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2019 Vol.32, Issue 6 Preview Page

Research Article

The Anti-inflammatory Mechanism of the Peel of Zanthoxylum piperitum D.C. is by Suppressing NF-κB/Caspase-1 Activation in LPS-Induced RAW264.7 Cells
Yun-Hee Choi1
,
Noh-Yil Myung1*
1Professor, Department of Oriental Medicine and Healthcare, Wonkwang Digital University, Iksan 570-749, Korea
* Corresponding Author
31 December 2019. pp. 669-676
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Abstract

Zanthoxylum piperitum D.C. (ZP) peels has been used as a natural spice and herb medicine for hypertension reduction, for strokes, and for its anti-bacterial and anti-oxidant activity. However, the anti-inflammatory mechanisms employed by ZP have yet to be completely understood. In this study, we elucidate the anti-inflammatory mechanism of ZP in lipopolysaccharide (LPS)-induced RAW264.7 cells. We evaluated the effects of ZP in LPS-induced levels of inflammatory cytokines, prostaglandin E2 (PGE2), and caspase-1 using ELISA. The expression levels of inflammatory- related genes, including cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS), were assayed by Western blot analysis. We elucidated the effect of ZP on nuclear factor (NF)-κB activation by means of a luciferase activity assay. The findings of this study demonstrated that ZP inhibited the production of inflammatory cytokine and PGE2 and inhibited the increased levels of COX-2 and iNOS caused by LPS. Additionally, we showed that the anti-inflammatory effect of ZP arises by suppressing the activation of NF-κB and caspase-1 in LPS- induced RAW264.7 cells. These results provide novel insights into the pharmacological actions of ZP as a potential candidate for development of new drugs to treat inflammatory diseases.

