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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

Comparative Inhibitory Efficacy on the iNOS/NO System of Curcuminand Tetrahydrocurcumin-Self-Microemulsifying Liquid Formulation in Chronic Gastric Ulcer Model

Author(s): Sirima Mahattanadul*, Sonsawan Kongpuckdee, Ruedeekorn Wiwattanapatapee, Pimpimon Tansakul, Anupong Nitiruangjaras and Pintusorn Hansakul

Volume 22, Issue 7, 2021

Published on: 07 August, 2020

Page: [1005 - 1012] Pages: 8

DOI: 10.2174/1389201021666200807105849

Price: $65

Abstract

Background: Curcumin was found to accelerate gastric ulcer healing by the main mechanism, i.e., the suppression of iNOS mediated inflammation. Although Tetrahydrocurcumin (THC) is claimed to be an active antioxidant element of curcumin, its antiulcer activity has not been systematically examined. The utility of Self-Microemulsifying Drug Delivery Systems (SMEDDSs) for curcumin and THC formulations in the liquid form was also found to increase the rate and extent of release of curcumin- and THC-SMEDDS. Nevertheless, the beneficial antiulcer effect of these nanoproducts has not yet been evaluated.

Objective: This study aimed to evaluate and compare the antiulcer efficacy of curcumin- and THCSMEDDS through the inhibition of the iNOS/NO system in the rat model.

Methods: Antiulcer efficacy was compared in terms of the ability to accelerate healing of gastric ulcer including the efficient inhibitory action on inflammatory NO production in activated macrophages and iNOS mRNA expression at the ulcerated area.

Results: THC was found to have less ulcer healing capacity than curcumin with a lack of significant inhibitory effect on the iNOS/NO system. The SMEDDS used in the study significantly increased the inhibitory efficacy of THC on iNOS/NO production and iNOS mRNA expression compared to the inhibitory potency of curcumin. An oral administration of curcumin- or THC-SMEDDS once a day was appropriate for exerting a comparable curative efficacy to a twice-daily oral administration of curcumin or THC.

Conclusion: The SMEDDS used in the study was observed to enhance the inhibitory efficacy of the antiulcer drug on the iNOS/NO system, leading to a reduction of daily dosing and dosing frequency.

Keywords: Curcumin, tetrahydrocurcumin, gastric ulcer, nitric oxide, inducible nitric oxide synthase, Self- Micro Emulsifying Drug Delivery Systems (SMEDDS).

