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Carvacrol effectively protects demyelination by suppressing transient receptor potential melastatin 7 (TRPM7) in Schwann cells


Peripheral neurodegenerative processes are essential for regenerating damaged peripheral nerves mechanically or genetically. Abnormal neurodegenerative processes induce peripheral neurodegenerative diseases via irreversible nerve damage. Carvacrol, a major component in Origanum vulgare, possesses various effects on organisms, such as antibiotic, anti-inflammatory and cytoprotective effects; although transient receptor potential (TRP) ankyrin 1 (TRPA1), TRP canonical 1 (TRPC1), TRP melastatin M7 (TRPM7), and TRP vanilloid 3 (TRPV3) are carvacrol-regulated TRPs, however, effect of carvacrol on the peripheral neurodegenerative process, and its underlying mechanism, remain unclear. Here, we investigated the specificity of carvacrol for TRPM7 in Schwann cells and the regulatory effect of carvacrol on TRPM7-dependent neurodegenerative processes. To construct peripheral nerve degeneration model, we used with a sciatic explant culture and sciatic nerve axotomy. Ex vivo, in vivo sciatic nerves were treated with carvacrol following an assessment of demyelination (ovoid fragmentation) and axonal degradation using morphometric indices. In these models, carvacrol effectively suppressed the morphometric indices, such as stripe, ovoid, myelin, and neurofilament indices during peripheral nerve degeneration. We found that carvacrol significantly inhibited upregulation of TRPM7 in Schwann cells. In this study, our results suggest that carvacrol effectively protects against the peripheral neurodegenerative process via TRPM7-dependent regulation in Schwann cells. Thus, pharmacological use of carvacrol could be helpful to protect against neurodegeneration that occurs with aging and peripheral neurodegenerative diseases, prophylactically.

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  1. Angienda PO, Hill DJ (2011) The effect of sodium chloride and pH on the antimicrobial effectiveness of essential oils against pathogenic and food spoilage bacteria: implications in food safety. Int J Nutr Food Eng 5:572–577

  2. Chen W, Xu B, Xiao A, Liu L, Fang X, Liu R, Turlova E, Barszczyk A, Zhong X, Sun CLF, Britto LRG, Feng ZP, Sun HS (2015a) TRPM7 inhibitor carvacrol protects brain from neonatal hypoxic-ischemic injury. Mol Brain 8:11

  3. Chen WL, Barszczyk A, Turlova E, Deurloo M, Liu B, Yang BB, Rutka JT, Feng ZP, Sun HS (2015b) Inhibition of TRPM7 by carvacrol suppresses glioblastoma cell proliferation, migration and invasion. Oncotarget 6:16321–16340

  4. Chen J, Dou Y, Zheng X, Leng T, Lu X, Ouyang Y, Sun H, Xing F, Mai J, Gu J, Lu B, Yan G, Lin J, Zhu W (2016) TRPM7 channel inhibition mediates midazolam-induced proliferation loss in human malignant glioma. Tumor Biol 37:14721–14731

  5. Chubanov V, Schäfer S, Ferioli S, Natural S (2014) Synthetic modulators of the TRPM7 channel. Cells 3:1089–1101

  6. Facer P, Casula MA, Smith GD, Benham CD, Chessell IP, Bountra C, Sinisi M, Birch R, Anand P (2007) Differential expression of the capsaicin receptor TRPV1 and related novel receptors TRPV3, TRPV4 and TRPM8 in normal human tissues and changes in traumatic and diabetic neuropathy. BMC Neurol 7:11

  7. Frieden C (1983) Polymerization of actin : Mechanism of the Mg2+-induced process at pH 8 and 20 ℃. Proc Natl Acad Sci USA 80:6513–6517

  8. Gholijani N, Gharagozloo M, Farjadian S, Amirghofran Z (2016) Modulatory effects of thymol and carvacrol on inflammatory transcription factors in lipopolysaccharide-treated macrophages. J Immunotoxicol 13:157–164

  9. Jung J, Cai W, Lee HK, Pellegatta M, Shin YK, Jang SY, Suh DJ, Wrabetz L, Feltri ML, Park HT (2011) Actin polymerization is essential for myelin sheath fragmentation during Wallerian degeneration. J Neurosci 31:2009–2015

  10. Logu F, De Nassini R, Materazzi S, Gonçalves MC, Nosi D, Rossi D, Innocenti D, Marone IM, Ferreira J, Puma SL, Benemei S, Trevisan G, Souza D, Araújo M, De Patacchini R, Bunnett NW, Geppetti P (2017) Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice. Nat Commun 8:1887

