Skip to main content

Development of Microemulsion Delivery System of Essential Oil from Zingiber cassumunar Roxb. Rhizome for Improvement of Stability and Anti-Inflammatory Activity

AAPS PharmSciTech volume 18, pages 1332–1342 (2017)Cite this article

Abstract

The present study aims to investigate the major constituents of the essential oil from Zingiber cassumunar rhizome (EO) and to develop microemulsions with enhanced chemical stability and anti-inflammatory activity of EO. The major constituents of EO were terpinen-4-ol (40.5 ± 6.6%) and sabinene (17.4 ± 1.4%) as determined by gas chromatography–mass spectrometry. These compounds were responsible for the anti-inflammatory activities of EO. Sabinene and terpinen-4-ol significantly reduced nuclear factor-kappa B (NF-kB) expression by 47 ± 5 and 78 ± 8%, respectively (p < 0.001) and significantly reduced the interleukin-6 (IL-6) secretion levels to 64 ± 4% (p < 0.05) and 50 ± 1% (p < 0.001), respectively. EO microemulsions, developed using the system of EO/Tween 20 and propylene glycol (2:1)/water, showed the internal droplet size in the range of 211.5 ± 63.3 to 366.7 ± 77.8 nm. Both EO and EO microemulsions were shown to be safe for human use since there was no apparent toxic effect on human peripheral blood mononuclear cells. Interestingly, EO microemulsion could significantly protect sabinene from the evaporation after heating–cooling stability test, which leads to a good stability and high efficacy. Moreover, EO microemulsions significantly enhanced the anti-inflammatory effect comparing to the native EO. Therefore, microemulsions were attractive delivery system for natural anti-inflammatory compounds since they could enhance both efficacy and stability of EO.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

References

  1. Habsah M, Amran M, Mackeen MM, Lajis NH, Kikuzaki H, Nakatani N, et al. Screening of Zingiberaceae extracts for antimicrobial and antioxidant activities. J Ethnopharmacol. 2000;72(3):403–10. doi:10.1016/S0378-8741(00)00223-3.

    CAS  Article  PubMed  Google Scholar 

  2. Kamazeri TSAT, Samah OA, Taher M, Susanti D, Qaralleh H. Antimicrobial activity and essential oils of Curcuma aeruginosa, Curcuma mangga, and Zingiber cassumunar from Malaysia. Asian Pac J Trop Med. 2012;5(3):202–9. doi:10.1016/S1995-7645(12)60025-X.

    CAS  Article  PubMed  Google Scholar 

  3. Bua-in S, Paisooksantivatana Y. Essential oil and antioxidant activity of Cassumunar ginger (Zingiberaceae: Zingiber montanum (Koenig) Link ex Dietr.) collected from various parts of Thailand. Kasetsart J (Nat Sci). 2009;43:467–75.

    CAS  Google Scholar 

  4. Peltola S, Saarinen-Savolainen P, Kiesvaara J, Suhonen TM, Urtti A. Microemulsions for topical delivery of estradiol. Int J Pharm. 2003;254(2):99–107. doi:10.1016/S0378-5.173(02)00632-4.

    CAS  Article  PubMed  Google Scholar 

  5. Špiclin P, Homar M, Zupančič-Valant A, Gašperlin M. Sodium ascorbyl phosphate in topical microemulsions. Int J Pharm. 2003;256(1):65–73. doi:10.1016/S0378-5173(03)00063-2.

    Article  PubMed  Google Scholar 

  6. Gallarate M, Carlotti ME, Trotta M, Bovo S. On the stability of ascorbic acid in emulsified systems for topical and cosmetic use. Int J Pharm. 1999;188(2):233–41. doi:10.1016/S0378-5173(99)00228-8.

    CAS  Article  PubMed  Google Scholar 

  7. Sintov AC, Botner S. Transdermal drug delivery using microemulsion and aqueous systems: influence of skin storage conditions on the in vitro permeability of diclofenac from aqueous vehicle systems. Int J Pharm. 2006;311(1):55–62. doi:10.1016/j.ijpharm.2005.12.019.

    CAS  Article  PubMed  Google Scholar 

  8. Sintov AC, Shapiro L. New microemulsion vehicle facilitates percutaneous penetration in vitro and cutaneous drug bioavailability in vivo. J Control Release. 2004;95(2):173–83. doi:10.1016/j.jconrel.2003.11.004.

    CAS  Article  PubMed  Google Scholar 

  9. Prince LM. A theory of aqueous emulsions I. Negative interfacial tension at the oil/water interface. J Colloid Interface Sci. 1967;23(2):165–73. doi:10.1016/0021-9797(67)90099-9.

