Spilanthol inhibits TNF‑α‑induced ICAM‑1 expression and pro‑inflammatory responses by inducing heme oxygenase‑1 expression and suppressing pJNK in HaCaT keratinocytes

Huang,Chun‑Hsun; Chang,Li‑Chun; Hu,Sindy; Hsiao,Chien‑Yu; Wu,Shu‑Ju

doi:10.3892/mmr.2018.9245

Spilanthol inhibits TNF‑α‑induced ICAM‑1 expression and pro‑inflammatory responses by inducing heme oxygenase‑1 expression and suppressing pJNK in HaCaT keratinocytes

Authors:
- Chun‑Hsun Huang
- Li‑Chun Chang
- Sindy Hu
- Chien‑Yu Hsiao
- Shu‑Ju Wu
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Affiliations: Department of Cosmetic Science, Research Center for Food and Cosmetic Safety, and Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan R.O.C., Department of Nutrition and Health Sciences, Research Center for Food and Cosmetic Safety, and Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan R.O.C., Department of Dermatology, Aesthetic Medical Center, Chang Gung Memorial Hospital, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan R.O.C.
Published online on: July 3, 2018 https://doi.org/10.3892/mmr.2018.9245
Pages: 2987-2994

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Abstract

Spilanthol has been reported to possess antioxidant, anti‑inflammatory, antimicrobial and antinociceptive properties. At present, the literature has reported the beneficial role of spilanthol on tumor necrosis factor‑α (TNF‑α)‑stimulated HaCaT cells. The present study investigated the effects of spilanthol on the expression of TNF‑α‑induced intercellular adhesion molecule 1 (ICAM‑1) and cyclooxygenase (COX)‑2 in the human keratinocyte cell line HaCaT. Cells were pretreated with various concentrations of spilanthol (10‑150 µM) followed by TNF‑α to induce inflammation. Pretreatment with spilanthol decreased TNF‑α‑induced COX‑2 expression by western blotting and suppressed the expression of pro‑inflammatory mediators, including interleukin (IL)‑6, IL‑8 and monocyte chemotactic protein 1 using ELISA. Spilanthol also decreased the expression of TNF‑α‑induced ICAM‑1 protein and mRNA assay by western blotting and RT‑qPCR, respectively, in addition to the monocyte adhesiveness of HaCaT cells. Furthermore, spilanthol significantly suppressed the phosphorylation of c‑Jun N‑terminal kinase (JNK), while pretreatment with spilanthol enhanced heme oxygenase (HO)‑1 protein expression by western blotting. These results demonstrated that spilanthol may exert its anti‑inflammatory activity by suppressing the TNF‑α‑induced expression of ICAM‑1, COX‑2 and pro‑inflammatory mediators by enhancing that of HO‑1, and inhibiting the activation of the phosphorylated JNK signaling pathway. It is hypothesized that spilanthol may be a natural anti‑inflammatory drug to attenuate skin inflammatory disease.

