Aim: The composition and activity of honey depend on its floral origin. Honey collected from Tulkarm was evaluated for physicochemical property and antioxidant content as well as a diuretic and wound healing activity. Its effect on kidney function was evaluated and compared with furosemide.

Materials and Methods: Honey was collected in Tulkarm, Palestine, and its phenol, flavones, and flavonol content were assessed. The antioxidant activity was determined with the use of colorimetric assays, 1,1-diphenyl-2-picrylhydrazyl, ferric reducing antioxidant power, and 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid). Two sets of experiments were conducted. First experiment: 18 rats were used for the evaluation of diuretic activity of honey. The rats received either honey or furosemide. Renal function test, uric acid, and serum and urine electrolytes assay were performed. Second experiment: 18 male mice were used to evaluate the wound healing property of honey. Wounds were created on mice skin and treated daily with honey or Madecassol. Measurements of wounds were performed over a period of 12 days.

Results: The physical and chemical parameters of Tulkarm honey are within the limits of the European legislation and fulfilling the criteria described in the standard codex for honey. It contains antioxidant compounds and shows antioxidant activity. Oral honey increased creatinine clearance and urine volume, sodium, and chloride without causing hypokalemia or affecting blood urea, uric acid, or serum creatinine level. The diuretic activity of furosemide was associated with hypokalemia. Topical honey application enhanced wound closure when compared with the Madecassol application.

Conclusion: The study is the first to report that honey collected from Tulkarm has a considerable diuretic effect without affecting serum electrolytes or kidney function test and exhibits strong antioxidant activity and wound healing property.

Keywords: furosemide, honey, kidney, Madecassol, wounds.

1. Iqbal, M., Anjum, A., Ali, M., Hussain, F., Ali, S., Muhammad, A., Irfan, M., Ahmad, A., Irfan, M. and Shabbir, A. (2015) Assessment of microbial load of unpasteurized fruit juices and in vitro antibacterial potential of honey against bacterial isolates. Open Microbiol. J., 9(2): 26-32. [PubMed] [PMC]

2. Yaghoobi, R., Kazerouni, A. and Kazerouni, O. (2013) Evidence for clinical use of honey in wound healing as an anti-bacterial, anti-inflammatory, anti-oxidant and anti-viral agent: A review. Jundishapur. J. Nat. Pharm. Prod., 8(2): 100-104. [Crossref] [PubMed] [PMC]

3. Aazza, S., Lyoussi, B., Antunes, D. and Miguel, M. (2013) Physicochemical characterization and antioxidant activity of 31 Moroccan honeys. J. Food Biochem., 13(1): 1-32.

4. Al-Waili, N.S., Al-Waili, F.S., Akmal, M., Ali, A., Salom, K.Y. and Al Ghamdi, A.A. (2014) Effects of natural honey on polymicrobial culture of various human pathogens. Arch. Med. Sci., 12(3): 246-250. [Crossref] [PubMed] [PMC]

5. AL-Waili, N., Al Ghamdi, A., Ansari, M.J., Al-Attal, Y., Al-Mubarak, A. and Salom, K. (2013) Differences in composition of honey samples and their impact on the antimicrobial activities against drug multiresistant bacteria and pathogenic fungi. Arch. Med. Res., 44(4): 307-316. [Crossref] [PubMed]

6. Al-Waili, N.S. (2004) Natural honey lowers plasma glucose, C-reactive protein, homocysteine, and blood lipids in healthy, diabetic, and hyperlipidemic subjects: Comparison with dextrose and sucrose. J. Med. Food, 7(1): 100-107. [Crossref] [PubMed]

7. Al-Waili, N. (2005) Effects of honey on the urinary total nitrite and prostaglandins concentration. Int. Urol. Nephrol., 37(1): 107-111. [Crossref] [PubMed]

8. El-Haskoury, R., Zizi, S., Touzani, S., Al-Waili, N., Al-Ghamdi, A. and Lyoussi, L. (2015) Diuretic activity of carob honey (Ceratonia siliqua L); Comparison with furosemide. Afr. J. Tradit. Complement. Altern. Med., 12(2): 128-133. [Crossref]

9. Fihri, A., Al-Waili, N.S., El-Haskoury, R., Bakour, M., Amarti, A., Ansari, M.J. and Lyoussi, B. (2016) Protective effect of morocco carob honey against lead-induced anemia and hepato-renal toxicity. Cell. Physiol. Biochem., 39(1): 115-122. [Crossref] [PubMed]

