Characterisation and anti-inflammatory evaluation of the inclusion complex of ellagic acid with hydroxypropyl-β-cyclodextrin
The aim of the present work was to examine ellagic acid hydroxypropyl-β-cyclodextrin complex (EA-HP-β-CD) obtained through the freeze-drying method via FTIR, XRD, SEM, NMR and molecular modeling, as well as to investigate it’s antioxidant and anti-inflammatory activity on carrageenan-induced paw oedema in rats. Phase-solubility study showed that ellagic acid (EA) formed 1:2 stoichiometric inclusion complex with hydroxypropyl-β-cyclodextrin (HP-β-CD). The XRD and SEM analysis were confirmed true inclusion complex formation of EA with HP-β-CD by freeze-drying method when compared with a physical mixture. The FTIR, NMR and molecular modeling studies suggested that the carbonyl groups and hydroxyl groups of EA were involved in the inclusion complexation with HP-β-CD. EA-HP-β-CD exhibited better protection from protein denaturation and lysis of erythrocyte membrane as compared to positive controls. In vivo anti-inflammatory evaluation of EA-HP-β-CD in rats showed significant anti-inflammatory and antioxidant activity on carrageenan-induced rat paw oedema. The present findings suggest that EA-HP-β-CD inclusion complex enhances the anti-inflammatory and antioxidant effect of EA in experimental animal models.
KeywordsEllagic acid Hydroxypropyl-β-cyclodextrin Inclusion complex Carrageenan Anti-inflammatory Molecular modeling
Authors are thankful to the University Grant Commission, India (UGC) for the research fellowship awarded under special assistance programme (SAP) and Sophisticated Analytical Instrument Facility, Indian Institute of Technology, Madras, India, for spectral analysis.
Conflict of interest
The authors declare that they have no conflicts of interest.
- 3.Grasser, G.: Synthetic Tannins. Enna F. G. A. (trans.) (3rd ed.) p. 20, London (1922)Google Scholar
- 5.Sonaje, K., Italia, J.L., Sharma, G., Bhardwaj, V., Tikoo, K., Ravi Kumar, M.N.V.: Development of biodegradable nanoparticles for oral delivery of ellagic acid and evaluation of their antioxidant efficacy against cyclosporine A-induced nephrotoxicity in rats. Pharm. Res. 24, 899–908 (2007)CrossRefGoogle Scholar
- 11.Chudasama, Y.N., Lugea, A., Lu, Q.Y., Pandol, S.J.: Beta-cyclodextrin increases bioavailability of ellagic acid in rats. Gastroenterology 140, S-860 (2011)Google Scholar
- 13.Higuchi, T., Connors, K.A.: Phase solubility techniques. In: Reiley, C.N. (ed.) Advance in Analytical Chemistry and Instrumentation, pp. 117–212. Wiley, New York (1965)Google Scholar
- 15.Maestro version 9.4, Schrödinger, LLC, New York, NY (2013)Google Scholar
- 16.MacroModel version 10.0, Schrödinger, LLC, New York, NY (2013)Google Scholar
- 18.Impact version 5.9, Schrödinger, LLC, New York, NY (2013)Google Scholar
- 19.Desmond version 3.4, D. E. Shaw Research, New York, NY (2013)Google Scholar
- 22.Winter, C.A., Risley, E.A., Nuss, G.W.: Anti-Inflammatory and antipyretic activities of indomethacin, 1-(P-Chlorobenzoyl)-5-Methoxy-2-Methylindole-3-Acetic Acid. J. Pharmacol. Exp. Ther. 141, 369–376 (1963)Google Scholar
- 24.Misra, H.P., Fridovich, I.: The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J. Biol. Chem. 247, 3170–3175 (1972)Google Scholar
- 25.Aebi, H.: Catalase in vitro. In: Packer, L. (ed.) Methods in Enzymology, pp. 121–126. Academic Press, New York (1984)Google Scholar
- 28.Dandawate, P.R., Vyas, A., Ahmad, A., Banerjee, S., Deshpande, J., Swamy, K.V., Jamadar, A., Dumhe-Klaire, A.C., Padhye, S., Sarkar, F.H.: Inclusion complex of novel curcumin analogue CDF and β-Cyclodextrin (1:2) and its enhanced in vivo anticancer activity against pancreatic cancer. Pharm. Res. 29, 1775–1786 (2012)CrossRefGoogle Scholar
- 30.Kim, S., Liu, Y., Gaber, M.W., Bumgardner, J.D., Haggard, W.O., Yang, Y.: Development of chitosan-ellagic acid films as a local drug delivery system to induce apoptotic death of human melanoma cells. J. Biomed. Mater. Res. B Appl. Biomater. 90, 145–155 (2009)Google Scholar
- 34.de Araujo, D.R., Tsuneda, S.S., Cereda, C.M.S., Carvalho, F.D.G.F., Prete, P.S.C., Fernandes, S.A., Fabiano, Y., Franco, M.K.K.D., Mazzaro, I., Fraceto, L.F., de Braga, F.A., de Paula, E.: Development and pharmacological evaluation of ropivacaine-2-hydroxypropyl-beta-cyclodextrin inclusion complex. Eur. J. Pharm. Sci. 33, 60–71 (2008)CrossRefGoogle Scholar
- 39.Lee, J., Kim, S., Namgung, H., Jo, Y.H., Bao, C., Choi, H.K., Auh, J.H., Lee, H.J.: Ellagic acid identified through metabolomic analysis is an active metabolite in Strawberry (‘Seolhyang’) regulating lipopolysaccharide-induced inflammation. J. Agric. Food Chem. 62, 3954–3962 (2013)CrossRefGoogle Scholar
- 42.Cuzzocrea, S., Salvemini, D.: The role of superoxide in acute and chronic inflammation. In Therapeutic Application of Superoxide Dismutase (SOD), Landes Bioscience, Georgetown, Texas, USA (Chapter 3) (2005)Google Scholar
- 47.Han, D.H., Lee, M.J., Kim, J.H.: Antioxidant and apoptosis-inducing activities of ellagic acid. Anticancer Res. 26, 3601–3606 (2006)Google Scholar