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1	Coman G, Blickenstaff NR and Maibach HI: Skin and the environment. Rev Environ Health. 29:1432014. View Article : Google Scholar : PubMed/NCBI
2	Subhan F, Kang HY, Lim Y, Ikram M, Baek SY, Jin S, Jeong YH, Kwak JY and Yoon S: Fish scale collagen peptides protect against CoCl2/TNF-α-induced cytotoxicity and inflammation via inhibition of ROS, MAPK, and NF-κB pathways in HaCaT cells. Oxid Med Cell Longev. 2017:97036092017. View Article : Google Scholar : PubMed/NCBI
3	Dustin ML, Singer KH, Tuck DT and Springer TA: Adhesion of T lymphoblasts to epidermal keratinocytes is regulated by interferon gamma and is mediated by intercellular adhesion molecule 1 (ICAM-1). J Exp Med. 167:1323–1340. 1988. View Article : Google Scholar : PubMed/NCBI
4	Youn GS, Kwon DJ, Ju SM, Choi SY and Park J: Curcumin ameliorates TNF-α-induced ICAM-1 expression and subsequent THP-1 adhesiveness via the induction of heme oxygenase-1 in the HaCaT cells. BMB Rep. 46:410–415. 2013. View Article : Google Scholar : PubMed/NCBI
5	Albanesi C, Scarponi C, Giustizieri ML and Girolomoni G: Keratinocytes in inflammatory skin diseases. Curr Drug Targets Inflamm Allergy. 4:329–334. 2005. View Article : Google Scholar : PubMed/NCBI
6	Middleton MH and Norris DA: Cytokine-induced ICAM-1 expression in human keratinocytes is highly variable in keratinocyte strains from different donors. J Invest Dermatol. 104:489–496. 1995. View Article : Google Scholar : PubMed/NCBI
7	Kim H, Youn GS, An SY, Kwon HY, Choi SY and Park J: 2,3-Dimethoxy-2′-hydroxychalcone ameliorates TNF-α-induced ICAM-1 expression and subsequent monocyte adhesiveness via NF-kappaB inhibition and HO-1 induction in HaCaT cells. BMB Rep. 49:57–62. 2016. View Article : Google Scholar : PubMed/NCBI
8	Nedoszytko B, Sokołowska-Wojdyło M, Ruckemann-Dziurdzińska K, Roszkiewicz J and Nowicki RJ: Chemokines and cytokines network in the pathogenesis of the inflammatory skin diseases: Atopic dermatitis, psoriasis and skin mastocytosis. Postepy Dermatol Alergol. 31:84–91. 2014. View Article : Google Scholar : PubMed/NCBI
9	Kim MY, Lim YY, Kim HM, Park YM, Kang H and Kim BJ: Synergistic inhibition of tumor necrosis factor-alpha-stimulated pro-inflammatory cytokine expression in HaCaT cells by a combination of rapamycin and mycophenolic acid. Ann Dermatol. 27:32–39. 2015. View Article : Google Scholar : PubMed/NCBI
10	Banno T, Gazel A and Blumenberg M: Effects of tumor necrosis factor-alpha (TNF alpha) in epidermal keratinocytes revealed using global transcriptional profiling. J Biol Chem. 279:32633–32642. 2004. View Article : Google Scholar : PubMed/NCBI
11	Karin M and Greten FR: NF-kappaB: Linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 5:749–759. 2005. View Article : Google Scholar : PubMed/NCBI
12	Chang CF, Liao KC and Chen CH: 2-phenylnaphthalene derivatives inhibit lipopolysaccharide-induced pro-inflammatory mediators by downregulating of MAPK/NF-κB pathways in RAW 264.7 macrophage cells. PLoS One. 12:e01689452017. View Article : Google Scholar : PubMed/NCBI
13	Wang JK, Xiong GM, Luo B, Choo CC, Yuan S, Tan NS and Choong C: Surface modification of PVDF using non-mammalian sources of collagen for enhancement of endothelial cell functionality. J Mater Sci Mater Med. 27:452016. View Article : Google Scholar : PubMed/NCBI
14	Listopad J, Asadullah K, Sievers C, Ritter T, Meisel C, Sabat R and Döcke WD: Heme oxygenase-1 inhibits T cell-dependent skin inflammation and differentiation and function of antigen-presenting cells. Exp Dermatol. 16:661–670. 2007. View Article : Google Scholar : PubMed/NCBI
15	Kirino M, Kirino Y, Takeno M, Nagashima Y, Takahashi K, Kobayashi M, Murakami S, Hirasawa T, Ueda A, Aihara M, et al: Heme oxygenase 1 attenuates the development of atopic dermatitis-like lesions in mice: Implications for human disease. J Allergy Clin Immunol. 122(290–297): 297.e1–e8. 2008.
16	Barbosa AF, de Carvalho MG, Smith RE and Sabaa-Srur AUO: Spilanthol: Occurrence, extraction, chemistry and biological activities. Rev bras Farmacogn. 26:128–133. 2016. View Article : Google Scholar
17	Elumalai A, Pendem N, Eswaraiah MC and Naresh V: An updated annual review on antipyretic medicinal plants. Int J Univers Pharm Life Sci. 2:207–215. 2012.
