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
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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.
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.
참고문헌 (25)
- Ahsan, M., "Constituents and cytotoxicity of Zanthoxylum rhesta stem bark", Fitoterapia, 71, pp.697~700 (2000)
- Beutler, B, "Tlr4 : central component of the sole mammalian LPS sensor", Curr. Opin. Immunol, 12, pp.20~26 (2000)
- Bouchier-Hayes, L., "CARDINAL roles in apoptosis and NFkappaB activation", Vitam. Horm, 67, pp.133~147 (2004)
- Bunikowski, R., "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, pp.344~348 (2001)
- Soo-Im Choi, "Antibacterial Activity of Essential Oils from Zanthoxylum piperitum A.P.DC. and Zanthoxylum schinifolium", Food Science and Biotechnology, 17(1), pp.195~198 (2008), 한국식품과학회
- Fedenko, E. S., "Cytokine gene expression in the skin and peripheral blood of atopic dermatitis patients and healthy individuals", Self Nonself, 2, pp.120~124 (2011)
- Gadaleta, R. M., "Activation of bile salt nuclear receptor FXR is repressed by pro-inflammatory cytokines activating NF-κB signaling in the intestine", Biochim. Biophys. Acta, 1812, pp.851~858 (2011)
- Gilmore, T. D., "Inhibition of NF-κB signaling as a strategy in disease therapy", Curr. Top. Microbiol. Immunol, 349, pp.245~263 (2011)
- Hawiger, J, "Innate immunity and inflammation : a transcriptional paradigm", Immunol. Res, 23, pp.99~109 (2001)
- Kanigur Sultuybek, G., "NF-κB as the mediator of metformin’s effect on ageing and ageing-related diseases", Clin. Exp. Pharmacol. Physiol, 46, pp.413~422 (2019)
- Kim, S. J., "The beneficial effect of vanillic acid on ulcerative colitis", Molecules, 15, pp.7208~7217 (2010)
- Kuida, K., "Altered cytokine export and apoptosis in mice deficient in interleukin‐1B converting enzyme", Science, 267, pp.2000~2002 (1995)
- Lamkanfi, M., "Caspase-1 activates nuclear factor of the kappa-enhancer in B cells independently of its enzymatic activity", J. Biol. Chem, 279, pp.24785~24793 (2004)
- Lee, S. H., "Cop, a caspase recruitment domain‐containing protein and inhibitor of caspase‐1 activation processing", J. Biol. Chem, 276, pp.34495~34500 (2001)
- Leiro, J. M., "Antioxidant activity and inhibitory effects of hydralazine on inducible NOS", COX-2 gene and protein expression in rat peritoneal macrophages, 2004, pp.4, 163~177
- Lind, L, "Circulating markers of inflammation and atherosclerosis", Atherosclerosis, 169, pp.203~214 (2003)
- 박해선, "Antimicrobial Activity of Seeds of Zanthoxylum piperitum against Oral Pathogen Streptococcus mutans", 생명과학회지, 18(2), pp.167~174 (2008), 한국생명과학회
- Shin, W. B., "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, pp.1001~1014 (2019)
- Siegmund, B., "IL-1 beta converting enzyme(caspase-1)in intestinal inflammation", PNASU, 98, pp.13249~13254 (2001)
- Cholpisut Tantapakul, "Antibacterial Compounds from Zanthoxylum rhetsa", Archives of Pharmacal Research, 35(7), pp.1139~1142 (2012), 대한약학회[DOI]
- Tegeder, I., "Cyclooxygenase-independent actions of cyclooxygenase inhibitors", FASEB J, 15, pp.2057~2072 (2001)
- Wang, X., "Dysregulation of receptor interacting protein‐2 and caspase recruitment domain only protein mediates aberrant caspase‐1 activation in Huntington’s disease", J. Neurosci, 25, pp.11645~11654 (2005)
- Wong, C. K., "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, pp.177~183 (2001)
- 우현심, "LPS로 유도된 RAW264.7 대식세포에 대한헛개나무(Hovenia dulcis) 추출물의 항염증 효과", 한국자원식물학회지, 31(5), pp.466~477 (2018), 한국자원식물학회[DOI]
- Yamazaki, E., "Antioxidant activity of Japanese pepper (Zanthoxylum piperitum DC.) fruit", Food Chem, 100, pp.171~177 (2007)