Stachydrine ameliorates the progression of intervertebral disc degeneration via the PI3K/Akt/NF-κB signaling pathway: in vitro and in vivo studies

被引:3
作者
Shao, Zhenxuan [1 ,2 ,3 ,4 ]
Lu, Jiajie [1 ,2 ,3 ,4 ]
Zhang, Chenxi [1 ,2 ,3 ,4 ]
Zeng, Guoling [1 ,2 ,3 ,4 ]
Chen, Boda [1 ,2 ,3 ,4 ]
Liang, Haibo [1 ,2 ,3 ,4 ]
Wu, Aimin [1 ,2 ,3 ,4 ]
Zhang, Xiaolei [1 ,2 ,3 ,4 ]
Wang, Xiangyang [1 ,2 ,3 ,4 ]
机构
[1] Wenzhou Med Univ, Dept Orthopaed, Affiliated Hosp 2, Wenzhou, Zhejiang, Peoples R China
[2] Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou, Zhejiang, Peoples R China
[3] Key Lab Orthopaed Zhejiang Prov, Wenzhou, Zhejiang, Peoples R China
[4] Wenzhou Med Univ, Sch Med 2, Wenzhou, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
LOW-BACK-PAIN; INDUCED CARDIAC-HYPERTROPHY; NF-KAPPA-B; OXIDATIVE STRESS; NEEDLE PUNCTURE; MODEL; INFLAMMATION; SENESCENCE; EXPRESSION; FIBROSIS;
D O I
10.1039/d0fo02323j
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Intervertebral disc degeneration (IDD) has been reported to be a major cause of low back pain. Stachydrine (STA) is present in the fruit juice of the Citrus genus and Leonurus heterophyllus, in non-negligible concentrations. In our study, we examined the protective effects of STA against IDD development as well as its underlying mechanism of action using both in vitro and in vivo experiments. STA exerted protective effects on the anabolism and catabolism of the extracellular matrix (ECM) in IL-1 beta-treated NPCs and inhibited the expression of pro-inflammatory factors in vitro. Mechanistically, STA suppressed the IL-1 beta-induced activation of PI3K/Akt/NF-kappa B signalling pathway cascades. Moreover, it was also demonstrated in molecular docking studies that STA has strong binding abilities to PI3K. Furthermore, STA ameliorated the progression of the IDD process in vivo in the puncture-induced rat model. In summary, our findings demonstrated that STA ameliorates the progression of IDD via the PI3K/Akt/NF-kappa B signalling pathway, which makes STA a promising therapeutic agent for the treatment of IDD.
引用
收藏
页码:10864 / 10875
页数:12
相关论文
共 41 条
[1]   Resveratrol Modulates Interleukin-1β-induced Phosphatidylinositol 3-Kinase and Nuclear Factor κB Signaling Pathways in Human Tenocytes [J].
Busch, Franziska ;
Mobasheri, Ali ;
Shayan, Parviz ;
Lueders, Cora ;
Stahlmann, Ralf ;
Shakibaei, Mehdi .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (45) :38050-38063
[2]   Stachydrine Protects Against Pressure Overload-Induced Cardiac Hypertrophy by Suppressing Autophagy [J].
Cao, Tong-Tong ;
Chen, Hui-Hua ;
Dong, Zhiwei ;
Xu, Yan-Wu ;
Zhao, Pei ;
Guo, Wei ;
Wei, Hong-Chang ;
Zhang, Chen ;
Lu, Rong .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2017, 42 (01) :103-114
[3]   Curcumin down-regulates the multidrug-resistance mdr1b gene by inhibiting the PI3K/Akt/NFκB pathway [J].
Choi, Byeong Hyeok ;
Kim, Chang Gun ;
Lim, Yoongho ;
Shin, Soon Young ;
Lee, Young Han .
CANCER LETTERS, 2008, 259 (01) :111-118
[4]   Degenerative Magnetic Resonance Imaging Changes in Patients With Chronic Low Back Pain A Systematic Review [J].
Chou, Dean ;
Samartzis, Dino ;
Bellabarba, Carlo ;
Patel, Alpesh ;
Luk, Keith D. K. ;
Kisser, Jeannette M. Schenk ;
Skelly, Andrea C. .
SPINE, 2011, 36 (21) :S43-S53
[5]   Low back pain: a major global challenge [J].
Clark, Stephanie ;
Horton, Richard .
LANCET, 2018, 391 (10137) :2302-2302
[6]   Interleukin-1 in the pathogenesis and treatment of inflammatory diseases [J].
Dinarello, Charles A. .
BLOOD, 2011, 117 (14) :3720-3732
[7]   17β-Estradiol protects against interleukin-1β-induced apoptosis in rat nucleus pulposus cells via the mTOR/caspase-3 pathway [J].
Guo, Hong-Tao ;
Yang, Si-Dong ;
Zhang, Feng ;
Liu, Sen ;
Yang, Da-Long ;
Ma, Lei ;
Wang, Hui ;
Ding, Wen-Yuan .
MOLECULAR MEDICINE REPORTS, 2019, 20 (02) :1523-1530
[8]  
Guo Wei, 2012, Zhong Yao Cai, V35, P940
[9]   A simple disc degeneration model induced by percutaneous needle puncture in the rat tail [J].
Han, Bin ;
Zhu, Kai ;
Li, Fang-cai ;
Xiao, Yu-xiang ;
Feng, Jie ;
Shi, Zhong-li ;
Lin, Min ;
Wang, Jun ;
Chen, Qi-xin .
SPINE, 2008, 33 (18) :1925-1934
[10]   What low back pain is and why we need to pay attention [J].
Hartvigsen, Jan ;
Hancock, Mark J. ;
Kongsted, Alice ;
Louw, Quinette ;
Ferreira, Manuela L. ;
Genevay, Stephane ;
Hoy, Damian ;
Karppinen, Jaro ;
Pransky, Glenn ;
Sieper, Joachim ;
Smeets, Rob J. ;
Underwood, Martin .
LANCET, 2018, 391 (10137) :2356-2367