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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

Vaccaria hypaphorine alleviates lipopolysaccharide-induced inflammation via inactivation of NFκB and ERK pathways in Raw 264.7 cells

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

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Abstract

Background

Activation of macrophage is involved in many inflammation diseases. Lipopolysaccharide (LPS) is a powerful inflammatory signal contributing to monocytes/macrophages activation associated with increased proinflammatory cytokines expressions. We recently identified that vaccarin was expected to protect endothelial cells from injury. Hypaphorine was abundantly found in vaccaria semen. However, the potential roles and underlying mechanisms of vaccaria hypaphorine on macrophage inflammation have been poorly defined.

Methods

This study was designed to determine the effects of vaccaria hypaphorine on LPS-mediated inflammation in RAW 264.7 cells.

Results

In this study, we demonstrated that vaccaria hypaphorine dramatically ameliorated LPS-induced nitric oxide (NO) release and productions of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1) and prostaglandin E2 (PGE2) in RAW 264.7 cells. LPS-stimulated expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were down-regulated by vaccaria hypaphorine. Furthermore, vaccaria hypaphorine retarded LPS-induced phosphorylation of ERK, nuclear factor kappa beta (NFκB), NFκB inhibitor IκBα, and IKKβ. Immunofluorescence staining revealed that vaccaria hypaphorine eliminated the nuclear translocation of NFκB in LPS-treated RAW 264.7 cells.

