Abstract
Aim and objective
Curcumin, a poly-phenolic compound, possesses diverse pharmacologic activities. However, the barrier protective functions of curcumin or its derivative have not yet been studied. The objective of this study was to investigate the barrier protective activities of curcumin and its derivative (bisdemethoxycurcumin, BDMC) on lipopolysaccharide (LPS) barrier disruption in human umbilical vein endothelial cells (HUVECs) were investigated.
Methods
The barrier protective effects of curcumin and BDMC such as permeability, expression of cell adhesion molecules, monocytes adhesion and migration toward HUVECs were tested.
Results
Curcumin and BDMC inhibited LPS-induced barrier permeability, monocyte adhesion and migration; inhibitory effects were significantly correlated with inhibitory functions of curcumin and BDMC on LPS-induced cell adhesion molecules (vascular cell adhesion molecules, intracellular cell adhesion molecule, E-selectin). Furthermore, LPS-induced nuclear factor-κB (NF-κB) activation and tumor necrosis factor-α (TNF-α) release from HUVECs were inhibited by curcumin and BDMC. Surprisingly, the barrier protective activities of BDMC were better than those of curcumin, indicating that the methoxy group in curcumin negatively regulated barrier protection function of curcumin.
Conclusion
Given these results, curcumin or its derivative, BDMC, showed barrier protective activities and they could be a therapeutic candidates for various systemic inflammatory diseases.
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Abbreviations
- LPS:
-
Lipopolysaccharide
- CAM:
-
Cell adhesion molecule
- VCAM:
-
Vascular cell adhesion molecules
- ICAM:
-
Intracellular cell adhesion molecule
- NF-κB:
-
Nuclear factor-κB
- TNF:
-
Tumor necrosis factor
- BDMC:
-
Bisdemethoxycurcumin
- TEM:
-
Transendothelial migration
References
Jurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev. 2009;14:141–53.
Bengmark S, Mesa MD, Gil A. Plant-derived health: the effects of turmeric and curcuminoids. Nutr Hosp. 2009;24:273–81.
Bao W, Li K, Rong S, Yao P, Hao L, Ying C, et al. Curcumin alleviates ethanol-induced hepatocytes oxidative damage involving heme oxygenase-1 induction. J Ethnopharmacol. 2010;128:549–53.
Ammon HP, Wahl MA. Pharmacology of Curcuma longa. Planta Med. 1991;57:1–7.
Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: the Indian solid gold. Adv Exp Med Biol. 2007;595:1–75.
Inoue K, Nomura C, Ito S, Nagatsu A, Hino T, Oka H. Purification of curcumin, demethoxycurcumin, and bisdemethoxycurcumin by high-speed countercurrent chromatography. J Agric Food Chem. 2008;56:9328–36.
Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol. 2009;41:40–59.
Gerritsen ME, Bloor CM. Endothelial cell gene expression in response to injury. FASEB J. 1993;7:523–32.
Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med. 2000;342:1334–49.
Dhillon SS, Mahadevan K, Bandi V, Zheng Z, Smith CW, Rumbaut RE. Neutrophils, nitric oxide, and microvascular permeability in severe sepsis. Chest. 2005;128:1706–12.
Harlan JM. Leukocyte–endothelial interactions. Blood. 1985;65:513–25.
Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 1994;76:301–14.
Hogg N, Berlin C. Structure and function of adhesion receptors in leukocyte trafficking. Immunol Today. 1995;16:327–30.
Lawrence MB, Springer TA. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 1991;65:859–73.
Lasky LA. Selectins: interpreters of cell-specific carbohydrate information during inflammation. Science. 1992;258:964–9.
Gimbrone MA Jr. Vascular endothelium: an integrator of pathophysiologic stimuli in atherosclerosis. Am J Cardiol. 1995;75:67B–70B.
Jerzak P. The role of adhesion molecules in the immunopathogenesis of atherosclerosis. Pol Tyg Lek. 1994;49:357–9.
Anand P, Thomas SG, Kunnumakkara AB, Sundaram C, Harikumar KB, Sung B, et al. Biological activities of curcumin and its analogues (Congeners) made by man and mother nature. Biochem Pharmacol. 2008;76:1590–611.
Zhang LJ, Wu CF, Meng XL, Yuan D, Cai XD, Wang QL, et al. Comparison of inhibitory potency of three different curcuminoid pigments on nitric oxide and tumor necrosis factor production of rat primary microglia induced by lipopolysaccharide. Neurosci Lett. 2008;447:48–53.
Yodkeeree S, Ampasavate C, Sung B, Aggarwal BB, Limtrakul P. Demethoxycurcumin suppresses migration and invasion of MDA-MB-231 human breast cancer cell line. Eur J Pharmacol. 2010;627:8–15.
Syu WJ, Shen CC, Don MJ, Ou JC, Lee GH, Sun CM. Cytotoxicity of curcuminoids and some novel compounds from Curcuma zedoaria. J Nat Prod. 1998;61:1531–4.
Devasena T, Rajasekaran KN, Gunasekaran G, Viswanathan P, Menon VP. Anticarcinogenic effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione a curcumin analog on DMH-induced colon cancer model. Pharmacol Res. 2003;47:133–40.
