Medicarpin, a legume phytoalexin, stimulates osteoblast differentiation and promotes peak bone mass achievement in rats

Evidence for estrogen receptor β-mediated osteogenic action of medicarpin

Biju Bhargavan, Divya Singh, Abnish K. Gautam, Jay Sharan Mishra, Amit Kumar, Atul Goel, Manish Dixit, Rashmi Pandey, Lakshmi Manickavasagam, Shailendra D. Dwivedi, Bandana Chakravarti, Girish K. Jain, Ravishankar Ramachandran, Rakesh Maurya, Arun Trivedi, Naibedya Chattopadhyay, Sabyasachi Sanyal

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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 17β-estradiol, Med had no uterine estrogenicity and blocked proliferation of MCF-7 cells. Med increased protein levels of ERβ in osteoblasts. Selective knockdown of ERα and ERβ in osteoblasts established that osteogenic action of Med is ERβ-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 ERβ, 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.

Original languageEnglish (US)
Pages (from-to)27-38
Number of pages12
JournalJournal of Nutritional Biochemistry
Volume23
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

Fingerprint

Osteoblasts
Fabaceae
Estrogen Receptors
Rats
Bone
Bone and Bones
Isoflavones
medicarpin
phytoalexins
Biological Availability
Estrogens
Equol
Signal transduction
Pharmacokinetics
Genistein
MCF-7 Cells
p38 Mitogen-Activated Protein Kinases
Weaning
Osteogenesis
Bone Marrow Cells

Keywords

  • Bone anabolic
  • Bone microarchitecture
  • Bone morphogenetic protein
  • Bone strength
  • Oral pharmacokinetics
  • Selective estrogen receptor modulator
  • Uterine estrogenicity

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Medicarpin, a legume phytoalexin, stimulates osteoblast differentiation and promotes peak bone mass achievement in rats : Evidence for estrogen receptor β-mediated osteogenic action of medicarpin. / Bhargavan, Biju; Singh, Divya; Gautam, Abnish K.; Mishra, Jay Sharan; Kumar, Amit; Goel, Atul; Dixit, Manish; Pandey, Rashmi; Manickavasagam, Lakshmi; Dwivedi, Shailendra D.; Chakravarti, Bandana; Jain, Girish K.; Ramachandran, Ravishankar; Maurya, Rakesh; Trivedi, Arun; Chattopadhyay, Naibedya; Sanyal, Sabyasachi.

In: Journal of Nutritional Biochemistry, Vol. 23, No. 1, 01.2012, p. 27-38.

Research output: Contribution to journalArticle

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 2012, 'Medicarpin, a legume phytoalexin, stimulates osteoblast differentiation and promotes peak bone mass achievement in rats: Evidence for estrogen receptor β-mediated osteogenic action of medicarpin', Journal of Nutritional Biochemistry, vol. 23, no. 1, pp. 27-38. https://doi.org/10.1016/j.jnutbio.2010.11.002
Bhargavan, Biju ; Singh, Divya ; Gautam, Abnish K. ; Mishra, Jay Sharan ; Kumar, Amit ; Goel, Atul ; Dixit, Manish ; Pandey, Rashmi ; Manickavasagam, Lakshmi ; Dwivedi, Shailendra D. ; Chakravarti, Bandana ; Jain, Girish K. ; Ramachandran, Ravishankar ; Maurya, Rakesh ; Trivedi, Arun ; Chattopadhyay, Naibedya ; Sanyal, Sabyasachi. / Medicarpin, a legume phytoalexin, stimulates osteoblast differentiation and promotes peak bone mass achievement in rats : Evidence for estrogen receptor β-mediated osteogenic action of medicarpin. In: Journal of Nutritional Biochemistry. 2012 ; Vol. 23, No. 1. pp. 27-38.
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AU - Gautam, Abnish K.

AU - Mishra, Jay Sharan

AU - Kumar, Amit

AU - Goel, Atul

AU - Dixit, Manish

AU - Pandey, Rashmi

AU - Manickavasagam, Lakshmi

AU - Dwivedi, Shailendra D.

AU - Chakravarti, Bandana

AU - Jain, Girish K.

AU - Ramachandran, Ravishankar

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