were determined.Secondly,qPCR and Western blot were used to determine whether the monomer components of ginsenoside and licorice can reduce the toxicity of aconitine by regulating the expression of CYP450 enzyme.1.The LD₅₀ of aconite was 22.862 g·kg^-1·d^-1.The LD₅₀ of aconite combined with ginseng was 31.346 g·kg^-1·d^-1,the LD₅₀ of aconite combined with licorice was 29.804g·kg^-1·d^-1,and the LD₅₀ of aconite combined with ginseng and licorice was 29.962 g·kg^-1·d^-1.2.QT-PCR and Western blot showed that the expressions of CYP1A2,CYP2C11,CYP3A1,CYP2J3 mRNA and protein were down-regulated by aconite in rat liver and heart,and the expressions of CYP4A3 and CYP4F11 mRNA and protein were up-regulated in rat heart.Meanwhile,the combination of ginseng,licorice and aconite could up-regulated the expressions of CYP1A2,CYP2C11,CYP3A1 and CYP2J3 mRNA and protein in rat liver and heart,and down-regulated the expressions of CYP4A3 and CYP4F11 mRNA and protein in rat heart.3.Aconitine could decrease the expressions of mRNA and protein of CYP1A2,CYP2C9and CYP3A4 in HepG2 cells,while the combination of ginsenoside Rb₁,glycyrrhizin and aconitine could increase the expressions of mRNA and protein of CYP1A2,CYP2C9 and CYP3A4.4.The expressions of CYP4A3 and CYP4F11 mRNA and protein were up-regulated,the expression of CYP2J3 was down-regulated by aconitine in H9c2 cells.The expressions of CYP4A3 and CYP4F11 mRNA and protein were down-regulated,and the expression of CYP2J3 was up-regulated by the combination of ginsenoside Re,isoglycyrrhizin and aconitine.Ginseng and licorice could reduce the hepatotoxicity and cardiotoxicity of aconite by regulating the expressions of CYP3A1 and CYP2J3 in rats.Ginsenoside Rb₁ and glycyrrhizin could attenuate the toxicity of aconitine by regulating the expression of CYP3A4 in HepG2cells.Ginsenoside Re and isoglycyrrhizin could attenuate the damage of aconitine by regulating the expression of CYP2J3 in H9c2 cells.The results provided a theoretical basis for the combination of drugs that regulate the toxicity of aconite in the compound.