Effect Of Different Doses Of Daidzein On Serum Lipids And Liver LDLR Expression In Ovariectomized Rats And Its Relation With ERs

Background.Phytoestrogen is widely used for the health of perimenopausal women.There are more and more studies about it.Isoflavone,as one of phytoestrogens,is reported of effects on serum lipids.And Daidzein,as an important ingredient of isoflavone,its effects on serum lipids and liver LDLR expression and the role of estrogen receptors in this process need to be researched.Partâ… Effects of Different Doses of Daidzein on Serum Lipids and Liver ERs and LDLR mRNA Expression in Ovariectomized RatsObjectiveTo investigate the effects of different doses of daidzein on serum lipids and liver ERs,LDLR mRNA expression in ovariectomized rats.Materials and methodSixty-six four-month-old female Sprague-Dawley(SD) rats were randomly allotted to one of the following groups:ovariectomized group,sham-ovariectomized group,E₂ group,low-dose daidzein group,medium-dose group and high-dose daidzein group. The OVX operation is believed success when there are no Keratinocytes in vaginal smear in the next five days from the 7^th day after operation.Then Sham group and control OVX were administrated with distilled water,whereas other groups received valerate estradiol(800μg/kg·d) and different doses of daidzein(10,50,200 mg/kg·d) by gavage respectively for three months.These parameters were measured after the sacrifice of rats.Serum lipids including TG,LDL-c and HDL-c were measured.The expressions of mRNA of ERα,ERβand LDLR in the liver were measured by realtime-RT-PCR.Results1,Serum LDL-c:LDL-c in OVX group is higher than Sham group,compared to OVX group,the LDL-c in E group,M-Dai group,and H-Dai group are lower,the LDL-c in daidzein are decreased with the increase in the dose of daidzein,and thers are significant difference between the groups.2,Serum TG:the TG in E₂ group is higher compared with Sham group and OVX group,while the TG in H-Dai group is lower than Sham group and OVX group, and the TG in H-Dai group is significantly lower than M-Dai group and L-Dai group.3,Serum HDL-c:the HDL-c in OVX group are lower than Sham group and E₂ group, there is no significant difference between Sham group and E₂ group,TG in daidzein groups are lower than Sham group,although there are no significant difference when compared with OVX group.4,The levels of ERαand ERβmRNA:ERαmRNA in OVX group is decreased compared with Sham group and E₂ group,the level is increased in M-Dai group and H-Dai group than OVX group,the level in daidzein groups are increased with the increase of daidzein doses,and there are significant difference between the daidzein groups.5,The level of LDLR mRNA:LDLR mRNA in OVX group is decreased compared with Sham group and E₂ group,the level is increased in M-Dai group and H-Dai group than OVX group,the level in daidzein groups are increased with the increase of daidzein doses,and there are significant difference between the daidzein groups.Conclusions1,Daidzein exerts some befinical effects on serum lipids in ovariectomized rats,and the effect of daidzen on LDL-c is dose dependent,it is more powerful with the dose increased.2,ERβmRNA expresion is not detected in all the six groups.Daidzein increases ERαand LDLR mRNA expression in the liver of ovariectomized rats3,Daidzein's effect on serum LDL-c is in accordance with its effects on liver ERαand LDLR mRNA expression,that is,the effects are more significant when the dose increased,so we speculate that the LDL-c-lowering effect of daidzein may be realized by increasing liver LDLR expression through the ERαpathway. Partâ…¡Effect of Daidzein on LDLR mRNA Expression in HepG2 cell and its relation with ERsObjictiveTo investigate effects of daidzein on LDLR expression in HepG2 cells and the role of ERs in the regulation of LDLR expression.Materials and methodsIn order to determine the concentition of daidzein,we analysed the proliferation of HepG2 cells by MTT,then calculated IC50.We treat HepG2 cells with different concentitions within(IC5010^-9 M,10^-7 M and10^-5 M),and measure LDLR protein expression by western-blot.Then we block ERs with ICI182780 and block ERαwith MPP,and again measure LDLR protein expression by western-blot.Results1,Compared with the control group,ERαand LDLR protein expression were higher in10^-7M daidzein group and 10^-5M daidzein group than the control group and 10^-9 M daidzein group.ERαand LDLR protein expression in 10^-5M daidzein group were higher than10^-7 M daidzein group.2,Compared with 10^-5M daidzein group,LDLR protein expression decreased after ERs or ERαwere blocked,but there were no difference between the two blocking groups.Conclusions1,Dadizein increases LDLR protein expression in HepG2 cells,and it is concentition dependent.2,Daidzein increases LDLR protein expression through ERα. Summary1,Daidzein exerts some befinicial effects on serum lipids in ovariectomized rats.2,Daidzein increases LDLR protein expression through ERα.