title: Synthesis, estrogenic activity, and anti-osteoporosis effects in ovariectomized rats of resveratrol oligomer derivatives.
abstract: Three series of resveratrol oligomer derivatives were synthesized, including the indenone-type, indene-type and octahydropentalene-type derivatives, among which ten derivatives were novel compounds. Compounds 2, 14f, and 4d were confirmed as ERβ agonists by yeast two-hybrid assay, and compound 2 (isopaucifloral F) was further chosen to evaluate its anti-osteoporosis activity in vivo. Compared with the sham-operated and the positive control groups, isopaucifloral F (10 μg/kg) showed a notable anti-osteoporosis effect in the ovariectomized (OVX) female rats based on a micro-CT analysis and the following measurements: bone mineral density, bone volume/tissue volume, trabecular thickness, trabecular separation/spacing, and the serum biochemical parameters. LD50 of isopaucifloral F was found to be greater than 5 mg/kg and its effective dose (ED) was found to be about 10 μg/kg. Therefore, isopaucifloral F may be a promising lead compound for the treatment of postmenopausal osteoporosis.
authors.affiliation: Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Hao
authors.affiliation: Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chang
authors.affiliation: Shanghai Public Health Clinical Center, 2901 Caolang Road, Shanghai 201508, China.
authors.forename: Bo-Yin
authors.initials: BY
authors.lastname: Qin
authors.affiliation: Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhong
authors.affiliation: Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Zhi-Bo
authors.initials: ZB
authors.lastname: Chu
authors.affiliation: School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Shanghai Public Health Clinical Center, 2901 Caolang Road, Shanghai 201508, China. Electronic address: wjzhou@shmu.edu.cn.
authors.forename: Wen-Jiang
authors.initials: WJ
authors.lastname: Zhou
authors.affiliation: Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China; Shanghai Key Laboratory of Clinical Geriatric Medicine, 221 West Yanan Road, Shanghai 200040, China. Electronic address: sunxunf@shmu.edu.cn.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D047629:Estrogen Receptor beta / Q000819:agonists*; D004967:Estrogens / Q000138:chemical synthesis / Q000494:pharmacology*; D005260:Female; D010024:Osteoporosis / Q000188:drug therapy* / Q000601:surgery; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D047629:Estrogen Receptor beta; D004967:Estrogens; D013267:Stilbenes; D000077185:Resveratrol
keywords: Bone mineral density; Estrogen receptor; Isopaucifloral F; Micro-CT; Osteoporosis