Baicalein Inhibits the IL-1β-Induced Inflammatory Response in Nucleus Pulposus Cells and Attenuates Disc Degeneration In vivo
Intervertebral disc degeneration (IDD) is widely considered one of the main causes of low back pain, which is a chronic progressive disease closely related to inflammation and degeneration of nucleus pulposus (NP) cells. Baicalein is a natural bioactive compound with anti-inflammatory effects in different diseases, including inhibition of the inflammatory response in chondrocytes, whose morphology and avascular supply are similar to those of NP cells. Therefore, we hypothesized that baicalein may have a therapeutic effect on IDD by suppressing the inflammatory response. In vitro, NP cells were pretreated with baicalein for 2 h and then incubated with IL-1β for 24 h. We found that baicalein not only inhibited the overexpression of inflammatory cytokine production, including NO, PGE2, TNF-α, and IL-6, but also suppressed the expression of COX-2 and iNOS. The IL-1β-induced overexpression of MMP13 and ADAMTS5 and degradation of aggrecan and type II collagen were reversed by baicalein in a dose-dependent manner. Mechanistically, we found that baicalein suppressed the IL-1β-induced activation of the NF-κB and MAPK pathways. Moreover, an in vivo study demonstrated that baicalein treatment could ameliorate IDD in a puncture-induced rat model. Thus, baicalein has great value as a potential therapeutic agent for IDD.
KEY WORDSintervertebral disc degeneration baicalein inflammation NF-κB MAPK
This work was supported by the National Natural Science Foundation of China (81871806 and 81501933), the Zhejiang Public Service Technology Research Program/Social Development (LGF18H060008), the Major Scientific and Technological Project of the Medical and Health Ministry of Zhejiang Province (WKJ-ZJ-1527), the Wenzhou Science and Technology Project (Y20170080), and the Zhejiang Provincial Natural Science Foundation of China (LY17H060008).
Compliance with Ethical Standards
The study was performed in accordance with the Declaration of Helsinki and relevant policies in China.
Conflict of Interest
The authors declare that they have no conflicts of interest.
This study was approved by the Committee of Wenzhou Medical University, and all surgical interventions, treatments, and postoperative animal care procedures were performed in accordance with the NIH Guide for the Care and Use of Laboratory Animals.
- 1.Katz, J.N. 2006. Lumbar disc disorders and low-back pain: socioeconomic factors and consequences. The Journal of bone and joint surgery American volume 88 (Suppl 2): 21–24.Google Scholar
- 6.Shamji, M.F., L.A. Setton, W. Jarvis, S. So, J. Chen, L. Jing, R. Bullock, R.E. Isaacs, C. Brown, and W.J. Richardson. 2010. Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues. Arthritis and Rheumatism 62: 1974–1982.Google Scholar
- 8.Lee, S., C.S. Moon, D. Sul, J. Lee, M. Bae, Y. Hong, M. Lee, S. Choi, R. Derby, B.J. Kim, J. Kim, J.S. Yoon, L. Wolfer, J. Kim, J. Wang, S.W. Hwang, and S.H. Lee. 2009. Comparison of growth factor and cytokine expression in patients with degenerated disc disease and herniated nucleus pulposus. Clinical Biochemistry 42: 1504–1511.CrossRefGoogle Scholar
- 14.Yang, W., H. Li, X. Cong, X. Wang, Z. Jiang, Q. Zhang, X. Qi, S. Gao, R. Cao, and W. Tian. 2016. Baicalin attenuates lipopolysaccharide induced inflammation and apoptosis of cow mammary epithelial cells by regulating NF-kappaB and HSP72. International Immunopharmacology 40: 139–145.CrossRefGoogle Scholar
- 18.Chen, W.P., Y. Xiong, P.F. Hu, J.P. Bao, and L.D. Wu. 2015. Baicalein inhibits MMPs expression via a MAPK-dependent mechanism in chondrocytes. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology 36: 325–333.CrossRefGoogle Scholar
- 19.Li, Y., J. Wang, X. Song, H. Bai, T. Ma, Z. Zhang, X. Li, R. Jiang, G. Wang, X. Fan, X. Liu, and L. Gao. 2017. Effects of baicalein on IL-1beta-induced inflammation and apoptosis in rat articular chondrocytes. Oncotarget 8: 90781–90795.Google Scholar
- 23.Sandy, J.D. 2001. Proteoglycan core proteins and catabolic fragments present in tissues and fluids. Methods in molecular biology (Clifton, NJ) 171: 335–345.Google Scholar
- 28.Chen, J., J. Xuan, Y.T. Gu, K.S. Shi, J.J. Xie, J.X. Chen, Z.M. Zheng, Y. Chen, X.B. Chen, Y.S. Wu, X.L. Zhang, and X.Y. Wang. 2017. Celastrol reduces IL-1beta induced matrix catabolism, oxidative stress and inflammation in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration in vivo. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 91: 208–219.CrossRefGoogle Scholar
- 31.Kang, J.D., M. Stefanovic-Racic, L.A. McIntyre, H.I. Georgescu, and C.H. Evans. 1997. Toward a biochemical understanding of human intervertebral disc degeneration and herniation. Contributions of nitric oxide, interleukins, prostaglandin E2, and matrix metalloproteinases. Spine 22: 1065–1073.CrossRefGoogle Scholar
- 32.Sasaki, K., T. Hattori, T. Fujisawa, K. Takahashi, H. Inoue, and M. Takigawa. 1998. Nitric oxide mediates interleukin-1-induced gene expression of matrix metalloproteinases and basic fibroblast growth factor in cultured rabbit articular chondrocytes. Journal of Biochemistry 123: 431–439.CrossRefGoogle Scholar
- 34.Yoon, S.T., and N.M. Patel. 2006. Molecular therapy of the intervertebral disc. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 15 (Suppl 3): S379–S388.CrossRefGoogle Scholar
- 36.Bachmeier, B.E., A. Nerlich, N. Mittermaier, C. Weiler, C. Lumenta, K. Wuertz, and N. Boos. 2009. Matrix metalloproteinase expression levels suggest distinct enzyme roles during lumbar disc herniation and degeneration. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 18: 1573–1586.CrossRefGoogle Scholar
- 37.Vo, N.V., R.A. Hartman, T. Yurube, L.J. Jacobs, G.A. Sowa, and J.D. Kang. 2013. Expression and regulation of metalloproteinases and their inhibitors in intervertebral disc aging and degeneration. The spine journal : official journal of the North American Spine Society 13: 331–341.CrossRefGoogle Scholar
- 39.Tu, J., W. Li, Y. Zhang, X. Wu, Y. Song, L. Kang, W. Liu, K. Wang, S. Li, W. Hua, and C. Yang. 2017. Simvastatin inhibits IL-1beta-induced apoptosis and extracellular matrix degradation by suppressing the NF-kB and MAPK pathways in nucleus pulposus cells. Inflammation 40: 725–734.CrossRefGoogle Scholar
- 42.Seguin, C.A., M. Bojarski, R.M. Pilliar, P.J. Roughley, and R.A. Kandel. 2006. Differential regulation of matrix degrading enzymes in a TNFalpha-induced model of nucleus pulposus tissue degeneration. Matrix biology : journal of the International Society for Matrix Biology 25: 409–418.CrossRefGoogle Scholar