The Biological Effect Of A Reconstructed Isoflavone On The Bone Metabolism And Serum-lipid Metabolism In Ovariectomized Rat

Background and ObjectiveThe decrease of Estrogen after menopause is connected with perimenopausal syndrome and osteoporosis etc,which affected the old-age-women' quality of life.The clinical therapy with Hormone(HT) can relieve the perimenopausal syndrome and has positive therapeutic effect on osteoporosis and Alzheimer's disease(AZ).It also may improve the genitourinary tract atrophy.But the conclusion of National Institutes of Health(NIH) from their five years study increases the caring and discussion about HT.This kind of therapy may increase the risk of disease.Long term of HT may influence the incidence rate of theoplegia, cardiopathy and breast cancer.So it's necessary to find a novel selective estrogen receptor modulators(SERMs) which not only has the activity of can protect estrogen but also doesn't improve the morbility of endometrial carcinoma.Isoflavone(IS) belongs to phytoestrogen(PE) family,and it's structure and bioactivity is similar to estradiol(E₂).It's a kind of SERMs and can active and bind with estrogen receptors of mammalian animals and human.It has estrogen-like and antiestrogen-like activities.Long term of it may relieve menopause symptoms such as hot flush and sweat, prevention osteoporosis.Meanwhile,it doesn't raise the possibility of Alzheimer's disease (AZ).The ability of combination to receptor of estrogen of IS is less than E₂,while_w it's bioactivity after combination with receptor is 1/1000 of E₂.By now,it's poisonous and side effect and its dosage are not understood clearly,which limits its application.In the early of 1990 and 1998,ipriflvone(IP) and raloxifene,as a medicine to osteoporosis with similar construction to estrogen,decreased the estrogen-like activity and incidence risk of cancer.It implied that the IP's biological effect can be changed after its structure has been changed.The pharmacy department of HUA XI medical centre of Si Chuan University added different active groups such as piperazine group,methoxy group to different parts of IS parent ring and synthesized 24 structure-changed isoflavone compounds. Based on the ability of inhibition the proliferation of cancer cells and endometria,the reconstructed isoflavone(F11) appears to be most powerful one.We applied F11 to ovariectomized rat and observed its effect on the bone metabolism and serum-lipid metabolism,in order to provide theoretical proof to the exploitation of new SERMs.MethodFirstly,we constructed the ovariectomized rat successfully.F11 was injected into the abdomen and successively administrated for 10 weeks.The rats were sacrificed by femoral artery blood letting.The serum and femoral bone were collected to detect the level of total cholesterol(TC),triglyeride(TG),lipoprotein(LDL/HDL),Osteocalcin(OC),Alkaline Phosphatase(ALPase) and blood calculus;the vitodynamics and histomorphology of femoral bone were also been observed.Result and Conclusion1.F11 could increase the maximum load of femoral bone.Compared to the OVX group,F11 enhanced elastic load and flexivity intensity obviously,and cut down the elastic modulus,compressive strength,yield strength and crushing strength significantly(P＜0.05). Low and moderate dose F11 couldn't improve the bending strength of femoral bone as much as high dose F11 did,which suggested even low dose F11 could affect the mechanics performance of femoral bone and this effect is connected with the dosage.2.Compared with OVX group,F11 groups had more regular bone layers-like structure. The bone trabecula was thicker and less broken.Three dimension frame was normal.The arch-bridge-like structure of bone trabecula appeared round,orbicular-ovate or fusiform shape.The high-dose group of F11 was more closed to sham group.These suggested that F11 could decrease the loss of bone mass,improve the structure and intensity of bone trabecula and os integumentale,enhance bone stress,maintain the dynamic equilibrium between bone resorption and bone formation.3.The level of blood calculus was higher in F11 groups than that in control group,The level of ALPase and OC in F11 groups was obviously lower than that in control group, which may caused by promoted intestinal absorption.It suggested that F11 may prevent osteoporosis by promoting the activity of osteoblast and inhibiting bone resorption.4.Low dose F11 increased the TC and HDL slightly and had not much effect on LDL, increase TG level significantly.Moderate dose F11 lowered the level of TC,HDL and LDL slightly,increase TG level significantly.High dose F11 obviously lowered the level of TC, HDL and LDL,increase TG level significantly.All these meant that this effect was dose-dependent manner5.F11 improved the rate of uterus wet weight/body weight;stimulated the mature of vagina epithelium;ameliorated the vagina and uterus atrophia in ovariectomized rat.Its biological effect was a dose-dependent manner and this meant it may have the estrogen biological effect.