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An isobolographic analysis of the anti-nociceptive effect of geraniin in combination with morphine or diclofenac

  • Eric Boakye-Gyasi EMAIL logo , Ella Anle Kasanga , Elvis Ofori Ameyaw , Wonder Kofi Mensah Abotsi , Robert Peter Biney , Christian Agyare and Eric Woode
Published/Copyright: October 9, 2017

Abstract

Background:

Geraniin, a dehydroellagitannin, is a major component of the aqueous extract of the aerial parts of Phyllanthus muellerianus (Kuntze) Exell. (Euphorbiaceae). Several Phyllanthus species are traditionally used for painful disorders. The anti-nociceptive effects of the aqueous extract of the aerial parts of P. muellerianus and of geraniin have been scientifically established. The aim of the paper is to determine whether a combination of geraniin and diclofenac or geraniin and morphine leads to better anti-nociceptive effects.

Methods:

The nature of the interactions of morphine and diclofenac with geraniin was evaluated by undertaking the isobolographic analysis. Mice were treated with geraniin (3–30 mg/kg), morphine (1–10 mg/kg), and diclofenac (10–100 mg/kg) to obtain the ED50 values of the agents in the formalin test. Dose-response curves were then obtained and analyzed after the co-administration of geraniin with morphine or diclofenac in fixed ratio (1:1) combinations based on specific fractions (1/2, 1/4, and 1/8) of their respective ED50 values for the formalin test.

Results:

Geraniin was less potent than morphine but more potent than diclofenac in the formalin-induced nociception. The isobolographic analysis of geraniin/morphine (G/M) and geraniin/diclofenac combinations (G/D) at different fractions revealed the potentiation of their anti-nociceptive effects. The degrees of potentiation, which were calculated as interaction indices, showed synergism for both combinations in both phase I (G/M: 0.040, G/D: 0.017) and phase II (G/M: 0.004, G/D: 0.002) of the formalin test.

Conclusions:

The present study demonstrates synergism for the co-administration of geraniin with both morphine and diclofenac.


Corresponding author: Dr. Eric Boakye-Gyasi, Faculty of Pharmacy and Pharmaceutical Science, Department of Pharmacology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana, Tel.: (+233)-244635194, Fax: +233-322-60366

Acknowledgments

The authors are grateful for the contributions and technical assistance offered by Mr. Edmund Dery and Mr. Thomas Ansah of the Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, KNUST, Kumasi.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Raffa RB. Pharmacology of oral combination analgesics: rational therapy for pain. J Clin Pharm Ther 2001;26:257–64.10.1046/j.1365-2710.2001.00355.xSearch in Google Scholar

2. Becker DE. Pain management: part 1: managing acute and postoperative dental pain. Anesth Prog 2010;57:67–79.10.2344/0003-3006-57.2.67Search in Google Scholar

3. Buvanendran A, Kroin, JS. Multimodal analgesia for controlling acute postoperative pain. Curr Opin Anesthesiol 2009;22: 588–93.10.1097/ACO.0b013e328330373aSearch in Google Scholar

4. Ben-Bala KD. Phyllanthus muellerianus (Kuntze) Exell. [Internet] Record from PROTA4U. Schmelzer GH & Gurib-Fakim A (Editors). PROTA (Plant Resources of Tropical Africa/Ressources végétales de l’Afrique tropicale), Wageningen, Netherlands. Available at: http://www.prota4u.org/search.asp. Accessed: 5 October 2016.Search in Google Scholar

5. Agyare C, Lechtenberg M, Deters A, Petereit F, Hensel A. Ellagitannins from Phyllanthus muellerianus (Kuntze) Exell.: Geraniin and furosin stimulate cellular activity, differentiation and collagen synthesis of human skin keratinocytes and dermal fibroblasts. Phytomedicine 2011;18:617–24.10.1016/j.phymed.2010.08.020Search in Google Scholar

6. Boakye-Gyasi E, Kasanga EA, Biney RP, Mensah KB, Agyare C, Woode E. Anti-nociceptive effects of geraniin and an aqueous extract of the aerial parts of Phyllanthus muellerianus (Kuntze) Exell. in murine models of chemical nociception. Iran J Pharm Sci 2016;12:17–30.Search in Google Scholar

7. Animal Care and Use Committee. Guidelines for the capture, handling, and care of mammals as approved by the American Society of Mammalogists. J Mammal 1998;79:1416–31.10.2307/1383033Search in Google Scholar

8. Dubuisson D, Dennis SG. The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain 1977;4:161–74.10.1016/0304-3959(77)90130-0Search in Google Scholar

9. Miranda HF, Noriega V, Zepeda RJ, Sierralta F, Prieto JC. Systemic synergism between codeine and morphine in three pain models in mice. Pharmacol Rep 2013;65:80–8.10.1016/S1734-1140(13)70966-6Search in Google Scholar

10. Woode E, Ameyaw EO, Abotsi WK, Boakye-Gyasi E. An isobolographic analysis of the anti-nociceptive effect of xylopic acid in combination with morphine or diclofenac. J Basic Clin Pharma 2015;6:103–8.10.4103/0976-0105.168055Search in Google Scholar PubMed PubMed Central

11. Ameyaw EO, Woode E, Kyei S, Biney RP, Boampong JN. Anti-nociceptive synergism of pregabalin and xylopic acid co-administration in paclitaxel-induced neuropathy: isobolographic analysis. Pharmacogn J 2015;7:363–68.10.5530/pj.2015.6.8Search in Google Scholar

12. Tallarida RJ. An overview of drug combination analysis with isobolograms. J Pharmacol Exp Ther 2006;319:1–7.10.1124/jpet.106.104117Search in Google Scholar PubMed

13. Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature 2001;413:203–10.10.1038/35093019Search in Google Scholar

14. Tallarida RJ, Cowan A, Raffa RB. Anti-nociceptive synergy, additivity, and subadditivity with combinations of oral glucosamine plus non-opioid analgesics in mice. J Pharmacol Exp Ther 2003;307:699–704.10.1124/jpet.103.054320Search in Google Scholar

15. Tjølsen A, Berge OG, Hunskaar S, Rosland JH, Hole K. The formalin test: an evaluation of the method. Pain 1992; 51:5–17.10.1016/0304-3959(92)90003-TSearch in Google Scholar

16. McNamara CR, Mandel-Brehm J, Bautista DM, Siemens J, Deranian KL, Zhao M, et al. TRPA1 mediates formalin-induced pain. Proc Natl Acad Sci 2007;104:13525–30.10.1073/pnas.0705924104Search in Google Scholar

17. Santa-Cecília FV, Freitas LA, Vilela FC, Veloso Cde C, da Rocha CQ, Moreira ME, et al. Anti-inflammatory and anti-nociceptive effects of Garcinia brasiliensis. J Ethnopharmacol 2011;133:467–73.10.1016/j.jep.2010.09.036Search in Google Scholar

18. Hunskaar S, Hole K. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain 1987;30:103–14.10.1016/0304-3959(87)90088-1Search in Google Scholar

19. Asomoza-Espinosa R, Alonso-López R, Mixcoatl-Zecuatl T, Aguirre-Bañuelos P, Torres-López JE, Granados-Soto V. Sildenafil increases diclofenac anti-nociception in the formalin test. Eur J Pharmacol 2001;418:195–200.10.1016/S0014-2999(01)00956-6Search in Google Scholar

20. Santos AR, Vedana EM, De Freitas GA. Anti-nociceptive effect of meloxicam in neurogenic and inflammatory nociceptive models in mice. Inflamm Res 1998;47:302–7.10.1007/s000110050333Search in Google Scholar PubMed

21. Boakye YD, Agyare C, Dapaah SO. In vitro and in vivo antioxidant properties of Phyllanthus muellerianus and its major constituent, geraniin. Oxid Antioxid Med Sci 2016;5:70–8.10.5455/oams..290616.or.099Search in Google Scholar

22. Boakye YD, Agyare C, Abotsi WK, Ayande PG, Ossei PP. Anti-inflammatory activity of aqueous leaf extract of Phyllanthus muellerianus (Kuntze) Exell. and its major constituent, geraniin. J Ethnopharmacol 2016;187:17–27.10.1016/j.jep.2016.04.020Search in Google Scholar PubMed

Received: 2017-3-13
Accepted: 2017-8-10
Published Online: 2017-10-9
Published in Print: 2018-3-28

©2018 Walter de Gruyter GmbH, Berlin/Boston

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