Wound healing effects of Plantago major extract and its chemical compounds in hyperglycemic rats

Impaired wound healing is among the serious complications of diabetes that can lead to amputation and even death. Plantago major has been used empirically to improve wound healing. The main bioactive compounds of P. major extracts, ursolic acid (UA) and oleanolic acid (OA), have also been studied for their benefits with non-hyperglycemic wounds. This study was done to examine the in vivo wound healing effects of P. major leaf extracts (PMLE), UA, and OA in hyperglycemic rats, to evaluate their in vitro diabetic wound healing activity, and to observe possible dermal irritation after topical application. Wound closure, duration of epithelialization, and histopathological profiles of healed tissue were observed in the hyperglycemic rats with excision wounds for 21 days. An anti-inflammatory test using the NO inhibitory assay, a fibroblast proliferation assay, and a migration assay with high-glucose medium were done to investigate the mechanism of action of the tested samples in wound healing. The acute dermal irritation test followed the international guidelines. PMLE, UA, and OA increased the percentage of wound closure and accelerated wound healing time. PMLE activities were assessed for the inhibition of NO production in the inflammation phase and enhancement of fibroblast proliferation. UA may contribute to this wound healing process through inhibition of NO production, whereas OA through activation of migration of fibroblast cells. Topical applications of PMLE, UA, and OA did not cause acute dermal irritation. PMLE, UA, and OA have the potential to improve wound healing with diabetes conditions.