[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to determine the mechanisms through which 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol (20GPPD) promotes the production of hyaluronic acid (HA) in human keratinocytes. 20GPPD is the primary bioactive metabolite of Rb1, a major ginsenoside found in ginseng (Panax ginseng). We sought to elucidate the underlying mechanisms behind the 20GPPD-induced production of HA. We found that 20GPPD induced an increase in HA production by elevating hyaluronan synthase 2 (HAS2) expression in human keratinocytes. The phosphorylation of extracellular signal-regulated kinase (ERK) and Akt was also enhanced by 20GPPD in a dose-dependent manner. The pharmacological inhibition of ERK (using U0126) or Akt (using LY294002) suppressed the 20GPPD-induced expression of HAS2, whereas treatment with an epidermal growth factor receptor (EGFR) inhibitor (AG1478) or an intracellular Ca2+ chelator (BAPTA/AM) did not exert any observable effects. The increased Src phosphorylation was also confirmed following treatment with 20GPPD in the human keratinocytes. Following pre-treatment with the Src inhibitor, PP2, both HA production and HAS2 expression were attenuated. Furthermore, the 20GPPD-enhanced ERK and Akt signaling decreased following treatment with PP2. Taken together, our results suggest that Src kinase plays a critical role in the 20GPPD-induced production of HA by acting as an upstream modulator of ERK and Akt activity in human keratinocytes.
International Journal of Molecular Medicine 03/2015; DOI:10.3892/ijmm.2015.2121 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although previous studies have reported that black soybean has chemopreventive potential, the underlying mechanisms remain unclear. Upregulation of cyclooxygenase-2 (COX-2) has been known to be a key mediator in the development of skin cancer. The present study investigated the effect of black soybean (Glycine max cv. Heugmi) seed coat extract (BSE) on 12-O-tetradecanoylphorbol-13-acetate (TPA) or ultraviolet-B-(UVB)-induced COX-2 expression, and its underlying mechanisms. The TPA- or UVB-induced COX-2 expression in mouse skin epithelial cells were dose-dependently inhibited by BSE treatment. BSE suppressed the COX-2 promoter activity. BSE also attenuated the transactivation of activator protein-1 (AP-1) and nuclear factor (NF)-κB, transcription factors of COX-2 expression in mouse skin epithelial cells transfected stably with AP-1 and NF-κB luciferase promoter, respectively. Furthermore, BSE inhibited the activation of MAPKKs/MAPKs pathways that otherwise induced by TPA or UVB. Collectively, BSE suppresses TPA or UVB-induced COX-2 expression by blocking the expressions of MAPKKs/MAPKs pathways, which may contribute to its chemopreventive potential.
[Show abstract][Hide abstract] ABSTRACT: The present study examined the effects of tangeretin, a polymethoxylated flavonone present in citrus fruits, on ultraviolet B (UVB)-induced cyclooxygenase-2 (COX-2) expression in JB6 P+ mouse skin epidermal cells. Tangeretin suppressed UVB-induced COX-2 expression and transactivation of nuclear factor-κB and activator protein-1 in JB6 P+ cells. Moreover, tangeretin blocked UVB-induced phosphorylation of Akt and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated protein kinase, c-Jun N-terminal kinase, and p38, and attenuated the phosphorylation of MAPK kinases 1/2, 3/6, and 4. Tangeretin also limited the endogenous generation of reactive oxygen species (ROS), thereby protecting the cells against oxidative stress. However, tangeretin did not scavenge the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and influence the nicotinamide adenine dinucleotide phosphate oxidase activity. These results suggest that the anti-inflammatory effects of tangeretin stem from its modulation of cell signaling and suppression of intracellular ROS generation. Tangeretin may have a potent chemopreventive effect in skin cancer.
Journal of Agricultural and Food Chemistry 01/2011; 59(1):222-8. DOI:10.1021/jf103204x · 3.11 Impact Factor