PECTINASE-MODIFIED RED GINSENG (GS-E3D) INHIBIT NF-ÎšB TRANSLOCATION AND NITRIC OXIDE PRODUCTION IN LIPOPOLYSACCHARIDE-STIMULATED RAW 264.7 CELLS
Objective: Red ginseng has been used as traditional medicines and functional foods in the world, because of its health benefits. The aim of this study was to elucidate the anti-inflammatory effect and mechanism of pectinase-modified red ginseng (GS-E3D) with a cellular model of lipopolysaccharide (LPS)-stimulated RAW264.7 cells.
Methods: To study the anti-inflammatory effect of GS-E3D, the key inflammation mediators such as nitric oxide (NO),prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), Cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-Î±), and interleukin (IL)-6 production as well as on nuclear factor kappa B (NF-ÎºB) and mitogen-activated protein kinases (MAPKs) activation, were measured by using the enzyme linked immunosorbent assay (ELISA)and Western blotting.
Results: GS-E3D potently inhibited TNF-Î± and IL-6 and also diminished NO over-production, which was accompanied by the down-regulation of iNOS expression. GS-E3D effectively suppressed LPS-induced NF-ÎºB activation through inhibiting the hyper-phosphorylation and degradation of IÎºB-Î± and phosphorylation of p38, ERK1/2 and JNK in MAPK signaling pathway.
Conclusion: GS-E3D has a potential to be as an anti-inflammatory agent for functional food or cosmetic materials targeting on the NF-ÎºB p65 and MAPKs signaling pathways.
2. Fujiwara N, Kobayashi K. Macrophages in inflammation. Curr Drug Targets: Inflammation Allergy 2005;4:281-6.
3. Nakagawa S, Arai Y, Kishida T, Hiraoka N, Tsuchida S, Inoue H, et al. Lansoprazole inhibits nitric oxide and prostaglandin E2 production in murine macrophage RAW 264.7 cells. Inflammation 2012;35:1062-8.
4. Zhang YL, Dong C. MAP kinases in immune responses. Cell Mol Immunol 2005;2:20-7.
5. Kim DH. Chemical diversity of panax ginseng, Panax quinquifolium, and Panax notoginseng. J Ginseng Res 2012;36:1-15.
6. Joh EH, Lee IA, Jung IH, Kim DH. Ginsenoside Rb1 and its metabolite compound K inhibit IRAK-1 activationâ€”the key step of inflammation. Biochem Pharmacol 2011;82:278-86.
7. Zhang YX, Wang L, Xiao EL, Li SJ, Chen JJ, Gao B, et al. Ginsenoside-Rd exhibits anti-inflammatory activities through elevation of antioxidant enzyme activities and inhibition of JNK and ERK activation in vivo. Int Immunopharmacol 2013;17:1094-100.
8. Chengwen L, Yongguang Y. Pulsed electric field treatment combined with commercial enzymes converts major ginsenoside Rb1 to minor ginsenoside Rd. Inovative Food Sci Emerging Technol 2014;22:95-101.
9. Yoon JH, Choi YJ, Cha SW, Lee SG. Anti-metastatic effects of ginsenoside Rd via inactivation of MAPK signaling and induction of focal adhesion formation. Phytomedicine 2012;19:284-92.
10. Wang L, Zhang Y, Wang Z, Li S, Min G, Wang L, et al. Inhibitory effect of ginsenoside-Rd on carrageenan-induced inflammation in rats. Can J Physiol Pharmacol 2012;90:229-36.
11. Liu X, Wang L, Wen A, Yang J, Yan Y, Song Y, et al. Ginsenoside-Rd improves outcome of acute ischaemic strokeâ€“a randomized, double-blind, placebo-controlled, multicenter trial. Eur J Neurol 2012;19:855â€“63.
12. Yang XL, Guo TK, Wang YH, Huang YH, Liu X, Wang XX, et al. Ginsenoside Rd attenuates the inflammatory response via modulating p38 and JNK signaling pathways in rats with TNBS-induced relapsing colitis. Int Immunopharmacol 2012;12:408-14.
13. Lee HY, Park KH, Park YM, Moon DI, Oh HG, Kwon DY, et al. Effects of pectin lyase-modified red ginseng extracts in high-fat diet (HFD)-fed obese mice. Lab Anim Res 2014;30:151-60.
14. Banskota AH, Tezuka Y, Nguyen NT, Awale S, Nobukawa T, Kadota S. DPPH radical scavenging and nitric oxide inhibitory activities of the constituents from the wood of Taxus yunnanensis. Planta Med 2003;69:500-5.
15. Guha M, Mackman N. LPS induction of gene expression in human monocytes. Cell Signal 2001;13:85-94.
16. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J 1992;6:3051-64.
17. Pan MH, Hong HM, Lin CL, Jhang AZ, Tsai JH, Badmaev V, et al. Semethylselenocysteine inhibits lipopolysaccharide-induced NF-kappaB activation and iNOS induction in RAW 264.7 muÂ¬rine macrophages. Mol Nutr Food Res 2011;55:723-32.
18. Yoon WJ, Kim SS, Oh TH, Lee NH, Hyun CG. Cryptomeria japonica essential oil inhibits the growth of drug-resistant skin pathogens and LPS-induced nitric oxide and pro-inflammatory cytokine production. Pol J Microbiol 2009;58:61-8.
19. Beutler B, Cerami A. The biology of cachectin/TNF-a primary mediator of the host response. Annu Rev Immunol 1989;7:625-55.
20. Balkwill F. TNF-alpha in promotion and progression of cancer. Cancer Metastasis Rev 2006;25:409-16.
21. Dinarello CA. Cytokines as endogenous pyrogens. J Infect Dis 1999;179:S294-304.
22. Lebovic DI, Bentzien F, Chao VA, Garrett EN, Meng YG, Taylor RN. Induction of an angiogenic phenotype in endometriotic stromal cell cultures by interleukin-1beta. Mol Hum Reprod 2000;6:269-75.
23. Yoshimura Y, Terabayashi T, Miki H. Par1b/MARK2 phosphorylates kinesin-like motor protein GAKIN/KIF13B to regulate axon formation. Mol Cell Biol 2010;30:2206-19.
24. Sung BK, Kim JW, Lee JH, Kim ND, Yoo MA, Kang HS, et al. The effect of lipopolysaccharide on enhanced inflammatory process with age: Modulation of NF-ÎºB. J Am Aging Assoc 2001;24:163-71.
25. Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 1999;18:6853-66.
26. Zhang G, Ghosh S. Molecular mechanisms of NF-kappaB activation induced by bacterial lipopolysaccharide through Toll-like receptors. J Endotoxin Res 2000;6:453-7.
27. Kim EK, Choi EJ. Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta 2010;2802:396-405.
28. Kim KN, Heo SJ, Yoon WJ, Kang SM, Ahn G, Yi TH, et al. Fucoxanthin inhibits the inflammatory response in lipopolysaccharide-induced RAW 264.7 macrophages. Eur J Pharmacol 2010b;649:369-75.