Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Calycosin regulates glucocorticoid-induced apoptosis via Nrf2/ARE signaling in MC3T3-E1 cells

Lifeng Fu¹, WeiLiang Wu², Jian Zhu², Shu Qiang², Jansong Chen²

¹Department of Orthopaedics, Hospital of Traditional Chinese Medicine, Keqiao District, Shaoxing, Zhejiang 312030; ²Department of Orthopaedics, Childrenâ€™s Hospital, School of Medicine, Zhejiang University, Zhejiang 310000, PR China.

For correspondence:- Jansong Chen Email: jsongchen@163.com

Accepted: 12 January 2018 Published: 28 February 2018

Citation: Fu L, Wu W, Zhu J, Qiang S, Chen J. Calycosin regulates glucocorticoid-induced apoptosis via Nrf2/ARE signaling in MC3T3-E1 cells. Trop J Pharm Res 2018; 17(2):205-212 doi: 10.4314/tjpr.v17i2.2

© 2018 The authors.
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Abstract

Purpose: To determine the anti-osteoporotic effect of calycosin (CA) and investigate the mechanism involved.

Methods: To establish a cell model of osteoporosis, MC3T3-E1 cells were treated with dexamethasone (DEX). Subsequently, the levels of accumulated reactive oxygen species (ROS) and subsequent apoptotic cell death (using flow cytometry) were determined. Relevant mRNA and protein expression levels were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunoblot respectively.

Results: CA reduced the apoptosis and accumulation of ROS in DEX-treated cells. DEX induced the expression of caspase-3/-8/-9 in the cleavage of poly ADPR09;ribose polymerase (PARP), whereas CA treatment decreased expression levels of caspase-3/-8/-9 and PARP. In addition, DEX treatment significantly suppressed the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) as well as its downstream targets, viz, heme oxygenase-1 and quinone oxidoreductase-1. Interestingly, CA treatment reversed this suppressive effect. It was also found that Nrf2 small interfering RNA effectively inhibited the protective effects of CA against DEXR09;induced ROS overproduction as well as apoptosis.

Conclusion: CA attenuates the cytotoxicity of DEX via inhibition of the generation of ROS and promotion of Nrf2 expression. These findings offer novel insights into a molecular approach to the treatment of glucocorticoid-induced osteoporosis via the application of natural compounds

Keywords: Calycosin, Osteoporosis, Nrf2, Antioxidant response elements, Apoptosis