Wound healing potential of quercetin-3-O-rhamnoside and myricetin-3-O-rhamnoside isolated from Pistacia lentiscus distilled leaves in rats model

The development of bioproducts able to accelerate wound healing is an important topic in biomedicine. In the current study, Pistacia lentiscus distilled leaves (PDL) extract and its two isolated glycosylated flavonoids, myricetin-3-O-rhamnoside (MM) and quercetin-3-O-rhamnoside (QM), were evaluated for their wound healing activity, including evaluation of wound closure, revascularization, wound re-epithelialization, fibroblast proliferation, and collagen deposition on rat skin samples. Moreover, hydroxyproline content, C-reactive protein (CRP) level, and immunohistochemistry study were evaluated on blood and tissues collected from rats on day 14 post-wounding. Results showed that the topical application of PDL (at a concentration of 20 mg/ml) (PDL 20), MM, and QM increased wound healing and decreased inflammatory cells infiltration compared to the negative control group. Moreover, the cutaneous wound tissues treated with PDL 20, MM, and QM exhibited significantly higher hydroxyproline content than the negative control group, which means a high collagen biosynthesis in wound tissues. Indeed, the level of the inflammatory protein CRP is significantly lower in groups treated with MM and QM than in the negative control group. Also, the expression of the pro-inflammatory factor TNF-α and the angiogenesis marker CD-31 in PDL 20, MM, and QM treated groups is lower than in the negative control group. Moreover, MM, and QM induced a good elastase inhibition at 100 µg/ml compared to the standard epigallocatechin gallate. Therefore, PDL 20, MM, and QM could be used as effective cutaneous wound healing agents