18	Chakraborty A, Devi RKB, Rita S, Sharatchandra KH and Singh THI: Preliminary studies on antiinflammatory and analgesic activities of Spilanthes acmella in experimental animal models. Indian J Pharmacol. 36:148–150. 2004.
19	Wu LC, Fan NC, Lin MH, Chu IR, Huang SJ, Hu CY and Han SY: Anti-inflammatory effect of spilanthol from Spilanthes acmella on murine macrophage by down-regulating LPS-induced inflammatory mediators. J Agric Food Chem. 56:2341–2349. 2008. View Article : Google Scholar : PubMed/NCBI
20	Hernández I, Márquez L, Martínez I, Dieguez R, Delporte C, Prieto S, Molina-Torres J and Garrido G: Anti-inflammatory effects of ethanolic extract and alkamides-derived from Heliopsis longipes roots. J Ethnopharmacol. 124:649–652. 2009. View Article : Google Scholar : PubMed/NCBI
21	Nair JJ, Aremu AO and Van SJ: Anti-inflammatory effects of Leucosidea sericea (Rosaceae) and identification of the active constituents. S Afr J Bot. 80:75–76. 2012. View Article : Google Scholar
22	Ratnasooriya WD and Pieris KPP: Attenuation of persistent pain and hyperalgesia by Spilanthus acmella flowers in rats. Pharm Biol. 43:614–619. 2005. View Article : Google Scholar
23	Déciga-Campos M, Rios MY and Aguilar-Guadarrama AB: Antinociceptive effect of Heliopsis longipes extract and affinin in mice. Planta Med. 76:665–670. 2010. View Article : Google Scholar : PubMed/NCBI
24	Arora S, Vijay S and Kumar D: Phytochemical and antimicrobial studies on the leaves of Spilanthes acmella. J Chem Pharm Res. 3:145–150. 2011.
25	Rosas-Piñón Y, Mejía A, Díaz-Ruiz G, Aguilar MI, Sánchez-Nieto S and Rivero-Cruz JF: Ethnobotanical survey and antibacterial activity of plants used in the Altiplane region of Mexico for the treatment of oral cavity infections. J Ethnopharmacol. 141:860–865. 2012. View Article : Google Scholar : PubMed/NCBI
26	Prachayasittikul S, Suphapong S, Worachartcheewan A, Lawung R, Ruchirawat S and Prachayasittikul V: Bioactive metabolites from Spilanthes acmella Murr. Molecules. 14:850–867. 2009. View Article : Google Scholar : PubMed/NCBI
27	Savadi R, Yadav R and Yadav N: Study on immunomodulatory activity of ethanolic extract Spilanthes acmella Murr. Leaves. Indian J Nat Prod Resour. 1:204–207. 2010.
28	Saritha KV and Naidu CV: Direct shoot regeneration from leaf explants of Spilanthes acmella. Biol Plant. 52:334–338. 2008. View Article : Google Scholar
29	Boonen J, Baert B, Roche N, Burvenich C and De Spiegeleer B: Transdermal behaviour of the N-alkylamide spilanthol (affinin) from Spilanthes acmella (Compositae) extracts. J Ethnopharmacol. 127:77–84. 2010. View Article : Google Scholar : PubMed/NCBI
30	Huang WC, Wu SJ, Tu RS, Lai YR and Liou CJ: Phloretin inhibits interleukin-1β-induced COX-2 and ICAM-1 expression through inhibition of MAPK, Akt, and NF-κB signaling in human lung epithelial cells. Food Funct. 6:1960–1967. 2015. View Article : Google Scholar : PubMed/NCBI
31	Huang WC, Fang LW and Liou CJ: Phloretin attenuates allergic airway inflammation and oxidative stress in asthmatic mice. Front Immunol. 8:1342017. View Article : Google Scholar : PubMed/NCBI
32	Kundu J, Chae IG and Chun KS: Fraxetin induces heme oxygenase-1 expression by activation of Akt/Nrf2 or AMP-activated protein kinase α/Nrf2 pathway in HaCaT cells. J Cancer Prev. 21:135–143. 2016. View Article : Google Scholar : PubMed/NCBI
33	Cho JW, Park K, Kweon GR, Jang BC, Baek WK, Suh MH, Kim CW, Lee KS and Suh SI: Curcumin inhibits the expression of COX-2 in UVB-irradiated human keratinocytes (HaCaT) by inhibiting activation of AP-1: p38 MAP kinase and JNK as potential upstream targets. Exp Mol Med. 37:186–192. 2005. View Article : Google Scholar : PubMed/NCBI
34	Seo WY, Youn GS, Choi SY and Park J: Butein, a tetrahydroxychalcone, suppresses pro-inflammatory responses in HaCaT keratinocytes. BMB Rep. 48:495–500. 2015. View Article : Google Scholar : PubMed/NCBI
35	Roy PK, Rashid F, Bragg J and Ibdah JA: Role of the JNK signal transduction pathway in inflammatory bowel disease. World J Gastroenterol. 14:200–202. 2008. View Article : Google Scholar : PubMed/NCBI
36	Zhai Y, Dang Y, Gao W, Zhang Y, Xu P, Gu J and Ye X: P38 and JNK signal pathways are involved in the regulation of phlorizin against UVB-induced skin damage. Exp Dermatol. 24:275–279. 2015. View Article : Google Scholar : PubMed/NCBI