ES2 as a Novel Verbascoside-Derived Compound in the Treatment of Cutaneous Wound Healing

Abstract

Several pathologies are characterized by chronic wounds and often resistant to many of the common therapies, leading to chronic infections that can become even life-threatening for patients. For this reason, the identification of new products able to ameliorate the healing process is still an on-going research. Natural compounds have been used to improve skin conditions due to their dermo-cosmetic and therapeutic activities including anti-inflammatory, antioxidant and cell-migratory properties. Among these compounds, it has been recently demonstrated that Verbascoside, a phenyl propanoid glycoside widely used in the cosmetic field, can improve keratinocytes proliferation. Because of its high hydrophilic character, Verbascoside has a limited range of possible topical applications and the synthesis of ES2, a semi-synthetic derivative of Verbascoside was performed to bypass some of the drawback aspects of this molecule. In the present study, the wound healing properties of Verbascoside and ES2 were compared in both keratinocytes “in vitro” wound scratch and in wounded SKH1 mice. The results showed that both compounds were not cytotoxic and ES2 showed an efficient ability to promote the proliferation of human keratinocytes compared to Verbascoside. The findings were also confirmed in vivo but only at early time points (2/3 days). Taken together, these data suggest that the Verbascoside-derivative ES2 could be considered a novel and promising candidate for the topical treatment of wounds.

Photoprotective Activity of Buddleja cordata Cell Culture Methanolic Extract on UVB-irradiated 3T3-Swiss Albino Fibroblasts

“…Likewise, the biological effects of the B. cordata cell culture methanolic extract at the highest tested concentration on fibroblasts were comparable to verbascoside ( Figure 1 b,c), thus, indicating the importance of the concentration in exerting significant biological effects. In other studies, the exposure of V79 fibroblasts and HaCaT keratinocytes to verbascoside over 24 h significantly reduced the cell viability by around 50% (78.8 and 31.23 µg/mL, respectively) [ 61 , 62 ]. This suggests that the cytotoxic effect of the verbascoside is caused by its ability to reduce the activity of cytoplasmic protein tyrosine phosphatases by binding to the Scr homology 2 (SH2) NH2-terminal domain (SHP1); these receptors are implicated in the growth, differentiation, and apoptosis of cells [ 37 , 63 , 64 ].…”

Therapeutic potential of ointment containing methanol extract of Lamium album L. on cutaneous wound healing in rats

“…Verbascoside has been widely used in the cosmetics with potential anti-inflammatory, antioxidant and photoprotecting activities [41,42]. It has been previously shown that the topical application of a semi-synthetic derivative of this compound was able to promote the wound healing in rats [41].…”

Plant In Vitro Systems as a Sustainable Source of Active Ingredients for Cosmeceutical Application

“…The skin is an organ that has protective functions towards the external environment and its physical integrity is essential to accomplish its functions [11]. Skin aging might happen via two mechanisms: The first termed intrinsic or age dependent, is initiated by several factors, such as telomere shortening, free radicals and antioxidants imbalance and hormonal changes, while the second mechanism-photoaging is due to exposure of the skin to UV solar radiation [20].…”

“…The wound healing properties of the water-soluble verbascoside derived from the cell suspension of Buddeleia davidii were improved by the obtaining of its lipophilic semi-synthetic derivative ES2. The ES2 is considered as a novel and potent candidate for topical treatment of wounds, since this compound improved the wound closure more than 2-folds in HaCaT cells and SKH1 mice, compared to that of verbascoside at 10 μM concentration [ 11 ]. Another derivative of verbascoside, denoted as verbascoside pentapropionate, also exhibited lower hydrophilic profile and improved antioxidant activities than verbascoside [ 85 ].…”

“…Over the past 10 years an increasing interest has been observed in plant cell culture extracts, which contain a wide range of primary and SMs, possessing multiple beneficial activities for skin-and hair care [11]. Alternatively, plant biotechnology techniques, and in particular plant in vitro systems, offer a reliable and sustainable platform for bioproduction of plant derived SMs.…”