10. Al-Waili, N.S., Saloom, K.Y., Akmal, M., Al-Waili, F., Al-Waili, T.N., Al-Waili, A.N. and Ali, A. (2006) Honey ameliorates influence of hemorrhage and food restriction on renal and hepatic functions, and hematological and biochemical variables. Int. J. Food. Sci. Nutr., 57(4): 353-362. [Crossref] [PubMed]

11. Al-Waili, N.S., Saloom, K.Y., Al-Waili, T.N., Al-Waili, A.N., Akmal, M., Al-Waili, F.S. and Al-Waili, H.N. (2006) Influence of various diet regimens on deterioration of hepatic function and hematological parameters following carbon tetrachloride: A potential protective role of natural honey. Nat. Prod. Res., 20(12): 1258-1264. [Crossref] [PubMed]

12. Al-Waili, N.S. (2003) Intravenous and intrapulmonary administration of honey solution to healthy sheep: Effects on blood sugar, renal and liver function tests, bone marrow function, lipid profile, and carbon tetrachloride-induced liver injury. J. Med. Food, 6(2): 231-247. [Crossref] [PubMed]

13. Al-Waili, N.S., Saloom, K.Y., Akmal, M., Al-Waili, F., Al-Waili, T.N., Al-Waili, A.N. and Ali, A. (2006) Honey ameliorates influence of hemorrhage and food restriction on renal and hepatic functions, and hematological and biochemical variables. Int. J. Food Sci. Nutr., 57(5-6): 353-362. [Crossref] [PubMed]

14. El Denshary, E.S., Al-Gahazali, M.A., Mannaa, F.A., Salem, H.A., Hassan, N.S. and Abdel-Wahhab, M.A. (2012) Dietary honey and ginseng protect against carbon tetrachloride-induced hepatonephrotoxicity in rats. Exp. Toxicol. Pathol., 64(7): 753-760. [Crossref] [PubMed]

15. Hamad, R., Jayakumar, C., Ranganathan, P., Mohamed, R., El-Hamamy, M.M., Dessouki, A.A., Ibrahim, A. and Ramesh, G. (2015) Honey feeding protects kidney against cisplatin nephrotoxicity through suppression of inflammation. Clin. Exp. Pharm. Physiol., 42(8): 843-848. [Crossref] [PubMed] [PMC]

16. Zoheir, K.M., Harisa, G.I., Abo-Salem, O.M. and Ahmad, S.F. (2015) Honeybee is a potential antioxidant against cyclophosphamide-induced genotoxicity in albino male mice. Pak. J. Pharm. Sci., 28(3): 973-981. [PubMed]

17. Al-Yahya, M., Mothana, R., Al-Said, M., Al-Dosari, M., Al-Musayeib, N., Al-Sohaibani, M., Parvez, M.K. and Rafatullah, S. (2013) Attenuation of ccl4-induced oxidative stress and hepatonephrotoxicity by Saudi Sidr honey in RATS. Evid. Based Complement Altern. Med., 2013: 569037. [Crossref] [PubMed] [PMC]

18. Al-Seeni, M.N., El Rabey, H.A. and Al-Solamy, S.M. (2015) The protective role of bee honey against the toxic effect of melamine in the male rat kidney. Toxicol. Ind. Health, 31(6): 485-493. [Crossref] [PubMed]

19. Erejuwa, O.O., Gurtu, S., Sulaiman, S.A., Ab Wahab, M.S., Sirajudeen, K.N. and Salleh, M.S. (2010) Hypoglycemic and antioxidant effects of honey supplementation in streptozotocin-induced diabetic rats. Int. J. Vitam. Nutr. Res., 80(1): 74-82. [Crossref] [PubMed]

20. Sawalha, A.F. (2007) Complementary and alternative medicine (CAM) in Palestine: Use and safety implications. J. Altern. Complement Med., 13(2): 263-269. [Crossref] [PubMed]

21. Abdul-Ghani, A.S., Dabdoub, N., Muhammad, R., Abdul-Ghani, R. and Qazzaz, M. (2008) Effect of Palestinian honey on spermatogenesis in rats. J. Med. Food, 11(4): 799-802. [Crossref] [PubMed]

22. Odeha, I., Abu-Lafia, S., Dewika, H., Al-Najjara, I., Imamb, A., Dembitskyc, V. and Hanusc, L.A. (2007) Variety of volatile compounds as markers in Palestinian honey from Thymus capitatus, Thymelaea hirsuta, and Tolpis virgate. Food Chem., 101(11): 1393-1397. [Crossref]

23. Odeh, I., Abu-Lafi, S. and Al-Najjar, I. (2013) Determination of potential volatiles markers from citrus, eucalyptus, cotton and wildflower Palestinian honeys using SPME followed by GCMS analysis. Int. Food Res. J., 20(11): 1243-1247.

