Ju Hye Yang

Yeungnam University, Asan, South Chungcheong, South Korea

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Publications (15)31.68 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a crucial role in the maintenance of cellular energy homeostasis, and several natural compounds that activate AMPK possibly enhance glucose uptake by muscle cells. In this study, we found that pinusolide stimulated AMPK phosphorylation and glucose uptake and these effects were significantly reduced by siRNA LKB1 or compound C, suggesting that enhanced glucose uptake by pinusolide is predominantly accomplished via an LKB1-mediated AMPK activation pathway. An insulin resistance state was induced by exposing cells to 30 mM glucose, as indicated by reduced insulin-stimulated tyrosine phosphorylation of IRS-1 and glucose uptake. Under these conditions, the phosphorylation of AMPK and ACC were decreased. Surprisingly, disrupted insulin signaling and decreased AMPK activity by high glucose concentrations were prevented by pinusolide. Moreover, this treatment increased insulin-stimulated glucose uptake via AMPK activation. Taken together, our findings suggest a link between high glucose and insulin resistance in muscle cells, and provide further evidence that pinusolide attenuates blockade of insulin signaling by enhancing IRS-1 tyrosine phosphorylation by the activating the AMPK pathway. In addition, this study indicates the targeting of AMPK represents a new therapeutic strategy for hyperglycemia-induced insulin resistance and type 2 diabetes.
    Biochemical and Biophysical Research Communications 07/2013; · 2.28 Impact Factor
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    ABSTRACT: The aim of the present study was to determine the effect of Tanshinone IIA (Tan IIA) on endoplasmic reticulum (ER) stress-induced insulin resistance in L6 myotubes and db/db mice. ER stress markers, RNA-activated protein kinase-like ER resident kinase (PERK), JNK, and AMPK activity were determined in tunicamycin-treated L6 myotubes. Insulin resistance was monitored using glucose uptake assays in vitro and blood glucose levels in vivo. Tan IIA clearly suppressed the phosphorylations of PERK and JNK and potentiated insulin-mediated Akt phosphorylation as well as glucose uptake via AMPK activation under ER stress. Furthermore, these effects are completely abrogated by siRNA-mediated knockdown of AMPK or LKB1. In addition, Tan IIA reduced blood glucose levels and body weights in db/db mice without altering food intake. These findings suggest that Tan IIA enhances insulin sensitivity and improves glucose metabolic disorders by increasing AMPK activity and attenuating ER stress-induced insulin resistance.
    Biochemical and Biophysical Research Communications 12/2012; · 2.28 Impact Factor
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    ABSTRACT: The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for the treatment of bronchitis, digestive disorders, and inflammation. However, the mechanisms underlying its anti-inflammatory effects remain yet to be elucidated. The objectives of this study were 1) to assess the anti-allergic activity of the ethanol extract of flowers of Inula japonica extract (IFE) in vivo, 2) to investigate the mechanism of its action on mast cells in vitro, and 3) to identify its major phytochemical compositions. The anti-allergic activity of IFE was evaluated using mouse bone marrow-derived mast cells (BMMCs) in vitro and a passive cutaneous anaphylaxis (PCA) animal model in vivo. The effects of IFE on mast cell activation were evaluated in terms of degranulation, eicosanoid generation, Ca(2+) influx, and immunoblotting of various signaling molecules. IFE inhibited degranulation and the generation of eicosanoids (PGD(2) and LTC(4)) in stem cell factor (SCF)-stimulated BMMCs. Biochemical analysis of the SCF-mediated signaling pathways demonstrated that IFE inhibited the activation of multiple downstream signaling processes including mobilization of intracellular Ca(2+) and phosphorylation of the mitogen-activated protein kinases (MAPKs), PLCγ1, and cPLA(2) pathways. When administered orally, IFE attenuated the mast cell-mediated PCA reaction in IgE-sensitized mice. Its major phytochemical composition included three sesquiterpenes, 1-O-acetylbritannilactone, britanin and tomentosin. This study suggests that IFE modulates eicosanoids generation and degranulation through the suppression of SCF-mediated signaling pathways that would be beneficial for the prevention of allergic inflammatory diseases. Anti-allergic activity of IFE may be in part attributed particularly to the presence of britanin and tomentosin as major components evidenced by a HPLC analysis.
