Therapeutic effects of ethanol extract of propolis on experimental cutaneous candidiasis in horse

Document Type : Original Article

Authors

1 DVM Graduate, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

2 Department of Internal Medicine, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

3 Department of Pathobiology, Faculty of Veterinary Medicine, Amol University of Special Modern, Amol, Iran

4 PhD Graduated from Pathobiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

10.30466/vrf.2025.2067879.4863
Abstract
Candida albicans is a commensal opportunistic yeast colonizing the skin and mucosal surfaces of humans and animals, which, under specific predisposing conditions, can proliferate excessively and lead to clinical manifestations of candidiasis. The widespread prophylactic and therapeutic use of antifungal agents has led to the emergence of drug-resistant strains, necessitating the exploration of novel therapeutic alternatives. Considering the clinical and conformational significance of equine skin health, the present study aimed to evaluate the therapeutic efficacy of ethanol extract of propolis in an experimental model of cutaneous candidiasis in horses. In 2022, two clinically healthy, six-year-old female horses (approximately 400 kg) were selected for the study. Immunosuppression was induced using dexamethasone and four intradermal inoculation sites were created on the shaved thoracic and flank regions of both lateral aspects using C. albicans (PTCC: 5027) suspension (5 × 10⁶ CFU mL-1). The experimental sites on the right thorax were treated with ethanol extract of propolis while those on the left thorax received topical nystatin. Lesions on the right flank were treated with glycerin as a vehicle control, and lesions on the left flank were left untreated. Cutaneous candidiasis was successfully induced within five days post-inoculation. Clinical resolution was observed following five days of treatment with ethanol extract of propolis, whereas, nystatin required eight days to achieve complete lesion resolution. The findings of this study suggested that topical ethanol extract of propolis demonstrated superior efficacy in accelerating the resolution of C. albicans-induced cutaneous lesions in horses compared to nystatin.

