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19.04.2018 | Original Article

In vitro anti-inflammatory activity of terpenes via suppression of superoxide and nitric oxide generation and the NF-κB signalling pathway

verfasst von: Franciane Martins Marques, Mariana Moreira Figueira, Elisângela Flávia Pimentel Schmitt, Tamara P. Kondratyuk, Denise Coutinho Endringer, Rodrigo Scherer, Marcio Fronza

Erschienen in: Inflammopharmacology | Ausgabe 2/2019

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Abstract

Background and Aims

Terpenes are considered the main components of essential oils and an important source for the identification of novel lead molecules. This study aimed to investigate the in vitro anti-inflammatory activity of l-carveol, l-carvone, and m-cimene (monoterpenes) and of valencene and guaiene (sesquiterpenes).

Methods

The influence on intracellular nitric oxide (NO) and pro- and anti-inflammatory cytokine (TNF-α, IL-1α and IL-10) production and on nuclear factor kappa B (NF-κB) activity was determined using Griess reagent, immunoenzymatic assay kits (ELISA) and chemiluminescence measurements in cell-based assays, respectively. Antioxidant activity was assayed through the protective effect against cellular oxidative damage produced by superoxide anion production (O ₂ ^·− ) and hydrogen peroxide on macrophages and by the quenching activity of the NO radical.

Results and Discussion

Terpenes reduced the pro-inflammatory cytokines TNF-α and IL-1α and increased the production of IL-10. In addition, the terpenes, especially guaiene (53.3 ± 2.4%) and m-cymene (38.1 ± 0.6%), significantly inhibited NO production in a macrophage cell culture-based assay, whereas no effect was observed in the scavenging activity of this radical. l-carveol and m-cymene significantly inhibited O ₂ ^·− production with reductions of approximately 68.6 ± 2.2% and 48.2 ± 4.2%, respectively, at a concentration of 10 μM. Moreover, these terpenes were verified to suppress NF-κB activity. The results indicate that these terpenes have therapeutic potential and may be used to suppress inflammatory diseases or as a leading compounds.

Adetutu A, Morgan WA, Corcoran O (2011) Antibacterial, antioxidant and fibroblast growth stimulation activity of crude extracts of Bridelia ferruginea leaf, a wound-healing plant of Nigeria. J Ethnopharmacol 133(1):116–119CrossRef

Ambrož M, Boušová I, Skarka A, Hanušová V, Králová V, Matoušková P, Szotáková B, Skálová L (2015) The influence of sesquiterpenes from Myrica rubra on the antiproliferative and pro-oxidative effects of doxorubicin and its accumulation in cancer cells. Molecules 20(8):15343–15358CrossRef

Annan K, Houghton PJ (2008) Antibacterial, antioxidant and fibroblast growth stimulation of aqueous extracts of Ficus asperifolia Miq. and Gossypium arboreum L., wound-healing plants of Ghana. J Ethnopharmacol 119(1):141–144CrossRef

Baker R, Hayden M, Ghosh S (2011) NF-κB, inflammation, and metabolic disease. Cell Metab 13(1):11–22CrossRef

Barreiros A, David J, David J (2006) Estresse oxidativo: relação entre geração de espécies reativas e defesa do organismo. Quím Nova 29(1):113–123CrossRef

Bates JN, Baker MT, Guerra R Jr, Harrison DG (1991) Nitric oxide generation from nitroprusside by vascular tissue: evidence that reduction of the nitroprusside anion and cyanide loss are required. Biochem Pharmacol 42:S157–S165CrossRef

Brune K, Patrignani P (2015) New insights into the use of currently available non-steroidal anti-inflammatory drugs. J Pain Res 8:105–118CrossRef

Choi HS, Kim JW, Cha YN, Kim C (2006) A quantitative nitroblue tetrazolium assay for determining intracellular superoxide anion production in phagocytic cells. J Immunoassay Immunochem 27(1):31–44CrossRef

Coleman JW (2001) Nitric oxide in immunity and inflammation. Int Immunopharmacol 8:1397–1406CrossRef

Crowell P, Kennan W, Haag J, Ahmad S, Vedejs E, Gould M (1992) Chemoprevention of mammary carcinogenesis by hydroxylated derivatives of d-limonene. Carcinogenesis 13(7):1261–1264CrossRef

