BIOACTIVE FRACTION DLBS2411 FROM CINNAMOMUM BURMANNII, (NEES AND T. NEES) BLUME AS COLON AND GASTROPROTECTOR BY STIMULATING MUC5AC AND CYCLOOXYGENASE-2 GENE EXPRESSION
Keywords:
DLBS2411, Mucus production, MUC5AC, Prostaglandin, Cinnamomum burmanniiAbstract
Objective: Mucus therapy is one of the therapies for gastric ulcer management aside from proton pump inhibitor (PPI) and H2-blocker medication. Bioactive fraction DLBS2411 which comes from Cinnamomum burmannii has been identified as a gastric acid anti-secretory agent by inhibiting the activity of hydrogen-potassium adenosine triphosphate (H+/K+ATPase). The study was aimed to evaluate the effect of DLBS2411 as a neuroprotective agent in gastric and colon by investigating its regulation on mucus related pathway.
Methods: Total RNA was extracted from gastric and colon cells followed by quantitative real-time polymerase chain reaction (qPCR) analysis for mucus synthesis and mucosal blood flow gene expression. Protein expression of prostaglandin E2 (PGE2) and phosphorylation of IĸB kinase subunit alpha (IKKα) was analyzed with enzyme-linked immunosorbent assay (ELISA) kit and western blot. Measurement of nitric oxide (NO), which is related to mucosal blood flow, was also analyzed.
Results: Treatment of DLBS2411 elevated phosphorylation of IKKα and activated nuclear factor-КB (NF-κB) which in turn stimulated mucus synthesis and mucosal blood flow. High level of NF-κB increased mucus synthesis pathway by promoting cyclooxygenase-2 (COX-2) and PGE2 expression, which increased the MUC5AC gene. Activation of NF-κB also increased production of NO, which stimulated mucosal blood flow.
Conclusion: DLBS2411 is a promising candidate for gastric and colon mucus protection by increasing mucus synthesis and stimulating mucosal blood flow.Â
Downloads
References
Smolka AJ, Backert S. How Helicobacter pylori infection controls gastric acid secretion. J Gastroenterol 2012;47:609–18.
Tjandrawinata RR, Nailufar F, Arifin PF. Hydrogen potassium adenosine triphosphatase activity inhibition and downregulation of its expression by bioactive fraction DLBS2411 from Cinnamomum burmannii in gastric parietal cells. Int J Gen Med 2013;6:807-15.
Luiz-Ferreira A, Cola M, Barbastefano V, Meira de-faria F, Almeida AB, Farias-silva E, et al. Healing, antioxidant and cytoprotective properties of Indigofera truxillensis in different models of gastric ulcer in rats. Int J Mol Sci 2012;13:14973-91.
Kwiecien S, Brzozowski T, Konturek SJ. Effect of reactive oxygen species action on gastric mucosa in various models of mucosal injury. J Physiol Pharmacol 2002;53:39-50.
Tandrasasmita OM, Wulan DD, Nailufar F, Sinambela J, Tjandrawinata RR. Glucose-lowering effect of DLBS3233 is mediated through phosphorylation of tyrosine and upregulation of PPARγ and GLUT4 expression. Int J General Glucose-Lowering Effect Med 2011;4:345-57.
Tandrasasmita OM, Sutanto AM, Arifin PF, Tjandrawinata RR. The anti-inflammatory, antiangiogenic, and apoptosis-inducing activity of DLBS1442, a bioactive fraction of Phaleria macrocarpa, in a RL95-2 cell line as a molecular model of endometriosis. Int J Women’s Health 2015;7:161-9.
Karsono AH, Tandrasasmita OM, Tjandrawinata RR. Molecular effects of bioactive fraction of Curcuma mangga (DLBS4847) as a downregulation of 5α-reductase activity pathways in prostatic epithelial cells. Cancer Manag Res 2014;6:267-78.
Nailufar F, Tandrasasmita OM, Tjandrawinata RR. DLBS3233 increases glucose uptake by mediating upregulation of PPARγ and PPARδ expression. Biomed Prev Nutr 2011;1:71–8.
Phillipson M, Johansson ME, Henriksnäs J, Petersson J, Gendler SJ, Sandler S, et al. The gastric mucus layers: constituents and regulation of accumulation. Am J Physiol Gastrointest Liver Physiol 2008;295:G806-12.
Brown JF, Hanson PJ, Whittle BJ. Nitric oxide donors increase mucus gel thickness in rat stomach. J Pharmacol 1992;223:103-4.
