title: Psoralidin, a prenylated coumestan, as a novel anti-osteoporosis candidate to enhance bone formation of osteoblasts and decrease bone resorption of osteoclasts.
abstract: Traditional Chinese medicines (TCM) have been proven to prevent osteoporosis, but their clinical applications are not widely recognized due to their complicated ingredients. Psoralidin, a prenylated coumestan, has been reported to prevent bone loss of ovariectomized rats, but detailed mechanisms are still not clear. In current study, we found that both psoralidin and coumestrol promoted osteoblast proliferation and differentiation, as evidenced by improvements in cell proliferation and alkaline phosphatase activity; increased formation of ALP colonies and calcified nodules; enhanced secretion of collagen-I, BMP-2, osteocalcin and osteopontin; and stimulation of the expression of IGF-1, β-catenin, Runx-2, Osterix, and OPG, as well as the mRNA ratio of OPG/RANKL, while significantly decreasing the expression of RANKL. In addition, both psoralidin and coumestrol inhibited osteoclast formation and osteoclastic bone resorption, as demonstrated by the lower tartrate-resistant acid phosphatase activity and smaller area, with fewer resorption pits formed. Interestingly, psoralidin showed much stronger effects than coumestrol at enhancing osteoblast proliferation/differentiation or inhibiting osteoclast differentiation and bone resorption. Moreover, we found that both psoralidin and coumestrol suppressed COX-2 and ROS production in rat osteoblastic calvarias cells, and psoralidin showed stronger effects than coumestrol. Furthermore, we detected that by blocking estrogen receptors with ICI 182.780 (an estrogen receptor antagonist), the osteoprotective effects of psoralidin and coumestrol were also blocked. Our findings demonstrated that psoralidin and coumestrol exert their bone-protective effects by enhancing bone formation of osteoblasts and inhibiting bone resorption of osteoclasts. These roles might be mediated by their antioxidant activity and transduced through estrogen receptor signaling.
authors.affiliation: Luoyang Orthopedic Hospital of Henan Province, Luoyang, Henan, China; Orthopedic Institute of Henan Province, Luoyang, Henan, China. Electronic address: zhaiyk1984@163.com.
authors.forename: Yuankun
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Luoyang Orthopedic Hospital of Henan Province, Luoyang, Henan, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Neurology Department, Nanyang City Center hospital, Nanyang, Henan, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Luoyang Orthopedic Hospital of Henan Province, Luoyang, Henan, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Cui
authors.affiliation: Orthopedic Institute of Henan Province, Luoyang, Henan, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Feng
authors.affiliation: Luoyang Orthopedic Hospital of Henan Province, Luoyang, Henan, China.
authors.forename: Xijian
authors.initials: X
authors.lastname: Kong
authors.affiliation: Molecular Endocrinology Laboratory (KMEB), Odense University Hospital, University of South Denmark, Odense C 5000, Denmark.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001862:Bone Resorption / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000150:complications / Q000188:drug therapy*; D054876:Prenylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000473:pathology
chemical_list: D001572:Benzofurans; D003374:Coumarins; D000469:Alkaline Phosphatase; C102768:psoralidin; C505898:coumestan
keywords: Coumestrol; Isopentenyl group; Osteoblasts; Osteoclasts; Psoralidin