Joa Sub Oh

Lupenone Isolated from Adenophora triphylla var. japonica Extract Inhibits Adipogenic Differentiation through the Downregulation of PPARγ in 3T3‐L1 Cells

Adenophora triphylla var. japonica (Campanulaceae) is known to have anti‐inflammatory and anti‐tussive effects. Dysfunction of adipocytes and adipose tissue in obesity is related to various inflammatory cytokines or adipokines. In this study, we investigated whether lupenone isolated from A. triphylla var. japonica extract inhibits adipocyte differentiation and expression of adipogenic marker genes in 3T3‐L1 preadipocytes. We demonstrated that lupenone resulted in a significant reduction in lipid accumulation and expression of adipogenic marker genes in a dose‐dependent manner. In addition, lupenone decreased the transcriptional activity of peroxisome proliferator‐activated receptor γ (PPARγ) induced by troglitazone, and we also demonstrated that lupenone suppressed the PPARγ and CCAAT‐enhancer‐binding protein α (C/EBPα) protein levels. These findings demonstrated that lupenone isolated from A. triphylla var. japonica extract effectively inhibited adipocyte differentiation through downregulation of related transcription factor, particularly the PPARγ gene. Copyright

Broussonetia kazinoki modulates the expression of VEGFR-2 and MMP-2 through the inhibition of ERK, Akt and p70S6K‑dependent signaling pathways: Its implication in endothelial cell proliferation, migration and tubular formation

Broussonetia kazinoki (BK) has been used as a traditional medicine to improve vision, as well as for inflammatory and infectious diseases. In the present study, we investigated the effects and molecular mechanism of the ethanolic extract of BK on cell proliferation, migration and tubular formation in vascular endothelial growth factor-A (VEGF-A)-treated human umbilical vein endothelial cells. BK treatment inhibited VEGF-A-stimulated endothelial cell proliferation through the downregulation of cell cycle-related proteins including cyclin-dependent kinases and cyclins. Moreover, BK treatment suppressed cell migration and tubular formation in response to VEGF-A. These anti-angiogenic activities of BK were associated with the inactivation of mitogenic signaling pathways including extracellular signal-regulated kinase, Akt and p70S6K, and the subsequent downregulation of VEGFR-2 and matrix metalloproteinase-2. Taken together, these findings suggest further evaluation and development of BK as a potential therapeutic agent for the treatment and prevention of angiogenesis-related diseases including cancer.

Regulatory effects of Siegesbeckia glabrescens on non-small cell lung cancer cell proliferation and invasion.

Siegesbeckia glabrescens (SG) Makino (Compositae) has been used as a traditional medicine for the treatment of allergic and inflammatory diseases. In the present study, we examined the effects and molecular mechanism of the ethanol extract of SG on cell proliferation and invasion in p53 wild-type A549 and p53-deficient H1299 non-small cell lung cancer (NSCLC) cells. SG treatment markedly inhibited the proliferation and invasion in both cell lines, independently of p53 expression. The anti-proliferative effect of SG on A549 cells was mediated by the inactivation of Akt and p70(S6K) as evidenced by treatment with LY294002 and rapamycin, respectively. In addition, anti-invasive activity of SG in A549 cells was found to be associated with the inhibition of p70(S6K). In contrast, in H1299 cells the inactivation of p38(MAPK) appeared to be involved in SG-mediated inhibition of cell proliferation and invasion. Collectively, these findings suggest that SG modulates cellular fates such as proliferation and invasion by differential regulation of signaling pathways, depending on the status of p53 expression in NSCLC, and support the development of SG as a potent therapeutic agent for the treatment of NSCLC.

A mechanistic study on the anti-cancer activity of ethyl caffeate in human ovarian cancer SKOV-3 cells

In the present study, we investigated the effect and molecular mechanism of ethyl caffeate (EC), a natural phenolic compound isolated from Ligularia fischeri, on human ovarian cancer cell proliferation and progression. EC-mediated inhibition of cell proliferation in SKOV-3 cells was accompanied by reduced expression of cell cycle-related proteins such as cyclin-dependent kinases and cyclins, resulting in pRb hypophosphorylation and G₁ phase cell cycle arrest. Moreover, EC treatment markedly inhibited cell migration and invasion. These regulatory effects of EC on ovarian cancer cell proliferation, migration and invasion were associated with inactivation of mitogenic signaling pathways such as Akt, ERK and p38(MAPK), and down-regulation of cell surface signaling molecules including receptor tyrosine kinases, integrin α3β1 and N-cadherin. Taken together, these findings suggest further evaluation and development of EC for the treatment and prevention of ovarian cancer.

Phenylpropanoid ester from Zingiber officinale and their inhibitory effects on the production of nitric oxide

A new phenylpropanoid ester mixture, (E)-geranylferulic acid (1a) and (Z)-geranylferulic acid (1b), along with 13 known compounds, [6]-gingerol (2), [8]-gingerol (3), [10]-gingerdione (4), 1-dehydro-[6]-gingerdione (5), 1-dehydro-[8]-gingerdione (6), [6]-paradol (7), [8]-paradol (8), [6]-gingeroldiacetate (9), 6-hydroxy-[6]-shogaol (10), galanolactone (11), trans-®-sesquiphellandrol (12), trans-sesquipiperitol (13), and 4α,5β-dihydroxybisabola-2,10-diene (14) were isolated from ethanol extract of Zingiber officinale. Their structures were determined based on the spectroscopic (1D, 2D-NMR and MS) and chemical evidence. All of the isolates were evaluated for their potential to inhibit LPS-induced production of nitric oxide in murine macrophage RAW264.7 cells. Compounds 1–12 were found to inhibit nitric oxide production with IC50 values ranging from 5.5 to 28.5 μM.

