Ji-Young Bae

(-)Epigallocatechin gallate hampers collagen destruction and collagenase activation in ultraviolet-B-irradiated human dermal fibroblasts : Involvement of mitogen-activated protein kinase

Ultraviolet (UV) irradiation leads to distinct changes in skin connective tissues by degradation of collagen, which is a major structural component in the extracellular matrix most likely mediated by matrix metalloproteinases (MMP), collagenases. These changes in collagenous skin tissues have been suggested to be causes of the skin wrinkling observed in premature aging of the skin. This study mimicked the action of environmental ultraviolet on skin and investigated whether (-)epigallocatechin gallate (EGCG), a bioactive catechin component of green tea, mechanistically inhibited activation of MMP-1, MMP-8, and MMP-13 and destruction of collagen in UV-B irradiated human dermal fibroblasts by modulating cellular signaling pathways. Cell viability was moderately decreased by > or = 30% in human dermal fibroblasts treated with 100 mJ/cm2 UV-B, accompanying a substantial generation of reactive oxygen species evidenced by DCF staining. Western blot analysis and immunocytochemical staining revealed that EGCG markedly suppressed collagen degradation enhanced in UV-B-exposed human dermal fibroblast. Pre-treatment of fibroblasts with EGCG also inhibited UV-B-induced production of collagenases, MMP-1, MMP-8 and MMP-13, in a dose-dependent manner. In addition, EGCG rapidly and substantially hampered UV-B irradiation-induced activation of ASK-1 and phosphorylation of MAPK, JNK, p38 MAPK, and ERK1/2, in dermal fibroblasts. These results demonstrate that EGCG has abilities to hamper UV-B-induced collagenolytic MMP production via interfering with the MAPK-responsive pathways. Therefore, EGCG may be a potential agent for the prevention and treatment of skin photoaging.

Dietary compound ellagic acid alleviates skin wrinkle and inflammation induced by UV-B irradiation

Please cite this paper as: Dietary compound ellagic acid alleviates skin wrinkle and inflammation induced by UV‐B irradiation. Experimental Dermatology 2010; 19: e182–e190.

Bog blueberry anthocyanins alleviate photoaging in ultraviolet-B irradiation-induced human dermal fibroblasts.

Fruits of bog blueberry (Vaccinium uliginosum L.) are rich in anthocyanins that contribute pigmentation. Anthocyanins have received much attention as agents with potentials preventing chronic diseases. This study investigated the capacity of anthocyanin-rich extract from bog blueberry (ATH-BBe) to inhibit photoaging in UV-B-irradiated human dermal fibroblasts. BBe anthocyanins were detected as cyanidin-3-glucoside, petunidin-3-glucoside, malvidin-3-glucoside, and delphinidin3-glucoside. ATH-BBe attenuated UV-B-induced toxicity accompanying reactive oxygen species (ROS) production and the resultant DNA damage responsible for activation of p53 and Bad. Preincubation of ATH-BBe markedly suppressed collagen degradation via blunting production of collagenolytic matrix metalloproteinases (MMP). Additionally, ATH-BBe enhanced UV-B-downregulated procollagen expression at transcriptional levels. We next attempted to explore whether ATH-BBe mitigated the MMP-promoted collagen degradation through blocking nuclear factor kappaB (NF-kappaB) activation and MAPK-signaling cascades. UV-B radiation enhanced nuclear translocation of NF-kappaB, which was reversed by treatment with ATH-BBe. The UV-B irradiation rapidly activated apoptosis signal-regulating kinase-1 (ASK-1)-signaling cascades of JNK and p38 mitogen-activated protein kinase (p38 MAPK), whereas ATH-BBe hampered phosphorylation of c-Jun, p53, and signal transducers and activators of transcription-1 (STAT-1) linked to these MAPK signaling pathways. ATH-BBe diminished UV-B augmented-release of inflammatory interleukin (IL)-6 and IL-8. These results demonstrate that ATH-BBe dampens UV-B-triggered collagen destruction and inflammatory responses through modulating NF-kappaB-responsive and MAPK-dependent pathways. Therefore, anthocyanins from edible bog blueberry may be protective against UV-induced skin photoaging.

