Topical administration of hydroethanolic extract of Trifolium pratense (red clover) accelerates wound healing by apoptosis and re-epithelialization

ABSTRACT

We investigated the wound healing effects of an ointment prepared from a hydroethanolic extract of Trifolium pratense (red clover) in Wistar rats. An animal model was prepared by making 314 mm² full thickness skin excisions in all animals. Rats were divided into four experimental groups. Group 1 was a non-intervention control. Groups 2, 3 and 4 were treated topically with ointments containing 1.5, 3.0 and 6% (w/v) T. pretense extract, respectively. We evaluated the effects of these ointments by histological analysis of collagen production, epidermis thickness, fibroblast distribution and wound contraction ratio, and also by estimating expression of Bax, Bcl-2 and p53. Collagen production, epidermis thickness, fibroblast distribution and wound contraction ratio were significantly increased in groups 2 − 4 compared to group 1. Groups 2 − 4 also exhibited significantly increased levels of Bcl-2 mRNA and reduced mRNA levels of Bax and p53 compared to group 1. Groups 2 − 4 exhibited accelerated healing by up-regulating Bcl-2 expression, reducing p53 and Bax levels, and by promoting the proliferative phase of healing. We suggest that a hydroethanolic extract of T. pratense in commercial ointments may be useful for promoting wound healing.

KEYWORDS:

• Antioxidant
• apoptosis
• collagen deposition
• rats
• Trifolium pratense (red clover)
• wound healing

Acknowledgments

The authors are grateful to the Ayandeh laboratory for laboratory assessment and to Dr. Keivan Razzaghi and Dr. Farahnaz Tahery for preparation of the extract and formulation of the ointment, respectively.

Disclosure statement

The authors declare no conflict of interest.