title: In vivo antifungal effect of Combretum and Terminalia species extracts on cutaneous wound healing in immunosuppressed rats.
abstract: Acetone leaf extracts of Combretaceae species Combretum imberbe Wawra, Combretum nelsonii Duemmer, Combretum albopunctatum Suesseng, and Terminalia sericea Burch ex DC and a mixture of asiatic acid and arjunolic acid isolated from C. nelsonii were tested for antifungal activity against Candida albicans, Cryptococcus neoformans, Microsporum canis, and Sporothrix schenckii on wounds of immunocompromised Wistar rats. The therapeutic agents were selected based on low MIC values ranging 0.02-2.5 mg/mL and low toxicity (LC50) ranging 75.7-168.6 microg/mL. Seven circular, full-thickness wounds were made on the back skin of 24 Wistar rats, under general anesthetic and using an aseptic technique. Rats were infected with different fungal pathogens in groups of six. The treatments were administered topically using 20% concentrations of each extract in aqueous cream. Amphotericin B was used as positive control. Erythema, exudate, crust formation, swelling, and ulceration were used to determine the wound healing process. Throughout the experiment, body temperature, measured using a subcutaneous probe, and weight of the rats were found to be within normal ranges. Epithelial closure in all rats occurred by 17 days. There was no significant difference in contraction of the lesion areas treated with different extracts. The variability in erythema at each lesion in rats infected with different fungal pathogens differed with treatments; the lesion without treatment took a longer time to heal in all cases. Exudate formation was observed until day 12 in rats infected with C. albicans and day 8 in rats infected with C. neoformans. In lesions infected with M. canis and S. schenckii, exudate formation was observed until day 10. The treated group presented a rigid, dark, and thick crust formation after day 3 until day 15. During histopathological evaluations, scant fungi were noted in all the wounds, indicating that infection had occurred but had generally cleared. The antifungal potential of crude extracts of selected plants and a mixture of asiatic acid and arjunolic acid on the wounds of immunocompromised rats was confirmed. The extracts of these plants may possibly be further developed into drugs for topical treatment of fungally infected wounds.
authors.affiliation: Phytomedicine Programme, Department of Paraclinical Sciences, Faculty of Veterinary Sciences, University of Pretoria, Onderstepoort, South Africa.
authors.forename: P
authors.initials: P
authors.lastname: Masoko
authors.forename: J
authors.initials: J
authors.lastname: Picard
authors.forename: R L
authors.initials: RL
authors.lastname: Howard
authors.forename: L J
authors.initials: LJ
authors.lastname: Mampuru
authors.forename: J N
authors.initials: JN
authors.lastname: Eloff
mesh_terms: D000287:Administration, Topical; D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D029765:Combretum / Q000737:chemistry*; D005658:Fungi / Q000187:drug effects; D016867:Immunocompromised Host; D008297:Male; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000188:drug therapy / Q000382:microbiology; D010936:Plant Extracts / Q000494:pharmacology* / Q000633:toxicity; D018515:Plant Leaves; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D029766:Terminalia / Q000737:chemistry*; D013997:Time Factors; D018675:Toxicity Tests; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000935:Antifungal Agents; D010936:Plant Extracts; D000666:Amphotericin B