Background Protopanaxatriol (PPT) is a secondary intestinal metabolite of ginsenoside in ginseng. Although the effects of PPT have been reported in various diseases including cancer, diabetes and inflammatory diseases, the skin protective effects of PPT are poorly understood. Methods HaCaT cells were treated with PPT in a dose-dependent manner. mRNA and protein levels which related to skin barrier and hydration were detected compared with retinol. Luciferase assay was performed to explore the relative signaling pathway. Western blot was conducted to confirm these pathways and excavated further signals. Results PPT enhanced the expression of filaggrin (FLG), transglutaminase (TGM)-1, claudin, occludin and hyaluronic acid synthase (HAS) −1, −2 and −3. The mRNA expression levels of FLG, TGM-1, HAS-1 and HAS-2 were suppressed under NF-κB inhibition. PPT significantly augmented NF-κB-luc activity and upregulated Src/AKT/NF-κB signaling. In addition, PPT also increased phosphorylation of the mitogen-activated protein kinases (MAPKs) ERK, JNK and p38 and upstream MAPK activators (MEK and MKK). Furthermore, transcriptional activity of AP-1 and CREB, which are downstream signaling targets of MAPK, was enhanced by PPT. Conclusion PPT improves skin barrier function and hydration through Src/AKT/NF-κB and MAPK signaling. Therefore, PPT may be a valuable component for cosmetics or treating skin disorders.

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Dehydrotrametenolic acid (DTA) is a lanostane-type triterpene acid isolated from Poria cocos Wolf (Polyporaceae). Several studies have reported the anti-inflammatory and antidiabetic effects of DTA; however, its effects on the skin are poorly understood. In this study, we investigated the effects of DTA on skin barrier function in vitro and its regulatory mechanism in human keratinocyte cell line HaCaT cells. DTA increased the microRNA (mRNA) expression of natural moisturizing factor-related genes, such as HAS-2, HAS-3, and AQP3 in HaCaT cells. DTA also upregulated the mRNA expression of various keratinocyte differentiation markers, including TGM-1, involucrin, and caspase-14. Moreover, the protein expression of HAS-2, HAS-3, and TGM-2 were significantly increased by DTA. To examine the regulatory mechanisms of DTA, Western blotting, luciferase-reporter assays, and RT-PCR were conducted. The phosphorylation of mitogen-activated protein kinases (MAPKs) and IκBα were increased in DTA-treated HaCaT cells. In addition, AP-1 and NF-κB transcriptional factors were dose-dependently activated by DTA. Taken together, our in vitro mechanism studies indicate that the regulatory effects of DTA on skin hydration and keratinocyte differentiation are mediated by the MAPK/AP-1 and IκBα/NF-κB pathways. In addition, DTA could be a promising ingredient in cosmetics for moisturizing and increased skin barrier function.

Canarium subulatum is a traditional medical herb used in South Asia. Recently, the anti-inflammatory effects of C. subulatum methanol extract (Cs-ME) have been reported; however, the effect of Cs-ME on skin physiology has not yet been elucidated. Therefore, in this study, we evaluated the protective effect of Cs-ME on UV-induced skin aging and cell death as well as the reinforcing effect on the skin barrier. According to viable cell counting and MTT assays, Cs-ME significantly reduced UV-evoked HaCaT cell death. Cs-ME blocked reactive oxygen species (ROS) generation in UV-irradiated HaCaT cells and showed radical scavenging activity against DPPH and ABTS. In addition, H2O2-induced cell death was inhibited by Cs-ME, indicating that Cs-ME protects cells from UV-derived cell death through the suppression of ROS. PCR analysis revealed that Cs-ME diminished the expression of aging-related HYAL-1 and MMP-1 genes in UV-treated HaCaT cells. Elevated HYAL-1 and MMP-1 mRNA expression in H2O2-stimulated HaCaT cells was also decreased by Cs-ME, suggesting that Cs-ME exerts antiaging activity via the inhibition of ROS. Expression of skin barrier components including filaggrin and hyaluronic acid synthase-1 was increased by Cs-ME and was modulated by ERK/p38-AP-1 signaling. Collectively, our data show that Cs-ME has cytoprotective and antiaging activity based on antioxidant properties. Furthermore, Cs-ME exerts skin barrier protective ability by regulating the AP-1 signaling pathway. Therefore, Cs-ME has the potential for use as an ingredient in cosmetics to protect the skin from UV irradiation, prevent photoaging, and strengthen the skin barrier.