Abstract
The purpose of the study was to prepare and evaluate the anti-inflammatory activity of cyclodextrin (CD) complex of curcumin for the treatment of inflammatory bowel disease (IBD) in colitis-induced rat model. Inclusion complexes of curcumin were prepared by common solvent and kneading methods. These complexes were further evaluated for increase in solubility of poorly soluble curcumin. The inclusion complexes were characterized for enhancement in solubility, in vitro dissolution, surface morphology, infrared, differential scanning calorimetry, and X-ray studies. Solubility, phase solubility, and in vitro dissolution studies showed that curcumin has higher affinity for hydroxypropyl-β-CD (HPβCD) than other CDs. HPβCD complex of curcumin was further investigated for its antiangiogenic and anti-inflammatory activity using chick embryo and rat colitis model. HPβCD complex of curcumin proved to be a potent angioinhibitory compound, as demonstrated by inhibition of angiogenesis in chorioallantoic membrane assay. Curcumin- and HPβCD-treated rats showed a faster weight gain compared to dextran sulfate solution (DSS) controls. Whole colon length appeared to be significantly longer in HPβCD-treated rats than pure curcumin and DSS controls. An additional finding in the DSS-treated rats was the predominance of eosinophils in the chronic cell infiltrate. Decreased mast cell numbers in the mucosa of the colon of CD of curcumin- and pure-curcumin-treated rats was observed. This study concluded that the degree of colitis caused by administration of DSS was significantly attenuated by CD of curcumin. Being a nontoxic natural dietary product, curcumin could be useful in the therapeutic strategy for IBD patients.
Similar content being viewed by others
References
Podolsky DK. Inflammatory bowel disease. N Eng J Med. 2002;347:417–29.
Hanauer SB. Inflammatory bowel disease. N Eng J Med. 1996;334:841–8.
Ruby AJ, Kuttan G, Babu KD, Rajasekharan KN, Kuttan R. Antitumour and antioxidant activity of natural curcuminoids. Cancer Lett. 1995;94:79–83.
Gescher AJ, Sharma RA, Steward WP. Cancer chemoprevention by dietary constituents: a tale of failure and promise. Lancet Oncol. 2001;2:371–9.
Sharma RA, Gescher AJ, Steward WP. Curcumin: the story so far. Eur J Cancer. 2005;41:1955–68.
Sharma RA, McLelland HR, Hill KA, Ireson CR, Euden SA, Manson MM, et al. Pharmacodynamic and pharmacokinetic study of oral curcuma extract in patients with colorectal cancer. Clin Cancer Res. 2001;7:1894–900.
Rao DS, Sekhara NC, Satyanarayana MN, Srinivasan M. Effect of curcumin on serum and liver cholesterol levels in the rat. J Nutrition. 1970;100:1307–15.
Ramaprasad C, Sirsi M. Indian medicinal plants: Curcuma longa; in vitro antibacterial activity of curcumin and the essential oil. J Sci Ind Res. 1956;15C:239–41.
Ammon HPT, Wahl MA. Pharmacology of Curcuma longa. Planta Med. 1991;57:1–7.
Subramanian L, Selvam R. Prevention of CCI4-induced hepatotoxicity by aqueous extract of turmeric. Nutra Res. 1999;19:429–41.
Ukil A, Maity S, Karmakar S, Datta N, Vedasiromoni JR, Das PK. Curcumin, the major component of food flavor turmeric, reduces mucosal injury in trinitrobenzene sulphonic acid-induced colitis. Br J Pharmacol. 2005;139(2):209–18.
Tonnesen HH, Greenhill JV. Studies on curcumin and curcuminoids XXII. Curcumin as a reducing agent and as a radical scavenger. Int J Pharm. 1992;87:79–87.
Wahlstrom B, Blennow G. A study on the fate of curcumin in the rat. Acta Pharmacol Toxicol. 1978;43:86–92.
Pan MH, Huang TM, Lin JK. Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos. 1999;27:486–94.
Holder GM, Plummer JL, Ryan AJ. The metabolism and excretion of curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) in the rat. Xenobiotica. 1978;8:761–8.
Ireson CR, Orr S, Jones DL, Verschoyle R, Lim CK, Luo JL, et al. Characterization of metabolites of the chemopreventive agent curcumin in humans and rat hepatocytes and in rat plasma and evaluation of their ability to inhibit cyclooxygenase-2 expression. Cancer Res. 2001;61:1058–64.
Fromming KH, Szejtli J. Cyclodextrins in pharmacy. Dordrecht: Kluwer Academic; 1994.
Loftsson T, Masson M, Brewster ME. Self-association of cyclodextrins and cyclodextrin complexes. J Pharm Sci. 2005;93:1091–9.
Folkman J, Klagsbrun M. Angiogenetic factors. Science. 1987;235(4787):442–7.
Higuchi T, Connors KA. Phase-solubility techniques. Adv Anal Chem Instrum. 1965;4:117–212.
Presta M, Belleri M, Vacca A, Ribatti D. Anti-angiogenic activity of the purine analog 6-thioguanine. Leukemia. 2002;16:1490–9.
Anupama EG, Belakavadi M, Venkatesh DA, Marme D, Salimatha BP. Molecular mechanisms of anti-angiogenic effect of curcumin. Biochem and Biophys Res Com. 2002;297:934–42.
Vilaseca J, Salas A, Guarner F, Rodinguez R, Martinez M, Malagelada JR. Dietary fish oil reduces progression of chronic inflammatory lesions in rat model of granulomatous colitis. Gut. 1990;31:539–44.
Wallace JL, Mac Naughton WK, Morris GP, Beck PL. Inhibition of leucotriene synthesis markedly accelerates healing in rat model of inflammatory bowel disease. Gastroenterology. 1989;96:29–36.
Skaper SD, Pollock M, Facci L. Mast cells differentially express and release active high molecular weight neurotrophins. Mol Brain Res. 2001;97:177–85.
Patel RP, Patel MM. Preparation and evaluation of inclusion complex of lipid lowering drug lovastatin with β-cyclodextrin. Dhaka Univ J Pharm Sci. 2007;6(1):25–36.
Baglole KN, Boland PG, Wagner BD. Fluorescence enhancement of curcumin upon inclusion into parent and modified cyclodextrins. J Photochem Photobiol. 2005;173:230–7.
Loftsson T, Brewster ME. Pharmaceutical application of cyclodextrin. Drug solubilization and stabilization. J Pharm Sci. 1996;85:1017–25.
Cooper HS, Murthy S, Kido K, Yoshitake H, Flanigan A. Dysplasia and cancer in the dextran sulfate sodium mouse colitis model. Relevance to colitis- associated neoplasia in the human: a study of histopathology, B-catenin and p53 expression and the role of inflammation. Carcinogenesis. 2000;21:757–68.
Acknowledgements
The authors would like to thank Prof. B.G. Shivananda, Principal, Al-Ameen College of Pharmacy, for his kind support and encouragement. This study was supported by SRF grant to Vivek Yadav from Indian Council of Medical Research, India
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yadav, V.R., Suresh, S., Devi, K. et al. Effect of Cyclodextrin Complexation of Curcumin on its Solubility and Antiangiogenic and Anti-inflammatory Activity in Rat Colitis Model. AAPS PharmSciTech 10, 752–762 (2009). https://doi.org/10.1208/s12249-009-9264-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1208/s12249-009-9264-8