Rutin and ascorbic acid cooperation in antioxidant and antiapoptotic effect on human skin keratinocytes and fibroblasts exposed to UVA and UVB radiation

Abstract

The combination of ascorbic acid and rutin is frequently used in oral preparations. However, despite numerous protective effects of each component individually, their combined effect on ultraviolet (UV)-irradiated skin cells has never been evaluated. The aim of this study was to evaluate the combined effect of ascorbic acid and rutin on human keratinocytes and fibroblasts exposed to UVA and UVB radiation. Skin keratinocytes and fibroblasts exposed to UVA and UVB radiation were treated with ascorbic acid or/and rutin. The total antioxidant properties of both components, as well as their effect on cellular pro-and antioxidant status, lipid and protein oxidation, transmembrane transport, and pro-inflammatory and pro/ antiapoptotic protein expression were measured. The combination of ascorbic acid and rutin had higher antioxidant properties compared to the activity of the single compound alone, and showed a stronger effect against UV-induced reactive oxygen species generation. The ascorbic acid and rutin combination also showed increased antioxidant enzyme activity (catalase, superoxide dismutase, thioredoxin reductase), which was impaired following UV irradiation. Moreover, ascorbic acid additional stimulated UV-induced bilitranslocase activity responsible for rutin transport, and therefore favored rutin effect on Nrf2 pathway, simultaneously differentiating the reaction of keratinocytes and fibroblasts. In keratinocytes, Nrf2 is strongly activated, while in fibroblasts decreased Nrf2 activity was observed. Used mixture, also significantly silenced UV-induced expression of pro-inflammatory factor NFκB and pro-apoptotic proteins such as caspases 3, 8, and 9. These results showed that ascorbic acid and rutin are complementary in their antioxidant actions, transport and signaling functions. Their combined antioxidant, antiinflammatory and antiapoptotic actions suggest rutin and ascorbic acid are a potentially cytoprotective team against UV-induced skin damage.

Cytoprotective Effect of Ascorbic Acid and Rutin against Oxidative Changes in the Proteome of Skin Fibroblasts Cultured in a Three-Dimensional System

“…Ascorbic acid and rutin used separately, and in combination, have a strong antioxidant potential and significantly decrease the expression of antioxidant proteins such as thioredoxin and glutaredoxin in both UV-irradiated and not-irradiated cells. In the case of thioredoxin, similar results are observed for skin fibroblasts cultured in a monolayer [32]. Polyphenols, including rutin, are known for their inhibitory effect on thioredoxin reductase, an enzyme that restores the level of reduced thioredoxin in cells under oxidative stress [53].…”

“…Alternatively, the interaction of ascorbic acid with rutin has primarily been demonstrated in terms of anti-inflammatory and vascular sealing effects when administered orally [31]. However, emerging data on the in vitro treatment of skin cells with ascorbic acid and rutin suggest that such a mixture is a potentially beneficial topical protection against skin damage caused by UV radiation [30,32]. Therefore, the aim of this study was to examine the cooperation of ascorbic acid and rutin in the protection of the proteomic profile in UVB-irradiated human skin fibroblasts cultured in a 3D system.…”

Antioxidative and Anti-Inflammatory Properties of Cannabidiol

“…An increase in GSH levels after CBD treatment was also observed in mouse microglia cells [37] and in the liver of cadmium poisoned mice [25]. This is of great practical importance because GSH cooperates with other low molecular weight compounds in antioxidant action, mainly with vitamins such as A, E, and C [38]. CBD exhibits much more antioxidant activity (30-50%) than α-tocopherol or vitamin C [4].…”

Ultraviolet A protective potential of plant extracts and phytochemicals

“…135 ). The UVB protection of RU is also quite well documented in vitro and in vivo 134,[136][137][138][139] .…”

“…RU especially stimu-lated antioxidant enzyme activity (CAT, SOD, TrxR) and reduced ROS generation. The effect of RU was increased by its combination with ascorbic acid, which besides other effects stimulated the UV-induced activity of the transmembrane transporter bilitranslocase, responsible for the transport of RU into cells 139 .…”