Piceatannol enhances hyaluronic acid synthesis through SIRT1-Mediated HAS2 upregulation in human dermal fibroblasts

Abstract

Dermal fibroblasts play a crucial role in skin structure and function by producing hyaluronic acid. Piceatannol (PIC), a polyphenol abundant in passion fruit seeds, has been reported to activate sirtuin 1 (SIRT1). Clinical trials have demonstrated that PIC intake improves skin moisture and maintains skin elasticity, yet the underlying mechanism remains unclear. This study aimed to investigate the effects of PIC on hyaluronic acid biosynthesis and the involvement of SIRT1 in this process. Human dermal fibroblast Hs68 cells were stimulated with PIC, and the expression levels of HAS2 and HYAL2, key enzymes in hyaluronic acid biosynthesis, as well as SIRT1 expression, were assessed using quantitative real-time PCR. Additionally, the role of SIRT1 in the hyaluronic acid biosynthesis pathway during PIC stimulation was examined using a SIRT1 inhibitor. The results demonstrated that PIC increased HAS2 expression while decreasing HYAL2 expression in human dermal fibroblasts. Furthermore, PIC enhanced SIRT1 expression, and pre-treatment with a SIRT1 inhibitor mitigated PIC-induced upregulation of HAS2, suggesting that PIC promotes hyaluronic acid synthesis by inducing SIRT1. These findings suggest that PIC could serve as a beneficial food ingredient, enhancing skin structure and function by promoting hyaluronic acid biosynthesis via SIRT1 induction.

Keywords: Fibroblast; HAS2; Hyaluronic acid; Piceatannol; Sirtuin 1.

Fig. 1

Effects of PIC on HAS2 and HYAL2 Expression in Human Dermal Fibroblasts Hs68 cells were subjected to treatment with either DMSO control (CTRL) or 20 μM piceatannol (PIC) for 16 h. Subsequently, mRNA expression levels of (A) HAS2 and (B) HYAL2 were assessed via quantitative real-time PCR and normalized to GAPDH expression. Data are presented as the mean ± standard deviation (n = 3). *p < 0.05 vs CTRL (Student's t-test).

Fig. 2

Effect of PIC on SIRT1 Expression in Human Dermal Fibroblasts Cells were treated with either DMSO control (CTRL) or piceatannol (PIC) at concentrations of 10 μM and 20 μM for 6 h. Subsequently, mRNA expression levels of SIRT1 were determined via quantitative real-time PCR and normalized to GAPDH expression. Data are presented as the mean ± standard deviation (n = 4). *p < 0.05 vs CTRL (Dunnett's test).

Fig. 3

Effects of SIRT1 Inhibitor on PIC-Induced Hyaluronic Acid Biosynthesis-Related Gene Expression Hs68 cells were subjected to treatment with or without 10 μM Ex527 for 6 h, followed by treatment with 20 μM PIC and incubation for 16 h. Subsequently, gene expression levels of (A) HAS2 and (B) HYAL2 were assessed via quantitative real-time PCR and normalized to GAPDH expression. Data are presented as mean ± standard deviation (n = 6). Different letters indicate significance (p < 0.05, Tukey's test).