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. 2024 Jan;38(1):156-173.
doi: 10.1002/ptr.8031. Epub 2023 Oct 17.

Taxifolin-mediated Nrf2 activation ameliorates oxidative stress and apoptosis for the treatment of glucocorticoid-induced osteonecrosis of the femoral head

Hongyi Jiang  1   2   3 , Chihao Lin  1   2   3 , Tingwen Cai  1   2   3 , Liting Jiang  1   2   3 , Chao Lou  1   2   3 , Shida Lin  1   2   3 , Weidan Wang  1   2   3 , Zijian Yan  1   2   3 , Xiaoyun Pan  1 , Xinghe Xue  1
Affiliations

Taxifolin-mediated Nrf2 activation ameliorates oxidative stress and apoptosis for the treatment of glucocorticoid-induced osteonecrosis of the femoral head

Hongyi Jiang et al. Phytother Res. 2024 Jan.

Abstract

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is the main complication secondary to long-term or excessive use of glucocorticoids (GCs). Taxifolin (TAX) is a natural antioxidant with various pharmacological effects, such as antioxidative stress and antiapoptotic properties. The purpose of this study was to explore whether TAX could regulate oxidative stress and apoptosis in GIONFH by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. We conducted qRT-PCR, Western blotting, TUNEL assays, flow cytometry, and other experiments in vitro. Microcomputed tomography analysis, hematoxylin-eosin staining, and immunohistochemical staining were performed to determine the therapeutic effect of TAX in vivo. TAX mitigated the overexpression of ROS and NOX gene expression induced by DEX, effectively reducing oxidative stress. Additionally, TAX could alleviate DEX-induced osteoblast apoptosis, as evidenced by qRT-PCR, Western blotting, and other experimental techniques. Our in vivo studies further demonstrated that TAX mitigates the progression of GIONFH in rats by combating oxidative stress and apoptosis. Mechanistic exploration revealed that TAX thwarts the progression of GIONFH through the activation of the Nrf2 pathway. Overall, our research herein reports that TAX-mediated Nrf2 activation ameliorates oxidative stress and apoptosis for the treatment of GIONFH.

Keywords: Nrf2 pathway; apoptosis; glucocorticoid-induced osteonecrosis of the femoral head (GIONFH); oxidative stress; taxifolin.

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References

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