Yodkeeree S, Chaiwangyen W, Garbisa S, Limtrakul P. Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit cancer cell invasion through the down-regulation of MMPs and uPA. J Nutr Biochem. 2009;20:87–95.
Bae JS, Rezaie AR. Protease activated receptor 1 (PAR-1) activation by thrombin is protective in human pulmonary artery endothelial cells if endothelial protein C receptor is occupied by its natural ligand. Thromb Haemost. 2008;100:101–9.
Kim TH, Bae JS. Ecklonia cava extracts inhibit lipopolysaccharide induced inflammatory responses in human endothelial cells. Food Chem Toxicol. 2010;48:1682–7.
Akeson AL, Woods CW. A fluorometric assay for the quantitation of cell adherence to endothelial cells. J Immunol Methods. 1993;163:181–5.
Che W, Lerner-Marmarosh N, Huang Q, Osawa M, Ohta S, Yoshizumi M, et al. Insulin-like growth factor-1 enhances inflammatory responses in endothelial cells: role of Gab1 and MEKK3 in TNF-alpha-induced c-Jun and NF-kappaB activation and adhesion molecule expression. Circ Res. 2002;90:1222–30.
Berman RS, Frew JD, Martin W. Endotoxin-induced arterial endothelial barrier dysfunction assessed by an in vitro model. Br J Pharmacol. 1993;110:1282–4.
Goldblum SE, Ding X, Brann TW, Campbell-Washington J. Bacterial lipopolysaccharide induces actin reorganization, intercellular gap formation, and endothelial barrier dysfunction in pulmonary vascular endothelial cells: concurrent F-actin depolymerization and new actin synthesis. J Cell Physiol. 1993;157:13–23.
Gearing AJ, Newman W. Circulating adhesion molecules in disease. Immunol Today. 1993;14:506–12.
Tedder TF, Steeber DA, Chen A, Engel P. The selectins: vascular adhesion molecules. FASEB J. 1995;9:866–73.
Collins T, Read MA, Neish AS, Whitley MZ, Thanos D, Maniatis T. Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine-inducible enhancers. FASEB J. 1995;9:899–909.
Li H, Cybulsky MI, Gimbrone MA Jr, Libby P. Inducible expression of vascular cell adhesion molecule-1 by vascular smooth muscle cells in vitro and within rabbit atheroma. Am J Pathol. 1993;143:1551–9.
Albelda SM, Smith CW, Ward PA. Adhesion molecules and inflammatory injury. FASEB J. 1994;8:504–12.
Sawa Y, Sugimoto Y, Ueki T, Ishikawa H, Sato A, Nagato T, et al. Effects of TNF-alpha on leukocyte adhesion molecule expressions in cultured human lymphatic endothelium. J Histochem Cytochem. 2007;55:721–33.
Mackay F, Loetscher H, Stueber D, Gehr G, Lesslauer W. Tumor necrosis factor alpha (TNF-alpha)-induced cell adhesion to human endothelial cells is under dominant control of one TNF receptor type, TNF-R55. J Exp Med. 1993;177:1277–86.
Chen C, Jamaluddin MS, Yan S, Sheikh-Hamad D, Yao Q. Human stanniocalcin-1 blocks TNF-alpha-induced monolayer permeability in human coronary artery endothelial cells. Arterioscler Thromb Vasc Biol. 2008;28:906–12.
Leirisalo-Repo M. The present knowledge of the inflammatory process and the inflammatory mediators. Pharmacol Toxicol. 1994;75(Suppl 2):1–3.
Tavadyan LA, Galoian KA, Harutunyan LA, Tonikyan HG, Galoyan AA. Antioxidant and electron donating function of hypothalamic polypeptides: galarmin and Gx-NH2. Neurochem Res. 2010;35:947–52.
Somparn P, Phisalaphong C, Nakornchai S, Unchern S, Morales NP. Comparative antioxidant activities of curcumin and its demethoxy and hydrogenated derivatives. Biol Pharm Bull. 2007;30:74–8.
Ruby AJ, Kuttan G, Babu KD, Rajasekharan KN, Kuttan R. Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett. 1995;94:79–83.
Jeong JM, Choi CH, Kang SK, Lee IH, Lee JY, Jung H. Antioxidant and chemosensitizing effects of flavonoids with hydroxy and/or methoxy groups and structure–activity relationship. J Pharm Pharm Sci. 2007;10:537–46.
Sandur SK, Pandey MK, Sung B, Ahn KS, Murakami A, Sethi G, et al. Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carcinogenesis. 2007;28:1765–73.
Acknowledgments
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government [MEST] (No. 2011-003410, 2011-0026695, 2011-0030124).
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Responsible Editor: Ian Ahnfelt-Rønne.
D.-C. Kim and S.-K. Ku equally contributed to this work.
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Kim, DC., Ku, SK., Lee, W. et al. Barrier protective activities of curcumin and its derivative. Inflamm. Res. 61, 437–444 (2012). https://doi.org/10.1007/s00011-011-0430-6
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DOI: https://doi.org/10.1007/s00011-011-0430-6