Neuroprotective effects of curcumin alleviate lumbar intervertebral disc degeneration through regulating the expression of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF in a rat model

  • Authors:
    • Yuan Hu
    • Jin‑Shu Tang
    • Shu‑Xun Hou
    • Xiu‑Xiu Shi
    • Jiang Qin
    • Tie‑Song Zhang
    • Xiao‑Jing Wang
  • View Affiliations

  • Published online on: September 12, 2017     https://doi.org/10.3892/mmr.2017.7464
  • Pages: 6864-6869
Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations

Abstract

Curcumin is a natural product with antimutagenic, antitumor, antioxidant and neuroprotective properties. However, to the best of our knowledge, curcumin has yet to be investigated for the treatment of lumbar intervertebral disc degeneration LIDD). The aim of the present study was to investigate whether curcumin can alleviate LIDD through regulating the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‑2, transforming growth factor (TGF)‑β1/2, matrix metalloproteinase (MMP)‑9 and brain‑derived neurotrophic factor (BDNF) in a rat model of LIDD. The results of the present study suggest that pretreatment with curcumin can prevent the development of LIDD in rats. It was revealed that treatment with curcumin significantly reduced interleukin (IL)‑1β and IL‑6, iNOS, COX‑2 and MMP‑9 levels in rats with LIDD. In addition, treatment with curcumin reduced the mRNA expression levels of TGF‑β1 and TGF‑β2, whereas it increased the mRNA expression levels of BDNF in rats with LIDD. In conclusion, the present findings indicate that curcumin may exert protective effects on LIDD development, exerting its action through the regulation of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF.

References

1 

Vieira LA, De Marchi PL, dos Santos AA, Christofolini DM, Barbosa CP, Fonseca FL, Bianco B and Rodrigues LM: Analysis of FokI polymorphism of vitamin D receptor gene in intervertebral disc degeneration. Genet Test Mol Biomarkers. 18:625–629. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Høy K, Bunger C, Niederman B, Helmig P, Hansen ES, Li H and Andersen T: Transforaminal lumbar interbody fusion (TLIF) versus posterolateral instrumented fusion (PLF) in degenerative lumbar disorders: A randomized clinical trial with 2-year follow-up. Eur Spine J. 22:2022–2029. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Brox JI, SØrensen R, Friis A, Nygaard Ø, Indahl A, Keller A, Ingebrigtsen T, Eriksen HR, Holm I, Koller AK, et al: Randomized clinical trial of lumbar instrumented fusion and cognitive intervention and exercises in patients with chronic low back pain and disc degeneration. Spine (Phila Pa 1976). 28:1913–1921. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Delecrin J, Allain J, Beaurain J, Steib JP, Huppert J, Chataigner H, Ameil M, Aubourg L and Nguyen JM: Effects of lumbar artificial disc design on intervertebral mobility: In vivo comparison between mobile-core and fixed-core. Eur Spine J. 21 Suppl 5:S630–S640. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Omair A, Holden M, Lie BA, Reikeras O and Brox JI: Treatment outcome of chronic low back pain and radiographic lumbar disc degeneration are associated with inflammatory and matrix degrading gene variants: A prospective genetic association study. BMC Musculoskelet Disord. 14:1052013. View Article : Google Scholar : PubMed/NCBI

6 

Sedighi M and Haghnegahdar A: Role of vitamin D3 in treatment of lumbar disc herniation-pain and sensory aspects: Study protocol for a randomized controlled trial. Trials. 15:3732014. View Article : Google Scholar : PubMed/NCBI

7 

Mochida J, Sakai D, Nakamura Y, Watanabe T, Yamamoto Y and Kato S: Intervertebral disc repair with activated nucleus pulposus cell transplantation: A three-year, prospective clinical study of its safety. Eur Cell Mater. 29:202–212. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Liu H, Wu W, Li Y, Liu J, Yang K and Chen Y: Protective effects of preserving the posterior complex on the development of adjacent-segment degeneration after lumbar fusion: Clinical article. J Neurosurg Spine. 19:201–206. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Deng Y, Lu X, Wang L, Li T, Ding Y, Cao H, Zhang Y, Guo X and Yu G: Curcumin inhibits the AKT/NF-kB signaling via CpG demethylation of the promoter and restoration of NEP in the N2a cell line. AAPS J. 16:649–657. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Yuan J, Zou M, Xiang X, Zhu H, Chu W, Liu W, Chen F and Lin J: Curcumin improves neural function after spinal cord injury by the joint inhibition of the intracellular and extracellular components of glial scar. J Surg Res. 195:235–245. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Pu Y, Zhang H, Wang P, Zhao Y, Li Q, Wei X, Cui Y, Sun J, Shang Q, Liu D and Zhu Z: Dietary curcumin ameliorates aging-related cerebrovascular dysfunction through the AMPK/uncoupling protein 2 pathway. Cell Physiol Biochem. 32:1167–1177. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Wang M, Liang L, Li L, Han K, Li Q, Peng Y, Peng X and Zeng K: Increased miR-424-5p expression in peripheral blood mononuclear cells from patients with pemphigus. Mol Med Rep. 15:3479–3484. 2017. View Article : Google Scholar : PubMed/NCBI