Keywords

Subjects

1.     McGavine DM, Zackary JF. Pathologic basis of veterinary disease. 5th ed. Philadelphia, USA: Elsevier Mosby 2012; 335-336.
2.     Gonzalez Santiago TM, Pritt B, Gibson LE, et al. Diagnosis of deep cutaneous fungal infections: correlation between skin tissue culture and histo-pathology. J Am Acad Dermatol 2014; 71(2): 293-301.
3.     Jubb KVF, Kennedy PC, Palmer N. Pathology of domestic animals. 6th ed. New York, USA: Elsevier 2016; 694-709.
4.     Verduyn Lunel FM, Meis JF, Voss A. Nosocomial fungal infections: candidemia. Diagn Microbiol Infect Dis 1999; 34(3): 213-220.
5.     Khosravi AR, Mardjanmehr H, Shokri H, et al. Mycological and histopathological findings of experimental disseminated candidiasis in dogs. IJVR 2009; 10(3): 228-234.
6.     Müller GG, Kara-José N, de Castro RS. Antifungals in eye infections: drugs and routes of administration. Rev Bras Oftalmol 2013; 72(2): 132-141.
7.     Radostits OM, Gay CC, Hinchcliff KW, et al., Veterinary medicine a textbook of the diseases of cattle, horses, sheep, pigs, and goats. 11th ed. Philadelphia, USA: Saunders Elsevier 2017; 1602-1603.
8.     Yenisehirli G, Bulut N, Yenisehirli A, et al. In vitro susceptibilities of Candida albicans isolates to antifungal agents in Tokat, Turkey. Jundishapur J Microbiol 2015; 8(9): e28057. doi: 10.5812/jjm.28057.
9.     Laniado- Laborín R, Cabrales-Vargas M. Amphotericin B: side effects and toxicity. Rev Iberoam Micol 2009; 26(4): 223-227.
10. Gupta AK, Lyons DC. The rise and fall of oral ketoconazole. J Cutan Med Surg 2015; 19(4): 352-357.
11. Lyu X, Zhao C, Yan ZM, et al. Efficacy of nystatin for the treatment of oral candidiasis: a systematic review and meta-analysis. Drug Des Devel Ther 2016; 10: 1161-1171.
12. Qiu S, Zhao GQ, Lin J, et al. Natamycin in the treatment of fungal keratitis: a systematic review and meta-analysis. Int J Ophthalmol 2015; 8(3): 597-602.
13. Ahangari Z, Naseri M, Vatandoost F. Propolis: Chemical composition and its applications in endodontics. Iran Endod J 2018; 13(3): 285-292.
14. Movaffagh J, Bazzaz BS, Yazdi AT, et al. Wound healing and antimicrobial effects of chitosan-hydrogel/honey compounds in a rat full-thickness wound model. Wounds 2019; 31(9): 228-235.
15. Sokeng SD, Talla E, Sakava P, et al. Anti-inflammatory and analgesic effect of arachic acid ethyl ester isolated from propolis. Biomed Res Int 2020; 2020: 8797284. doi: 10.1155/2020/8797284.
16. Zulhendri F, Chandrasekaran K, Kowacz M, et al. Antiviral, antibacterial, antifungal, and antiparasitic properties of propolis: a review. Foods 2021; 10(6): 1360. doi: 10.3390/foods10061360.
17. Abd Rashid N, Mohammed SNF, Syed Abd Halim SA, et al. Therapeutic potential of honey and propolis on ocular disease. Pharmaceuticals (Basel) 2022; 15(11): 1419. doi: 10.3390/ph15111419
18. Yazdanian M, Motallaei MN, Tahmasebi E, et al. Chemical characterization and cytotoxic/antibacterial effects of nine Iranian propolis extracts on human fibroblast cells and oral bacteria. Biomed Res Int 2022; 2022: 6574997. doi: 10.1155/2022/6574997.
19. Bahmani T, Najarnezhad V, Ownagh A. Therapeutic effects of propolis ethanolic extract on infectious bovine keratoconjunctivitis in cows. J Adv Vet Res 2024; 14(4): 586-590.
20. Sforcin JM. Propolis and the immune system: a review. J Ethnopharmacol 2007; 113(1): 1-14.
21. Hartwich A, Legutko J, Wszołek J. Propolis: its properties and administration to patients treated for some surgical diseases [Polish]. Przegl Lek 2000; 57(4): 191-194.
22. Alamyel FB, Abushaala FA, Abshwigir RM, et al. Antibacterial and antifungal activity of the propolis growing in the basin of Mediterranean city Misurata, Libya. Pharm Chem J 2018; 5(4): 63-70.
23. Ramón-Sierra J, Peraza-Lópeza E, Rodríguez-Borges R, et al. Partial characterization of ethanolic extract of Melipona beecheii propolis and in vitro evaluation of its antifungal activity. Rev Bras Farmacogn 2019; 29: 319-324.