Dang T, Süssmuth RD (2017) Bioactive peptide natural products as lead structures for medicinal use. Acc Chem Res 50(7):1566–1576CrossRef

De Sousa DP, de Farias Nóbrega FF, de Almeida RN (2007) Influence of the chirality of (R)-(−)- and (S)-(+)-carvone in the central nervous system: a comparative study. Chirality 19(4):264–268CrossRef

De Stefano D, Maiuri MC, Simeon V, Grassia G, Soscia A, Cinelli MP, Carnuccio R (2007) Lycopene, quercetin and tyrosol prevent macrophage activation induced by gliadin and IFN-gamma. Eur J Pharmacol 566(1–3):192–199CrossRef

Deutschman CS, Tracey KJ (2014) Sepsis: current dogma and new perspectives. Immunity 40:463–475CrossRef

Echeverrigaray S, Zacaria J, Beltrão R (2010) Nematicidal activity of monoterpenoids against the root-knot nematode Meloidogyne incognita. Phytopathology 100(2):199–203CrossRef

Feghali CA, Wright TM (1997) Cytokines in acute and chronic inflammation. Front Biosci 2:12–26

Filippin LI, Vercelino R, Marroni NP, Xavier RM (2008) Influência de processos redox na resposta inflamatória da artrite reumatóide. Revista Brasileira de Reumatologia 48(1):17–24CrossRef

Fullerton JN, Gilroy DW (2016) Resolution of inflammation: a new therapeutic frontier. Nat Rev Drug Discov 15:551–567CrossRef

Gautam R, Jachak SM (2009) Recent developments in anti-inflammatory natural products. Med Res Rev 29(5):767–820CrossRef

Gonçalves JC, Oliveira Fde S, Benedito RB, de Sousa DP, de Almeida RN, de Araújo DA (2008) Antinociceptive activity of (−)-carvone: evidence of association with decreased peripheral nerve excitability. Biol Pharm Bull 31(5):1017–1020CrossRef

Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 126(1):131–138CrossRef

Hamidzadeh K, Christensen SM, Dalby E, Chandrasekaran P, Mosser DM (2017) Macrophages and the recovery from acute and chronic inflammation. Annu Ver Physiol 79:567–592CrossRef

Homhual S, Zhang HJ, Bunyapraphatsara N, Kondratyuk TP, Santarsiero BD, Mesecar AD, Herunsalee A, Chaukul W, Pezzuto JM, Fong HH (2006) Bruguiesulfurol, a new sulfur compound from Bruguiera gymnorrhiza. Planta Med 72(3):255–260CrossRef

Hussain AI, Anwar F, Nigam PS, Ashraf M, Gilani AH (2010) Seasonal variation in content, chemical composition and antimicrobial and cytotoxic activities of essential oils from four Mentha species. J Sci Food Agric 90:1827–1836PubMed

Kim S, Jung E, Kim JH, Park YH, Lee J, Park D (2011) Inhibitory effects of (−)-α-bisabolol on LPS-induced inflammatory response in RAW264.7 macrophages. Food Chem Toxicol 49(10):2580–2585CrossRef

Kolaczkowska E, Kubes P (2013) Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol 13(3):159–175CrossRef

Kondratyuk TP, Park EJ, Yu R, Van Breemen RB, Asolkar RN, Murphy BT, Fenical W, Pezzuto JM (2012) Novel marine phenazines as potential cancer chemopreventive and anti-inflammatory agents. Mar Drugs 10:451–464CrossRef

Koo HJ, Song YS, Kim HJ, Lee YH, Hong SM, Kim SJ, Kim BC, Jin C, Lim CJ, Park EH (2004) Antiinflammatory effects of genipin, an active principle of gardenia. Eur J Pharmacol 495(2–3):201–208CrossRef

Kopf M, Bachmann MF, Marsland BJ (2010) Averting inflammation by targeting the cytokine environment. Nat Rev Drug Discov 9(9):703–718CrossRef

Lawrence T (2009) The Nuclear Factor NF-κB Pathway in Inflammation. Cold Spring Harb Perspect Biol 1(6):a001651CrossRef

Low P, Clark AM, Chou TC, Chang TC, Reynolds M, Ralph SJ (2015) Immunomodulatory activity of Melaleuca alternifolia concentrate (MAC): inhibition of LPS-induced NF-κB activation and cytokine production in myeloid cell lines. Int Immunopharmacol 26(1):257–264CrossRef

