, Volume 38, Issue 1, pp 61–69 | Cite as

Anti-Inflammatory and Membrane-Stabilizing Properties of Two Semisynthetic Derivatives of Oleanolic Acid

  • Benedicta N. Nkeh-Chungag
  • Opeoluwa O. Oyedeji
  • Adebola O. Oyedeji
  • Eugene J. Ndebia


Acetylation and methylation semisynthesis of oleanolic acid (OA) isolated from Syzygium aromaticum L. yielded two compounds: 3-acetoxyoleanolic acid (3-AOA) and 3-acetoxy, 28-methylester oleanolic acid (3-A,28-MOA). Anti-inflammatory properties of these compounds were assessed using the serotonin and fresh egg albumin-induced inflammatory test models in male Wistar rats weighing 250–300 g. Furthermore, erythrocyte membrane-stabilizing property of these compounds was evaluated in the heat- and hypotonicity-induced in vitro hemolysis test models. The two semisynthetic compounds significantly (p < 0.05) inhibited albumin-induced inflammation better than OA and indomethacin from 1–5 h post administration. Both compounds were membrane stabilizing in heat-induced hemolysis test while only 3-AOA showed membrane-stabilizing effects in a hypotonic milieu. Semisynthesis of OA yielded two compounds which had better in vivo anti-inflammatory and in vitro membrane-stabilizing properties.


oleanolic acid anti-inflammatory membrane stabilization 



This work was supported by the Walter Sisulu University Institutional Research Grant, the Govan Mbeki Research and Development Center, University of Fort Hare, and the National Research Foundation (NRF).

Conflict of Interest

All authors declare that they have no conflict of interest.


