Advanced Oxidation Protein Products Regulate the Pharmacokinetics of Aloe-emodin,Emodin,Rhein,and Chrysophanol in Chronic Kidney Disease Rats  

作　　者：Tianrong Xun Xiaokang Wang Jingqian Zhao Zhufen Lin Haixing Feng Liqian Mo Xixiao Yang 

机构地区：[1]Department of Pharmacy,Shenzhen Hospital,Southern Medical University,Shenzhen 518100,Guangdong,China [2]Department of Pharmacy,Shenzhen Longhua District Central Hospital,Shenzhen 518100,Guangdong,China [3]Department of Pharmacy,Nanfang Hospital,Southern Medical University,Guangzhou 510515,Guangdong,China

出　　处：《Clinical Complementary Medicine and Pharmacology》2023年第3期8-18,共11页临床补充医学和药理学（英文）

基　　金：supported by Guangdong Science and Technology Program(No.2015B020211006);the Technology Project of Guangzhou City in China(No.201604020137);Shenzhen Foundation of Science and Technology(No.JCYJ20190814112205770);Research Foundation of Shenzhen Hospital of Southern Medical University(No.PY2021YM03);the Project of Traditional Chinese Medicine Bureau of Guangdong Province(No.20221273).

摘　　要：Background:As accelerators and products of the progression of chronic kidney disease(CKD),advanced oxidation protein products(AOPPs)affect the function of the liver.Huang Gan granules(HGGs)are commonly used to prevent the progression of CKD,but the pharmacokinetics of aloe-emodin,emodin,rhein,and chrysophanol in HGGs in CKD remain unknown.Objective:To investigate the influence and its molecular mechanism of AOPPs on the in vivo pharmacokinetics of aloe-emodin,emodin,rhein,and chrysophanol in HGGs.Methods:We constructed 5/6 nephrectomised(5/6 nx),adenine-induced(adenine)and AOPP-treated rat models.After oral administration of HGG,the concentrations of aloe-emodin,emodin,rhein,and chrysophanol in the plasma samples were detected by high-performance liquid chromatography(HPLC),and their pharmacokinetics were analysed with the PKSolver software.The plasma concentrations of IL-6 and TNF-αare detected by enzyme linked immunosorbent assay(ELISA).The RT-PCR was performed in the HepG2 cells to explore the effect of TNF-αand IL-6 on the mRNA expression of CYP1A2 and CYP3A4.Result:The results showed that the method was suitable for the quantification of four anthraquinones in plasma and excreta samples with satisfactory linear(R R^(2)>0.9931),precision(<9.4%)and accuracy(±10%).In 5/6 nx,adenine and AOPPs-treated rats,the concentrations of TNF-αand IL-6 were increased.In 5/6 nx and adenine rats,the pharmacokinetic parameters(t_(1/2),MRT_(0-∞)and AUC_(0-∞))of aloe-emodin,emodin,rhein,and chryso-phanol were,respectively,significantly increased and correlated with the concentration of AOPPs.In AOPPs-treated rats,the concentration of AOPPs was significantly increased and the pharmacokinetic parameters of four anthraquinones were also increased.Conclusion:In summary,inflammatory cytokine production may be one of the important causes in AOPPs’regulat-ing the pharmacokinetic of aloe-emodin,emodin,rhein,and chrysophanol in the CKD rats.Studies of aloe-emodin,emodin,rhein,and chrysophanol in CKD facilitate the appropriate p

关 键 词：Advanced oxidation protein products(AOPPs) Chronic kidney disease(CKD) Huang Gan granules(HGGs) ALOE-EMODIN EMODIN RHEIN CHRYSOPHANOL 

分 类 号：R285[医药卫生—中药学]