Tjandrawinata RR, Dahiya R, Hughes-Fulford M. Induction of cyclo-oxygenase-2 mRNA by prostaglandin E2 in human prostatic carcinoma cells. Br J Cancer 1997;75:1111-8.
Tjandrawinata RR, Hawell L, Byus CV. Characterization of putrescine and cadaverine export in mammalian cells. Biochemical Pharmacol 1994:48:2237-49.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951;93:265-75.
Tjandrawinata RR, Byus CV. Regulation of the efflux of putrescine and cadaverine from rapidly growing cultured RAW 264 cells by extracellular putrescine. Biochemical J 1995;1:291-9.
Hughes-Fulford M, Tjandrawinata RR, Li CF, Sayyah S. Arachidonic acid, an omega-6 fatty acid, induces cytoplasmic phospholipase A2 in prostate carcinoma cells. Carcinogenesis 2005;26:1520-6.
Alqasoumi S. Anti-secretagogue and antiulcer effects of 'Cinnamon' Cinnamomum zeylanicum in rats. J Pharmacogn Phytother 2012;4:53-61.
Ho SB, Takamura K, Anway R, Shekels LL, Toribara NW, Ota H. The adherent gastric mucous layer is composed of alternating layers of MUC5AC and MUC6 mucin proteins. Dig Dis Sci 2004;49:1598–606.
Ho SB, Roberton AM, Shekels LL, Lyftogt CT, Niehans GA, Toribara NW. Expression cloning of gastric mucin complementary DNA and localization of mucin gene expression. Gastroenterology 1995;109:735-47.
Bu X, Li N, Tian X, Huang P. Caco-2 and LS174T cell lines provide different models for studying mucin expression in colon cancer. Tissue Cell 2011;43:201–6.
Halter F, Tarnawski AS, Schmassmann A. Cyclooxygenase 2-implications on maintenance of gastric mucosal integrity and ulcer healing: controversial issues and perspectives. Gut 2001;49:443-53.
Bickel M. Effect of 16,16-dimethyl prostaglandin E2 on gastric mucus gel thickness. Prostaglandins 1981;2:63-5.
Tanigawa T, Watanabe T, Ohkawa F, Nadatani Y, Otani K, Machida K, et al. Rebamipide, a mucoprotective drug, inhibits NSAIDs-induced gastric mucosal injury: possible involvement of the downregulation of 15-hydroxyprostaglandin dehydrogenase. J Clin Biochem Nutr 2011;48:149-53.
Choi SM, Shin JH, Kang KK, Ahn B, Yoo M. Gastroprotective effects of DA-6034, a new flavonoid derivative in various gastric mucosal damage models. Dig Dis Sci 2007;52:3075–80.
Shindo K, Iizuka M, Sasaki K, Konno S, Itou H, Horie Y, et al. Sucralfate prevents the delay of wound repair in intestinal epithelial cells by hydrogen peroxide through NF-κB pathway. J Gastroenterol 2006;41:450–61.
Lawrence T. The nuclear factor NF-ĸB pathway in inflammation. Cold Spring Harbor Perspect Biol 2009;1:a001651. Doi:10.1101/cshperspect.a001651. [Article in Press]
Xue Y, Zhang H, Wang H, Hu J, Du M, Zhu M. Host inflammatory response inhibits Escherichia coli O157:H7 adhesion to gut epithelium through augmentation of mucin expression. Infect Immun 2014;82:1921-30.
Slomiany BL, Slomiany A. Cytosolic phospholipase A2 activation in Helicobacter pylori lipopolysaccharide-induced interference with gastric mucin synthesis. Life 2006;58:217-33.
Backlund MG, Mann JR, Holla VR, Buchanan FG, Tai H, Musiek ES, et al. 15-hydroxyprostaglandin dehydrogenase is down-regulated in colorectal cancer. J Biol Chem 2005;280:3217–23.
Liu Z, Wang X, Lu Y, Han S, Zhang F, Zhai H, et al. Expression of 15-PGDH is downregulated by COX-2 in gastric cancer. Carcinogenesis 2008;29:1219-27.
Lamont JT. Mucus: the front line of intestinal mucosal defense. Ann N Y Acad Sci 1992;664:190–201.
Wallace JL. Prostaglandin, NSAIDs and gastric mucosal protection: why doesn't the stomach digest itself? Physiol Rev 2008;88:1547-65.
Hollander D, Tarnawski A. The protective and therapeutic mechanisms of sucralfate. Scand J Gastroenterol 1990;25 Suppl 173:1-5.