PI3K-Mediated Proliferation of Fibroblasts by Calendula officinalis Tincture: Implication in Wound Healing

Calendula officinalis, a member of theAsteraceae family, is a flowering plant and has been used for its antibacterial, antifungal, antiviral, antiinflammatory, anticancer and wound healing activity. The mode of action of C. officinalis tincture on wound healing is poorly understood.Here, we investigated the role of C. officinalis tincture (CDOT) on cell viability and wound closure. C. officinalis tincture stimulated both proliferation and migration of fibroblasts in a statistically significant manner in a PI3K-dependent pathway. The increase in phosphorylation of FAK(Tyr 397) and Akt (Ser 473) was detected after treatment of CDOT. Inhibition of the PI3K pathway by wortmannin and LY294002 decreased both cell proliferation and cell migration. HPLC-ESIMS revealed the presence of flavonol glycosides as themajor compounds of CDOT.Altogether, our results showed that CDOT potentiated wound healing by stimulating proliferation and migration of fibroblast in a PI3K-dependent pathway, and the identified compounds are likely to be responsible for wound healing activit