Čes. slov. farm. 2014, 63(1):26-31 | DOI: 10.36290/csf.2014.006
Inhibition of 12/15 lipoxygenase by curcumin and an extract from Curcuma longa L.
- 1 Comenius University, Faculty of Pharmacy, Department of Cell and Molecular Biology of Drugs, Bratislava, Slovak Republic
- 2 Slovak University of Technology, Faculty of Chemical and Food Technology, Institute of Biochemistry, Nutrition and Health Protection, Bratislava, Slovak Republic
Curcumin (diferuloylmethane) is an orange-yellow secondary metabolic compound from the rhizome of turmeric (Curcuma longa L.), a spice often found in curry powder. It is one of the major curcuminoids of turmeric. For centuries, curcumin has been used in some medicinal preparations or as a food colouring agent. A variety of enzymes that are closely associated with inflammation and cancer were found to be modulated by curcumin. This paper summarized the results of the inhibitory effect of curcumin and a Curcuma longa L. ethanolic extract on lipoxygenase from the rat lung cytosolic fraction. The positional specificity determination of arachidonic acid dioxygenation by RP- and SP-HPLC methods showed that in a purified enzyme preparation from the rat lung cytosol the specific form of lipoxygenase (LOX) is present exhibiting 12/15-LOX dual specificity (with predominant 15-LOX activity). The inhibitory activity of curcumin and Curcuma longa extract on LOX from cytosolic fraction of rat lung was expressed in the percentage of inhibition and as IC50. Lineweaver-Burk plot analysis has indicated that curcumin is the competitive inhibitor of 12/15 LOX from the rat lung cytosolic fraction.
Keywords: Curcuma longa L.; curcumin; turmeric extract; linoleic acid; lipoxygenase inhibition
Grants and funding:
This work was also supported in part by the Agency of the Ministry of Education, Science and Sport - VEGA 1/0885/13 and by the Comenius University Grant for Young Researchers UK/234/2013.
Received: November 14, 2013; Accepted: December 16, 2013; Published: January 1, 2014 Show citation
ACS | AIP | APA | ASA | Harvard | Chicago | Chicago Notes | IEEE | ISO690 | MLA | NLM | Turabian | Vancouver |
References
- Jayaprakasha G. K., Jagan L., Rao M., Sakariah K. K. Chemistry and biological activities of C. longa. Trends in Food Science Technology 2005; 16, 533-548.
Go to original source...
- Gupta S. C., Prasad S., Kim J. H., Patchva S., Webb L., Priyadarsini I. K., Aggarwal B. B. Multitargeting by curcumin as revealed by molecular interaction studies. Nat. Prod. Rep. 2011; 28, 1937-1953.
Go to original source...
Go to PubMed...
- Ak T., Gúlcin I. Antioxidant and radical scavenging properties of curcumin. Chemico-Biological Interaction 2008; 174, 27-37.
Go to original source...
Go to PubMed...
- Basnet P., Skalko-Basnet N. Curcumin: An anti-inflammatory molecule from a curry spice on the path to cancer treatment. Molecules 2011; 16, 4567-4598.
Go to original source...
Go to PubMed...
- Shehzad A., Khan S., Shehzad D., Lee Y. S. Curcumin therapeutic promises and bioavailability in colorectal cancer. Drug Today 2010; 47(7), 523-532.
Go to original source...
Go to PubMed...
- Caroll R. E., Bena R. V., Turgeon D. K., Varee S., et al. Phase II clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev. Res. 2011; 4(3), 354-364.
Go to original source...
Go to PubMed...
- Shureiqi I., Baron J. A. Curcumin Chemoprevention: The long road to clinical translation. Cancer Prev. Res. 2011; 4(3), 296-298.
Go to original source...
Go to PubMed...
- Ammon H. P., Safayhi H., Mack T., Sabieraj J. Mechanism of anti-inflammatory actions of curcumine and boswellic acids. J Ethnopharmacol. 1993; 38(2-3): 113-119.
Go to original source...
Go to PubMed...
- Kohll K., All J., Ansari J., Raheman Z. Curcumin: A natural antiinflammatory agent. Indian J. Pharmacol. 2005; 37(3), 141-147.
Go to original source...
