Rosmarinus Improved Skin Flap Survival Through mTOR Dependent Pathway

Abstract

Introduction: Skin flap application in the clinical practice is restricted due to the ischemic damage and flap necrosis. Rosmarinus oil has been shown to improve a skin flap survival. In the present work we studied the role of mammalian target of rapamycin (mTOR) signaling on rosmarinus-induced flap protection. Methods: A flap surgery was performed on Sprauge-Dawley rats (8 cm in by 3 cm). A week before and a week after the surgery the flaps were treated with topical rosmarinus oil (twice per day). Rapamycin (m-TOR inhibitor) was administered 30 minutes before the flap surgery in rosmarinus-treated or not treated groups. A week after the surgery the malondialdehyde (MDA) contents, myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, expression of Bax, Bcl-2, mTOR and p-mTOR were measured in the flap tissue. Results: Topical application of the rosmarinus increased the flap survival (p<0.05), anti-oxidative enzyme activity (SOD, p<0.05) and anti-apoptotic protein Bcl-2 expression. Rosmarinus treatment decreased the flap MDA content, MPO activity, and pro-apoptotic protein Bax expression (p<0.05). Rosmarinus topical application did not change mTOR expression and phosphorylation in the flap tissue. Expression of p-mTOR in rosmarinus treated group was suppressed by rapamycin pre-treatment, which also abolished rosmarinus effects on the flap survival (p<0.05). Conclusion: These data suggested p-mTOR dependent mechanism in rosmarinus-induced flap survival.

The Novel Role of Crocus sativus L. in Enhancing Skin Flap Survival by Affecting Apoptosis Independent of mTOR: A Data-Virtualized Study

“…Oral administration has numerous benefits, such as easily applicability, availability, and being more physiologic. All of these results are consistent with pervious findings which mentioned above [ 5 , 49 ]. Another study [ 30 ] has evaluated Saffron effect on mitogen-activated protein kinase (MAPK) signaling pathways, in mediation of endothelial cell-survival against oxidative stress.…”

“…However, this effect did not change much with increasing the dose of Saffron in our experiment, and in both groups of Saffron 40 and Saffron 80, the rate of MPO activity decrease, was the same. Other studies [ 1 , 49 , 54 ] confirm our results about increasing the survival of skin flaps following a decrease in MPO activity.…”

“…Therefore, the activity of MPO enzyme is a manifestation of inflammation and chemotaxis of neutrophils. In addition to other effects of inflammation, these ROS also cause damage to the skin flap tissue [ 1 , 36 , 49 ]. In our study, skin flap surgery increased MPO activity, but in the groups that received Saffron, the enzyme activity level decreased significantly and resulted in an increase of skin flap survival.…”