Methoxylated isoflavones, cajanin and isoformononetin, have non-estrogenic bone forming effect via differential mitogen activated protein kinase (MAPK) signaling

Biju Bhargavan, Abnish Kumar Gautam, Divya Singh, Amit Kumar, Sumit Chaurasia, Abdul Malik Tyagi, Dinesh Kumar Yadav, Jay Sharan Mishra, Amar Bahadur Singh, Sabyasachi Sanyal, Atul Goel, Rakesh Maurya, Naibedya Chattopadhyay

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

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 antiapoptotic 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.

Original languageEnglish (US)
Pages (from-to)388-399
Number of pages12
JournalJournal of Cellular Biochemistry
Volume108
Issue number2
DOIs
StatePublished - Oct 1 2009
Externally publishedYes

Fingerprint

Isoflavones
Mitogen-Activated Protein Kinases
Osteoblasts
Bone
Bone and Bones
Osteogenesis
Minerals
Mitogen-Activated Protein Kinase Kinases
Bone Density
Butea
Genistein
Structure-Activity Relationship
Estrogen Receptors
Chemical activation
Sprague Dawley Rats
Rats

Keywords

  • Apoptosis
  • Cajanin
  • Isoformononetin
  • MAPK signaling
  • Osteogenic
  • Peak bone mass

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Methoxylated isoflavones, cajanin and isoformononetin, have non-estrogenic bone forming effect via differential mitogen activated protein kinase (MAPK) signaling. / 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.

In: Journal of Cellular Biochemistry, Vol. 108, No. 2, 01.10.2009, p. 388-399.

Research output: Contribution to journalArticle

Bhargavan, B, Gautam, AK, Singh, D, Kumar, A, Chaurasia, S, Tyagi, AM, Yadav, DK, Mishra, JS, Singh, AB, Sanyal, S, Goel, A, Maurya, R & Chattopadhyay, N 2009, 'Methoxylated isoflavones, cajanin and isoformononetin, have non-estrogenic bone forming effect via differential mitogen activated protein kinase (MAPK) signaling', Journal of Cellular Biochemistry, vol. 108, no. 2, pp. 388-399. https://doi.org/10.1002/jcb.22264
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. / Methoxylated isoflavones, cajanin and isoformononetin, have non-estrogenic bone forming effect via differential mitogen activated protein kinase (MAPK) signaling. In: Journal of Cellular Biochemistry. 2009 ; Vol. 108, No. 2. pp. 388-399.
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AU - Tyagi, Abdul Malik

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