Pharmacological effect of Ageratina pichinchensis on wound healing in diabetic rats and genotoxicity evaluation

Abstract

Ethnopharmacological relevance: Among the main causes affecting the wound healing process, we find diabetes mellitus, which is due to the occurrence of a prolonged inflammation phase, defects in angiogenesis, and a diminution in fibroblast proliferation. The species Ageratina pichinchensis has been utilized in Mexican traditional medicine for the treatment of skin wounds. Pharmacological models have demonstrated that an extract obtained from this species improves wound healing and, through a clinical study, it was evidenced that the extract (in a pharmaceutical form) is effective in the treatment of patients with chronic venous ulcers. The 7-O-(β-D-glucopyranosyl)-galactin compound was recently identified as responsible for the pharmacological activity. The objective of the present study was to evaluate the wound healing activity of an aqueous extract and another hexane-ethyl acetate extract from Ageratina pichinchensis (both standardized in the active compound) in a diabetic foot ulcer rat model, as well as evaluating the possible genotoxic effects produced by the same species.

Materials and methods: Rats with streptozotocin-induced diabetes were submitted (under anesthesia with pentobarbital) to a circular lesion on the skin (excisional) on the rear of the paw. All animals were topically treated daily until healing. 5-methyl-1 phenyl-2-(1H) Pyridone was used as a positive control treatment. Once the wound was healed, a skin sample was obtained and utilized for histopathological analysis. The possible genotoxic effects produced by the extract, in a model of spermatozoid viability and morphology, were evaluated.

Results: The results showed that 100% of animals treated with Ageratina pichinchensis extracts presented wound healing between days 4 and 11 of treatment, while in the positive control group (treated with 5-methyl-1 phenyl-2-(1H) pyridone) and in the negative control group (vehicle), only 70% and 40%, respectively, exhibited wound healing at day 11. Histological analysis demonstrated evidences of an active regenerative process in animals that received the extracts, in addition to that in the study, the effects of the plant extracts that could be compatible with genotoxicity were not observed.

Conclusions: Aqueous and hexane-ethyl acetate extracts of the aerial parts of Ageratina pichinchensis (standardized in its content of 7-O-(β-D-glucopyranosyl)-galactin), consistently improve wound healing induced on the skin of rats with streptozotocin-induced diabetes. The capacity was evidenced of the extracts to promote histological tissue regeneration, without exhibiting genotoxicity.

Keywords: Ageratina pichinchensis; Asteraceae; Diabetes; Diabetic foot ulcer; Wound healing.