    CAS  Article  Google Scholar 

  10. Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Deliv Rev. 2000;45:89–121. doi:10.1016/S0169-409X(00)00103-4.

    CAS  Article  PubMed  Google Scholar 

  11. Ryan GB, Majno G. Acute inflammation. A review. Am J Pathol. 1977;86(1):183.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Ferrero‐Miliani L, Nielsen OH, Andersen PS, Girardin SE. Chronic inflammation: importance of NOD2 and NALP3 in interleukin‐1β generation. Clin Exp Immunol. 2007;147(2):227–35. doi:10.1111/j.1365-2249.2006.03261.

    PubMed  PubMed Central  Google Scholar 

  13. Vane JR, Botting RM. New insights into the mode of action of anti-inflammatory drugs. Inflamm Res. 1995;44(1):1–10. doi:10.1007/BF01630479.

    CAS  Article  PubMed  Google Scholar 

  14. Padmanabhan P, Jangle SN. Evaluation of in-vitro anti-inflammatory activity of herbal preparation, a combination of four medicinal plants. Int J Appl Basic Med Res. 2012;2:109–16. doi:10.1186/s13104-015-1384-5.

    Google Scholar 

  15. Mizushima Y, Kobayashi M. Interaction of anti‐inflammatory drugs with serum proteins, especially with some biologically active proteins. J Pharm Pharmacol. 1968;20(3):169–73. doi:10.1111/j.2042-7158.1968.tb09718.x.

    CAS  Article  PubMed  Google Scholar 

  16. Maroon JC, Bost JW, Borden MK, Lorenz KM, Ros NA. Natural antiinflammatory agents for pain relief in athletes. Neurosurg Focus. 2005;21, E11. doi:10.4103/2152-7806.73804.

    Google Scholar 

  17. Gilroy DW, Colville-Nash PR, Willis D, Chivers J, Paul-Clark MJ, Willoughby DA. Inducible cyclooxygenase may have anti-inflammatory properties. Nat Med. 1999;5(6):698–701. doi:10.1038/9550.

    CAS  Article  PubMed  Google Scholar 

  18. Ghosh S, May MJ, Kopp EB. NF-kB and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 1998;16(1):225–60. doi:10.1146/annurev.immunol.16.1.225.

    CAS  Article  PubMed  Google Scholar 

  19. Lee KM, Kang BS, Lee HL, Son SJ, Hwang SH, Kim DS, et al. Spinal NF‐kB activation induces COX‐2 upregulation and contributes to inflammatory pain hypersensitivity. Eur J Neurosci. 2004;19(12):3375–81. doi:10.1111/j.0953-816X.2004.03441.x.

    Article  PubMed  Google Scholar 

  20. Tilg H, Trehu E, Atkins MB, Dinarello CA, Mier JW. Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood. 1994;83(1):113–8.

    CAS  PubMed  Google Scholar 

  21. Mueller M, Hobiger S, Jungbauer A. Anti-inflammatory activity of extracts from fruits, herbs and spices. Food Chem. 2010;122(4):987–96. doi:10.1016/j.foodchem.2010.03.041.

    CAS  Article  Google Scholar 

  22. Adams RP. Quadrupole mass spectra of compounds listed in order of their retention time on DB-5. In: (ed). Identification of essential oils components by gas chromatography/quadrupole mass spectroscopy. Carol Stream: Allured Publishing Corporation; 2001.

  23. Orafidiya LO, Oladimeji FA. Determination of the required HLB values of some essential oils. Int J Pharm. 2002;237(1):241–9. doi:10.1016/S0378-5173(02)00051-0.

    CAS  Article  PubMed  Google Scholar 

  24. Shahin M, Hady SA, Hammad M, Mortada N. Development of stable O/W emulsions of three different oils. Int J Pharm Stud Res. 2011;2:45–51. doi:10.1208/s12249-010-9491-z.

    Google Scholar 

  25. Chaiyana W, Saeio K, Hennink WE, Okonogi S. Characterization of potent anticholinesterase plant oil based microemulsion. Int J Pharm. 2010;401(1):32–40. doi:10.1016/j.ijpharm.2010.09.005.

    CAS  Article  PubMed  Google Scholar 

  26. Balsinde J, Mollinedo F. Specific activation by concanavalin A of the superoxide anion generation capacity during U937 differentiation. Biochem Biophys Res Commun. 1988;151(2):802–8. doi:10.1016/S0006-291X(88)80352-8.

