Inhibition of Lipopolysaccharide-Induced Interleukin-1β and Tumor Necrosis Factor-α Production by Menthone through Nuclear Factor-κB Signaling Pathway in HaCat Cells

Hui-Man Cheng；Chien-Yun Hsiang；Guang-Wei Chen；Shih-Lu Wu；Jaw-Chyun Chen；Chih-Yang Huang；Da-Tian Bau；Tin-Yun Ho

cutaneous inflammation ； lipopolysaccharide LPS ； cytokine ； nuclear factor-κB ； menthone

The Chinese Journal of Physiology

51卷3期（2008 / 06 / 30）

160 - 166

英文

Menthone, the Chinese old remedy extracted from genus Mentha, has been widely used as a cooling agent, a counterirritant for pain relief, and for the treatment of pruritus. However, its detail mechanisms for interfering inflammatory reaction remain unknown. In this study, we found that menthone can suppress the lipopolysaccharide (LPS)-induced proinflammatory cytokines, interleukin-1β(IL-1β) and tumor necrosis factor-k. (TNF-α), as well as nuclear factor kB (NF-kB) activity induced by LPS and other inflammatory agents, including 12-O-tetradecanoylphorbol-13-acetate, hydrogen peroxide, okadaic acid, and ceramide. Furthermore, our data also demonstrated that the translocation of NF-kB activated by LPS into the nucleus was suppressed by menthone, and I-kB and β-transducin repeat containing protein (β-TrCP)were both involved in this suppression. To sum up, this study has provided molecular evidence for menthone effect on the LPS-induced cytokine production, NF-kB activation, and the involvement of I-kB and β-TrCP.

1. Abeyama, K.,Eng, W.,Jester, J.V.,Vink, A.A.,Edelbaum, D.,Cockerell, C.J.,Bergstresser, P.R.,Takashima, A.(2000).A role for NF-kappaB-dependent gene transactivation in sunburn.J. Clin. Invest.,105,1751-1759.
2. Baldwin, A.S.(1996).The NF-kappa B and I kappa B proteins: new discoveries and insights.Annu. Rev. Immunol.,14,649-683.
3. Bierhaus, A.,Chen, J.,Liliensiek, B.,Nawroth, P.P.(2000).LPS and cytokine-activated endothelium.Semin. Thromb. Hemost.,26,571-587.
4. Bromm, B.,Scharein, E.,Darsow, U.,Ring, J.(1995).Effects of menthol and cold on histamine-induced itch and skin reactions in man.Neurosci. Lett.,187,157-160.
5. Eccles, R.(1994).Menthol and related cooling compounds.J. Pharm. Pharmacol.,46,618-630.
6. Hong, C.Z.,Shellock, F.G.(1991).Effects of a topically applied counterirritant (Eucalyptamint) on cutaneous blood flow and on skin and muscle temperatures. A placebo-controlled study.Am. J. Phys. Med. Rehabil.,70,29-33.
7. Hsiang, C.Y.,Lai, I.L.,Chao, D.C.,Ho, T.Y.(2002).Differential regulation of activator protein 1 activity by glycyrrhizin.Life Sci.,70,1643-1656.
8. Kim, J.,Modlin, R.L.,Freedberg, I.M.,Eisen, A.Z.,Wolff, K.,Austen, K.F.,Goldsmith, L.A.,Katz, S.I.(eds.)(2003).Fitzpatrick`s Dermatology in General Medicine.New York:McGraw-Hill.
9. Lin, J.P.,Lu, H.F.,Lee, J.H.,Lin, J.G.,Hsia, T.C.,Wu, L.T.,Chung, J.G.(2005).(-)-Menthol inhibits DNA topoisomerases I, II alpha and beta and promotes NF-kappaB expression in human gastric cancer SNU-5 cells.Anticancer Res.,25,2069-2074.
10. Mishra, V.,Pandeya, S.N.,Pannecouque, C.,Witvrouw, M.,De Clercq, E.(2002).Anti-HIV activity of thiosemicarbazone and semicarbazone derivatives of (+/-)-3-menthone.Arch. Pharm. (Weinheim),335,183-186.
11. Mukaida, N.,Ishikawa, Y.,Ikeda, N.,Fujioka, N.,Watanabe, S.,Kuno, K.,Matsushima, K.(1996).Novel insight into molecular mechanism of endotoxin shock: biochemical analysis of LPS receptor signaling in a cell-free system targeting NF-kappaB and regulation of cytokine production/action through beta 2 integrin in vivo.J. Leukoc. Biol.,59,145-151.
12. Narishetty, S.T.,Panchagnula, R.(2004).Transdermal delivery of zidovudine: effect of terpenes and their mechanism of action.J. Control Release,95,367-379.
13. Nokhodchi, A.,Sharabiani, K.,Rashidi, M.R.,Ghafourian, T.(2007).The effect of terpene concentrations on the skin penetration of diclofenac sodium.Int. J. Pharm.,335,97-105.
14. Polano, M.K. (ed)(1984).Topical skin therapeutics: Churchill Livingstone.London:
15. Pons, J.,Evrard-Todeschi, N.,Bertho, G.,Gharbi-Benarous, J.,Sonois, V.,Benarous, R.,Girault, J.P.(2007).Structural studies on 24PIkβα peptide derived from a human Ikβα protein related to the inhibition of the activity of the transcription factor NF-kappaB.Biochemistry,46,2958-2972.
16. Spencer, E.,Jiang, J.,Chen, Z.J.(1999).Signal-induced ubiquitination of IkappaBalpha by the F-box protein Slimb/beta-TrCP.Genes Dev.,13,284-294.
17. Ulmer, A.J.,Flad, H.,Rietschel, T.,Mattern, T.(2000).Induction of proliferation and cytokine production in human T lymphocytes by lipopolysaccharide (LPS).Toxicology,152,37-45.
18. Winston, J.T.,Strack, P.,Beer-Romero, P.,Chu, C.Y.,Elledge, S.J.,Harper, J.W.(1999).The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro.Genes Dev.,13,270-283.
19. Yaron, A.,Hatzubai, A.,Davis, M.,Lavon, I.,Amit, S.,Manning, A.M.,Andersen, J.S.,Mann, M.,Mercurio, F.,Ben-Neriah, Y.(1998).Identification of the receptor component of the IkappaBalphaubiquitin ligase.Nature,396,590-594.
20. Yosipovitch, G.,Szolar, C.,Hui, X.Y.,Maibach, H.(1996).Effect of topically applied menthol on thermal, pain and itch sensations and biophysical properties of the skin.Arch. Dermatol. Res.,288,245-248.
21. Zhao, K.,Singh, S.,Singh, J.(2001).Effect of menthone on the in vitro percutaneous absorption of tamoxifen and skin reversibility.Int. J. Pharm.,219,177-181.