Premium
Methoxylated isoflavones, cajanin and isoformononetin, have non‐estrogenic bone forming effect via differential mitogen activated protein kinase (MAPK) signaling
Author(s) -
Bhargavan Biju,
Gautam Abnish Kumar,
Singh Divya,
Kumar Amit,
Chaurasia Sumit,
Tyagi Abdul Malik,
Yadav Dinesh Kumar,
Mishra Jay Sharan,
Singh Amar Bahadur,
Sanyal Sabyasachi,
Goel Atul,
Maurya Rakesh,
Chattopadhyay Naibedya
Publication year - 2009
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22264
Subject(s) - genistein , osteoblast , mapk/erk pathway , chemistry , endocrinology , protein kinase b , medicine , daidzein , bone mineral , protein kinase a , isoflavones , apposition , kinase , signal transduction , osteoporosis , biochemistry , in vitro
Following a lead obtained from stem‐bark extract of Butea monosperma , two structurally related methoxyisoflavones; cajanin and isoformononetin were studied for their effects in osteoblasts. Cajanin had strong mitogenic as well as differentiation‐promoting effects on osteoblasts that involved subsequent activation of MEK‐Erk and Akt pathways. On the other hand, isoformononetin exhibited potent anti‐apoptotic effect in addition to promoting osteoblast differentiation that involved parallel activation of MEK‐Erk and Akt pathways. Unlike genistein or daidzein, none of these two compounds appear to act via estrogen receptors in osteoblast. Once daily oral (by gavage) treatment for 30 consecutive days was given to recently weaned female Sprague–Dawley rats with each of these compounds at 10.0 mg kg −1 day −1 dose. Cajanin increased bone mineral density (BMD) at all skeletal sites studied, bone biomechanical strength, mineral apposition rate (MAR) and bone formation rate (BFR), compared with control. BMD levels at various anatomic positions were also increased with isoformononetin compared with control however, its effect was less potent than cajanin. Isoformononetin had no effect on the parameters of bone biomechanical strength although it enhanced MAR and BFR compared with control. Isoformononetin had very mild uterotrophic effect, whereas cajanin was devoid of any such effect. Our data suggest that cajanin is more potent than isoformononetin in accelerating peak bone mass achievement. To the best of our knowledge, this work represents the first attempt to elucidate structure‐activity relationship between the two methoxylated isoflavones regarding their effects in osteoblasts and bone formation. J. Cell. Biochem. 108: 388–399, 2009. © 2009 Wiley‐Liss, Inc.