- Jankun L., Aleem A. M., Malgorzewicz S., Szkudlarek M., Zavodszky M. I., Devitt D. L., Feig M., Selman S. H., Skrzypczak-Jankun E. Synthetic curcuminoids modulate the arachidonic acid metabolism of human platelet 12-lipoxygenase and reduce sprout formation of human endothelial cells. Mol. Cancer Ther. 2006; 5(5), 1371-1382.
Go to original source...
Go to PubMed...
- Wu J., Xiang Xia H. H., Ping Tu S., Fan D. M., Lin M. Ch., Kung H. F., Lam S. K., Wong B. Ch. 15-lipoxygenase-1 mediates cyclooxygenase-2 inhibitor-induced apoptosis in gastric cancer. Carcinogenesis. 2003; 24(2), 243-247.
Go to original source...
Go to PubMed...
- Segraves S., Walther M, Ivanov I., et al. Sequence determinants for the reaction specificity of murine (12R)-lipoxygenase: targeted substrate modification and site-directed mutagenesis. J. Biol. Chem. 2005; 280, 36633-36641.
Go to original source...
Go to PubMed...
- Werz O., Steinhilber D. Therapeutic options for 5-lipoxygenase inhibitors. Pharmacol. Therapeut. 2006; 112: 701-718.
Go to original source...
Go to PubMed...
- Montuschi P., Sala A., Dahlén S. E., Folco G. Pharmacological modulation of the leukotriene pathway in allergic airway disease. Drug Discov. Today 2007; 12, 404-412.
Go to original source...
Go to PubMed...
- Wen Y., Gu J., Vandenhoff G. E., Liu X, Nadler J. L. The role of 12/15-lipoxygenase in the expression of MCP-1 in mouse macrophages. Am. J. Physiol. Heart Circ. Physiol. 2008; 294, H1933-H1938.
Go to original source...
Go to PubMed...
- Chakrabarti S. K, Cole B. K, Wen Y., Keller S. R., Nadler J. L. 12/15-lipoxygenase products induce inflammation and impair insulin signaling in 3T3-L1 adipocytes. Obesity 2009; 17, 1657-1663.
Go to original source...
Go to PubMed...
- Yuan H., Lanting L., Xu Z. G., Li S. L., Swiderski P., Putta S., Jonnalagadda M., Kato M., Natarajan R. Effects of cholesterol-tagged small interfering RNAs targeting 12/15-lipoxygenase on parameters of diabetic nephropathy in a mouse model of type 1 diabetes. Am. J. Physiol-Renal 2008; 295, F605-F617.
Go to original source...
Go to PubMed...
- Martínez-Clemente M., Ferré N., Titos E., Horrilo R., González-Périz A., Morán-Salvador E., López-Vicario C., Miquel R., Arroyo V., Funk C. D., Claria J. Disruption of the 12/15-lipoxygenase gene (Alox15) protects hyperlipidemic mice from nonalcoholic fatty liver disease. Hepatology 2010; 52, 1980-1991.
Go to original source...
Go to PubMed...
- Krönke G., Katzenbeisser J., Uderhardt S., Zaiss M. M., Scholtysek C., Schabbauer G., Zarbock A., Koenders M. I., Axmann R., Baencler H. W, van den Berg W., Voll R. E., Kuhn H., Joosten L. A., Schett G. 12/15-lipoxygenase counteracts inflammation and tissue damage in arthritis. J. Immunol. 2009; 183, 3383-3389.
Go to original source...
Go to PubMed...
- Rossaint J., Nadler J. L., Ley K., Zarbock A. Eliminating or blocking 12/15-lipoxygenase reduces neutrophil recruitment in mouse models of acute lung injury. Crit. Care 2012; 16, R166.
Go to original source...
Go to PubMed...
- Kulkarni A. P., Cai Y., Richards I. S. Rat pulmonary lipoxygenase: dioxygenase activity and role in xenobiotic metabolism. Int. J. Biochem. 1992; 24, 255-261.
Go to original source...
Go to PubMed...
- Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976; 72, 248-254.
Go to original source...
- Kemal C., Louis-Flamberg P., Krupinski-Olsen R., Shorter A. R. Reductive inactivation of soybean lipoxygenase 1 by catechols: a possible mechanism for regulation of lipoxygenase activity. Biochemistry. 1987; 26, 7064-7068.
