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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

Nomilin Attenuates Lipopolysaccharide-Induced Inflammatory Response by Binding with Myeloid Differentiation Protein-2

Author(s): Yuting Chen, Song Guo*, Guirong Chen*, Chang Liu, Mingbo Zhang and Xiaobo Wang*

Volume 26, Issue 14, 2023

Published on: 10 May, 2023

Page: [2469 - 2475] Pages: 7

DOI: 10.2174/1386207326666230418112827

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Abstract

Background: Nomilin shows anti-inflammatory activity by inhibiting the activation of the Toll-like receptor 4 (TLR 4)/NF-κB pathway. However, the key target of the anti-inflammatory activity of nomilin has not been elaborated and needs further exploration.

Objective: This study aimed to assess the drug potential of nomilin and its ability to target myeloid differentiation protein 2 (MD-2) as a mechanism underlying the anti-inflammatory activity of nomilin on the lipopolysaccharide (LPS)-TLR4/MD-2-NF-κB signaling pathways.

Methods: The methods of ForteBio and molecular docking were used to investigate the internation between MD-2 and nomilin. 3-(4,5)-Dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide experiment was performed to test the effect of nomilin on cell viability. Enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blot experiments were carried out to assess the anti-inflammatory activity and possible mechanism of nomilin in vitro.

Results: The results indicated that nomilin exhibited binding affinity with MD-2. Nomilin significantly reduced the release and expression of NO, IL-6, TNF-α, and IL-1β induced by LPS in vitro. It inhibited the expression of LPS-TLR4/MD-2-NF-κB signaling pathway proteins, such as TLR4, Myd88, P65, P-P65, and iNOS.

Conclusion: Our results suggested that nomilin had therapeutic potential and was bound to MD-2. Nomilin exhibited anti-inflammatory activity by binding to the key protein MD-2 and inhibiting the LPS-TLR4/MD-2-NF-κB signaling pathway.

