Consumption of ellagic acid and dihydromyricetin synergistically protects against UV-B induced photoaging, possibly by activating both TGF-β1 and wnt signaling pathways.

Ellagic acid (EGA) and dihydromyricetin (DHM) are both found in fruits and vegetables are used for anti-aging treatment for the skin. The anti-photoaging efficacy of EGA and DHM was investigated in UV-B irradiated skin in vivo and the involvement of transforming growth factor (TGF)-β1 and wnt signaling pathways were examined in vitro. HaCaT cells were treated with either 50μM EGA, 50μM DHM or 25μM EGA+25μM DHM before 100mJ/cm ² UV-B exposure, and then oxidative stress and inflammation was measured. The involvement of TGF-β1 and wnt signaling was measured using their inhibitors, respectively, in HaCaT cells. Mice were fed a high fat diet with either 0.7% cellulose, 0.7% EGA, 0.7% DHM or 0.35% EGA+0.35% DHM for 3weeks and the dorsal skin of the mice had UV-B irradiation. 3% cellulose, 3% EGA, 3% DHM or 1.5% EGA+1.5% DHM in 1,3-buthylene glycol was applied onto the dorsal skin at 30min before 1 MED UV-B exposure. In 100mJ/cm ² UVB irradiation, EGA and DHM mainly decreased oxidative stress and inflammation, respectively in HaCaT cells. Their activities were blocked by the TGF-β1 inhibitor, indicating their actions were mediated by TGF-β1 signaling (TGF-β1➔pSmad3➔Smad7). DHM enhanced wnt signaling by increasing β-catenin and decreasing Dickkopf-related protein-1. In mice, 1 MED UV-B exposure induced sunburn, redness, and blistering. EGA, DHM and especially EGA+DHM lessened their severity. UV-B increased epidermal thickness and damaged epidermal nucleus and cell structures. DHM and especially EGA+DHM prevented damage to the nucleus and cell structures. Expressions of circulating and dorsal skin IL-1β and TNF-α mRNA were lower in descending order of: control, EGA, DHM, EGA+DHM and normal-control. In conclusion, the consumption of EGA+DHM had a synergistically protective action against UV-B damage in the skin tissues of mice and HaCaT cells, and it may be associated with activating of both TGF-β1 and wnt signaling.
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