Effects of Flavonoids in Lysimachia clethroides Duby on the Activities of Cytochrome P450 CYP2E1 and CYP3A4 in Rat Liver Microsomes.
Incubation systems were established to investigate the effects of quercetin, kaempferol, isoquercitrin and astragalin in Lysimachia clethroides Duby on the activities of CYP2E1 and CYP3A4 in rat liver microsomes in vitro. Probe substrates of 4-nitrophenol and testosterone as well as flavonoids at different concentrations were added to the incubation systems. After incubation, a validated high performance liquid chromatography (HPLC) method was applied to separate and determine the relevant metabolites. The results suggested that kaempferol exhibited a weak inhibition of CYP2E1 activity with an IC50 of 60.26 ± 2.54 μM, while quercetin and kaempferol caused a moderate inhibition of CYP3A4 activity with IC50 values of 18.77 ± 1.69 μM and 32.65 ± 1.32 μM, respectively. Isoquercitrin and astragalin had no effects on the activities of either CYP2E1 or CYP3A4. It could be speculated from these results that the inhibitory effects of quercetin and kaempferol on the activities of CYP2E1 and CYP3A4 could be the mechanisms underlying the hepatoprotective effects of L. clethroides.
Institute of Chinese Materia Medica, Henan University, Kaifeng 475004, China. 13101788597@163.com.
Zhi-Juan
ZJ
Zhang
Institute of Chinese Materia Medica, Henan University, Kaifeng 475004, China. lancerevolution@foxmail.com.
Zhao-Yang
ZY
Xia
Institute of Chinese Materia Medica, Henan University, Kaifeng 475004, China. wangjinmeiscp@126.com.|Kaifeng Key Laboratory of Functional Components in Health Food, Kaifeng 475004, China. wangjinmeiscp@126.com.
Jin-Mei
JM
Wang
Minsheng College, Henan University, Kaifeng 475004, China. 15537870395@163.com.
Xue-Ting
XT
Song
Institute of Chinese Materia Medica, Henan University, Kaifeng 475004, China. weijinfeng20112011@hotmail.com.|Kaifeng Key Laboratory of Functional Components in Health Food, Kaifeng 475004, China. weijinfeng20112011@hotmail.com.|Minsheng College, Henan University, Kaifeng 475004, China. weijinfeng20112011@hotmail.com.
Jin-Feng
JF
Wei
Institute of Chinese Materia Medica, Henan University, Kaifeng 475004, China. kangweny@hotmail.com.|Kaifeng Key Laboratory of Functional Components in Health Food, Kaifeng 475004, China. kangweny@hotmail.com.
Wen-Yi
WY
Kang
D000818:Animals; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis*; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis*; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000008:administration & dosage; D005419:Flavonoids / Q000008:administration & dosage; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D044949:Kaempferols / Q000008:administration & dosage; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D029623:Primulaceae / Q000737:chemistry; D011794:Quercetin / Q000008:administration & dosage / Q000031:analogs & derivatives; D051381:Rats
D065607:Cytochrome P-450 Enzyme Inhibitors; D005419:Flavonoids; D044949:Kaempferols; C016527:isoquercitrin; C006552:kaempferol; D011794:Quercetin; C001579:astragalin; D019392:Cytochrome P-450 CYP2E1; D051544:Cytochrome P-450 CYP3A
CYP2E1; CYP3A4; HPLC; Lysimachia clethroides Duby; flavonoids; liver microsomes