« Previous Next »
[1]
Herman, Z.; Hasegawa, S.; Ou, P. Nomilin acetyl-lyase, a bacterial enzyme for nomilin debittering of citrus juices. J. Food Sci., 1985, 50(1), 118-120.
[http://dx.doi.org/10.1111/j.1365-2621.1985.tb13290.x]
[2]
Rouseff, R.L.; Matthews, R.F. Nomilin, taste threshold and relative bitterness. J. Food Sci., 1984, 49(3), 777-779.
[http://dx.doi.org/10.1111/j.1365-2621.1984.tb13209.x]
[3]
Luo, X.R.; FAN, J.D.; Mo, B.B.; Yang, J. Response surface optimization of supercritical carbon dioxide extraction of nomilin from citrus seeds. Shipin Kexue, 2010, 31, 74-76.
[4]
Zheng, S.Z.; Yang, H.P.; Meng, J.C.; Ma, X.M.; Shen, X.W. Studies on the constituents from the seeds of M.sikkimensis H. J. Northwest Univ. Nat., 2003, 39, 54-57.
[5]
Hasegawa, S.; Lam, L.K.T. Antitumor agent. U.S.Patent 5041425, 1991.
[6]
Battinelli, L.; Mengoni, F.; Lichtner, M.; Mazzanti, G.; Saija, A.; Mastroianni, C.M.; Vullo, V. Effect of limonin and nomilin on HIV-1 replication on infected human mononuclear cells. Planta Med., 2003, 69(10), 910-913.
[http://dx.doi.org/10.1055/s-2003-45099] [PMID: 14648393]
[7]
Liu, Z.M.; Sun, Y.; Gao, Y.C.; Long, H.C.; Lei, T.; Du, H.J. Effects of Nomilin on inflammatory response in Klebsiella-induced geriatric pneumonia rats. Chin. J. Immunol., 2019, 35, 970-975.
[8]
Pratheeshkumar, P.; Kuttan, G. Nomilin inhibits tumor-specific angiogenesis by downregulating VEGF, NO and proinflammatory cytokine profile and also by inhibiting the activation of MMP-2 and MMP-9. Eur. J. Pharmacol., 2011, 668(3), 450-458.
[http://dx.doi.org/10.1016/j.ejphar.2011.07.029] [PMID: 21839074]
[9]
Rajaiah, R.; Perkins, D.J.; Ireland, D.D.C.; Vogel, S.N. CD14 dependence of TLR4 endocytosis and TRIF signaling displays ligand specificity and is dissociable in endotoxin tolerance. Proc. Natl. Acad. Sci., 2015, 112(27), 8391-8396.
[http://dx.doi.org/10.1073/pnas.1424980112] [PMID: 26106158]
[10]
Ren, W.; Wang, Z.; Hua, F.; Zhu, L. Plasminogen activator inhibitor-1 regulates LPS-induced TLR4/MD-2 pathway activation and inflammation in alveolar macrophages. Inflammation, 2015, 38(1), 384-393.
[http://dx.doi.org/10.1007/s10753-014-0042-8] [PMID: 25342286]
[11]
Alexander, C.; Rietschel, E.T. Bacterial lipopolysaccharides and innate immunity. J. Endotoxin Res., 2001, 7(3), 167-202.
[PMID: 11581570]
[12]
Miyake, K. Endotoxin recognition molecules, Toll-like receptor 4-MD-2. Semin. Immunol., 2004, 16(1), 11-16.
[http://dx.doi.org/10.1016/j.smim.2003.10.007] [PMID: 14751758]
[13]
Hsu, C.C.; Lien, J.C.; Chang, C.W.; Chang, C.H.; Kuo, S.C.; Huang, T.F. Yuwen02f1 suppresses LPS-induced endotoxemia and adjuvant-induced arthritis primarily through blockade of ROS formation, NFkB and MAPK activation. Biochem. Pharmacol., 2013, 85(3), 385-395.
[http://dx.doi.org/10.1016/j.bcp.2012.11.002] [PMID: 23142712]
[14]
Akashi, S.; Saitoh, S.; Wakabayashi, Y.; Kikuchi, T.; Takamura, N.; Nagai, Y.; Kusumoto, Y.; Fukase, K.; Kusumoto, S.; Adachi, Y.; Kosugi, A.; Miyake, K. Lipopolysaccharide interaction with cell surface Toll-like receptor 4-MD-2: higher affinity than that with MD-2 or CD14. J. Exp. Med., 2003, 198(7), 1035-1042.
[http://dx.doi.org/10.1084/jem.20031076] [PMID: 14517279]
[15]
Baomin, F.; Yuehu, P. Chemical constituents of the peels of citrus grandis. J. Shenyang Pharm. Univ., 2000, 17, 332-333.
[16]
Nagai, Y.; Akashi, S.; Nagafuku, M.; Ogata, M.; Iwakura, Y.; Akira, S.; Kitamura, T.; Kosugi, A.; Kimoto, M.; Miyake, K. Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat. Immunol., 2002, 3(7), 667-672.
[http://dx.doi.org/10.1038/ni809] [PMID: 12055629]
[17]
Nagata, M. Inflammatory cells and oxygen radicals. Curr. Drug Targets Inflamm. Allergy, 2005, 4(4), 503-504.
[http://dx.doi.org/10.2174/1568010054526322] [PMID: 16101529]
[18]
Gordon, S.; Taylor, P.R. Monocyte and macrophage heterogeneity. Nat. Rev. Immunol., 2005, 5(12), 953-964.
[http://dx.doi.org/10.1038/nri1733] [PMID: 16322748]
[19]
Zhang, X.; Song, Y.; Ci, X.; An, N.; Ju, Y.; Li, H.; Wang, X.; Han, C.; Cui, J.; Deng, X. Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice. Inflamm. Res., 2008, 57(11), 524-529.
[http://dx.doi.org/10.1007/s00011-008-8007-8] [PMID: 19109745]
[20]
Snyder, S.H.; Bredt, D.S. Nitric oxide as a neuronal messenger. Trends Pharmacol. Sci., 1991, 12(4), 125-128.
[http://dx.doi.org/10.1016/0165-6147(91)90526-X] [PMID: 1712138]
[21]
Lai, L.; Chen, Y.; Tian, X.; Li, X.; Zhang, X.; Lei, J.; Bi, Y.; Fang, B.; Song, X. Artesunate alleviates hepatic fibrosis induced by multiple pathogenic factors and inflammation through the inhibition of LPS/TLR4/NF-κB signaling pathway in rats. Eur. J. Pharmacol., 2015, 765, 234-241.
[http://dx.doi.org/10.1016/j.ejphar.2015.08.040] [PMID: 26318197]
[22]
Tak, P.P.; Firestein, G.S. NF-κB: A key role in inflammatory diseases. J. Clin. Invest., 2001, 107(1), 7-11.
[http://dx.doi.org/10.1172/JCI11830] [PMID: 11134171]
[23]
Aupperle, K.R.; Bennett, B.L.; Han, Z.; Boyle, D.L.; Manning, A.M.; Firestein, G.S. NF-κ B regulation by I κ B kinase-2 in rheumatoid arthritis synoviocytes. J. Immunol., 2001, 166(4), 2705-2711.
[http://dx.doi.org/10.4049/jimmunol.166.4.2705] [PMID: 11160335]
[24]
Scheidereit, C. IκB kinase complexes: Gateways to NF-κB activation and transcription. Oncogene, 2006, 25(51), 6685-6705.
[http://dx.doi.org/10.1038/sj.onc.1209934] [PMID: 17072322]
[25]
Arend, W.P.; Dayer, J.M. Inhibition of the production and effects of interleukins-1 and tumor necrosis factor α in rheumatoid arthritis. Arthritis Rheum., 1995, 38(2), 151-160.
[http://dx.doi.org/10.1002/art.1780380202] [PMID: 7848304]
[26]
Jung, W.K.; Choi, I.; Lee, D.Y.; Yea, S.S.; Choi, Y.H.; Kim, M.M.; Park, S.G.; Seo, S.K.; Lee, S.W.; Lee, C.M.; Park, Y.M.; Choi, I.W. Caffeic acid phenethyl ester protects mice from lethal endotoxin shock and inhibits lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW 264.7 macrophages via the p38/ERK and NF-κB pathways. Int. J. Biochem. Cell Biol., 2008, 40(11), 2572-2582.
[http://dx.doi.org/10.1016/j.biocel.2008.05.005] [PMID: 18571461]
[27]
He, T.; Jia, W.J.; Wang, W.W. Screening of 14-3-3τ protein inhibitors from natural products based on fluorescence spectroscopy, surface plasmon resonance and molecular docking technique. J Int. Pharm. Res., 2019, 46(8), 582-590.

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