Licorice isoliquiritigenin dampens angiogenic activity via inhibition of MAPK-responsive signaling pathways leading to induction of matrix metalloproteinases

The aberrant expression of matrix metalloproteinases (MMPs) has been implicated in matrix degradation leading to angiogenesis. This study examined the inhibitory effects of isoliquiritigenin (ISL) on phorbol myristate acetate (PMA)-induced MMP production and its tissue inhibitor of MMP (TIMP) in endothelial cells. No induction of either necrotic or apoptotic cell death was observed in response to a treatment with ISL at <or=25 microM. ISL dose-dependently suppressed PMA-induced expression and activity of MMP-2 and membrane type 1-MMP at >or=1 microM while diminishing the elevated MMP-2 transcript level. In addition, ISL inhibited PMA-triggered migration and tube formation in a dose-dependent manner. ISL further increased the TIMP production up-regulated by PMA with a biphasic effect on TIMP-2 expression. This study further attempted to investigate whether a c-Jun N-terminal kinase (JNK)- or p38 mitogen-activated protein kinase (MAPK)-responsive mechanism was responsible for the MMP production and whether ISL disturbed these signaling pathways. PMA stimulated signaling of JNK and p38 MAPK, which was dampened by >or=10 microM ISL. These results demonstrate that ISL blocked JNK- or p38 MAPK-responsive pathways leading to direct MMP activation of PMA-exposed endothelial cells. Therefore, the ISL inhibition of MMP may boost a therapeutic efficacy during angiogenesis.

Attenuation of monocyte adhesion and oxidised LDL uptake in luteolin-treated human endothelial cells exposed to oxidised LDL.

Oxidative modification of LDL is causally involved in the development of atherosclerosis and occurs in vivo in the blood as well as within the vascular wall. The present study attempted to explore whether polyphenolic flavonoids influence monocyte-endothelium interaction and lectin-like oxidised LDL receptor 1 (LOX-1) expression involved in the early development of atherosclerosis. The flavones luteolin and apigenin inhibited THP-1 cell adhesion onto oxidised LDL-activated human umbilical vein endothelial cells (HUVEC), while the flavanols of (-)epigallocatechin gallate and (+)catechin, the flavonols of quercetin and rutin, and the flavanones of naringin, naringenin, hesperidin and hesperetin did not have such effects. Consistently, Western blot analysis revealed that the flavones at 25 microM dramatically and significantly abolished HUVEC expression of vascular cell adhesion molecule-1 and E-selectin evidently enhanced by oxidised LDL; these inhibitory effects were exerted by drastically down regulating mRNA levels of these cell adhesion molecules. In addition, quercetin and luteolin significantly attenuated expression of LOX-1 protein up regulated in oxidised LDL-activated HUVEC with a fall in transcriptional mRNA levels of LOX-1. In addition, quercetin and luteolin clearly blunted oxidised LDL uptake by HUVEC treated with oxidised LDL. The results demonstrate that the flavones luteolin and apigenin as well as quercetin were effective in the different initial steps of atherosclerosis process by inhibiting oxidised LDL-induced endothelial monocyte adhesion and/or oxidised LDL uptake. Therefore, certain flavonoids qualify as anti-atherogenic agents in LDL systems, which may have implications for strategies attenuating endothelial dysfunction-related atherosclerosis.

Resveratrol Inhibits IgE-Mediated Basophilic Mast Cell Degranulation and Passive Cutaneous Anaphylaxis in Mice