  11. Loreti S, Vilaro MT, Visentin S, Rees H, Levey H, Level A, Tata AM (2006) Rat Schwann cells express M1–M4 muscarinic receptor subtypes. J Neurosci Res 84:97–105

  12. Luo Y, Wu J, Lu M, Shi Z, Na N, Di J (2016) Carvacrol alleviates prostate cancer cell proliferation, migration, and invasion through regulation of PI3K/Akt and MAPK signaling pathways. Oxid Med Cell Longev 2016:1469693

  13. Park BS, Kim HW, Rhyu IJ, Park C, Yeo SG, Huh Y, Jeong NY, Jung J (2015) Hydrogen sulfide is essential for Schwann cell responses to peripheral nerve injury. J Neurochem. 132:230–242

  14. Parkinson DB, Bhaskaran A, Arthur-Farraj P, Noon LA, Woodhoo A, Lloyd AC, Feltri ML, Wrabetz L, Behrens A, Mirsky R, Jessen KR (2008) c-Jun is a negative regulator of myelination. J Cell Biol 181:625–637

  15. Parnas M, Peters M, Dadon D, Lev S, Vertkin I, Slutsky I, Minke B (2009) Carvacrol is a novel inhibitor of Drosophila TRPL and mammalian TRPM7 channels. Cell Calcium 45:00–309

  16. Peier AM, Reeve AJ, Andersson DA, Moqrich A, Earley TJ, Hergarden AC, Story GM, Colley S, Hogenesch JB, Mcintyre P, Bevan S, Patapoutian A (2002) A heat-sensitive TRP channel expressed in keratinocytes. Science 296:2046–2049

  17. Peters M, Trembovler V, Alexandrovich A, Parnas M (2012) Carvacrol together with TRPC1 elimination improve functional recovery after traumatic brain injury in mice. J Neurotrauma 29:2831–2834

  18. Ryazanova LV, Rondon LJ, Zierler S, Hu Z, Galli J, Yamaguchi TP, Mazur A, Fleig A, Ryazanov AG (2010) TRPM7 is essential for Mg2+ homeostasis in mammals. Nat Commun 1:109

  19. Tong F, Gross AD, Dolan MC, Coats JR (2013) The phenolic monoterpenoid carvacrol inhibits the binding of nicotine to the housefly nicotinic acetylcholine receptor. Pest Manag Sci 69:775–780

  20. Turlova E, Bae CYJ, Deurloo M, Chen W, Barszczyk A, Horgen FD, Fleig A, Feng ZP, Sun HS (2016) TRPM7 regulates axonal outgrowth and maturation of primary hippocampal neurons. Mol Neurobiol 53:595–610

  21. Uqqenti C, De Stefano ME, Costantino M, Loreti S, Pisano A, Avallone B, Talora C, Magnaghi V, Tata AM (2014) M2 muscarinic receptor activation regulates Schwann cell differentiation and myelin organization. Dev Neurobiol 74:676–691

  22. Xu H, Delling M, Jun JC, Clapham DE (2006) Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels. Nat Neurosci 9:628–635

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We thank Ms. Hyun Woo Jo (Department of Anatomy and Neurobiology, Kyung Hee University, Seoul, Korea) for her valuable discussion. This work was supported by Basic Science Research Program through National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIT) (Grant No. 2019R1F1A1048656) and a Grant from Kyung Hee University in 2019 (KHU-20191219).

Author information

YLC, MK, JJ, CP, and YH designed this study and interpreted experimental results. YLC, MK, YHK, NK, HJY, JJ, CP, and YH defined intellectual contents. YLC, MK, JJ, CP, and YH performed experiments. JJ, CP, and YH wrote the manuscript. JJ and YH obtained funds from government and Kyung Hee University. All authors read and approved the final manuscript.

Correspondence to Chan Park or Youngbuhm Huh or Junyang Jung.

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Chun, Y.L., Kim, M., Kim, Y.H. et al. Carvacrol effectively protects demyelination by suppressing transient receptor potential melastatin 7 (TRPM7) in Schwann cells. Anat Sci Int 95, 230–239 (2020). https://doi.org/10.1007/s12565-019-00514-1

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  • Carvacrol
  • Transient receptor potential melastatin 7 (TRPM7)
  • Schwann cells
  • Demyelination
  • Axonal degradation