Conclusion

It was seen that vaccaria hypaphorine counteracted inflammation via inhibition of ERK or/and NFκB signaling pathways. Collectively, we concluded that vaccaria hypaphorine can be served as an anti-inflammatory candidate.
Appendix
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Literature
1.
2.
McMorrow JP, Murphy EP. Inflammation: a role for NR4A orphan nuclear receptors? Biochem Soc Trans. 2011;39:688–93.CrossRefPubMed
3.
Badimon L, Suades R, Fuentes E, Palomo I, Padro T. Role of Platelet-Derived Microvesicles As Crosstalk Mediators in Atherothrombosis and Future Pharmacology Targets: A Link between Inflammation, Atherosclerosis, and Thrombosis. Front Pharmacol. 2016;7:293.CrossRefPubMedPubMedCentral
4.
5.
Ruiz-Nunez B, Dijck-Brouwer DA, Muskiet FA. The relation of saturated fatty acids with low-grade inflammation and cardiovascular disease. J Nutr Biochem. 2016;36:1–20.CrossRefPubMed
6.
Pesic M, Greten FR. Inflammation and cancer: tissue regeneration gone awry. Curr Opin Cell Biol. 2016;43:55–61.CrossRefPubMed
7.
Nguyen XT, Le L. Therapeutic Development of Interrelated Metabolic and Neurodegenerative Disorders. Curr Pharm Des. 2016;22:3608–18.CrossRefPubMed
8.
Fujiwara N, Kobayashi K. Macrophages in inflammation. Curr Drug Targets Inflamm Allergy. 2005;4:281–6.CrossRefPubMed
9.
Patel U, Rajasingh S, Samanta S, Cao T, Dawn B, Rajasingh J. Macrophage polarization in response to epigenetic modifiers during infection and inflammation. Drug Discov Today. 2017;22(1):186–93.CrossRefPubMed
10.
Berenbaum F. Proinflammatory cytokines, prostaglandins, and the chondrocyte: mechanisms of intracellular activation. Joint Bone Spine. 2000;67:561–4.CrossRefPubMed
11.
Karpurapu M, Wang X, Deng J, Park H, Xiao L, Sadikot RT, Frey RS, Maus UA, Park GY, Scott EW, Christman JW. Functional PU.1 in macrophages has a pivotal role in NF-kappaB activation and neutrophilic lung inflammation during endotoxemia. Blood. 2011;118:5255–66.CrossRefPubMedPubMedCentral
12.
Kang YJ, Mbonye UR, DeLong CJ, Wada M, Smith WL. Regulation of intracellular cyclooxygenase levels by gene transcription and protein degradation. Prog Lipid Res. 2007;46:108–25.CrossRefPubMedPubMedCentral
13.
Robertson Remen KM, Gustafsson JA, Andersson G. The liver X receptor promotes macrophage differentiation and suppresses osteoclast formation in mouse RAW264.7 promyelocytic leukemia cells exposed to bacterial lipopolysaccharide. Biochem Biophys Res Commun. 2013;430:375–80.CrossRefPubMed
14.
Huang BP, Lin CH, Chen YC, Kao SH. Anti-inflammatory effects of Perilla frutescens leaf extract on lipopolysaccharide-stimulated RAW264.7 cells. Mol Med Rep. 2014;10:1077–83.PubMed
15.
Lee HS, Kim DH, Hong JE, Lee JY, Kim EJ. Oxyresveratrol suppresses lipopolysaccharide-induced inflammatory responses in murine macrophages. Hum Exp Toxicol. 2015;34:808–18.CrossRefPubMed
16.
Sang SM, Xia ZH, Mao SL, Lao A, Chen ZL. Studies on the flavonol glycosides from the seeds of Vaccaria segetalis. Zhongguo Zhong Yao Za Zhi. 2000;25:221–2.PubMed
17.
Balsevich JJ, Ramirez-Erosa I, Hickie RA, Dunlop DM, Bishop GG, Deibert LK. Antiproliferative activity of Saponaria vaccaria constituents and related compounds. Fitoterapia. 2012;83:170–81.CrossRefPubMed
18.
Sun Y, Wang S, Li T, Li X, Jiao L, Zhang L. Purification, structure and immunobiological activity of a new water-soluble polysaccharide from the mycelium of Polyporus albicans (Imaz.) Teng. Bioresour Technol. 2008;99:900–4.CrossRefPubMed
19.
Xie F, Feng L, Cai W, Qiu Y, Liu Y, Li Y, Du B, Qiu L. Vaccarin promotes endothelial cell proliferation in association with neovascularization in vitro and in vivo. Mol Med Rep. 2015;12:1131–6.PubMed
20.
Qiu Y, Qiu L, Cui J, Wei Q. Bacterial cellulose and bacterial cellulose-vaccarin membranes for wound healing. Mater Sci Eng C Mater Biol Appl. 2016;59:303–9.CrossRefPubMed
21.
Xie F, Cai W, Liu Y, Li Y, Du B, Feng L, Qiu L. Vaccarin attenuates the human EA.hy926 endothelial cell oxidative stress injury through inhibition of Notch signaling. Int J Mol Med. 2015;35:135–42.PubMed
22.
Qiu Y, Du B, Xie F, Cai W, Liu Y, Li Y, Feng L, Qiu L. Vaccarin attenuates high glucose-induced human EA*hy926 endothelial cell injury through inhibition of Notch signaling. Mol Med Rep. 2016;13:2143–50.PubMed
23.
