Effects of galangin on autophagy and apoptosis of chondrocytes in knee osteoarthritis rats

YANG Qing; HUANG Wei; LIU Qingyi; ZHOU Zhongyu

doi:10.6039/j.issn.1001-0408.2025.03.09

您当前的位置：

首页 >

文章列表页 >

Effects of galangin on autophagy and apoptosis of chondrocytes in knee osteoarthritis rats

更新时间：2025-09-26

- Effects of galangin on autophagy and apoptosis of chondrocytes in knee osteoarthritis rats
- ZHONGGUO YAOFANG Vol. 36, Issue 3, Pages: 312-317(2025)
- 作者机构：
  
  1.湖北省妇幼保健院康复理疗科，武汉　430070
  2.湖北省中医院针灸科，武汉　430070
  3.武汉市青山区冶金街社区卫生服务中心中医科，武汉　430070
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2025.03.09
  CLC： R965;R285.5
- Received：05 August 2024，
  
  Revised：2024-12-30，
  
  Accepted：30 December 2024，
  
  Published：15 February 2025
- 稿件说明：
移动端阅览
杨青,黄伟,刘清毅,等.高良姜素对膝关节炎大鼠软骨细胞自噬和凋亡的影响[J].中国药房,2025,36(03):312-317.

YANG Qing,HUANG Wei,LIU Qingyi,et al.Effects of galangin on autophagy and apoptosis of chondrocytes in knee osteoarthritis rats[J].ZHONGGUO YAOFANG,2025,36(03):312-317.
杨青,黄伟,刘清毅,等.高良姜素对膝关节炎大鼠软骨细胞自噬和凋亡的影响[J].中国药房,2025,36(03):312-317. DOI： 10.6039/j.issn.1001-0408.2025.03.09.

YANG Qing,HUANG Wei,LIU Qingyi,et al.Effects of galangin on autophagy and apoptosis of chondrocytes in knee osteoarthritis rats[J].ZHONGGUO YAOFANG,2025,36(03):312-317. DOI： 10.6039/j.issn.1001-0408.2025.03.09.

摘要

目的

探讨高良姜素（GLA）调节腺苷一磷酸活化的蛋白质激酶（AMPK）/哺乳动物雷帕霉素靶蛋白（mTOR）/UNC-51样激酶1（ULK1）信号通路对膝关节炎（KOA）大鼠软骨细胞自噬和凋亡的影响。

方法

构建KOA大鼠模型，将其分为模型组，GLA低、中、高剂量组（皮下注射100、200、400 μg/kg的GLA），GLA+Compound C组（皮下注射400 μg/kg的GLA+0.2 mg/kg的AMPK抑制剂Compound C），每组10只；另选取10只正常饲养的大鼠作为假手术组。末次给药后，检测大鼠膝关节肿胀程度，观察大鼠膝关节软骨组织病理学；检测大鼠血清中基质金属蛋白酶13（MMP-13）、白细胞介素1β（IL-1β）水平；观察大鼠骨细胞自噬情况；检测大鼠软骨细胞凋亡情况；检测大鼠膝关节软骨组织中AMPK/mTOR/ULK1信号通路相关蛋白磷酸化水平。

结果

与假手术组相比，模型组大鼠关节软骨细胞排列紊乱，细胞核固缩，关节软骨层纤维化严重，且伴有大量炎症细胞浸润；膝关节肿胀程度，软骨细胞自噬空泡数、凋亡率，血清中MMP-13、IL-1β水平，膝关节软骨组织中mTOR蛋白的磷酸化水平均显著升高（

＜0.05）；膝关节软骨组织中AMPK、ULK1蛋白的磷酸化水平均显著降低（

＜0.05）。与模型组相比，GLA低、中、高剂量组大鼠膝关节软骨损伤明显改

善，炎症细胞浸润减轻，上述定量指标除自噬空泡数进一步升高外均显著逆转，且具有剂量依赖性（

＜0.05）。与GLA高剂量组比较，GLA+Compound C组大鼠膝关节软骨损伤和炎症细胞浸润加重，上述定量指标均显著逆转（

＜0.05）。

结论

GLA可促进KOA大鼠软骨细胞自噬，抑制细胞凋亡，其作用机制可能与激活AMPK/mTOR/ULK1信号通路有关。

Abstract

OBJECTIVE

To investigate the effects of galangin （GLA） on autophagy and apoptosis of chondrocytes in knee osteoarthritis （KOA） rats by regulating the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/UNC-51-like kinase 1 （ULK1） signaling pathway.