    Journal of ethnopharmacology 06/2012; 143(1):151-7. · 2.32 Impact Factor
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    ABSTRACT: The high-affinity receptor for immunoglobulin E (IgE) (FcεRI)-mediated activation of mast cells plays an important role in various allergic diseases. To assess the anti-allergic activity of natural vanadium-containing Jeju groundwater (JW), an in vivo passive cutaneous anaphylaxis (PCA) animal model and in vitro mouse bone marrow-derived mast cells (BMMCs) was used. JW inhibited cyclooxygenase-2 (COX-2)-dependent prostaglandin D(2) (PGD(2)) generation in a dose-dependent manner, with a concomitant reduction of COX-2 protein expression in IgE-induced BMMCs. In addition, JW inhibited 5-lipoxygenase (5-LOX)-dependent generation of leukotriene C(4) (LTC(4)) as well as degranulation in a dose-dependent manner. These results demonstrate that JW has dual COX-2/5-LOX inhibitory activity. In addition, vanadium pentoxide (V(2)O(5)), which is the major vanadium component of JW, also inhibited PGD(2) and LTC(4) generation as well as degranulation in IgE-induced BMMCs. Furthermore, oral administration of JW dose-dependently inhibited mast cell-dependent passive anaphylactic reaction in IgE-sensitized mice. Taken together, these results suggest that JW may be useful in regulating mast cell-mediated allergic response through the suppression of eicosanoid generation and degranulation in mast cells.
    Biological & Pharmaceutical Bulletin 01/2012; 35(2):216-22. · 1.85 Impact Factor
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    ABSTRACT: The high-affinity receptor for IgE (FcɛRI)-mediated activation of mast cells plays an important role in allergic diseases such as asthma, allergic rhinitis and atopic dermatitis. Emodin, a naturally occurring anthraquinone derivative in oriental herbal medicines, has several beneficial pharmacologic effects, such as anti-cancer and anti-diabetic activities. However, the anti-allergic effect of emodin has not yet been investigated. To assess the anti-allergic activity of emodin, in vivo passive anaphylaxis animal model and in vitro mouse bone marrow-derived mast cells were used to investigate the mechanism of its action on mast cells. Our results showed that emodin inhibited degranulation, generation of eicosanoids (prostaglandin D(2) and leukotriene C(4)), and secretion of cytokines (TNF-α and IL-6) in a dose-dependent manner in IgE/Ag-stimulated mast cells. Biochemical analysis of the FcɛRI-mediated signaling pathways demonstrated that emodin inhibited the phosphorylation of Syk and multiple downstream signaling processes including mobilization of intracellular Ca(2+) and activation of the mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and NF-κB pathways. When administered orally, emodin attenuated the mast cell-dependent passive anaphylactic reaction in IgE-sensitized mice. Thus, emodin inhibits mast cell activation and thereby the anaphylactic reaction through suppression of the receptor-proximal Syk-dependent signaling pathways. Therefore, emodin might provide a basis for development of a novel anti-allergic drug.
    Biochemical pharmacology 09/2011; 82(11):1700-8. · 4.25 Impact Factor
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    ABSTRACT: 6-Hydroxy-2,7-dimethoxy-1,4-phenanthraquinone (PAQ) isolated from the tuberous roots of Yam (Dioscorea batatas) inhibited cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) dependent prostaglandin D(2) (PGD(2)) generation in mouse bone marrow-derived mast cells in a concentration-dependent manner with IC(50) values of 0.08 μM and 0.27 μM, respectively. In the Western blotting with specific anti-COX-2 antibodies, the decrease of the quantity of PGD(2) was accompanied by a decrease in the COX-2 protein level. But PAQ did not affect COX-1 protein level. In addition, this compound inhibited 5-lipoxygenase (5-LOX) dependent production of leukotriene C(4) in a dose-dependent manner, with an IC(50) of 0.032 μM. These results demonstrate that PAQ has a dual COX-2/5-LOX inhibitory activity. This compound also inhibited the degranulation reaction in a dose-dependent manner with an IC(50) of 2.7 μM. Thus, these results suggest that PAQ may be useful in regulating mast cell-mediated inflammatory diseases.