Ozawa M, Honda K, Nakai I, Kishida A, Ohsaki A. Hypaphorine, an indole alkaloid from Erythrina velutina, induced sleep on normal mice. Bioorg Med Chem Lett. 2008;18:3992–4.CrossRefPubMed
24.
Mollica A, Locatelli M, Stefanucci A, Pinnen F. Synthesis and bioactivity of secondary metabolites from marine sponges containing dibrominated indolic systems. Molecules. 2012;17:6083–99.CrossRefPubMed
25.
Kawano T, Kawano N, Hosoya H, Lapeyrie F. Fungal auxin antagonist hypaphorine competitively inhibits indole-3-acetic acid-dependent superoxide generation by horseradish peroxidase. Biochem Biophys Res Commun. 2001;288:546–51.CrossRefPubMed
26.
Zeng KW, Yu Q, Liao LX, Song FJ, Lv HN, Jiang Y, Tu PF. Anti-Neuroinflammatory Effect of MC13, a Novel Coumarin Compound From Condiment Murraya, Through Inhibiting Lipopolysaccharide-Induced TRAF6-TAK1-NF-kappaB, P38/ERK MAPKS and Jak2-Stat1/Stat3 Pathways. J Cell Biochem. 2015;116:1286–99.CrossRefPubMed
27.
Kurland DB, Gerzanich V, Karimy JK, Woo SK, Vennekens R, Freichel M, Nilius B, Bryan J, Simard JM. The Sur1-Trpm4 channel regulates NOS2 transcription in TLR4-activated microglia. J Neuroinflammation. 2016;13:130.CrossRefPubMedPubMedCentral
28.
Sun HJ, Zhang LL, Fan ZD, Chen D, Zhang L, Gao XY, Kang YM, Zhu GQ. Superoxide anions involved in sympathoexcitation and pressor effects of salusin-beta in paraventricular nucleus in hypertensive rats. Acta Physiol (Oxf). 2014;210:534–45.CrossRef
29.
Nicholas C, Batra S, Vargo MA, Voss OH, Gavrilin MA, Wewers MD, Guttridge DC, Grotewold E, Doseff AI. Apigenin blocks lipopolysaccharide-induced lethality in vivo and proinflammatory cytokines expression by inactivating NF-kappaB through the suppression of p65 phosphorylation. J Immunol. 2007;179:7121–7.CrossRefPubMed
30.
Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991;43:109–42.PubMed
31.
Bogdan C. Nitric oxide synthase in innate and adaptive immunity: an update. Trends Immunol. 2015;36:161–78.CrossRefPubMed
32.
Kim KY, Kang H. Sakuranetin Inhibits Inflammatory Enzyme, Cytokine, and Costimulatory Molecule Expression in Macrophages through Modulation of JNK, p38, and STAT1. Evid Based Complement Alternat Med. 2016;2016:9824203.PubMedPubMedCentral
33.
Jin X, Han J, Yang S, Hu Y, Liu H, Zhao F. 11-O-acetylcyathatriol inhibits MAPK/p38-mediated inflammation in LPS-activated RAW 264.7 macrophages and has a protective effect on ethanol-induced gastric injury. Mol Med Rep. 2016;14:874–80.PubMed
34.
Qureshi AA, Tan X, Reis JC, Badr MZ, Papasian CJ, Morrison DC, Qureshi N. Inhibition of nitric oxide in LPS-stimulated macrophages of young and senescent mice by delta-tocotrienol and quercetin. Lipids Health Dis. 2011;10:239.CrossRefPubMedPubMedCentral
35.
Kang HJ, Hong SH, Kang KH, Park C, Choi YH. Anti-inflammatory effects of Hwang-Heuk-San, a traditional Korean herbal formulation, on lipopolysaccharide-stimulated murine macrophages. BMC Complement Altern Med. 2015;15:447.CrossRefPubMedPubMedCentral
36.
Yan S, Zhang X, Zheng H, Hu D, Zhang Y, Guan Q, Liu L, Ding Q, Li Y. Clematichinenoside inhibits VCAM-1 and ICAM-1 expression in TNF-alpha-treated endothelial cells via NADPH oxidase-dependent IkappaB kinase/NF-kappaB pathway. Free Radic Biol Med. 2015;78:190–201.CrossRefPubMed
37.
Killian PH, Kronski E, Michalik KM, Barbieri O, Astigiano S, Sommerhoff CP, Pfeffer U, Nerlich AG, Bachmeier BE. Curcumin inhibits prostate cancer metastasis in vivo by targeting the inflammatory cytokines CXCL1 and -2. Carcinogenesis. 2012;33:2507–19.CrossRefPubMed
38.
Killeen MJ, Linder M, Pontoniere P, Crea R. NF-kappabeta signaling and chronic inflammatory diseases: exploring the potential of natural products to drive new therapeutic opportunities. Drug Discov Today. 2014;19:373–8.CrossRefPubMed
39.
Francois A, Milliat F, Guipaud O, Benderitter M. Inflammation and immunity in radiation damage to the gut mucosa. Biomed Res Int. 2013;2013:123241.PubMedPubMedCentral
40.
Cheng CY, Lee YC. Anti-Inflammatory Effects of Traditional Chinese Medicines against Ischemic Injury in In Vivo Models of Cerebral Ischemia. Evid Based Complement Alternat Med. 2016;2016:5739434.PubMedPubMedCentral
41.
Lin LL, Shan JJ. Application of Traditional Chinese Medical Herbs in Prevention and Treatment of Respiratory Syncytial Virus. Evid Based Complement Alternat Med. 2016;2016:6082729.PubMedPubMedCentral