METHODS

KOA rat model was constructed and separated into model group， L-GLA， M-GLA， H-GLA groups [subcutaneous injection of 100， 200， 400 μg/kg GLA]， GLA+Compound C group [subcutaneous injection of 400 μg/kg GLA+0.2 mg/kg AMPK inhibitor Compound C]， with 10 rats in each group. Additionally， 10 normally fed rats were selected as the sham operation group. After the last medication， the degree of knee joint swelling of rats in each group was detected； the pathology of knee joints in KOA rats was observed. The serum expressions of matrix metalloproteinase 13 （MMP-13） and interleukin-1β （IL-1β） in KOA rats were detected； the autophagy of chondrocytes in KOA rats was observed； the chondrocyte apoptosis in KOA rats was detected； the phosphorylation of AMPK/mTOR/ULK1 pathway-related proteins in cartilage tissue of knee joint were detected in rats.

RESULTS

Compared with the sham operation group， the arrangement of articular chondrocytes in the model group was disordered， with nuclear pyknosis and severe fibrosis of the articular cartilage layer， accompanied by a large amount of inflammatory cell infiltration； the degree of joint swelling， the number of autophagic vacuoles and apoptosis rate of chondrocytes， serum levels of MMP-13 and IL-1β， and the phosphorylation of mTOR protein in cartilage tissue of knee joint were all increased significa

ntly （

＜0.05）， while the phosphorylation of AMPK and ULK1 protein were all decreased significantly in cartilage tissue of knee joint （

＜0.05）. Compared with the model group， L-GLA， M-GLA， H-GLA groups showed significant improvement in joint cartilage injury and reduced infiltration of inflammatory cells in rats. The above quantitative indicators were significantly reversed in a dose-dependent manner， except the number of autophagic vacuoles increased significantly （

＜0.05）. Compared with the H-GLA group， the GLA+Compound C group showed aggravated cartilage tissue of joint cartilage injury and inflammatory cell infiltration in rats， and the above quantitative indicators were reversed significantly （

＜0.05）.

CONCLUSIONS

GLA can promote autophagy and inhibit apoptosis of chondrocytes in KOA rats， the mechanism of which may be associated with activating AMPK/mTOR/ULK1 signaling pathway.

关键词

Keywords

references

WANG S ， YANG J Y ， XIANG R A ， et al . Research and publication trends on knee osteoarthritis and cellular senescence：a bibliometric analysis [J ] . Front Physiol ， 2023 ， 14 ： 1269338 .

WANG Y H ， ZHOU Y ， GAO X ， et al . Duhuo jisheng decoction regulates intracellular zinc homeostasis by enhan- cing autophagy via PTEN/Akt/mTOR pathway to improve knee cartilage degeneration [J ] . PLoS One ， 2024 ， 19 （ 1 ）： e0290925 .

JIANG W ， CHEN H X ， LIN Y ， et al . Mechanical stress abnormalities promote chondrocyte senescence：the pathogenesis of knee osteoarthritis [J ] . Biomed Pharmacother ， 2023 ， 167 ： 115552 .

LU M ， MENG D H ， SHE Z Y ， et al . Promotion and mechanism of acupotomy on chondrocyte autophagy in knee osteoarthritis rabbits [J ] . Chin J Integr Med ， 2024 ， 30 （ 9 ）： 809 - 817 .

WANG D B ， CHEN J R ， PU L ， et al . Galangin：a food-derived flavonoid with therapeutic potential against a wide spectrum of diseases [J ] . Phytother Res ， 2023 ， 37 （ 12 ）： 5700 - 5723 .

ARAB H H ， ASHOUR A M ， EID A H ， et al . Targeting oxidative stress，apoptosis，and autophagy by galangin mitigates cadmium-induced renal damage：role of SIRT1/Nrf2 and AMPK/mTOR pathways [J ] . Life Sci ， 2022 ， 291 ： 120300 .

陈俊，林洁，赵忠胜，等 . 乌头汤对膝骨关节炎模型大鼠滑膜组织TLR4/NF-κB信号通路的影响 [J ] . 中国组织工程研究， 2019 ， 23 （ 27 ）： 4381 - 4386 .

CHEN J ， LIN J ， ZHAO Z S ， et al . Effect of Wutou decoction on TLR4/NF-κB signaling pathway in synovial tissue of rat models with knee osteoarthritis [J ] . Chin J Tissue Eng Res ， 2019 ， 23 （ 27 ）： 4381 - 4386 .

李旭峰，冷冬月，施斌 . 高良姜素对膝骨关节炎大鼠软骨损伤的影响 [J ] . 中国中医骨伤科杂志， 2024 ， 32 （ 6 ）： 7 - 12 .

LI X F ， LENG D Y ， SHI B . Efficacy of galangin on cartilage damage in rats with knee osteoarthritis [J ] . Chin J Tradit Med Traumatol Orthop ， 2024 ， 32 （ 6 ）： 7 - 12 .

李庆贵，陈康，郭召，等 . 汉黄芩素调节AMPK/SIRT1信号通路对骨质疏松大鼠骨折愈合的影响 [J ] . 实用医学杂志， 2023 ， 39 （ 4 ）： 410 - 416 .