Marmesin is a novel angiogenesis inhibitor: Regulatory effect and molecular mechanism on endothelial cell fate and angiogenesis

In the present study, we investigated the effects and molecular mechanism of marmesin, a coumarin compound isolated from Broussonetia kazinoki, on vascular endothelial growth factor-A (VEGF-A)-induced endothelial cell responses in vitro and angiogenic sprouting in aortic rings ex vivo. Marmesin treatment inhibited VEGF-A-stimulated endothelial cell proliferation through down-regulation of cell cycle-related proteins including cyclin-dependent kinases and cyclins, leading to pRb hypophosphorylation and G1 phase cell cycle arrest. In addition, marmesin treatment abrogated VEGF-A-induced endothelial cell migration, invasion and capillary-like structure formation in vitro as well as angiogenic sprouting ex vivo. These anti-angiogenic activities of marmesin were mediated through inactivation of VEGF-A-stimulated signaling pathways, and down-regulation of cell surface signaling molecules including VEGF receptor-2, human epidermal growth factor receptor-2, integrin β1 and integrin-liked kinase. Taken together, these findings clearly support the pharmacological roles of marmesin in regulating angiogenesis, and warrant further evaluation and development as a potential therapeutic agent for the treatment and prevention of angiogenesis-related diseases including cancer.

Inhibitory Effect of Galanolactone Isolated from Zingiber officinale Roscoe Extract on Adipogenesis in 3T3-L1 Cells

Zingiber officinale Roscoe commonly known as ginger, has been used in traditional medicine. Inhibtion effect of galanolactone isolated from Z. officinale Roscoe on adipogenesis in 3T3-L1 cells was evaluated. Effect of galanolactone on 3T3-L1 adipocyte differentiation was measured by Oil Red O staining, and cytotoxicity effect of galanolactone was analyzed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The expression of various genes involved in adipogenic action of galanolactone was determined by real-time PCR and Western blot. Peroxisome proliferator-activated receptor γ (PPARγ) luciferase transactivation assay was used to evaluate the PPARγ transcriptional activity of galanolactone in HEK 293T cells. Galanolactone inhibited lipid accumulation and expression of adipocyte fatty acid-binding protein (aP2) and resistin in a dose-dependent manner in 3T3-L1 cells. Treatment with 50 and 100 μM of galanolactone significantly decreased the troglitazone-induced PPARγ transcripitional activity in HEK 293T cells, and suppressed expressions of PPARγ and CCAAT-enhancer-binding protein α (C/EBPα) at mRNA and protein levels in 3T3-L1 cells. These findings suggest that galanolactone isolated from Z. officinale Roscoe exerts anti-obesity effect through downregulation of adipogenic transcription factors and adipogenic marker genes.

Neolignan inhibitors of antigen-induced degranulation in RBL-2H3 cells from the needles of Pinus thunbergii

The ethanolic extract of the needles of Pinus thunbergii was found to suppress antigen mediated degranulation of rat basophilic leukemia (RBL-2H3) cells. A new neolignan glycoside, named pinusthunbergiside A (1), as well as six known neolignan glycosides (2-7) were isolated from the ethanolic extract using bioassay-guided fractionation. Their structures were elucidated by a combination of 1D and 2D NMR, HRESI-MS, and circular dichroism (CD) data. Compounds 2-7 were found for the first time in this plant. The inhibitory effects of isolated constituents on the release of β-hexosaminidase from RBL-2H3 cells were examined, and compounds 2, 3, 5, and 6 were found to show the inhibitory activity with IC₅₀ values ranging between 52.3 and 75.3 μM.

Ligularia fischeri regulates lung cancer cell proliferation and migration through down-regulation of epidermal growth factor receptor and integrin β1 expression

In the present study, we report the effect and molecular mechanism of Ligularia fischeri (LF) on proliferation and migration in human lung cancer cells. LF-mediated inhibition of cell proliferation in p53 wild-type A549 and p53-deficient H1299 cells is accompanied by reduced expression of cell cycle-related proteins such as cyclin-dependent kinases and cyclins, resulting in pRb hypophosphorylation and G1 phase cell cycle arrest. In contrast, LF inhibits cell migration in A549 cells, but not in H1299 cells. These regulatory effects of LF on cell proliferation and migration are associated with inactivation of mitogenic signaling pathways such as ERK, Akt and p70S6K, and down-regulation of epidermal growth factor receptor and integrin β1 expression. Collectively, these findings suggest further development and evaluation of LF for the prevention and treatment of lung cancer with mutated p53 as well as wild-type p53.

Inhibitors of antigen-induced degranulation of RBL-2H3 cells isolated from wheat bran

Chromatographic separation of ethanol extract of wheat bran led to the isolation of five 5-alk(en)ylresorcinols, four aliphatic compounds, and one phenolic glycoside. These were, respectively: 5-n-heptadecylresorcinol (1), 5-n-14′-(Z)-heneicosylresorcinol (2), 5-n-nonadecylresorcinol (3), 5-n-heneicosylresorcinol (4), 5-n-tricosylresorcinol (5), 1-O-(9Z,12Z,15Z-octadecatrienoate) glycerol (6), 2-linoleoylglycerol (7), 1-O-(9Z,12Z-octadecatrienoate)glycerol (8), pinellic acid (9), and tachioside (10). Their structures were determined by 1D- & 2D-NMR and mass spectroscopy data analysis. The inhibitory effects of isolated constituents on the release of β-hexosaminidase from RBL-2H3 cells were examined. Inhibition was shown by 5-n-nonadecylresorcinol (3), 5-n-heneicosylresorcinol (4), pinellic acid (9), and tachioside (10).