42.
Lai F, Zhang Y, Xie DP, Mai ST, Weng YN, Du JD, Wu GP, Zheng JX, Han Y. A Systematic Review of Rhubarb (a Traditional Chinese Medicine) Used for the Treatment of Experimental Sepsis. Evid Based Complement Alternat Med. 2015;2015:131283.PubMedPubMedCentral
43.
Kouakou K, Schepetkin IA, Jun S, Kirpotina LN, Yapi A, Khramova DS, Pascual DW, Ovodov YS, Jutila MA, Quinn MT. Immunomodulatory activity of polysaccharides isolated from Clerodendrum splendens: beneficial effects in experimental autoimmune encephalomyelitis. BMC Complement Altern Med. 2013;13:149.CrossRefPubMedPubMedCentral
44.
Oppeltz RF, Rani M, Zhang Q, Schwacha MG. Burn-induced alterations in toll-like receptor-mediated responses by bronchoalveolar lavage cells. Cytokine. 2011;55:396–401.CrossRefPubMedPubMedCentral
45.
Mazur-Bialy AI, Pochec E, Plytycz B. Immunomodulatory effect of riboflavin deficiency and enrichment - reversible pathological response versus silencing of inflammatory activation. J Physiol Pharmacol. 2015;66:793–802.PubMed
46.
Qin X, Jiang X, Jiang X, Wang Y, Miao Z, He W, Yang G, Lv Z, Yu Y, Zheng Y. Micheliolide inhibits LPS-induced inflammatory response and protects mice from LPS challenge. Sci Rep. 2016;6:23240.CrossRefPubMedPubMedCentral
47.
Schwager J, Richard N, Mussler B, Raederstorff D. Tomato Aqueous Extract Modulates the Inflammatory Profile of Immune Cells and Endothelial Cells. Molecules. 2016;21:168.CrossRefPubMed
48.
Kaufmann KB, Gothwal M, Schallner N, Ulbrich F, Rucker H, Amslinger S, Goebel U. The anti-inflammatory effects of E-alpha-(p-methoxyphenyl)-2',3,4,4'-tetramethoxychalcone are mediated via HO-1 induction. Int Immunopharmacol. 2016;35:99–110.CrossRefPubMed
49.
Park JU, Kim SJ, Na CS, Choi CH, Seo CS, Son JK, Kang BY, Kim YR. Chondroprotective and anti-inflammatory effects of ChondroT, a new complex herbal medication. BMC Complement Altern Med. 2016;16:213.CrossRefPubMedPubMedCentral
50.
Kim SY, Park SM, Hwangbo M, Lee JR, Byun SH, Ku SK, Cho IJ, Kim SC, Jee SY, Park SJ. Cheongsangbangpung-tang ameliorated the acute inflammatory response via the inhibition of NF-kappaB activation and MAPK phosphorylation. BMC Complement Altern Med. 2017;17:46.CrossRefPubMedPubMedCentral
51.
Pektas MB, Koca HB, Sadi G, Akar F. Dietary Fructose Activates Insulin Signaling and Inflammation in Adipose Tissue: Modulatory Role of Resveratrol. Biomed Res Int. 2016;2016:8014252.CrossRefPubMedPubMedCentral
52.
Pansanit A, Park EJ, Kondratyuk TP, Pezzuto JM, Lirdprapamongkol K, Kittakoop P. Vermelhotin, an anti-inflammatory agent, suppresses nitric oxide production in RAW 264.7 cells via p38 inhibition. J Nat Prod. 2013;76:1824–7.CrossRefPubMed
53.
Li W, Zhou W, Cha JY, Kwon SU, Baek KH, Shim SH, Lee YM, Kim YH. Sterols from Hericium erinaceum and their inhibition of TNF-alpha and NO production in lipopolysaccharide-induced RAW 264.7 cells. Phytochemistry. 2015;115:231–8.CrossRefPubMed
54.
Huang N, Rizshsky L, Hauck CC, Nikolau BJ, Murphy PA, Birt DF. The inhibition of lipopolysaccharide-induced macrophage inflammation by 4 compounds in Hypericum perforatum extract is partially dependent on the activation of SOCS3. Phytochemistry. 2012;76:106–16.CrossRefPubMedPubMedCentral
55.
Yoo SR, Kim Y, Lee MY, Kim OS, Seo CS, Shin HK, Jeong SJ. Gyeji-tang water extract exerts anti-inflammatory activity through inhibition of ERK and NF-kappaB pathways in lipopolysaccharide-stimulated RAW 264.7 cells. BMC Complement Altern Med. 2016;16:390.CrossRefPubMedPubMedCentral
56.
Kim KJ, Yoon KY, Yoon HS, Oh SR, Lee BY. Brazilein Suppresses Inflammation through Inactivation of IRAK4-NF-kappaB Pathway in LPS-Induced Raw264.7 Macrophage Cells. Int J Mol Sci. 2015;16:27589–98.CrossRefPubMedPubMedCentral
57.
58.
Kim HG, Yang WS, Sung GH, Kim JH, Baek GS. IKK beta -Targeted Anti-Inflammatory Activities of a Butanol Fraction of Artificially Cultivated Cordyceps pruinosa Fruit Bodies. Evid Based Complement Alternat Med. 2014;2014:562467.PubMedPubMedCentral
Metadata
Title
Vaccaria hypaphorine alleviates lipopolysaccharide-induced inflammation via inactivation of NFκB and ERK pathways in Raw 264.7 cells
Publication date
01-12-2017
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-017-1635-1

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