    CAS  Article  PubMed  Google Scholar 

  27. Phongpradist R, Chittasupho C, Okonogi S, Siahaan T, Anuchapreeda S, Ampasavate C, et al. LFA-1 on leukemic cells as a target for therapy or drug delivery. Curr Pharm Des. 2010;16(21):2321–30.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. Shishodia S, Amin HM, Lai R, Aggarwal BB. Curcumin (diferuloylmethane) inhibits constitutive NF-kB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma. Biochem Pharmacol. 2005;70(5):700–13. doi:10.1016/j.bcp.2005.04.043.

    CAS  Article  PubMed  Google Scholar 

  29. Williams LAD, O’Connar A, Latore L, Dennis O, Ringer S, Whittaker JA, et al. The in vitro anti-denaturation effects induced by natural products and non-steroidal compounds in heat treated (immunogenic) bovine serum albumin is proposed as a screening assay for the detection of anti-inflammatory compounds, without the use of animals, in the early stages of the drug discovery process. West Indian Med J. 2008;57(4):327–31.

    CAS  PubMed  Google Scholar 

  30. Bordoloi AK, Sperkova J, Leclercq PA. Essential oils of Zingiber cassumunar Roxb. from northeast India. J Essent Oil Res. 1999;11(4):441–15. doi:10.1080/10412905.1999.9701179.

    CAS  Article  Google Scholar 

  31. Sukatta U, Rugthaworn P, Punjee P, Chidchenchey S, Keeratinijakal V. Chemical composition and physical properties of oil from Plai (Zingiber cassumunar Roxb.) obtained by hydro distillation and hexane extraction. Kasetsart J (Nat Sci). 2009;43:212–7.

    CAS  Google Scholar 

  32. Bhuiyan MNI, Chowdhury JU, Begum J. Volatile constituents of essential oils isolated from leaf and rhizome of Zingiber cassumunar Roxb. Bangladesh J Pharmacol. 2008;3(2):69–73. doi:10.3329/bjp.v3i2.844.

    Google Scholar 

  33. Fernandes CP, Mascarenhas MP, Zibetti FM, Lima BG, Oliveira RP, Rocha L, et al. HLB value, an important parameter for the development of essential oil phytopharmaceuticals. Braz J Pharmacogn. 2013;23(1):108–14. doi:10.1590/S0102-695X2012005000127.

    CAS  Article  Google Scholar 

  34. Okonogi S, Chaiyana W. Enhancement of anti-cholinesterase activity of Zingiber cassumunar essential oil using a microemulsion technique. Drug Discov Ther. 2012;6(5):249–55. doi:10.5582/ddt.2012.v6.5.249.

    CAS  PubMed  Google Scholar 

  35. Kale NJ, Allen Jr LV. Studies on microemulsions using Brij 96 as surfactant and glycerin, ethylene glycol and propylene glycol as cosurfactants. Int J Pharm. 1989;57(2):87–93. doi:10.1016/0378-5173(89)90296-2.

    CAS  Article  Google Scholar 

  36. Gao ZG, Choi HG, Shin HJ, Park KM, Lim SJ, Hwang KJ, et al. Physicochemical characterization and evaluation of a microemulsion system for oral delivery of cyclosporin A. Int J Pharm. 1998;161(1):75–86. doi:10.1016/S0378-5173(97)00325-6.

    CAS  Article  Google Scholar 

  37. Chen CM, Lu CH, Chang CH, Yang YM, Maa JR. Influence of pH on the stability of oil-in-water emulsions stabilized by a splittable surfactant. Colloids Surf A Physicochem Eng Asp. 2000;170(2):173–9. doi:10.1016/S0927-7757(00)00480-5.

    CAS  Article  Google Scholar 

  38. Maroon JC, Bost JW, Borden MK, Lorenz KM, Ross NA. Natural antiinflammatory agents for pain relief in athletes. Neurosurg Focus. 2006;21(4):1–13. doi:10.4103/2152-7806.73804.

    Article  Google Scholar 

  39. Brand C, Ferrante A, Prager RH, Riley TV, Carson CF, Finlay-Jones JJ, et al. The water-soluble components of the essential oil of Melaleuca alternifolia (tea tree oil) suppress the production of superoxide by human monocytes, but not neutrophils, activated in vitro. Inflamm Res. 2001;50(4):213–129. doi:10.1007/s000110050746.