Keywords
Inflammation
Nuclear factor-kappa B
Caspase-1
Zanthoxylum piperitum D.C.
References
1
Ahsan, M., T.A. Zaman, C.M. Hasan, C. Ito and S.K. Islam. 2000. Constituents and cytotoxicity of Zanthoxylum rhesta stem bark. Fitoterapia 71:697-700.
10.1016/S0367-326X(00)00214-8
2
Beutler, B. 2000. Tlr4: central component of the sole mammalian LPS sensor. Curr. Opin. Immunol. 12:20-26.
10.1016/S0952-7915(99)00046-1
3
Bouchier-Hayes, L. and S.J. Martin. 2004. CARDINAL roles in apoptosis and NFkappaB activation. Vitam. Horm. 67:133-147.
10.1016/S0083-6729(04)67008-7
4
Bunikowski, R., K. Gerhold, M. Bräutigam, E. Hamelmann, H. Renz and U. Wahn. 2001. Effect of low-dose cyclosporin a microemulsion on disease severity, interleukin-6, interleukin -8 and tumor necrosis factor alpha production in severe pediatric atopic dermatitis. Int. Arch. Allergy Immunol. 125:344-348.
10.1159/00005383611574757
5
Choi, S.I., K.M. Chang, Y.S. Lee and G.H. Kim. 2008. Antibacterial activity of essential oils from Zanthoxylum piperitum A.P. DC. and Zanthoxylum schinifolium. Food Sci. Biotechnol. 17:195-198.
6
Fedenko, E.S., O.G. Elisyutina, T.M. Filimonova, M.N. Boldyreva, O.V. Burmenskaya, O.Y. Rebrova, A.A. Yarilin and R.M. Khaitov. 2011. Cytokine gene expression in the skin and peripheral blood of atopic dermatitis patients and healthy individuals. Self Nonself 2:120-124.
10.4161/self.2.2.1693922299064PMC3268998
7
Gadaleta, R.M., B. Oldenburg, E.C. Willemsen, M, Spit, S. Murzilli, L. Salvatore, L.W. Klomp, P.D. Siersema, K.J. van Erpecum and S.W. van Mil. 2011. Activation of bile salt nuclear receptor FXR is repressed by pro-inflammatory cytokines activating NF-κB signaling in the intestine. Biochim. Biophys. Acta. 1812:851-858.
10.1016/j.bbadis.2011.04.00521540105
8
Gilmore, T.D. and M.R. Garbati. 2011. Inhibition of NF-κB signaling as a strategy in disease therapy. Curr. Top. Microbiol. Immunol. 349:245-263.
10.1007/82_2010_10521113699
9
Hawiger, J. 2001. Innate immunity and inflammation: a transcriptional paradigm. Immunol. Res. 23:99-109.
10.1385/IR:23:2-3:099
10
Kanigur Sultuybek, G., T. Soydas and G. Yenmis. 2019. NF-κB as the mediator of metformin's effect on ageing and ageing-related diseases. Clin. Exp. Pharmacol. Physiol. 46:413-422.
10.1111/1440-1681.1307330754072
11
Kim, S.J., M.C. Kim, J.Y. Um and S.H. Hong. 2010. The beneficial effect of vanillic acid on ulcerative colitis. Molecules 15:7208-7217.
10.3390/molecules1510720820959795PMC6259113
12
Kuida, K., J.A. Lippke and G. Ku. 1995. Altered cytokine export and apoptosis in mice deficient in interleukin‐1B converting enzyme. Science 267: 2000-2002.
10.1126/science.75354757535475
13
Lamkanfi, M., M. Kalai, X. Saelens, W. Declercq and P. Vandenabeele. 2004. Caspase-1 activates nuclear factor of the kappa-enhancer in B cells independently of its enzymatic activity. J. Biol. Chem. 279:24785-24793.
10.1074/jbc.M40098520015039421
14
Lee, S.H., C. Stehlik and J.C. Reed. 2001. Cop, a caspase recruitment domain‐containing protein and inhibitor of caspase‐1 activation processing. J. Biol. Chem. 276:34495- 34500.
10.1074/jbc.M10141520011432859
15
Leiro, J.M., E. Alvarez, J.A. Arranz, E. Cano and F. Orallo. 2004. Antioxidant activity and inhibitory effects of hydralazine on inducible NOS/COX-2 gene and protein expression in rat peritoneal macrophages. Int. Immunopharmacol. 4:163-177.
10.1016/j.intimp.2003.10.00414996408
16
Lind, L. 2003. Circulating markers of inflammation and atherosclerosis. Atherosclerosis 169:203-214.
10.1016/S0021-9150(03)00012-1
17
Park, H.S., D.Y. Jun, Z. Fang, M.H. Woo and Y.H. Kim. 2008. Antimicrobial activity of seeds of Zanthoxylum piperitum against oral pathogen Streptococcus mutants. J. Life Sci. 18:167-174.
10.5352/JLS.2008.18.2.167
18
Shin, W.B., X. Dong, Y.S. Kim, J.S. Park, S.J. Kim, E.A. Go, E.K. Kim and P.J. Park. 2019. Anti-inflammatory effects of Batillaria multiformis water extracts via NF-кB and MAPK signaling pathways in LPS-induced RAW264.7 cells. Adv. Exp. Med. Biol. 1155:1001-1014.
10.1007/978-981-13-8023-5_8331468463
19
Siegmund, B., H.A. Lehr, G. Fantuzzi and C.A. Dinarello. 2001. IL-1 beta converting enzyme (caspase-1) in intestinal inflammation. PNASU. 98:13249-13254.
10.1073/pnas.23147399811606779PMC60856
20
Tantapakul, C., W. Phakhodee, T. Ritthiwigrom, K. Yossathera, S. Deachathai and S. Laphookhieo. 2012. Antibacterial compounds from Zanthoxylum rhetsa. Arch. Pharm. Res. 35:1139-1142.
10.1007/s12272-012-0703-922864735
21
Tegeder, I., J. Pfeilschifter and G. Geisslinger. 2001. Cyclooxygenase-independent actions of cyclooxygenase inhibitors. FASEB J. 15:2057-2072.
10.1096/fj.01-0390rev11641233
22
Wang, X., H.Y. Wang and E.F. Bryan. 2005. Dysregulation of receptor interacting protein‐2 and caspase recruitment domain only protein mediates aberrant caspase‐1 activation in Huntington's disease. J. Neurosci. 25:11645-11654.
10.1523/JNEUROSCI.4181-05.200516354923PMC6726023
23
Wong, C.K., C.Y. Ho, F.W. Ko, C.H. Chan, A.S. Ho, D.S. Hui and C.W. Lam. 2001. Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-gamma, IL-4, IL-10 and IL-13) in patients with allergic asthma. Clin. Exp. Immunol. 125:177-183.
10.1046/j.1365-2249.2001.01602.x11529906PMC1906135
24
Woo, H.S., S.M. Lee, J.D. Heo, M.S. Lee, Y.S. Kim and D.W. Kim. 2018. Anti-inflammatory activity of extracts of Hovenia dulcis on lipopolysaccharides-stimulated RAW 264.7 cells. Korean J. Plant Res. 31:466-477.
25
Yamazaki, E., M. Inagaki, O. Kurita and T. Inoue. 2007. Antioxidant activity of Japanese pepper (Zanthoxylum piperitum DC.) fruit. Food Chem. 100:171-177.
10.1016/j.foodchem.2005.09.036
Information
  • Publisher :The Plant Resources Society of Korea
  • Publisher(Ko) :한국자원식물학회
  • Journal Title :Korean Journal of Plant Resources
  • Journal Title(Ko) :한국자원식물학회지
  • Volume : 32
  • No :6
  • Pages :669-676
  • Received Date : 2019-10-18
  • Revised Date : 2019-11-18
  • Accepted Date : 2019-11-19
  • DOI :https://doi.org/10.7732/kjpr.2019.32.6.669
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