13 

Siepe CJ, Heider F, Haas E, Hitzl W, Szeimies U, Stäbler A, Weiler C, Nerlich AG and Mayer MH: Influence of lumbar intervertebral disc degeneration on the outcome of total lumbar disc replacement: A prospective clinical, histological, X-ray and MRI investigation. Eur Spine J. 21:2287–2299. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Akeda K, Yamada T, Inoue N, Nishimura A and Sudo A: Risk factors for lumbar intervertebral disc height narrowing: A population-based longitudinal study in the elderly. BMC Musculoskelet Disord. 16:3442015. View Article : Google Scholar : PubMed/NCBI

15 

Gao B, Chang C, Zhou J, Zhao T, Wang C, Li C and Gao G: Pycnogenol protects against rotenone-induced neurotoxicity in PC12 cells through regulating NF-kB-iNOS signaling pathway. DNA Cell Biol. 34:643–649. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Xue Y, Wu J and Sun J: Four types of inorganic nanoparticles stimulate the inflammatory reaction in brain microglia and damage neurons in vitro. Toxicol Lett. 214:91–98. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Jimbo K, Park JS, Yokosuka K, Sato K and Nagata K: Positive feedback loop of interleukin-1beta upregulating production of inflammatory mediators in human intervertebral disc cells in vitro. J Neurosurg Spine. 2:589–595. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Cabraja M, Endres M, Abbushi A, Zenclussen M, Blechschmidt C, Lemke AJ, Kroppenstedt S, Kaps C and Woiciechowsky C: Effect of degeneration on gene expression of chondrogenic and inflammatory marker genes of intervertebral disc cells: A preliminary study. J Neurosurg Sci. 57:307–316. 2013.PubMed/NCBI

19 

Zigouris A, Alexiou GA, Batistatou A, Voulgaris S and Kyritsis AP: The role of matrix metalloproteinase 9 in intervertebral disc degeneration. J Clin Neurosci. 18:1424–1425. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Sun ZM, Miao L, Zhang YG and Ming L: Association between the −1562 C/T polymorphism of matrix metalloproteinase-9 gene and lumbar disc disease in the young adult population in North China. Connect Tissue Res. 50:181–185. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Li X, Lu Y, Sun Y and Zhang Q: Effect of curcumin on permeability of coronary artery and expression of related proteins in rat coronary atherosclerosis heart disease model. Int J Clin Exp Pathol. 8:7247–7253. 2015.PubMed/NCBI

22 

Zhan Z, Shao Z, Xiong X, Yang S, Du J, Zheng Q, Wang H, Guo X and Liu Y: Ad/CMV-hTGF-beta1 treats rabbit intervertebral discs degeneration in vivo. J Huazhong Univ Sci Technolog Med Sci. 24:599–601, 624. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Kartha S, Zeeman ME, Baig HA, Guarino BB and Winkelstein BA: Upregulation of BDNF and NGF in cervical intervertebral discs exposed to painful whole-body vibration. Spine (Phila Pa 1976). 39:1542–1548. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Orita S, Eguchi Y, Kamoda H, Arai G, Ishikawa T, Miyagi M, Inoue G, Suzuki M, Toyone T, Aoki Y, et al: Brain-derived neurotrophic factor inhibition at the punctured intervertebral disc downregulates the production of calcitonin gene-related peptide in dorsal root ganglia in rats. Spine (Phila Pa 1976). 36:1737–1743. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Fanaei H, Khayat S, Kasaeian A and Javadimehr M: Effect of curcumin on serum brain-derived neurotrophic factor levels in women with premenstrual syndrome: A randomized, double-blind, placebo-controlled trial. Neuropeptides. 56:25–31. 2016. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

November 2017
Volume 16 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Hu, Y., Tang, J., Hou, S., Shi, X., Qin, J., Zhang, T., & Wang, X. (2017). Neuroprotective effects of curcumin alleviate lumbar intervertebral disc degeneration through regulating the expression of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF in a rat model. Molecular Medicine Reports, 16, 6864-6869. https://doi.org/10.3892/mmr.2017.7464
MLA
Hu, Y., Tang, J., Hou, S., Shi, X., Qin, J., Zhang, T., Wang, X."Neuroprotective effects of curcumin alleviate lumbar intervertebral disc degeneration through regulating the expression of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF in a rat model". Molecular Medicine Reports 16.5 (2017): 6864-6869.
Chicago
Hu, Y., Tang, J., Hou, S., Shi, X., Qin, J., Zhang, T., Wang, X."Neuroprotective effects of curcumin alleviate lumbar intervertebral disc degeneration through regulating the expression of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF in a rat model". Molecular Medicine Reports 16, no. 5 (2017): 6864-6869. https://doi.org/10.3892/mmr.2017.7464