Skip to main content

Advertisement

SpringerLink
Log in

Effect of Cyclodextrin Complexation of Curcumin on its Solubility and Antiangiogenic and Anti-inflammatory Activity in Rat Colitis Model

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Podolsky DK. Inflammatory bowel disease. N Eng J Med. 2002;347:417–29.

    Article  CAS  Google Scholar 

  2. Hanauer SB. Inflammatory bowel disease. N Eng J Med. 1996;334:841–8.

    Article  CAS  Google Scholar 

  3. Ruby AJ, Kuttan G, Babu KD, Rajasekharan KN, Kuttan R. Antitumour and antioxidant activity of natural curcuminoids. Cancer Lett. 1995;94:79–83.

    Article  PubMed  CAS  Google Scholar 

  4. Gescher AJ, Sharma RA, Steward WP. Cancer chemoprevention by dietary constituents: a tale of failure and promise. Lancet Oncol. 2001;2:371–9.

    Article  PubMed  CAS  Google Scholar 

  5. Sharma RA, Gescher AJ, Steward WP. Curcumin: the story so far. Eur J Cancer. 2005;41:1955–68.

    Article  PubMed  CAS  Google Scholar 

  6. 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.

    PubMed  CAS  Google Scholar 

  7. 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.

    CAS  Google Scholar 

  8. 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.

    Google Scholar 

  9. Ammon HPT, Wahl MA. Pharmacology of Curcuma longa. Planta Med. 1991;57:1–7.

    Article  PubMed  CAS  Google Scholar 

  10. Subramanian L, Selvam R. Prevention of CCI4-induced hepatotoxicity by aqueous extract of turmeric. Nutra Res. 1999;19:429–41.

    Article  CAS  Google Scholar 

  11. 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.

    Article  Google Scholar 

  12. 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.

    Article  Google Scholar 

  13. Wahlstrom B, Blennow G. A study on the fate of curcumin in the rat. Acta Pharmacol Toxicol. 1978;43:86–92.

    CAS  Google Scholar 

  14. Pan MH, Huang TM, Lin JK. Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos. 1999;27:486–94.

    PubMed  CAS  Google Scholar 

  15. 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.

    Article  PubMed  CAS  Google Scholar 

  16. 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.

    PubMed  CAS  Google Scholar 

  17. Fromming KH, Szejtli J. Cyclodextrins in pharmacy. Dordrecht: Kluwer Academic; 1994.

    Google Scholar 

  18. Loftsson T, Masson M, Brewster ME. Self-association of cyclodextrins and cyclodextrin complexes. J Pharm Sci. 2005;93:1091–9.

    Article  Google Scholar 

  19. Folkman J, Klagsbrun M. Angiogenetic factors. Science. 1987;235(4787):442–7.

    Article  PubMed  CAS  Google Scholar 

  20. Higuchi T, Connors KA. Phase-solubility techniques. Adv Anal Chem Instrum. 1965;4:117–212.

    CAS  Google Scholar 

  21. Presta M, Belleri M, Vacca A, Ribatti D. Anti-angiogenic activity of the purine analog 6-thioguanine. Leukemia. 2002;16:1490–9.

    Article  PubMed  CAS  Google Scholar 

  22. 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.

    Article  Google Scholar 

  23. 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.

    Article  PubMed  CAS  Google Scholar 

  24. 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.

    PubMed  CAS  Google Scholar 

  25. Skaper SD, Pollock M, Facci L. Mast cells differentially express and release active high molecular weight neurotrophins. Mol Brain Res. 2001;97:177–85.

    Article  PubMed  CAS  Google Scholar 

  26. 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.

    Article  Google Scholar 

  27. Baglole KN, Boland PG, Wagner BD. Fluorescence enhancement of curcumin upon inclusion into parent and modified cyclodextrins. J Photochem Photobiol. 2005;173:230–7.

    Article  CAS  Google Scholar 

  28. Loftsson T, Brewster ME. Pharmaceutical application of cyclodextrin. Drug solubilization and stabilization. J Pharm Sci. 1996;85:1017–25.

    Article  PubMed  CAS  Google Scholar 

  29. 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.

    Article  PubMed  CAS  Google Scholar 

Download references

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

  1. Department of Pharmaceutics, Al-Ameen College of Pharmacy, Hosur Road, Bangalore, 560027, India

    Sarasija Suresh, Kshama Devi & Seema Yadav

  2. Department of Pharmaceutics, Nootan Dental College, Hosur Road, Bangalore, 560027, India

    Vivek R. Yadav

Authors
  1. Vivek R. Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarasija Suresh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kshama Devi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seema Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sarasija Suresh.

Rights and permissions

Reprints 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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-009-9264-8

Key words

Search

Navigation