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Crocin exerts anti-inflammatory and anti-catabolic effects on rat intervertebral discs by suppressing the activation of JNK

  • Authors:
    • Kang Li
    • Yan Li
    • Zhenjiang Ma
    • Jie Zhao
  • View Affiliations / Copyright

    Affiliations: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1291-1299
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    Published online on: September 30, 2015
       https://doi.org/10.3892/ijmm.2015.2359
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Abstract

As intervertebral disc (IVD) degeneration has been proven to contribute to low back pain (LBP), drug treatment aiming at attenuating IVD degeneration may prove to be benefiical. Crocin, a bioactive component of saffron, has been found to exert anti-inflammatory effects on cartilage. In the present study, the anti-inflammatory and anti-catabolic effects of crocin on rat IVDs were analyzed in vitro and ex vivo. Nucleus pulposus (NP) cells were isolated from the lumbar IVDs of Sprague-Dawley rats. The NP cells were first treated with various concentrations of crocin, and then stimulated with lipopolysaccharide (LPS) to induce inflammation. Subsequently, RT-qPCR and enzyme-linked immunosorbent assay were carried out to measure the expression levels of catabolic enzymes, pro-inflammatory factors and the components of the extracellular matrix (ECM). In addition, western blot analysis was also used to investigate the related signaling pathways. The whole spinal motion segment (vertebra-IVD-vertebra section) of the rats was isolated and cultured in the presence or absence of LPS and crocin for 7 days. The ex vivo effects of crocin on the ECM of the IVD structures were determined by histological and biochemical analysis. In vitro, crocin significantly inhibited the LPS-induced overexpression of catabolic enzymes [matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif (ADAMTS)-4 and ADAMTS‑5], pro-inflammatory factors [interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6 and inducible nitric oxide synthase (iNOS)] and Toll-like receptor (TLR)‑2 in a concentration-dependent manner. Notably, crocin partly prevented the downregulation of aggrecan and type II collagen (collagen‑II). Moreover, crocin suppressed the LPS-induced activation of the mitogen-activated protein kinase (MAPK) pathway by inhibiting the phosphorylation of c-Jun N-terminal kinase (JNK). Ex vivo experiments demonstrated that crocin protected the rat IVDs from the LPS-induced depletion of the ECM components, including proteoglycan and collagen-II. In conclusion, crocin effectively suppressed the degeneration-related inflammation and catabolism in rat IVDs in vitro and ex vivo, suggesting that crocin has potential for use as a therapuetic strategy in the treatment of LBP.
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Spandidos Publications style
Li K, Li Y, Ma Z and Zhao J: Crocin exerts anti-inflammatory and anti-catabolic effects on rat intervertebral discs by suppressing the activation of JNK. Int J Mol Med 36: 1291-1299, 2015.
APA
Li, K., Li, Y., Ma, Z., & Zhao, J. (2015). Crocin exerts anti-inflammatory and anti-catabolic effects on rat intervertebral discs by suppressing the activation of JNK. International Journal of Molecular Medicine, 36, 1291-1299. https://doi.org/10.3892/ijmm.2015.2359
MLA
Li, K., Li, Y., Ma, Z., Zhao, J."Crocin exerts anti-inflammatory and anti-catabolic effects on rat intervertebral discs by suppressing the activation of JNK". International Journal of Molecular Medicine 36.5 (2015): 1291-1299.
Chicago
Li, K., Li, Y., Ma, Z., Zhao, J."Crocin exerts anti-inflammatory and anti-catabolic effects on rat intervertebral discs by suppressing the activation of JNK". International Journal of Molecular Medicine 36, no. 5 (2015): 1291-1299. https://doi.org/10.3892/ijmm.2015.2359
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Spandidos Publications style
Li K, Li Y, Ma Z and Zhao J: Crocin exerts anti-inflammatory and anti-catabolic effects on rat intervertebral discs by suppressing the activation of JNK. Int J Mol Med 36: 1291-1299, 2015.
APA
Li, K., Li, Y., Ma, Z., & Zhao, J. (2015). Crocin exerts anti-inflammatory and anti-catabolic effects on rat intervertebral discs by suppressing the activation of JNK. International Journal of Molecular Medicine, 36, 1291-1299. https://doi.org/10.3892/ijmm.2015.2359
MLA
Li, K., Li, Y., Ma, Z., Zhao, J."Crocin exerts anti-inflammatory and anti-catabolic effects on rat intervertebral discs by suppressing the activation of JNK". International Journal of Molecular Medicine 36.5 (2015): 1291-1299.
Chicago
Li, K., Li, Y., Ma, Z., Zhao, J."Crocin exerts anti-inflammatory and anti-catabolic effects on rat intervertebral discs by suppressing the activation of JNK". International Journal of Molecular Medicine 36, no. 5 (2015): 1291-1299. https://doi.org/10.3892/ijmm.2015.2359
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