24. Bogdanov, S. (2002) Harmonized Methods of the International Honey Commission. Swiss Bee Research Centre, FAM, Liebefeld.: http://www.ihc-platform.net/ihcmethods2009.pdf.

25. Borrell, R., Visconti, A., Mennella, C., Anese, M. and Fogliano, V. (2002) Chemical characterization and antioxidant properties of coffee melanoidins. J. Agric. Food Chem., 50(12): 6527-6533. [Crossref]

26. Gorjanovic, S., Alvarez-Suarez, J., Novakovic, M., Pastor, F., Pezo, L., Battino, M. and Suz?njevic D. (2013) Comparative analysis of antioxidant activity of honey of different floral sources using recently developed polarographic and various spectrophotometric assays. J. Food Comp. Anal., 30(1): 13-18. [Crossref]

27. Aazza, S., Lyoussi, B., Antune, D. and Miguel, M. (2013) Physicochemical characterization and antioxidant activity of commercial Portuguese honeys. J. Food Sci., 78(12): 1159-1165. [Crossref] [PubMed]

28. Miguel, M., Doughmi, O., Aazza, S., Antunes, D. and Lyoussi, B. (2014) Antioxidant, anti-inflammatory and acetylcholinesterase inhibitory activities of propolis from different regions of Morocco. Food Sci. Biotechnol., 23(1): 313-322. [Crossref]

29. Sarmento, S., Pereira, D.S., Adriana, E., Sarmento, D., Sarmento, D. and Santos, D. (2013) Phenolic compounds, melissopalynological, physicochemical analysis and antioxidant activity of jandaira (Melipona subnitida) honey. J. Food Comp. Anal., 29(1): 10-18. [Crossref]

30. Padmanabhan, P. and Jangle, S.N. (2012) Evaluation of DPPH radical scavenging activity and reducing power of four selected medicinal plants and their combinations. Int. J. Pharm. Sci. Drug Res., 4(2): 143-146.

31. Marghitas, A., Stanciu, G., Dezmirean, S., Bobis, B., Olimpia, P., Stefan, B. and Graca, C. (2009) In vitro antioxidant capacity of honeybee-collected pollen of selected floral origin harvested from Romania. Food Chem., 115(9): 878-883. [Crossref]

32. Prieto, P., Pineda, M. and Aguilar, M. (1999) Spectrophotometric quantitation of antioxidant capacity through the formulation of a phosphomolybdenum complex: Specific application of Vitamin E. Anal. Biochem., 269(3): 337-341. [Crossref] [PubMed]

33. Bogdanov, S., Ruoff, K. and Oddo, L.P. (2004) Physico-chemical methods for the characterisation of unifloral honeys: A review. Apidologie, 35(1): S4-S17. [Crossref]

34. EU Council. (2002) Council directive 2001/11 O/EC of 20 December 2001 relating to honey. Off. J. Eur. Commun., L 10(1): 47-52.

35. Aazza, S., Lyoussi, B., Antune, D. and Miguel, M. (2014) Physicochemical characterization and antioxidant activity of 17 commercial Moroccan honeys. Int. J. Food Sci. Nutr., 65(4): 449-457. [Crossref] [PubMed]

36. Ferrauto, G. and Pavone, P. (2013) Palynological, physicochemical and organoleptic characteristics of carob tree (Ceratonia siliqua L.) honey from Sicily. Int. J. Food Sci. Tech., 48(12): 1596-1602. [Crossref]

37. Gomes, S., Dias, L., Moreira, L., Rodrigues, P. and Estevinho, L. (2010) Physicochemical, microbiological, and antimicrobial properties of commercial honeys from Portugal. Food Chem. Toxicol., 48(4): 544-548. [Crossref] [PubMed]

38. El-Haskoury, R., Kriaa, W., Lyoussi, B. and Makni, M. (2018) Ceratonia siliqua honeys from Morocco: Physicochemical properties, mineral contents, and antioxidant activities. J. Food Drug Anal., 26(1): 67-73. [Crossref] [PubMed]

39. Yucel, Y. and Sultanog, P. (2013) Characterization of honeys from Hatay region by their physicochemical properties combined with chemometrics. Food Biosci., 1(1): 16-25. [Crossref]

40. Codex Alimentarius Commission. (2001) Revised codex standard for honey, codex STAN 12-1981, Rev. 1 1987, Rev. 2 2001. Codex Stand., 12(1): 1-7.

