Isoformononetin, a methoxydaidzein present in medicinal plants, reverses bone loss in osteopenic rats and exerts bone anabolic action by preventing osteoblast apoptosis - PubMed (original) (raw)
. 2013 Apr 15;20(6):470-80.
doi: 10.1016/j.phymed.2012.12.021. Epub 2013 Feb 8.
A M Tyagi, K Khan, M Dixit, S Lahiri, A Kumar, B Changkija, M P Khan, G K Nagar, D K Yadav, R Maurya, S P Singh, G K Jain, Wahajuddin, R Trivedi, N Chattopadhyay, D Singh
Affiliations
- PMID: 23395215
- DOI: 10.1016/j.phymed.2012.12.021
Isoformononetin, a methoxydaidzein present in medicinal plants, reverses bone loss in osteopenic rats and exerts bone anabolic action by preventing osteoblast apoptosis
K Srivastava et al. Phytomedicine. 2013.
Abstract
Purpose: Daidzein (Daid) has been implicated in bone health for its estrogen-'like' effects but low bioavailability, unfavorable metabolism and uterine estrogenicity impede its clinical potential. This study was aimed at assessing isoformononetin (Isoformo), a naturally occurring methoxydaidzein, for bone anabolic effect by overcoming the pitfalls associated with Daid.
Methods: Sprague-Dawley ovariectomized (OVx) rats with established osteopenia were administered Isoformo, 17β-oestradiol (E2) or human parathyroid hormone. Efficacy was evaluated by bone microarchitecture using microcomputed tomography and determination of new bone formation by fluorescent labeling of bone. Osteoblast apoptosis was measured by co-labeling of bone sections with Runx-2 and TUNEL. Biochemical markers of bone metabolism were measured by ELISA. Plasma and bone marrow levels of Isoformo and Daid were determined by LC-MS-MS. Rat bone marrow stromal cells were harvested to study osteoblastic differentiation by Isoformo and Daid. New born rat pups were injected with Isoformo and Daid to study the effect of the compounds on the expression of osteogenic genes in the calvaria by real time PCR.
Results: In osteopenic rats, Isoformo treatment restored trabecular microarchitecture, increased new bone formation, increased the serum osteogenic marker (procollagen N-terminal propeptide), decreased resorptive marker (urinary C-terminal teleopeptide of type I collagen) and diminished osteoblast apoptosis in bone. At the most effective osteogenic dose of Isoformo, plasma and bone marrow levels were comprised of ~90% Isoformo and the rest, Daid. Isoformo at the concentration reaching the bone marrow achieved out of its most effective oral dosing induced stromal cell mineralization and osteogenic gene expression in the calvaria of neonatal rats. Isoformo exhibited uterine safety.
Conclusions: Our study demonstrates that Isoformo reverses established osteopenia in adult OVx rats likely via its pro-survival effect on osteoblasts. Given its bone anabolic and anti-catabolic effects accompanied with safety at uterine level we propose its potential in the management of postmenopausal osteoporosis.
Copyright © 2013 Elsevier GmbH. All rights reserved.
Similar articles
- A novel flavonoid C-glucoside from Ulmus wallichiana preserves bone mineral density, microarchitecture and biomechanical properties in the presence of glucocorticoid by promoting osteoblast survival: a comparative study with human parathyroid hormone.
Khan MP, Mishra JS, Sharan K, Yadav M, Singh AK, Srivastava A, Kumar S, Bhaduaria S, Maurya R, Sanyal S, Chattopadhyay N. Khan MP, et al. Phytomedicine. 2013 Nov 15;20(14):1256-66. doi: 10.1016/j.phymed.2013.07.007. Epub 2013 Aug 6. Phytomedicine. 2013. PMID: 23928508 - Methoxyisoflavones formononetin and isoformononetin inhibit the differentiation of Th17 cells and B-cell lymphopoesis to promote osteogenesis in estrogen-deficient bone loss conditions.
Mansoori MN, Tyagi AM, Shukla P, Srivastava K, Dev K, Chillara R, Maurya R, Singh D. Mansoori MN, et al. Menopause. 2016 May;23(5):565-76. doi: 10.1097/GME.0000000000000646. Menopause. 2016. PMID: 27070807 - Formononetin reverses established osteopenia in adult ovariectomized rats.
Tyagi AM, Srivastava K, Singh AK, Kumar A, Changkija B, Pandey R, Lahiri S, Nagar GK, Yadav DK, Maurya R, Trivedi R, Singh D. Tyagi AM, et al. Menopause. 2012 Aug;19(8):856-63. doi: 10.1097/gme.0b013e31824f9306. Menopause. 2012. PMID: 22781783 - [Isoflavones and calcified tissues].
Sukmanskiĭ OI. Sukmanskiĭ OI. Usp Fiziol Nauk. 2002 Apr-Jun;33(2):83-94. Usp Fiziol Nauk. 2002. PMID: 12004580 Review. Russian. - A systematic review and meta-analysis of the effects of isoflavone formulations against estrogen-deficient bone resorption in peri- and postmenopausal women.
Lambert MNT, Hu LM, Jeppesen PB. Lambert MNT, et al. Am J Clin Nutr. 2017 Sep;106(3):801-811. doi: 10.3945/ajcn.116.151464. Epub 2017 Aug 2. Am J Clin Nutr. 2017. PMID: 28768649 Review.
Cited by
- Unveiling the Complexity of Red Clover (Trifolium pratense L.) Transcriptome and Transcriptional Regulation of Isoflavonoid Biosynthesis Using Integrated Long- and Short-Read RNAseq.
Shi K, Liu X, Pan X, Liu J, Gong W, Gong P, Cao M, Jia S, Wang Z. Shi K, et al. Int J Mol Sci. 2021 Nov 23;22(23):12625. doi: 10.3390/ijms222312625. Int J Mol Sci. 2021. PMID: 34884432 Free PMC article. - Preventive effects of Polygonum multiflorum on glucocorticoid-induced osteoporosis in rats.
Zhou M, Li J, Wu J, Yang Y, Zeng X, Lv X, Cui L, Yao W, Liu Y. Zhou M, et al. Exp Ther Med. 2017 Sep;14(3):2445-2460. doi: 10.3892/etm.2017.4802. Epub 2017 Jul 18. Exp Ther Med. 2017. PMID: 28962180 Free PMC article. - Cyclic Compressive Stress Regulates Apoptosis in Rat Osteoblasts: Involvement of PI3K/Akt and JNK MAPK Signaling Pathways.
Song F, Wang Y, Jiang D, Wang T, Zhang Y, Ma H, Kang Y. Song F, et al. PLoS One. 2016 Nov 2;11(11):e0165845. doi: 10.1371/journal.pone.0165845. eCollection 2016. PLoS One. 2016. PMID: 27806136 Free PMC article. - Identification of GRP78 as a molecular target of medicarpin in osteoblast cells by proteomics.
Kureel J, John AA, Raghuvanshi A, Awasthi P, Goel A, Singh D. Kureel J, et al. Mol Cell Biochem. 2016 Jul;418(1-2):71-80. doi: 10.1007/s11010-016-2734-x. Epub 2016 Jun 17. Mol Cell Biochem. 2016. PMID: 27316719 - Natural Products from Chinese Medicines with Potential Benefits to Bone Health.
Che CT, Wong MS, Lam CW. Che CT, et al. Molecules. 2016 Feb 27;21(3):239. doi: 10.3390/molecules21030239. Molecules. 2016. PMID: 26927052 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical