Ginkgetin attenuates the osteoarthritis progression by inhibiting the tumor necrosis factor α from chondrocytes

WANG Yun; ZHOU Ying; YANG Lan

doi:10.14188/j.1671-8852.2023.0468

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Ginkgetin attenuates the osteoarthritis progression by inhibiting the tumor necrosis factor α from chondrocytes

更新时间：2026-11-05

- Ginkgetin attenuates the osteoarthritis progression by inhibiting the tumor necrosis factor α from chondrocytes
- Medical Journal of Wuhan University Vol. 46, Issue 3, Pages: 302-306(2025)
- 作者机构：
  
  1.武汉市第四医院中医科湖北武汉 430022
  1.武汉大学中南医院，医保部，湖北武汉 430071
  2.武汉大学中南医院，医务处，湖北武汉 430071
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2023.0468
  CLC： R961.1
- Received：29 August 2023，
  
  Published：25 March 2025
- 稿件说明：
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王芸,周颖,杨岚.银杏双黄酮通过抑制软骨细胞肿瘤坏死因子α改善膝骨关节炎表型的研究[J].武汉大学学报（医学版）,2025,46(03):302-306.

WANG Yun,ZHOU Ying,YANG Lan.Ginkgetin attenuates the osteoarthritis progression by inhibiting the tumor necrosis factor α from chondrocytes[J].Medical Journal of Wuhan University,2025,46(03):302-306.
王芸,周颖,杨岚.银杏双黄酮通过抑制软骨细胞肿瘤坏死因子α改善膝骨关节炎表型的研究[J].武汉大学学报（医学版）,2025,46(03):302-306. DOI： 10.14188/j.1671-8852.2023.0468.

WANG Yun,ZHOU Ying,YANG Lan.Ginkgetin attenuates the osteoarthritis progression by inhibiting the tumor necrosis factor α from chondrocytes[J].Medical Journal of Wuhan University,2025,46(03):302-306. DOI： 10.14188/j.1671-8852.2023.0468.

摘要

目的

探索银杏双黄酮是否具有抗骨关节炎（OA）功效并探讨其机制。

方法

利用前交叉韧带切断建立大鼠膝关节骨关节炎模型，关节腔注射银杏双黄酮，观察大鼠膝关节软骨退变表型；利用重组白细胞介素1β（IL⁃1β）构建体外退变软骨模型，予以50 μmol·L

-1

银杏双黄酮处理，检测软骨退变指标。

结果

在体研究发现，银杏双黄酮关节腔注射可显著改善大鼠膝关节OA表型，降低关节软骨肿瘤坏死因子α（TNF⁃α）蛋白表达水平及关节液TNF⁃α浓度；体外研究发现，银杏双黄酮可显著降低IL⁃1β诱导的原代软骨细胞TNF

⁃

α mRNA及蛋白表达水平，并降低培养基TNF⁃α浓度；另外，银杏双黄酮可上调软骨细胞2型胶原（Col2a1)、蛋白多糖（Acan）mRNA水平，抑制基质金属蛋白酶13（MMP⁃13）、聚蛋白多糖酶5（Adamts⁃5）mRNA水平，并通过上调凋亡抑制基因B淋巴细胞瘤⁃2基因（Bcl⁃2）mRNA表达水平、抑制凋亡诱导基因硫胱胺酸蛋白酶3（Caspase 3）mRNA水平起到抗凋亡的作用。

结论

银杏双黄酮可能通过抑制软骨细胞TNF⁃α、促进软骨基质合成、抑制软骨基质降解及软骨细胞凋亡，进而起到抗OA的作用。

Abstract

Objective

To study the possible effect and mechanism of Ginkgetin in osteoarthritis (OA) treatment.

Methods

Rat knee OA models were developed by cutting the anterior cruciate ligament

and then the degeneration of the cartilage was observed after 4 times of intra⁃articular Ginkgetin (50 μL of 100 μg·mL

-1

) injection in the knee. Also

chondrocytes were treated with 50 μmol·L

-1

Ginkgetin after induced by 10 ng·mL

-1

IL⁃1β for 24 h

in vitro

and the degenerative features of the chondrocytes was detected.

Results

Intra⁃articular Ginkgetin injection could partially rescue the cartilage from degeneration during OA progression

in vivo

by down⁃regulating the protein expression of tumor necrosis factor α (TNF⁃α) in the cartilage and the level of TNF⁃α in the synovial fluid. Also

Ginkgetin attenuated the stimulated gene expression of TNF⁃α by interleukin 1β in the primary chondrocyte

in vitro

as well as down⁃regulating the concentration of TNF⁃α in the culture supernatant. Further

we found that Ginkgetin also up⁃regulated the stimulated gene expression of collagen type 2a1 (Col2a1)

aggrecan (Acan) and B⁃cell lymphoma 2 (Bcl⁃2)

and down⁃regulated the gene expression of matrix metalloproteinase 13 (MMP⁃13)

Adamts⁃5 (a disintegrin and metalloproteinase with thrombospondin motif 5)

and Caspase 3

Conclusion

Ginkgetin might be a potential anti⁃OA agent

which promotes the biosynthesis and inhibits the degeneration of cartilage matrix

and inhibits the apoptosis of chondrocyte during OA progression.

关键词

Keywords

references

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HO L J , HUNG L F , LIU F C , et al . Ginkgo biloba extract individually inhibits JNK activation and induces c⁃Jun degradation in human chondrocytes: Potential therapeutics for osteoarthritis [J ] . PLoS One , 2013 , 8 ( 12 ): e82033 .

ZHANG L , LIU J , GENG T . Ginkgetin aglycone attenuates the apoptosis and inflammation response through nuclear factor⁃κB signaling pathway in ischemic⁃reperfusion injury [J ] . J Cell Biochem , 2019 , 120 ( 5 ): 8078 ⁃ 8085 .

XU B , HE X , SUI Y , et al . Ginkgetin aglycone attenuates neuroinflammation and neuronal injury in the rats with ischemic stroke by modulating STAT3/JAK2/SIRT1 [J ] . Folia Neuropathol , 2019 , 57 ( 1 ): 16 ⁃ 23 .

KAPOOR M , MARTEL⁃PELLETIER J , LAJEUNESSE D , et al . Role of proinflammatory cytokines in the pathophysiology of osteoarthritis [J ] . Nat Rev Rheumatol , 2011 , 7 ( 1 ): 33 ⁃ 42 .

GÜLER⁃YÜKSEL M , ALLAART C F , WATT I , et al . Treatment with TNF⁃α inhibitor infliximab might reduce hand osteoarthritis in patients with rheumatoid arthritis [J ] . Osteoarthritis Cartilage , 2010 , 18 ( 10 ): 1256 ⁃ 1262 .

MAKSYMOWYCH W P , RUSSELL A S , CHIU P , et al . Targeting tumour necrosis factor alleviates signs and symptoms of inflammatory osteoarthritis of the knee [J ] . Arthritis Res Ther , 2012 , 14 ( 5 ): R206 .

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