41. Cetkovic, G., Saponjac, V., Stajcic, S., Vulic, J., Djilas, S., Stajner, D. and Popovic, B. (2014) Evaluation of phenolic content, antioxidant activity and sensory characteristics of Serbian honey-based product. Ind. Crop. Prod., 62(1): 1-7.

42. Saxena, S., Gautam, S. and Sharma, A. (2010) Physical, biochemical, and antioxidant properties of some Indian honeys. Food Chem., 118(3): 391-397. [Crossref]

43. Mouhoubi-Tafinine, Z., Ouchemoukh, S. and Tamendjari, A. (2016) Antioxidant activity of some Algerian honey and propolis. Ind. Crop. Prod., 88(1): 85-90. [Crossref]

44. Al-Mamary, M., Al-Meeri, A. and Al-Habori, M. (2002) Antioxidant activities and total phenolics of different types of honeys. Nutr. Res., 22(12): 1041-1047. [Crossref]

45. El-Guendouz, S., Al-Waili, N., Aazza, S., Elamine, Y., Zizi, S., Al-Waili, T. and Lyoussi, B. (2017) Antioxidant and diuretic activity of co-administration of Capparis spinosa honey and propolis in comparison to furosemide. Asian Pac. J. Trop. Med., 10(11): 974-980. [Crossref] [PubMed]

46. Can, Z., Yildiz, O., Sahin, H., Turumtay, E.A., Silici, S. and Kolayli, S. (2015) An investigation of Turkish honeys: Their physicochemical properties, antioxidant capacities and phenolic profiles. Food Chem., 180(2): 133-141. [Crossref] [PubMed]

47. Jackson, E. (1996) Drugs affecting renal and cardiovascular function. In: Hardman, J.C., Gilman, A.G. and Limbird, L.E. (Eds.). Goodman and Gilman's the Pharmacological Basis of Therapeutics. 9th ed. Pergamon Press, New York. p685-713.

48. Jouad, H., Lacaille-Dubois, M., Lyoussi, B. and Eddouks, M. (2001) Effects of the flavonoids extracted from Spergularia purpurea Pers. On arterial blood pressure and renal function in normal and hypertensive rats. J. Ethnopharmacol., 76(2): 159-163. [Crossref]

49. Wu, J. and Muir, A. (2008) Isoflavone content and its potential contribution to the antihypertensive activity in soybean angiotensin I converting enzyme inhibitory peptides. J. Agric. Food Chem., 56(12): 9899-9904. [Crossref] [PubMed]

50. Hadagali, M. and Chua, L. (2014) The anti-inflammatory and wound healing properties of honey. Eur. Food Res. Technol., 23(9): 1003-1014. [Crossref]

51. Vallianou, N., Gounari, P., Skourtis, A., Panagos, J. and Kazazis, C. (2014) Honey and its anti-inflammatory, anti-bacterial and anti-oxidant properties. Gen. Med. (Los Angel), 291(2): 1-5. [Crossref]

52. Bashkaran, K., Zunaina, E., Bakiah, S., Sulaiman, S., Sirajudeen, K. and Naik, V. (2011) Anti-inflammatory and antioxidant effects of Tualang honey in alkali injury on the eyes of rabbits: Experimental animal study. BMC Complement Altern. Med., 11(1): 1-11. [Crossref] [PubMed] [PMC]

53. Atrott, J. and Henle, T. (2009) Methylglyoxal in Manuka honey - Correlation with antibacterial properties. Czech. J. Food Sci., 27: S163-S165. [Crossref]

54. Tonks, A.J., Cooper, R.A., Jones, K.P., Blair, S., Parton, J. and Tonks, A. (2003) Honey stimulates inflammatory cytokine production from monocytes. Cytokine, 21(3): 242-247. [Crossref]

55. Al-Waili, N. and Boni, N. (2003) Natural honey lowers plasma prostaglandin concentrations in normal individuals. J. Med. Food, 6(2): 129-133. [Crossref] [PubMed]

56. Shetty, B.S., Udupa, S.L. and Udupa, A.L. (2008) Biochemical analysis of granulation tissue in steroid and Centella asiatica (Linn) treated rats. Pharm. Online, 2(6): 624-632.

57. Lee, J., Jung, E., Lee, H., Seo, Y., Koh, J. and Park, D. (2008) Evaluation of the effects of a preparation containing asiaticoside on periocular wrinkles of human volunteers. Int. J. Cosmet. Sci., 30(3): 167-173. [Crossref] [PubMed]

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