    CAS  Article  PubMed  Google Scholar 

  40. Hart PH, Brand C, Carson CF, Riley TV, Prager RH, Finlay-Jones JJ. Terpinen-4-ol, the main component of the essential oil of Melaleuca alternifolia (tea tree oil), suppresses inflammatory mediator production by activated human monocytes. Inflamm Res. 2000;49(11):619–26. doi:10.1007/s000110050639.

    CAS  Article  PubMed  Google Scholar 

  41. Pongprayoon U, Soontornsaratune P, Jarikasem S, Sematong T, Wasuwat S, Claeson P. Topical antiinflammatory activity of the major lipophilic constituents of the rhizome of Zingiber cassumunar. Part I: the essential oil. Phytomedicine. 1997;3(4):319–22. doi:10.1016/S0944-7113(97)80004-9.

    CAS  Article  PubMed  Google Scholar 

  42. Valente J, Zuzarte M, Goncalves MJ, Lopes MC, Cavaleiro C, Salgueiro L, et al. Antifungal, antioxidant and anti-inflammatory activities of Oenanthe crocata L. essential oil. Food Chem Toxicol. 2013;62:349–54. doi:10.1016/j.fct.2013.08.083.

    CAS  Article  PubMed  Google Scholar 

  43. Kaplanski G, Marin V, Montero-Julian F, Mantovani A, Farnarier C. IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation. Trends Immunol. 2003;24(1):25–9. doi:10.1016/S1471-4906(02)00013-3.

    CAS  Article  PubMed  Google Scholar 

  44. Natta L, Krittik N, Pantip B, Orapin K. Essential oil from five Zingiberaceae for anti food-borne bacteria. Int Food Res J. 2008;15(3):1–10.

    Google Scholar 

  45. Grant NH, Alburn HE, Kryzanauskas C. Stabilization of serum albumin by anti-inflammatory drugs. Biochem Pharmacol. 1970;19(3):715–22. doi:10.1016/0006-2952(70)90234-0.

    CAS  Article  PubMed  Google Scholar 

  46. Shendkar AK, Chaudhari SG, Shendkar YK. In vitro antiartthritic activity of Withania coagulans Dunal fruits. Indo Am J Pharm Res. 2014;4(2):915–24.

    Google Scholar 

  47. Dymerski T, Namieśnik J, Vearasilp K, Arancibia-Avila P, Toledo F, Weisz M, et al. Comprehensive two-dimensional gas chromatography and three-dimensional fluorometry for detection of volatile and bioactive substances in some berries. Talanta. 2015;134:460–7. doi:10.1016/j.talanta.2014.11.061.

    CAS  Article  PubMed  Google Scholar 

  48. Adams MM, Anslyn EV. Differential sensing using proteins: exploiting the cross-reactivity of serum albumin to pattern individual terpenes and terpenes in perfume. J Am Chem Soc. 2009;131(47):17068–9. doi:10.1021/ja908319m.

    CAS  Article  PubMed  Google Scholar 

  49. Wang W. Protein aggregation and its inhibition in biopharmaceutics. Int J Pharm. 2005;289(1):1–30. doi:10.1016/j.ijpharm.2004.11.014.

    CAS  Article  PubMed  Google Scholar 

  50. Katakam M, Bell LN, Banga AK. Effect of surfactants on the physical stability of recombinant human growth hormone. J Pharm Sci. 1995;84(6):713–6. doi:10.1002/jps.2600840609.

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Thailand Research Fund (Grant numbers TRG 5780029, 2014) and Austrian Academic Exchange Service (ÖAD).

Author information

Affiliations

  1. Department of Pharmaceutical Science, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200, Thailand

    Wantida Chaiyana, Pimporn Leelapornpisid & Rungsinee Phongpradist

  2. Division of Clinical Microscopy, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand

    Songyot Anuchapreeda

  3. Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstrasse 14, Vienna, Austria

    Helmut Viernstein & Monika Mueller

Authors
  1. Wantida Chaiyana
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Songyot Anuchapreeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pimporn Leelapornpisid
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rungsinee Phongpradist
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Helmut Viernstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Monika Mueller
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wantida Chaiyana.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Chaiyana, W., Anuchapreeda, S., Leelapornpisid, P. et al. Development of Microemulsion Delivery System of Essential Oil from Zingiber cassumunar Roxb. Rhizome for Improvement of Stability and Anti-Inflammatory Activity. AAPS PharmSciTech 18, 1332–1342 (2017). https://doi.org/10.1208/s12249-016-0603-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-016-0603-2

KEY WORDS

  • anti-inflammation
  • essential oil
  • microemulsion
  • stability
  • Zingiber cassumunar