title: Osteogenic activities of genistein derivatives were influenced by the presence of prenyl group at ring A.
abstract: Our recent report indicated that the crude extract from stem bark of Erythrina variegata L. (Leguminosae) (EV) exerted beneficial effects against osteoporosis induced by estrogen deficiency in vivo. Follow-up phytochemical study has isolated genistein-derivatives mainly in the form of prenylgenistein from this extract, including 6-prenylgenistein, 8-prenylgenistein, and 6, 8-diprenylgenistein. The present study was performed to investigate the structure-function relationship of these compounds on osteoblastic proliferation, differentiation and mineralization in UMR 106 cells. Our results showed that genistein did not stimulate cell growth while 8-prenylgenistein promoted cell growth significantly by 10 approximately 23%. In contrast, the treatment by 6-prenylgenistein for 48 h reduced UMR 106 cell proliferation when compared to cells treated with genistein. The proliferation of 6,8-diprenylgenistein-treated cells was greater than those treated by 6-prenylgenistein at all testing concentrations. For ALP activity, significant increase was found in cells treated by either 8-prenylgenistein or 6,8-diprenylgenistein for 48 h at the concentration of 10(-10) M. In mineralization study, the content of Ca and P in extracellular matrix were significantly increased in 8-prenylgenistein treated cells. The results showed that genistein derivatives isolated from EV demonstrated stimulatory effects on osteogenesis in UMR 106 cells. Based on the study of structure-activity relationship, it appears that prenylation at C-8, but not at C-6, could increase the bone-protective effect of genistein.
authors.affiliation: State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Shenzhen Research Institute of The Hong Kong Polytechnic University, Shenzhen, 518057, PRC.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Li
authors.forename: Xin-Sheng
authors.initials: XS
authors.lastname: Yao
authors.forename: Man-Sau
authors.initials: MS
authors.lastname: Wong
mesh_terms: D000469:Alkaline Phosphatase / Q000737:chemistry / Q000378:metabolism; D001846:Bone Development / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000648:ultrastructure; D002113:Calcification, Physiologic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019833:Genistein / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects; D010758:Phosphorus / Q000378:metabolism; D024301:Plant Bark / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D054876:Prenylation; D013329:Structure-Activity Relationship
chemical_list: D010758:Phosphorus; D019833:Genistein; D000469:Alkaline Phosphatase; D002118:Calcium