    Archives of Pharmacal Research 09/2011; 34(9):1495-501. · 1.54 Impact Factor
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    ABSTRACT: Atherosclerosis is accompanied by the proliferation of human aortic smooth muscle cells (HASMC) and their movement into the intima. Many reports have indicated the involvement of gelatinases (MMP-9 and MMP-2) in this pathogenesis. The ethylacetate fraction from starfish, Asterias amurensis (EFA), harvested from the Korean seaside has an inhibitory effect on MMP-9 and MMP-2 activities, as well as on the expression of MMP-9 in TNF-α induced HASMC in a dose-dependent manner. Also, EFA inhibits the migration of TNF-α induced HASMC in transwells containing gelatin coated plugs. EFA was not cytotoxic to HASMC over the range 0-1mg/ml. By Western-blot analysis, it was revealed that the phosphorylation of extracellular signal regulated kinase (ERK) in TNF-α induced cells was inhibited and nuclear factor kappa B (NF-κB) p65 levels in nuclear extracts were decreased by EFA treatment. In addition, ERK inhibitor (U0126) treated cells exhibited decreased MMP-9 activity in the zymographic assay. From these results, it was found that the gelatinolytic activity was regulated (1) by enzymatic inhibition of both MMP-9 and MMP-2, as well as (2) by the decreased production of MMP-9 via ERK pathways in EFA treated HASMCs. Taken together, it has been shown that EFA has a putative anti-atherosclerotic effect.
    Toxicology in Vitro 06/2011; 25(4):767-73. · 2.65 Impact Factor
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    ABSTRACT: We identified a bioactive herbal medicine with anti-inflammatory activity from an ethanol extract derived from the bark of Dioscorea batatas DECNE (BDB) in RAW264.7 cells. We examined the effects of BDB on nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in LPS-induced RAW264.7 cells. BDB consistently inhibited both NO and PGE(2) production in a dose-dependent manner, with an IC(50) of 87-71 μg/ml, respectively. The reduction of NO and PGE(2) production were accompanied by a reduction in iNOS and COX-2 protein expression, as evaluated by Western blotting. To evaluate the action mode of BDB and its ability to inhibit iNOS and COX-2 protein expression, we assessed the effects of BDB on nuclear factor-κB (NF-κB) DNA-binding activity, NF-κB-dependent reporter gene activity, inhibitory factor-κB (IκB) phosphorylation and degradation, and p65 nuclear translocation. BDB suppressed DNA-binding activity and reporter gene activity as well as translocation of the NF-κB p65 subunit. BDB also down-regulated IκB kinase (IKK), thus inhibiting LPS-induced both phosphorylation and the degradation of IκBα. In addition, BDB also inhibited the LPS-induced activation of ERK1/2.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 11/2010; 48(11):3073-9. · 2.99 Impact Factor
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    ABSTRACT: The aerial part of Saururus chinensis has been used in folk medicine to treat several inflammatory diseases in China and Korea. Previously, our group reported that anti-asthmatic activity of an ethanol extract of Saururus chinensis (ESC) might occur, in part, via the inhibition of prostaglandin D(2) (PGD(2)) and leukotriene C(4) (LTC(4)) production, and degranulation reaction in vitro, as well as through the down-regulation of interleukin (IL)-4 and eotaxin mRNA expression in an in vivo ovalbumin-sensitization animal model. However, the effects of Saururus chinensis on eicosanoid generation, as well as Th2 cytokines and eotaxin production in an in vivo asthma model, have not been fully investigated. Moreover, it has not been determined whether ESC can ameliorate airway inflammation in vivo. In the present study, we investigated the therapeutic activity of Saururus chinensis on ovalbumin (OVA)-sensitized airway inflammation and its major phytochemical compositions. Asthma was induced in BALB/c mice by ovalbumin-sensitization and inhalation. ESC (10-100 mg/kg) or dexamethasone (5 mg/kg), a positive control, was administered 7 times orally every 12 h from one day before the first challenge to 1 h before the second challenge. The recruitment of inflammatory cells and hyperplasia of goblet cells were evaluated by H&E and PAS staining. Levels of Th2 cytokines, eotaxin, PGD(2) and LTC(4) were measured to evaluate the anti-inflammatory activity of ESC in OVA-sensitized mice. Contents of major components were analyzed by HPLC using a reversed-phase C18 column. ESC (10 mg/kg) suppressed allergic airway inflammation by inhibition of the production of IL-4 (P<0.001), IL-5 (P<0.05), IL-13 (P<0.001), eotaxin (P<0.001), PGE(2) (P<0.001), LTC(4) (P<0.001) in lung extract and IgE level (P<0.001) in the serum. In addition, ESC (50 mg/kg) reduced the infiltration of inflammatory cells and hyperplasia of goblet cells in the lung tissues. The anti-inflammatory effect of ESC was comparable to that of the positive control drug, dexamethasone. Its major phytochemical composition includes manassantin A, B and sauchinone. These results suggest that ESC decreased inflammation and mucus secretion in the OVA-induced bronchial asthma model, and its anti-asthmatic activity may occur in part via the inhibition of Th2 cytokines and eotaxin protein expression, as well as through prostaglandin E(2) (PGE(2)) and leukotriene C(4) (LTC(4)) generation. This effects may be attributed particularly to the presence of manassantin A, B and sauchinone major component evidenced by a HPLC analysis.
