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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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
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
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
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
Chubanov V, Schäfer S, Ferioli S, Natural S (2014) Synthetic modulators of the TRPM7 channel. Cells 3:1089–1101
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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).
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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
- Transient receptor potential melastatin 7 (TRPM7)
- Schwann cells
- Axonal degradation