24. Sayyadi F, Mahdavi S, Moghadamnia AA, et al. The effect of aqueous and ethanolic extract of Iranian propolis on Candida albicans isolated from the mouth of patients with colorectal malignancy undergone chemotherapy: an in vitro study. Caspian J Intern Med 2020; 11(1): 62-66.
25. Koc AN, Silici S, Ayangil D, et al. Comparison of in vitro activities of antifungal drugs and ethanolic extract of propolis against Trichophyton rubrum and T. Mentagrophytes by using a microdilution assay. Mycoses 2005; 48(3): 205-210.
26. Ownagh A, Tukmechi A, Adibhesam M, et al. Comparative study on the effect of ethanol extract of propolis collected from west Azarbaijan apiaries against dermatophytes and non-dermathophytes fungi. Stud Med Sci 2010; 21(3): 206-214.
27. Ahangari AA, Ownagh A, Tehrani A, et al. The effects of ethanol extract of propolis (EEP) on the experimentally induced Candida keratitis in rabbits. Tehran Univ Med J 2011; 69(1): 22-28.
28. Eslami Milanee K, Tehrani A, Najjarnejad V, et al. Histopathology of propolis ethanolic extract (EEP) effects on inflammatory reactions in experimental cutaneous candidiasis in goats. Med J Tabriz Univ Med Sci 2018; 40(3): 16-25.
29. Mohammadzadeh S, Shariatpanahi M, Hamedi M, et al. Chemical composition, oral toxicity and antimicrobial activity of Iranian Propolis. Food Chem 2007; 103(4): 1097-1103.
30. Behrens-Baumann W. Mycosis of the eye and its adnexa. Basle, Switzerland: S. Karger 1999; 84-90.
31. Ownagh A, Adibhesami M. Treatment of Candidia albicans cutaneous infection by ethanol extract of propolis in an experimental model. Med J Tabriz Univ Med Sci 2012; 35(2): 6-11.
32. Pichard DC, Freeman AF, Cowen EW. Primary immunodeficiency update; Part II. syndromes associated with mucocutaneous candidiasis and non-infectious cutaneous manifestations. J Am Acad Dermatol 2015; 73(3): 367-381.
33. Maccallum D. Hosting infection: experimental models to assay Candida virulence. Int J Microbiol 2012; 2012: 363764. doi: 10.1155/2012/363764.
34. Rhew Z, Han Y. Synergic effect of combination of glycyrol and fluconazole against experimental cutaneous candidiasis due to Candida albicans. Arch Pharm Res 2016; 39(10): 1482-1489.
35. Pupim ACE, Campois TG, Araújo EJA, et al. Infection and tissue repair of experimental cutaneous candidiasis in diabetic mice. J Med Microbiol 2017; 66(6): 808-815.
36. Chase C, Lutz K, McKenzie E, et al. Blackwell’s Five-Minute Veterinary Consult: Ruminant. 2nd ed. Hoboken, USA: Wiley-Blackwell. 2017; 172-173.
37. Doyle A, López A, Pack L, et al. Candida osteomyelitis in a gelding. Can Vet J 2013; 54(2): 176-178.
38. Hey R. Therapy of skin, hair and nail fungal infections. J Fungi (Basel) 2018; 4(3): 99. doi: 10.3390/jof4030099.
39. Hill PB, Moriello KA, Shaw SE. A review of systemic antifungal agents. Vet Dermatol 1995; 6(2): 59-66.
40. Pfaller MA, Diekema DJ. Epidemiology of invasive mycoses in North America. Crit Rev Microbiol 2010; 36(1): 1-53.
41. Ibrahim N', Wong SK, Mohamed IN, et al. Wound healing properties of selected natural products. Int J Environ Res Public Health 2018; 15(11): 2360. doi: 10.3390/ijerph15112360.
42. Oryan A, Alemzadeh E, Moshiri A. Potential role of propolis in wound healing: biological properties and therapeutic activities. Biomed Pharmacother 2018; 98: 469-483.
43. Patton LL, Bonito AJ, Shugars DA. A systematic review of the effectiveness of antifungal drugs for the prevention and treatment of oropharyngeal candidiasis in HIV-positive patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001; 92(2): 170-179.
44. Araujo MAR, Libério SA, Guerra RNM, et al. Mechanisms of action underlying the antiinflammatory and immunomodulatory effects of propolis: a brief review. Rev Bras Farmacogn 2012; 22(1): 208-219.
45. Anjuma SI, Ullaha A, Khan KA, et al. Composition and functional properties of propolis (bee glue): a review. Saudi J Biol Sci 2019; 26(7): 1695-1703.
46. Burdock GA. Review of the biological properties and toxicity of bee propolis (propolis). Food Chem Toxicol 1998; 36(4): 347-363.
Volume 17, Issue 7
July 2026
Pages 511-518

  • Receive Date 04 August 2025
  • Revise Date 08 September 2025
  • Accept Date 21 October 2025