In the present study,we aimed to investigate the interaction between atractylenolideⅡ(AT-Ⅱ)and CYP450 enzyme in human liver microsomes,and to lay a theoretical foundation for predicting the possible interaction of ...In the present study,we aimed to investigate the interaction between atractylenolideⅡ(AT-Ⅱ)and CYP450 enzyme in human liver microsomes,and to lay a theoretical foundation for predicting the possible interaction of AT-Ⅱin combination with drugs.The chemical inhibition experiment was carried out with specific inhibitors to clarify the CYP450 subtypes affecting the metabolism of AT-Ⅱ,and the mechanism,kinetics,and type of inhibition of CYP450 enzyme by AT-Ⅱwere studied by using the probe-based determination method of human liver microsome system with the related data of IC50 and Ki as evaluation indexes.The metabolism of AT-Ⅱwas affected by CYP1A2,CYP2C9 and CYP3A4 inhibitors,and the highest inhibition rates were41.35%,41.97%and 82.45%,respectively.The IC50 values of AT-Ⅱto five subtypes of P450 CYP2C9,CYP1A2,CYP2C19,CYP3A4 and CYP2D6 were 69.7,84.3,92.4,173.8 and 190.1μmol/L,respectively.The Ki values of AT-Ⅱto five subtypes of P450 CYP2C9,CYP1A2,CYP2C19,CYP3A4 and CYP2D6 were 190.6,179.1,>200,72.2 and 66.8,respectively.Among these enzymes,AT-Ⅱexhibited non-competitive inhibition on CYP1A2,showed competitive inhibition on CYP2C9 and CYP3A4,and displayed mixed AT-Ⅱinhibition on CYP2C19 and CYP2D6.CYP1A2,CYP2C9 and CYP3A4 were involved in the AT-Ⅱmetabolism,and AT-Ⅱexhibited different inhibitory mechanisms and strengths for the five subtypes of CYP450.展开更多
在Banach空间中引入了一类新的几乎渐进拟非扩张映像,人们熟知的非扩张映像类、渐进非扩张映像类以及渐进非扩张型映像类都是这种映像的特例．本文研究了用于逼近几乎渐进拟非扩张型映像的具混合误差的修改了的Ishikawa迭代序列收敛性问...在Banach空间中引入了一类新的几乎渐进拟非扩张映像,人们熟知的非扩张映像类、渐进非扩张映像类以及渐进非扩张型映像类都是这种映像的特例．本文研究了用于逼近几乎渐进拟非扩张型映像的具混合误差的修改了的Ishikawa迭代序列收敛性问题,并给出了此迭代序列收敛到不动点的充分必要条件．本文的结果推广了Chang S S等人的最新结果．展开更多
基金National Natural Science Foundation of China(Grant No.81660757)Jiangxi Provincial Academic+1 种基金Technical Leader Training Program for Major Disciplines(Grant No.20162BCB22015)The Science Foundation of Health and Family Planning Commission of Jiangxi Province(Grant No.20181140)。
文摘In the present study,we aimed to investigate the interaction between atractylenolideⅡ(AT-Ⅱ)and CYP450 enzyme in human liver microsomes,and to lay a theoretical foundation for predicting the possible interaction of AT-Ⅱin combination with drugs.The chemical inhibition experiment was carried out with specific inhibitors to clarify the CYP450 subtypes affecting the metabolism of AT-Ⅱ,and the mechanism,kinetics,and type of inhibition of CYP450 enzyme by AT-Ⅱwere studied by using the probe-based determination method of human liver microsome system with the related data of IC50 and Ki as evaluation indexes.The metabolism of AT-Ⅱwas affected by CYP1A2,CYP2C9 and CYP3A4 inhibitors,and the highest inhibition rates were41.35%,41.97%and 82.45%,respectively.The IC50 values of AT-Ⅱto five subtypes of P450 CYP2C9,CYP1A2,CYP2C19,CYP3A4 and CYP2D6 were 69.7,84.3,92.4,173.8 and 190.1μmol/L,respectively.The Ki values of AT-Ⅱto five subtypes of P450 CYP2C9,CYP1A2,CYP2C19,CYP3A4 and CYP2D6 were 190.6,179.1,>200,72.2 and 66.8,respectively.Among these enzymes,AT-Ⅱexhibited non-competitive inhibition on CYP1A2,showed competitive inhibition on CYP2C9 and CYP3A4,and displayed mixed AT-Ⅱinhibition on CYP2C19 and CYP2D6.CYP1A2,CYP2C9 and CYP3A4 were involved in the AT-Ⅱmetabolism,and AT-Ⅱexhibited different inhibitory mechanisms and strengths for the five subtypes of CYP450.
文摘在Banach空间中引入了一类新的几乎渐进拟非扩张映像,人们熟知的非扩张映像类、渐进非扩张映像类以及渐进非扩张型映像类都是这种映像的特例．本文研究了用于逼近几乎渐进拟非扩张型映像的具混合误差的修改了的Ishikawa迭代序列收敛性问题,并给出了此迭代序列收敛到不动点的充分必要条件．本文的结果推广了Chang S S等人的最新结果．
