Tiliroside, a Constituent of Strawberry Seeds, Slightly Enhances Hyaluronan Production via Hyaluronan Synthase 2 Expression in Mouse Skin and Human Fibroblasts

Strawberry seeds are consumed with the sarcocarps, but their effects on the skin have not been well evaluated. We examined the effect of strawberry seed extract (SSE) and tiliroside, a major flavonol glycoside in SSE, on hyaluronan synthase (HAS) 2 expression and hyaluronan production in mouse skin and human fibroblasts. SSE and tiliroside were given orally to mice on a high-fat diet (HFD) or standard diet, and skin HAS2 mRNA expression and the skin hyaluronan content were evaluated. In addition, HAS2 protein expression and hyaluronan release were determined after fibroblasts were treated with SSE and tiliroside. Furthermore, binding of tiliroside to retinoic acid receptor (RAR) γ was examined. SSE (10 and 50 mg/kg) significantly increased HAS2 mRNA expression and the hyaluronan level in the skin of HFD-fed mice. Tiliroside (0.2 and 1 mg/kg) also increased skin HAS2 mRNA expression in HFD-fed mice. Moreover, SSE (10 mg/kg) increased HAS2 mRNA expression in mice on the standard diet. In human fibroblasts, both SSE (1 ug/mL) and tiliroside (0.3 ug/mL) significantly increased hyaluronan production, with HAS2 protein expression also being increased by SSE (10 ug/mL) and tiliroside (0.1 ug/mL). In the RARγ ligand assay, tiliroside (1 and 10 ug/mL) showed binding to RARγ. In conclusion, SSE and tiliroside increased hyaluronan synthase 2 expression in mouse skin and binding of tiliroside to RARγ was suggested to be involved.