  1. 1.
    Katiyar, C., A. Dupta, S. Kanjilal, and S. Katiyar. 2012. Drug discovery from plant sources: an integrated approach. Ayurveda 33: 10–9.Google Scholar
  2. 2.
    Salim, A. A., Chin, Y. W and Kinghorn AD. 2008. Drug discovery from plants. In: Bioactive Molecules and Medicinal Plants. pp. 1–24. Ramawat and Merillon (eds). Accessed 29 March 2014.
  3. 3.
    Lu, Y.F., X.L. Wan, Y. Xu, and J. Liu. 2013. Repeated oral administration of oleanolic acid produces cholestatic liver injury in mice. Molecules 18: 3060–3071.CrossRefPubMedGoogle Scholar
  4. 4.
    Chen, Q., Y. Zhang, and Z. Chen. 2011. Identification and quantification of oleanolic acid and ursolic acid in Chinese herbs by liquid chromatography-ion trap mass spectrometry. Biomed Chromatogr 25: 1381–1388.CrossRefPubMedGoogle Scholar
  5. 5.
    Wang, X., Y.L. Li, H. Wu, J.Z. Lui, J.X. Hu, N. Liao, J. Peng, P.P. Cao, X. Liang, and C.X. Hai. 2011. Antidiabetic effects of oleanolic acid: a promising use of a traditional pharmacological agent. Phytother Res 25: 1031–1040.CrossRefPubMedGoogle Scholar
  6. 6.
    Petronelli, A., G. Pannitteri, and U. Testa. 2009. Triterpenoids as new promising anticancer drugs. Anticancer Drugs 20: 880–892.CrossRefPubMedGoogle Scholar
  7. 7.
    Sultana, N., and A. Ata. 2008. Oleanolic acid and related derivatives as medicinally important compounds. J Enzym Inhib Med Chem 23: 739–756.CrossRefGoogle Scholar
  8. 8.
    Ma, C.M., X.H. Wui, H. Masao, X.J. Wang, and Y. Kanoi. 2009. HCV protease inhibitory, cytotoxic and apoptosis-inducing effects of oleanolic acid derivatives. J Pharmacol Pharm Sci 12: 243–248.Google Scholar
  9. 9.
    Cayman Chemicals. 2014. Product information, Oleanolic acid Item No: 11726. Accessed 29 March 2014.
  10. 10.
    Yang, R., X. Huang, J. Dou, G. Zhai, and L. Su. 2013. Self-microemulsifying drug delivery system for improved oral bioavailability of oleanolic acid: design and evaluation. Int J Nanomed 8: 2917–2926.Google Scholar
  11. 11.
    Habila, J.D., F.O. Shode, G.I. Ndukwe, J.O. Amupitan, and A.J. Nok. 2012. Effects of C-3 modification of oleanolic acid on Candida spp., Trichophyton tonsurans and Microsporum canis inhibition. Pharmacol 3: 313–324.Google Scholar
  12. 12.
    Dos Santos, F.M., M.G. de Souza, A.E.M. Crotti, C.H.G. Martins, S.R. Ambrosio, R.C.S. Veneziani, A. e Silva, and W.H. Cunha. 2012. Evaluation of antimicrobial activity of extracts of Tibouchina candolleana (melastomataceae) isolated compounds and semi-synthetic derivatives against endodontic bacteria. Braz J Microbiol 43: 793–799.CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Althagafy, H.S., T.N. Grat, A.A. Sy-Cordero, B.T. Gufford, M.F. Paine, J. Wagoner, S.K. Polyak, M.P. Croatt, and N.H. Oberlies. 2013. Semisynthesis, cytotoxicity, antiviral and drug interaction liability of 7-O-methylated analogues of flavonolignans from milk thistle. Bio Med Chem 21: 3919–3926.CrossRefGoogle Scholar
  14. 14.
    Mapanga, R.F., M.A. Tufts, F.O. Shode, and C.T. Musabayane. 2009. Renal effects of plant-derived oleanolic acid in Streptozotocin-induced diabetic rats. Ren Fail 31: 481–491.CrossRefPubMedGoogle Scholar
  15. 15.
    Umapathy, E., E.J. Ndebia, A. Meeme, B.N. Nkeh-Chungag, and J.E. Iputo. 2010. An experimental evaluation of Albuca setosa aqueous extract on membrane stabilization, protein denaturation and white blood cell migration during acute inflammation. J Med Plant Res 4: 789–795.Google Scholar
  16. 16.
    Anisoke, A.C., O. Obidoa, and U.S.L. Ezeanyika. 2012. Membrane stabilization as a mechanism of the anti-inflammatory activity of methanol extract of garden egg (Solanum aethiopicum). DARU J of Pharm Sci 20: 76–82.CrossRefGoogle Scholar
  17. 17.
    Qin, L., D. Zhao, J. Xu, X. Ren, E.F. Terwilliger, S. Parangi, H.F. Dvorak, and H. Zeng. 2013. The vascular permeabilizing factors histamine and serotonin induce angiogenesis through TR3/Nur77 and subsequently truncate it through thrombospondin-1. Blood 121: 2154–2164.CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Olorunju, A.E., A. Adewala, and M.J. Modupe. 2012. Anti-inflammatory activity of Russelia equisetiformis Schlecht & Cham: identification of its active constituent. J Intercul Ethnopharm 1: 25–9.Google Scholar
  19. 19.
    Ricciotti, E., and G.A. FitGerald. 2011. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol 31: 986–1000.CrossRefPubMedCentralPubMedGoogle Scholar
  20. 20.
    Dharmappa, K.K., R.V. Kumar, A. Nataraju, R. Mohamed, H.V. Shivaprasad, and B.S. Vishwanath. 2009. Anti inflammatory activity of oleanolic acid by inhibition of secretory phospholipase A2. Planta Med 75: 211–215.CrossRefPubMedGoogle Scholar
  21. 21.
    Liu, J. 1995. Pharmacology of oleanolic acid and ursolic acid. J Ethnopharmacol 49: 57–68.CrossRefPubMedGoogle Scholar
  22. 22.
    Kim, S.H., J.H. Hong, and Y.C. Lee. 2014. Oleanolic acid suppresses ovalbumin-induced airway inflammation and Th2-mediated allergic asthma by modulating the transcription factor T-bet, GATA-3, RORyt and Foxp3 in asthmatic mice. Int Immunopharmacol 18: 311–324.CrossRefPubMedGoogle Scholar
  23. 23.
    Lee, W., E.J. Yang, S.K. Ku, K.S. Song, and J.S. Bae. 2013. Anti-inflammatory effects of oleanolic acid on LPS-induced inflammation in vitro and in vivo. Inflammation 36: 94–102.CrossRefPubMedGoogle Scholar
  24. 24.
    Kitsiouli, E., G. Nakos, and M.E. Lekka. 2009. Phospholipase A2 subclasses in acute respiratory distress syndrome. Bio Biophys Acta (BBA) Molec Basis Dis 1792: 941–953.CrossRefGoogle Scholar
  25. 25.
    Aksoy, M.O., M. Li, Y. Borenstein, and S.G. Kelsen. 1999. Effects of topical corticosteroids on inflammatory mediator-induced eicosanoid release by human airway epithelial cells. J Allergy Clin Immunol 103: 1081–1091.CrossRefPubMedGoogle Scholar
  26. 26.
    Senthil, S., M. Sridevi, and K.V. Pugalendi. 2007. Cardioprotective effect of oleanolic acid on isoproterenol induced myocardial ischemia in rats. Toxicol pathol 35: 418–423.CrossRefPubMedGoogle Scholar
  27. 27.
    Meyer, M.C., P. Rastogi, C.S. Beckett, and J. McHowat. 2005. Phospholipase A2 inhibitors as potential anti-inflammatory agents. Curr Pharm Des 11: 1301–1312.CrossRefPubMedGoogle Scholar
  28. 28.
    Zhou, C.C., X.B. Sun, W. Liu, H.B. Shi, H.B. Gao, and Y.B. Miao. 1993. Effects of oleanolic acid on the immune complex, allergic reaction and inflammation. J Chinese Pharm Sci 2: 69–79.Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Benedicta N. Nkeh-Chungag
    • 1
  • Opeoluwa O. Oyedeji
    • 2
  • Adebola O. Oyedeji
    • 3
  • Eugene J. Ndebia
    • 4
  1. 1.Department of Zoology, Faculty of Science, Engineering & TechnologyMthathaSouth Africa
  2. 2.Department of Chemistry, Faculty of Science and AgricultureUniversity of Fort HareAliceSouth Africa
  3. 3.Department of Chemistry and Chemical Technology, Faculty of Science, Engineering & TechnologyMthathaSouth Africa
  4. 4.Department of Physiology, Faculty of Health ScienceMthathaSouth Africa

Personalised recommendations