Lozon Y, Sultan A, Lansdell S, Prytkova T, Sadek B, Yang KH, Howarth FC, Millar NS, Oz M (2016) Inhibition of human α7 nicotinic acetylcholine receptors by cyclic monoterpene carveol. Eur J Pharmacol 776:44–51CrossRef

Marchese A, Arciola CR, Barbieri R, Silva AS, Nabavi SF, Tsetegho Sokeng AJ, Izadi M, Jafari NJ, Suntar I, Daglia M, Nabavi SM (2017) Update on monoterpenes as antimicrobial agents: a particular focus on p-cymene. Materials 10(8):E947. https://doi.org/10.3390/ma10080947 CrossRefPubMed

Mendes S, Mansoor T, Rodrigues A, Armas J, Ferreira M (2013) Anti-inflammatory guaiane-type sesquiterpenes from the fruits of Pittosporum undulatum. Phytochemistry 95:308–314CrossRef

Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63CrossRef

Omolo MO, Okinyo D, Ndiege IO, Lwande W, Hassanali A (2004) Repellency of essential oils of some Kenyan plants against Anopheles gambiae. Phytochemistry 65(20):2797–2802CrossRef

Patel P, Thakkar V (2014) l-carvone induces p53, caspase 3 mediated apoptosis and inhibits the migration of breast cancer cell lines. Nutr Cancer 66(3):453–462CrossRef

Pereira-Leite C, Nunes C, Jamal SK, Cuccovia IM, Reis S (2017) nonsteroidal anti-inflammatory therapy: a journey toward safety. Med Res Rev 37(4):802–859CrossRef

Rozza AL, Meira de Faria F, Souza Brito AR, Pellizzon CH (2014) The gastroprotective effect of menthol: involvement of anti-apoptotic, antioxidant and anti-inflammatory activities. PLoS One 9(1):e86686CrossRef

Salminen A, Lehtonen M, Suuronen T, Kaarniranta K, Huuskonen J (2008) Terpenoids: natural inhibitors of NF-kappaB signaling with anti-inflammatory and anticancer potential. Cell Mol Life Sci 65(19):2979–2999CrossRef

Schett G, Elewaut D, McInnes IB, Dayer JM, Neurath MF (2013) How cytokine networks fuel inflammation: toward a cytokine-based disease taxonomy. Nat Med 19(7):822–824CrossRef

Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, Warren JT, Bokesch H, Kenney S, Boyd MR (1990) New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst 82(13):1107–1112CrossRef

Surh YJ, Chun KS, Cha HH, Han SS, Keum YS, Park KK, Lee SS (2001) Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat Res 480–481:243–268CrossRef

Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84CrossRef

Wagner KH, Elmadfa I (2003) Biological relevance of terpenoids. Overview focusing on mono-, di- and tetraterpenes. Ann Nutr Metab 47:95–106CrossRef

Yadav VR, Prasad S, Sung B, Kannappan R, Aggarwal BB (2010) Targeting inflammatory pathways by triterpenoids for prevention and treatment of cancer. Toxins (Basel) 2(10):2428–2466CrossRef

Yang I, Lee D, Shin H (2016) Inhibitory effect of valencene on the development of atopic dermatitis-like skin lesions in nc/nga mice. J Evid-Based Complement Altern Med 2016:1–11

Zhang K, Song F, Lu X, Chen W, Huang C, Li L, Liang D, Cao S, Dai H (2017) MicroRNA-322 inhibits inflammatory cytokine expression and promotes cell proliferation in LPS-stimulated murine macrophages by targeting NF-κB1 (p50). Biosci Rep 37(1):BSR20160239CrossRef

Titel: In vitro anti-inflammatory activity of terpenes via suppression of superoxide and nitric oxide generation and the NF-κB signalling pathway
verfasst von: Franciane Martins Marques
Mariana Moreira Figueira
Elisângela Flávia Pimentel Schmitt
Tamara P. Kondratyuk
Denise Coutinho Endringer
Rodrigo Scherer
Marcio Fronza
Publikationsdatum: 19.04.2018
Verlag: Springer International Publishing
Erschienen in: Inflammopharmacology / Ausgabe 2/2019
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-018-0483-z

Springer Medizin

Abstract

Background and Aims

Methods

Results and Discussion

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