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Graphical Abstract

[1]
The U.S. Food and Drug Administration. 2018. www.accessdata.fda.gov/scripts/fdcc/?set=GRAS Notices [3 December 2018];
[2]
Mahattanadul, S.; Nakamura, T.; Panichayupakaranant, P.; Phdoongsombut, N.; Tungsinmunkong, K.; Bouking, P. Comparative antiulcer effect of bisdemethoxycurcumin and curcumin in a gastric ulcer model system. Phytomedicine, 2009, 16(4), 342-351.
[http://dx.doi.org/10.1016/j.phymed.2008.12.005] [PMID: 19188055]
[3]
Aggarwal, B.B.; Deb, L.; Prasad, S. Curcumin differs from tetrahydrocurcumin for molecular targets, signaling pathways and cellular responses. Molecules, 2014, 20(1), 185-205.
[http://dx.doi.org/10.3390/molecules20010185] [PMID: 25547723]
[4]
Pan, M.H.; Lin-Shiau, S.Y.; Lin, J.K. Comparative studies on the suppression of nitric oxide synthase by curcumin and its hydrogenated metabolites through down-regulation of IkappaB kinase and NFkappaB activation in macrophages. Biochem. Pharmacol., 2000, 60(11), 1665-1676.
[http://dx.doi.org/10.1016/S0006-2952(00)00489-5] [PMID: 11077049]
[5]
Murakami, Y.; Ishii, H.; Takada, N.; Tanaka, S.; Machino, M.; Ito, S.; Fujisawa, S. Comparative anti-inflammatory activities of curcumin and tetrahydrocurcumin based on the phenolic O-H bond dissociation enthalpy, ionization potential and quantum chemical descriptor. Anticancer Res., 2008, 28(2A), 699-707.
[PMID: 18507010]
[6]
Setthacheewakul, S.; Mahattanadul, S.; Phadoongsombut, N.; Pichayakorn, W.; Wiwattanapatapee, R. Development and evaluation of self-microemulsifying liquid and pellet formulations of curcumin, and absorption studies in rats. Eur. J. Pharm. Biopharm., 2010, 76(3), 475-485.
[http://dx.doi.org/10.1016/j.ejpb.2010.07.011] [PMID: 20659556]
[7]
Setthacheewakul, S.; Kedjinda, W.; Maneenuan, D.; Wiwattanapatapee, R. Controlled release of oral tetrahydrocurcumin from a novel Self-Emulsifying Floating Drug Delivery System (SEFDDS). AAPS PharmSciTech, 2011, 12(1), 152-164.
[http://dx.doi.org/10.1208/s12249-010-9568-8] [PMID: 21181511]
[8]
Surh, Y.J.; Chun, K.S.; Cha, H.H.; Han, S.S.; Keum, Y.S.; Park, K.K.; Lee, S.S. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: Down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat. Res., 2001, 480-481, 243-268.
[http://dx.doi.org/10.1016/S0027-5107(01)00183-X] [PMID: 11506818]
[9]
Coleman, J.W. Nitric oxide in immunity and inflammation. Int. Immunopharmacol., 2001, 1(8), 1397-1406.
[http://dx.doi.org/10.1016/S1567-5769(01)00086-8] [PMID: 11515807]
[10]
Hussain, S.P.; Trivers, G.E.; Hofseth, L.J.; He, P.; Shaikh, I.; Mechanic, L.E.; Doja, S.; Jiang, W.; Subleski, J.; Shorts, L.; Haines, D.; Laubach, V.E.; Wiltrout, R.H.; Djurickovic, D.; Harris, C.C. Nitric oxide, a mediator of inflammation, suppresses tumorigenesis. Cancer Res., 2004, 64(19), 6849-6853.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-2201] [PMID: 15466171]
[11]
Pavlick, K.P.; Laroux, F.S.; Fuseler, J.; Wolf, R.E.; Gray, L.; Hoffman, J.; Grisham, M.B. Role of reactive metabolites of oxygen and nitrogen in inflammatory bowel disease. Free Radic. Biol. Med., 2002, 33(3), 311-322.
[http://dx.doi.org/10.1016/S0891-5849(02)00853-5] [PMID: 12126753]
[12]
Okabe, S.; Roth, J.L.; Pfeiffer, C.J. A method for experimental, penetrating gastric and duodenal ulcers in rats. Observations on normal healing. Am. J. Dig. Dis., 1971, 16(3), 277-284.
[http://dx.doi.org/10.1007/BF02235252] [PMID: 5554507]
[13]
Tewtrakul, S.; Tansakul, P.; Panichayupakaranant, P. Effects of rhinacanthins from Rhinacanthus nasutus on nitric oxide, prostaglandin E2 and tumor necrosis factor-alpha releases using RAW264.7 macrophage cells. Phytomedicine, 2009, 16(6-7), 581-585.
[http://dx.doi.org/10.1016/j.phymed.2008.12.022] [PMID: 19303271]
[14]
Huang, M.T.; Lysz, T.; Ferraro, T.; Abidi, T.F.; Laskin, J.D.; Conney, A.H. Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis. Cancer Res., 1991, 51(3), 813-819.
[PMID: 1899046]
[15]
Zhang, F.; Altorki, N.K.; Mestre, J.R.; Subbaramaiah, K.; Dannenberg, A.J. Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells. Carcinogenesis, 1999, 20(3), 445-451.
[http://dx.doi.org/10.1093/carcin/20.3.445] [PMID: 10190560]
[16]
Chan, M.M. Inhibition of tumor necrosis factor by curcumin, a phytochemical. Biochem. Pharmacol., 1995, 49(11), 1551-1556.
[http://dx.doi.org/10.1016/0006-2952(95)00171-U] [PMID: 7786295]
[17]
