Effects of Osthole on Postmenopausal Osteoporosis Using Ovariectomized Rats; Comparison to the Effects of Estradiol
Biological and Pharmaceutical Bulletin
Osthole (7-methoxy-8[3-methylpent 2-enyl]coumarin), a plant coumarin compound, is extracted from a Chinese herb Cnidium monnieri (L.) CUSS which has been used since ancient times in China as a tonic and aphrodisiac. It was reported that castrated mouse received subcutaneous injections of an alcoholic extract of Cnidium monnieri (L.) CUSS once a day for 21 d, the copulation period appeared, 1) this suggests that this alcoholic extract (including osthole) may have the estrogen-related activities.
... It has also been found that both total coumarins and osthole, extracted from Cnidium monnieri (L.) CUSS, have the positive effects on bone loss due to ovariectomy in rats, 2,3) where cancellous bone histomorphometric variables in tibiae were preserved. However, even in animal experiments, little is known about the effects of osthole on other skeletal sites or other indices of bone metabolism such as biochemical markers of bone turnover, bone mechanical testing, etc. Ovariectomy induced bone loss in rats and postmenopausal bone loss in humans share many similar characteristics, and similar skeletal response to therapy with 17bestradiol. 4,5) These similarities are strong evidence that the ovariectomized (OVX) rat bone loss model is suitable for studying the prevention and treatment of postmenopausal bone loss. Furthermore, the femoral neck of OVX rats, is a more clinically relevant sample site than other skeletal sites (i.e., proximal tibia) for preclinical testing of new therapeutic agents for the prevention and treatment of osteopenia.    The purpose of this study was to examine whether osthole has positive effects on bone loss due to OVX using the femoral neck of OVX rats; and, if so, whether osthole functions at the tissue level in a manner similar to 17b-estradiol. The purpose of this study was to examine effects of osthole on postmenopausal osteoporosis using ovariectomized (OVX) rats. All of the rats were divided into sham and OVX groups. At 2 weeks post-operation, the sham-operated rats received solvent vehicle (97% corn oil and 3% ethanol, 1.0 ml/kg, subcutaneously); the OVX rats were divided into three groups which were treated with solvent vehicle (same the sham rats, 1.0 ml/kg, subcutaneously), 17b b-estradiol (30 m mg/kg, subcutaneously) or osthole (9.0 mg/kg, orally) 5 d/week for 4 weeks, respectively. In OVX rats, the increases of body weight, spleen and thymus weight were significantly decreased and the atrophy of uterus was preserved by 17b b-estradiol treatment, but not by osthole. Treatment with either 17b b-estradiol or osthole significantly protected cancellous bone loss owing to estrogen deficiency and significantly increased the maximal load in the femoral neck of OVX rats. In addition, the increases of serum osteocalcin (OC) and urinary deoxypyridinoline (DPD) levels caused by ovariectomy were all significantly suppressed by 17b bestradiol. However, only urinary DPD was significantly reduced by osthole and no change was found in serum OC. Our results demonstrate that osthole may be just as effective as 17b b-estradiol in suppressing bone loss due to ovariectomy but osthole perhaps does not work through the estrogen pathway.