Resveratrol is a phytoalexin abundantly found in red grape skin and is effective in antitumor and antiinflammation associated with immune responses. This study investigated whether resveratrol suppressed immunoglobulin (Ig)E-mediated allergic responses and passive cutaneous anaphylaxis (PCA) in rat RBL-2H3 mast cells and in BALB/c mice. The release of β-hexosaminidase and histamine was enhanced in mast cells sensitized with anti-dinitrophenyl (DNP)-IgE and subsequently stimulated by DNP-human serum albumin (HSA), indicative of mast cell degranulation. When mast cells were pretreated with nontoxic resveratrol at 1-25 μmol/L, such induction was dose dependently diminished. Spleen tyrosine kinase (Syk) and phospholipase Cγ (PLCγ) of sensitized mast cells were activated by stimulation with DNP-HSA antigen, which was dampened by ≥5 μmol/L resveratrol. The phosphorylation of protein kinase C (PKC)μ and PKCθ was attenuated by administering resveratrol to DNP-HSA-exposed mast cells, whereas quiescent PKCζ/λ in sensitized cells was dose-dependently activated by resveratrol. Male BALB/c mice were sensitized for 24 h with DNP-IgE and orally administered with resveratrol 1 h before the DNP-HSA challenge. The histamine concentration was enhanced in sensitized mice challenged to DNP-HSA, which was reversed by administration of 10 mg/kg resveratrol. Additionally, it encumbered the tissue activation of Syk, PLCγ, and PKCμ in antigen-exposed mice. Resveratrol decreased IgE-mediated PCA and alleviated allergic edema of mouse ear and dorsal skin. Mast cell degranulation and allergic inflammation, accompanying the induction of monocyte chemotactic protein-1 and macrophage inflammatory protein-2, were inhibited by supplementing resveratrol to antigen-challenged mice. Resveratrol inhibited mast cell-derived, immediate-type allergic reactions, and these responses of resveratrol suggest possible therapeutic strategies in preventing allergic inflammatory diseases.

Blockade of vascular angiogenesis by Aspergillus usamii var. shirousamii-transformed Angelicae Gigantis Radix and Zizyphus jujuba

The matrix metalloproteinases (MMP) play an important role in tumor invasion, angiogenesis and inflammatory tissue destruction. Increased expression of MMP was observed in benign tissue hyperplasia and in atherosclerotic lesions. Invasive cancer cells utilize MMP to degrade the extracellular matrix and vascular basement membrane during metastasis, where MMP-2 has been implicated in the development and dissemination of malignancies. The present study attempted to examine the antiangiogenic activity of the medicinal herbs of Aspergillus usamii var. shirousamii-transformed Angelicae Gigantis Radix and Zizyphus jujube (tAgR and tZj) with respect to MMP-2 production and endothelial motility in phorbol 12-myristate 13-acetate (PMA)- or VEGF-exposed human umbilical vein endothelial cells (HUVEC). Nontoxic tAgR and tZj substantially suppressed PMA-induced MMP-2 secretion. In addition, 25 µg/mL tAgR and tZj prevented vascular endothelial growth factor-stimulated endothelial cell transmigration and tube formation. The results reveal that tAgR and tZj dampened endothelial MMP-2 production leading to endothelial transmigration and tube formation. tAgR and tZj-mediated inhibition of endothelial MMP may boost a therapeutic efficacy during vascular angiogenesis.

Protective actions of Rubus coreanus ethanol extract on collagenous extracellular matrix in ultraviolet-B irradiation-induced human dermal fibroblasts

Solar ultraviolet (UV) irradiation leads to distinct changes in the skin connective tissues by degradation of collagen, which is a major structural component in the extracellular matrix. UV irradiation induces the production of matrix metalloproteinases (MMP) capable of attacking native fibrillar collagen and responsible for inhibiting the construction of collagenous extracellular matrix. In this study, we attempted to investigate the protective actions of Rubus coreanus ethanol extract (RCE) on the MMP production and the consequent procollagen/collagen degradation in UV-B-irradiated human dermal fibroblasts. The analytical data showed that Rubus coreanus ethanol extract was mostly comprised of cyanidin 3-rutinoside. Pre-treatment of fibroblasts with this extract inhibited UV-B-induced production of MMP-1, MMP-8 and MMP-13 in dose-dependent manners. In addition, Western blot analysis and immunocytochemical staining assay revealed that RCE markedly augmented the cellular levels of procollagen/collagen declined in UV-B-exposed dermal fibroblasts. These results demonstrate that RCE blocks UV-B-induced increase of the collagen degradation by inhibiting MMP production. Thus, RCE may act as an agent inhibiting excessive dermal collagen degradation leading to the skin photoaging.