Medicarpin, a Legume Phytoalexin, Stimulates Osteoblast Differentiation and Promotes Peak Bone Mass Achievement in Rats: Evidence for Estrogen Receptor -mediated Osteogenic Action of Medicarpin
 
   

Medicarpin, a Legume Phytoalexin,
Stimulates Osteoblast Differentiation
and Promotes Peak Bone Mass Achievement
in Rats: Evidence for Estrogen Receptor
-mediated Osteogenic Action of Medicarpin

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:
   Frankp@chiro.org
 
   

FROM:   J Nutr Biochem. 2012 (Jan);   23 (1):   2738   [Epub 2-16-2011]

Bhargavan B, Singh D, Gautam AK, Mishra JS, Kumar A, Goel A, Dixit M, Pandey R, Manickavasagam L, Dwivedi SD, Chakravarti B, Jain GK, Ramachandran R, Maurya R, Trivedi A, Chattopadhyay N, Sanyal S.

Division of Endocrinology,
Central Drug Research Institute
(Council of Scientific and Industrial Research),
Chattar Manzil,
P.O. Box 173,
Lucknow, India.


Dietary isoflavones including genistein and daidzein have been shown to have favorable bone conserving effects during estrogen deficiency in experimental animals and humans. We have evaluated osteogenic effect of medicarpin (Med); a phytoalexin that is structurally related to isoflavones and is found in dietary legumes. Med stimulated osteoblast differentiation and mineralization at as low as 10(-10) M. Studies with signal transduction inhibitors demonstrated involvement of a p38 mitogen activated protein kinase-ER-bone morphogenic protein-2 pathway in mediating Med action in osteoblasts. Co-activator interaction studies demonstrated that Med acted as an estrogen receptor (ER) agonist; however, in contrast to 17-estradiol, Med had no uterine estrogenicity and blocked proliferation of MCF-7 cells. Med increased protein levels of ER in osteoblasts. Selective knockdown of ERa and ER in osteoblasts established that osteogenic action of Med is ER-dependent. Female Sprague-Dawley (weaning) rats were administered Med at 1.0- and 10.0 mg.kg(-1) doses by gavage for 30 days along with vehicle control. Med treatment resulted in increased formation of osteoporgenitor cells in the bone marrow and osteoid formation (mineralization surface, mineral apposition/bone formation rates) compared with vehicle group. In addition, Med increased cortical thickness and bone biomechanical strength. In pharmacokinetic studies, Med exhibited oral bioavailability of 22.34% and did not produce equol. Together, our results demonstrate Med stimulates osteoblast differentiation likely via ER, promotes achievement of peak bone mass, and is devoid of uterine estrogenicity. In addition, given its excellent oral bioavailability, Med can be potential osteogenic agent.


Return to the ALFALFA Page

Since 7-06-2011

         © 19952017 ~ The Chiropractic Resource Organization ~ All Rights Reserved