Go to original source...
Go to PubMed...
- Hoffman P., Rauová D., Bezáková L., Obložinský M., Mikuš P. HPLC method for determination of lipoxygenase positional specific products. J. Pharm. Biomed. Anal. 2013; 84, 53-58.
Go to original source...
Go to PubMed...
- Aggarwal B., Harikumar K. 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.
Go to original source...
Go to PubMed...
- Lev-Ari S., Strier L., Kazanov D., Shapiro L. M., Sobol H. D., Pinchuk I., Marian B., Lichtenberg D., Arber N. Celecoxib and curcumin synergistically inhibit the growth of colerectal cancer cells. Clin. Cancer Res. 2005; 11, 6738.
Go to original source...
Go to PubMed...
- Basnet P., Skalko-Basnet N. Curcumin: An anti-inflammatory molecule from a curry spice on the path to cancer treatment. Molecules. 2011; 16, 4567-4598.
Go to original source...
Go to PubMed...
- Caroll R. E., Bena R. V., Turgeon D. K., Varee S., et al. Phase II clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev. Res. 2011; 4(3), 354-364.
Go to original source...
Go to PubMed...
- Gupta S. C., Prasad S., Kim J. H., Patchva S., Webb L., Priyadarsini I. K., Aggarwal B. B. Multitargeting by curcumin as revealed by molecular interaction studies. Nat. Prod. Rep. 2011; 28, 1937-1953.
Go to original source...
Go to PubMed...
- Shureiqi I., Baron J.A. Curcumin Chemoprevention: The long road to clinical translation. Cancer Prev. Res. 2011; 4(3), 296-298.
Go to original source...
Go to PubMed...
- Began G., Sudharshan E., Appu Rao A. G. Inhibition of lipoxygenase 1 by Phospatidylcholine micelles-bound curcumin. Lipids. 1998; 33(12), 1223-1228.
Go to original source...
Go to PubMed...
- Skrzypczak-Jankun E., McCabe N. P., Selman S. H., Jankun J. Curcumin inhibits lipoxygenase by binding to its central cavity: theoretical and X-ray. evidence. Int°. J. Mol. Med. 2000; 6, 521-526.
Go to original source...
Go to PubMed...
- Hajek A. R., Lindley A. R., Favoreto S., Carter R., Schleime R. P., Kuperman, D. A. 12/15-lipoxygenase deficiency protects mice from allergic airways inflammation and increases secretory IgA levels. J. Allergy Clin. Immunol. 2008; 122, 633-639.
Go to original source...
Go to PubMed...
- Zarbock A., Distasi M. R., Smith E., Sanders J. M., Kronke G., Hardy B. L., Vietinghoff S. Improved survival and reduced vascular permeability by eliminating or blocking 12/15- lipoxygenase in mouse models of acute lung injury (ALI). J. Immunol. 2009; 183, 4715-4722.
Go to original source...
Go to PubMed...
- Kawakami Y., Hosokawa T., Morinaka T., Irino S., Hirano S., Kobayashi H., Yoshioka A., Suzuki-Yamamoto T., Yokoro M., Kimoto M., Tsuji H., Yamashita H., Doi S., Yutani C., Kato R., Itabe H., Kanada T., Hada T., Takahashi Y. Antiatherogenic effect of guava leaf extracts inhibiting leukocyte-type 12-lipoxygenase activity. Food Chem. 2012; 131, 1069-1075.
Go to original source...
- Rong S., Cao Q., Liu M., Seo J., Lia L., Boudyguina E., Gebre R. K. Macrophage 12/13 lipoxygenase expression increases plasma and hepatic lipid levels and extracerebrates atherosclerosis. J. Lipid Res. 2012; doi: 10.1194/jlr.MO22723.
Go to original source...
Go to PubMed...
- Huo Y., Zhao L., Hyman M. C., Shashkin P., Harry B. L., Burcin T., Forlow S. B., Stark M. A., Smidth D. F., Clarke S. Critical role of macrophage 12/15-lipoxygenase for atherosclerosis in apolipoprotein E-deficient mice. Circulation 2004; 110, 2024-2031.
Go to original source...
Go to PubMed...