%0 Journal Article %J Journal of Cellular Physiology %D 2019 %T Estrogen receptor activation in response to Azadirachtin A stimulates osteoblast differentiation and bone formation in mice %A Kushwaha, Priyanka %A Ahmad, Naseer %A Dhar, V. Yogeshwar %A Verma, Ashwni %A Haldar, Saikat %A Mulani, Fayaj A. %A Trivedi, Prabodh K. %A Mishra, Prabhat R. %A Thulasiram, V. Hirekodathakallu %A Trivedi, Ritu %K ALP %K Gene expression %K micro-CT %K mineralization %K osteoblast cells %X

The positive effectsof the sex hormone in sustaining bone homeostasis areexercised by maintaining the equilibrium betweencell activity and apoptosis. In this regard, the importance of estrogen receptors in maintaining the bone is that it is anattractive drug target,if devoid of known side effects. In this study, we show that a natural pure compound Azadirachtin A (Aza A) isolated from Azadirachta indica binds selectively to a site in the estrogen receptor, identifying itself to bea selective tissue modifier. Using computational and medicinal chemistry, we show that Aza A binds potentially and selectively to estrogen receptor-alpha (ER alpha) as compared with ER beta. This preferential binding of Aza A to ER alpha with good pharmacokinetic distribution in the body forms metabolites, showing that it is well absorbed. In in vivo estrogen deficiency models for osteoporosis, Aza A at a much lower dose enhances new bone formation at both sites of the trabecular and cortical bone with increased bone strength and presentswith no hyperplastic effect in the uterus.

%B Journal of Cellular Physiology %V 234 %P 23719-23735 %8 DEC %G eng %N 12 %9 Article %3

Foreign

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3.923

%R 10.1002/jcp.28940