Kumar, A.; Dhawan, S.; Hardegen, N.J.; Aggarwal, B.B. Curcumin (Diferuloylmethane) inhibition of Tumor Necrosis Factor (TNF)-mediated adhesion of monocytes to endothelial cells by suppression of cell surface expression of adhesion molecules and of nuclear factor-kappaB activation. Biochem. Pharmacol., 1998, 55(6), 775-783.
[http://dx.doi.org/10.1016/S0006-2952(97)00557-1] [PMID: 9586949]
[18]
Chan, M.M.; Huang, H.I.; Fenton, M.R.; Fong, D. In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with anti-inflammatory properties. Biochem. Pharmacol., 1998, 55(12), 1955-1962.
[http://dx.doi.org/10.1016/S0006-2952(98)00114-2] [PMID: 9714315]
[19]
Jobin, C.; Bradham, C.A.; Russo, M.P.; Juma, B.; Narula, A.S.; Brenner, D.A.; Sartor, R.B. Curcumin blocks cytokine-mediated NF-κ B activation and proinflammatory gene expression by inhibiting inhibitory factor I-κ B kinase activity. J. Immunol., 1999, 163(6), 3474-3483.
[PMID: 10477620]
[20]
Ireson, C.; Orr, S.; Jones, D.J.; Verschoyle, R.; Lim, C.K.; Luo, J.L.; Howells, L.; Plummer, S.; Jukes, R.; Williams, M.; Steward, W.P.; Gescher, A. Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production. Cancer Res., 2001, 61(3), 1058-1064.
[PMID: 11221833]
[21]
Sandur, S.K.; Pandey, M.K.; Sung, B.; Ahn, K.S.; Murakami, A.; Sethi, G.; Limtrakul, P.; Badmaev, V.; Aggarwal, B.B. Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carcinogenesis, 2007, 28(8), 1765-1773.
[http://dx.doi.org/10.1093/carcin/bgm123] [PMID: 17522064]
[22]
Yang, J.Y.; Zhong, X.; Kim, S.J.; Kim, D.H.; Kim, H.S.; Lee, J.S.; Yum, H.W.; Lee, J.; Na, H.K.; Surh, Y.J. Comparative effect of curcumin and tetrahydrocurcumin on dextran sulfate sodium-induced colitis and inflammatory signaling in mice. J. Cancer Prev., 2018, 23(1), 18-24.
[http://dx.doi.org/10.15430/JCP.2018.23.1.18] [PMID: 29629345]
[23]
Zhang, Z.B.; Luo, D.D.; Xie, J.H.; Xian, Y.F.; Lai, Z.Q.; Liu, Y.H.; Liu, W.H.; Chen, J.N.; Lai, X.P.; Lin, Z.X.; Su, Z.R. Curcumin’s metabolites, tetrahydrocurcumin and octahydrocurcumin, possess superior anti- inflammatory effects in vivo though suppression of TAK1-NF-κB pathway. Front. Pharmacol., 2018, 9, 1-12.
[http://dx.doi.org/10.3389/fphar.2018.01181]
[24]
Rezvani, M.; Ross, G.A. Modification of radiation-induced acute oral mucositis in the rat. Int. J. Radiat. Biol., 2004, 80(2), 177-182.
[http://dx.doi.org/10.1080/09553000310001654693] [PMID: 15164799]
[25]
Tejada, S.; Manayi, A.; Daglia, M.; Nabavi, S.F.; Sureda, A.; Hajheydari, Z.; Gortzi, O.; Pazoki-Toroudi, H.; Nabavi, S.M. Wound healing effects of curcumin: A short review. Curr. Pharm. Biotechnol., 2016, 17(11), 1002-1007.
[http://dx.doi.org/10.2174/1389201017666160721123109] [PMID: 27640646]
[26]
Masaoka, T.; Suzuki, H.; Ishii, H. Effect of Proton Pump Inhibitors (PPIs) on wound healing of gastric mucosal cell injury. Nihon Rinsho, 2004, 62(3), 556-560.
[PMID: 15038103]
[27]
Trivedi, M.K.; Gangwar, M.; Mondal, S.C.; Jana, S. Protective effects of Tetrahydrocurcumin (THC) on fibroblast and melanoma cell lines in vitro: It’s implication for wound healing. J. Food Sci. Technol., 2017, 54(5), 1137-1145.
[http://dx.doi.org/10.1007/s13197-017-2525-8] [PMID: 28416863]
[28]
Charman, S.A.; Charman, W.N.; Rogge, M.C.; Wilson, T.D.; Dutko, F.J.; Pouton, C.W. Self-emulsifying drug delivery systems: Formulation and biopharmaceutic evaluation of an investigational lipophilic compound. Pharm. Res., 1992, 9(1), 87-93.
[http://dx.doi.org/10.1023/A:1018987928936] [PMID: 1589415]
[29]
Shah, N.H.; Carvajal, M.T.; Patel, C.I.; Infeld, M.H.; Malicket, A.W. Self-Emulsifying Drug Delivery Systems (SEDDS) with polyglycolyzed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs. Int. J. Pharm., 1994, 106, 15-23.
[http://dx.doi.org/10.1016/0378-5173(94)90271-2]
[30]
Griffiths, M.J.; Messent, M.; MacAllister, R.J.; Evans, T.W. Aminoguanidine selectively inhibits inducible nitric oxide synthase. Br. J. Pharmacol., 1993, 110(3), 963-968.
[http://dx.doi.org/10.1111/j.1476-5381.1993.tb13907.x] [PMID: 7507781]
[31]
Motilva, V.; Martín, M.J.; Luque, M.I.; Alarcón de la Lastra, C. Role of polymorphonuclear leukocytes and oxygen-derived free radicals in chronic gastric lesion induced by acetic acid in rat. Gen. Pharmacol., 1996, 27(3), 545-550.
[http://dx.doi.org/10.1016/0306-3623(95)02025-X] [PMID: 8723542]
[32]
Mahattanadul, S.; Reanmongkol, W.; Yano, S.; Panichayupakaranant, P.; Phdoongsombut, N.; Tungsinmunkong, K. Preventive and curative effects of curcumin on the development of gastric inflammatory diseases in rats. J. Nat. Med., 2006, 60(3), 191-197.
[http://dx.doi.org/10.1007/s11418-006-0035-5] [PMID: 29435886]

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