Wogonin mitigates intervertebral disc degeneration through the Nrf2/ARE and MAPK signaling pathways

被引：59

作者：

Fang, Weijing ^{[1
,2
]}

Zhou, Xiaopeng ^{[1
,2
]}

Wang, Jingkai ^{[1
,2
]}

Xu, Langhai ^{[1
,2
]}

Zhou, Lijuan ^{[3
]}

Yu, Wei ^{[1
,2
]}

Tao, Yiqing ^{[1
,2
]}

Zhu, Jian ^{[1
,2
]}

Hu, Bin ^{[1
,2
]}

Liang, Chengzhen ^{[1
,2
]}

Li, Fangcai ^{[1
,2
]}

Hua, Jianming ^{[4
]}

Chen, Qixin ^{[1
,2
]}

机构：

[1] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Orthoped Surg, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China

[2] Zhejiang Univ, Orthoped Res Inst, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China

[3] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Dermatol, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China

[4] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Radiol, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China

来源：

INTERNATIONAL IMMUNOPHARMACOLOGY | 2018年 / 65卷

基金：

中国国家自然科学基金;

关键词：

Wogonin; Intervertebral disc degeneration; Anti-inflammatory effect; Nrf2/ARE; MARK; NUCLEUS PULPOSUS CELLS; NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; NEEDLE PUNCTURE; MOUSE MODEL; IN-VITRO; INFLAMMATION; ACTIVATION; EXPRESSION; INHIBITION;

D O I：

10.1016/j.intimp.2018.10.024

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Intervertebral disc degeneration (IVDD) is a prevalent disease characterized by the progressive loss of the extracellular matrix in the local nucleus pulposus region. Metalloproteinases and pro-inflammatory cytokines play an important role in this process. Thus, anti-inflammatory strategies are an important component of IVDD treatment. Wogonin, a naturally existing monoflavonoid, has been reported to have potential anti-inflammatory effects in some inflammatory diseases. Hence, in our present study we investigated the protective effects and potential mechanisms of wogonin in rat nucleus pulposus cells that had been treated with interleuldn-lbeta (IL-1 beta) to induce severe IVDD. An in vivo rat caudal vertebrae needle-stab model was also designed and its validity was evaluated as an IVDD model. The results demonstrated that wogonin suppressed IL-1 beta-induced inflammatory mediators (iNOS, IL-6 and COX2) and matrix-degrading proteinases (MMP1, MMP3, MMP13 and ADAMTS4). Wogonin also upregulated some of the key components of the extracellular matrix, such as collagen II. Furthermore, we discovered that wogonin exerted anti-inflammatory effects by activating the Nrf2/HO-1-SOD2-NQO1-GCLC signaling axis. Moreover, the IL-1 beta-induced stimulation of the MAPK signaling pathway was reversed by wogonin treatment. The in vivo MRI and histological results also revealed that wogonin protected the nucleus pulposus from the progression of IVDD. Therefore, wogonin may be a potential agent for the treatment of IVDD.

引用

页码：539 / 549

页数：11

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