Animal Experimental Study On The Anti-osteoporosis Of Costunolide

Costunolide(CTL)is a natural sesquiterpene lactone with various biological activities,such as antioxidant,anti-inflammatory,anti-allergic,anti-cancer and antidiabetic,extracted and isolated from traditional Chinese medicine Saussurea lappa C.B.Clarke.Our research group found in the previous study that CTL has the activity of promoting the osteogenic differentiation of rat bone marrow mesenchymal stem cells,suggesting that it may have anti-osteoporosis effect.To this end,this paper carried out CTL anti-osteoporosis animal experiments.The first part is to study the effect on the bone quality of rats in the growth period.30 1-month-old SD female rats were selected and randomly divided into 3 groups: control group(Control),9 mg/kg/d CTL administration group(CTL-9)and 18 mg/kg/d CTL administration group(CTL-18),10 animals in each group.All rats were sacrificed after 8 weeks,and bone mineral density was measured,and bone microstructure analysis was performed.The second part is the anti-postmenopausal osteoporosis experiment.60 3-month-old Wistar female rats were selected and randomly divided into 5 groups: sham-operated group(Sham),ovariectomized group(OVX),ethinylestradiol group(EE),CTL-9 group and CTL-18 group,12 per group.Except for Sham,the rat models of postmenopausal osteoporosis were established by ovariectomy.The intragastric dose of the CTL-9 group was 9mg/kg/d,the CTL-18 group was 18 mg/kg/d,and the EE group was administered the intragastric dose of 200 μg/kg/d,the OVX and Sham groups were only given an equal volume of normal saline.All rats were sacrificed after 8 weeks,and the bone mineral density,biomechanical indexes,serum bone metabolism indexes in vitro were detected,and Micro-CT scanning and bone histomorphometric analysis were performed.The safety of the drug was evaluated by the changes of body weight,organ index and histopathological observation of organ slices in rats.The main experimental results are as follows:1.Both 9 mg/kg/d and 18 mg/kg/d CTL can significantly increase the bone mineral density,optimize the bone microstructure,and improve the bone quality in the growing rats;2.18 mg/kg/d CTL can prevent osteoporosis in ovariectomized rats;3.18 mg/kg/d CTL can maintain the bone mineral density and the biomechanical properties of femur and vertebra in ovariectomized rats,and avoid the degradation of bone microstructure;4.The detection results of serum bone metabolism biochemical indexes showed that CTL exerted anti-osteoporosis activity by promoting bone formation and inhibiting bone resorption;5.The results of the drug safety evaluation showed that Costunolide had no obvious toxic and side effects on the main organs of rats and might have estrogen-like activity.The above results show that: Costunolide can prevent the occurrence of osteoporosis in ovariectomized rats,and significantly improve the bone quality of rats in the growth period,which has the potential value of developing as a new antiosteoporosis drug.