LI Q G ， CHEN K ， GUO Z ， et al . Effect of wogonin on bone fracture healing in rats with osteoporosis by regula- ting AMPK/SIRT1 signaling pathway [J ] . J Pract Med ， 2023 ， 39 （ 4 ）： 410 - 416 .

HU S L ， ZHANG C W ， NI L B ， et al . Stabilization of HIF-1α alleviates osteoarthritis via enhancing mitophagy [J ] . Cell Death Dis ， 2020 ， 11 （ 6 ）： 481 .

ZHANG W ， ZHANG L L ， YANG S ， et al . Electroacupuncture ameliorates knee osteoarthritis in rats via inhibiting NLRP3 inflammasome and reducing pyroptosis [J ] . Mol Pain ， 2023 ， 19 ： 17448069221147792 .

DONG J ， ZHANG K J ， LI G C ， et al . CDDO-Im ameliorates osteoarthritis and inhibits chondrocyte apoptosis in mice via enhancing Nrf2-dependent autophagy [J ] . Acta Pharmacol Sin ， 2022 ， 43 （ 7 ）： 1793 - 1802 .

CHEN W J ， ZHONG Y J ， FENG N ， et al . New horizons in the roles and associations of COX-2 and novel natural inhibitors in cardiovascular diseases [J ] . Mol Med ， 2021 ， 27 （ 1 ）： 123 .

LIN Q ， ZHANG Y X ， HONG W S ， et al . Galangin ameliorates osteoarthritis progression by attenuating extracellular matrix degradation in chondrocytes via the activation of PRELP expression [J ] . Eur J Pharmacol ， 2022 ， 936 ： 175347 .

WANG Y B ， ZHANG T ， YANG Q C ， et al . Galangin attenuates IL-1β-induced catabolism in mouse chondrocytes and ameliorates murine osteoarthritis [J ] . Am J Transl Res ， 2021 ， 13 （ 8 ）： 8742 - 8753 .

DENG X W ， LE H L ， WAN T H ， et al . Galangin alleviates rheumatoid arthritis in rats by downregulating the pho- sphatidylinositol 3-kinase/protein kinase B signaling pathway [J ] . Bioengineered ， 2022 ， 13 （ 4 ）： 11192 - 11201 .

BU H Q ， LIU D L ， ZHANG G L ， et al . AMPK/mTOR/ULK1 axis-mediated pathway participates in apoptosis and autophagy induction by oridonin in colon cancer DLD-1 cells [J ] . Onco Targets Ther ， 2020 ， 13 ： 8533 - 8545 .

XIAO J ， SHEN X F ， KOU R M ， et al . Kirenol inhibits inflammation challenged by lipopolysaccharide through the AMPK-mTOR-ULK1 autophagy pathway [J ] . Int Immunopharmacol ， 2023 ， 116 ： 109734 .

吴伟欣，郑珍萍，顾富城，等 . 龟鹿二仙胶对IL-1β诱导的AMPK/mTOR/ULK1通路介导的体外培养软骨细胞自噬的影响 [J ] . 时珍国医国药， 2024 ， 35 （ 4 ）： 799 - 804 .

WU W X ， ZHENG Z P ， GU F C ， et al . Effect of Guilu erxian jiao on IL-1β-induced AMPK/mTOR/ULK1 pathway mediated autophagy in cultured chondrocytes in vitro [J ] . Lishizhen Med Mater Med Res ， 2024 ， 35 （ 4 ）： 799 - 804 .

蔡猛，陈文恒，徐琳琳，等 . 基于AMPK/ULK1介导的自噬通路探究牛蒡子苷元对骨关节炎大鼠软骨细胞焦亡的影响 [J ] . 中国药学杂志， 2023 ， 58 （ 20 ）： 1839 - 1848 .

CAI M ， CHEN W H ， XU L L ， et al . Effect of arctigenin on chondrocyte pyroptosis in osteoarthritis rats based on AMPK/ULK1-mediated autophagy pathway [J ] . Chin Pharm J ， 2023 ， 58 （ 20 ）： 1839 - 1848 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effect of neferine on mitophagy in Parkinson’s disease cells

Related Author

TAN Chenchen

WANG Diancui

CHEN Cuiqing

JIANG Min

Related Institution

Dept. of Neurology， Qingdao Central Hospital， Rehabilitation University/Qingdao Central Hospital

Dept. of Hematology， Qingdao Central Hospital， Rehabilitation University/Qingdao Central Hospital

Dept. of Neurology， the Sixth People’s Hospital of Qingdao

Address：8th Floor, Sihuan Building, No. 129 Daping Main Street, Yuzhong District, Chongqing, China Postal code：400042
Technical support is provided by Beijing Founder Electronics co., LTD 渝ICP备15012710号公网安备50010302001817
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