    Journal of ethnopharmacology 10/2010; 132(1):143-9. · 2.32 Impact Factor
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    ABSTRACT: Intercellular adhesion molecule-1 (ICAM-1) is associated with processes of inflammation. We investigated the effects of deoxypodophyllotoxin (DPT) on tumor necrosis factor-alpha (TNF-alpha) induced ICAM-1 expression in the mouse lung epithelial cell line, LA4. DPT (5 to 20 nM) inhibited TNF-alpha-induced ICAM-1 expression through nuclear factor-kappa B (NF-kappaB) in a dose-dependent manner and repressed ICAM-1 promoter activity. NF-kappaB reporter gene activity and DNA binding activity were also strongly inhibited. In addition, DPT inhibited degradation by the TNF-alpha induced inhibitory kappaB-alpha (IkappaB-alpha) in a concentration-dependent manner. Taken together with our previous results suggest DPT might provide a basis for novel anti-inflammatory drug development.
    Biological & Pharmaceutical Bulletin 01/2010; 33(1):1-5. · 1.85 Impact Factor
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    ABSTRACT: Previously, we reported that an ethanol extract of Ailanthus altissima has antiinflammatory activity in an ovalbumin (OVA)-sensitized murine asthmatic model. To determine the biological compounds from this plant, luteolin-7-O-glucoside (L7G) was isolated and its antiasthmatic activity was evaluated in an in vivo murine asthmatic model. L7G (10 to 100 mg/kg, per os (p.o.)) reduced the amount of eosinophil infiltration in bronchoalveolar lavage (BAL) fluid in a dose-dependent manner. In comparison, dexamethasone (5 mg/kg, p.o.), which was used as a positive control, also strongly inhibited the number of infiltrating eosinophils. L7G inhibited both the prostaglandin E(2) (PGE(2)) and serum immunoglobulin E level in BAL fluid in a dose-dependent manner. In addition, L7G inhibited the transcript profiles of interleukin (IL)-4, IL-5, and IL-13 mRNA expression levels in the murine asthma model, as determined using reverse transcription-polymerase chain reaction (RT-PCR). These results suggest that the antiasthmatic activity of L7G in OVA-induced lung inflammation may occur in part via the downregulation of T helper 2 cytokine transcripts as well as the inhibition of PGE(2) production.
    Biological & Pharmaceutical Bulletin 10/2009; 32(9):1500-3. · 1.85 Impact Factor
  • Biological & Pharmaceutical Bulletin - BIOL PHARM BULL. 01/2009; 32(9):1500-1503.
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    ABSTRACT: As part of an ongoing investigation aimed at the discovery of novel bioactive medicinal herbs with anti-inflammatory properties, the effects of an ethanolic extract from the parts of Salviae miltiorrhiza Bunge (ESM) were evaluated using in vitro and in vivo animal model analysis. ESM inhibited cyclooxygenase-2 (COX-2) and COX-1-dependent phases of prostaglandin D2 (PGD2) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC50 values of 3.96 microg/mL and 21.54 microg/mL, respectively. Furthermore, ESM inhibited leukotriene C4 (LTC4) production with an IC50 value of 2.6 microg/mL. These results clearly demonstrated the dual COX-2 selective/5-lipoxygenase inhibitory activity that ESM possessed. ESM strongly inhibited a degranulation reaction in a dose dependent manner within a BMMC system, with an IC50 value of 22.4 microg/mL. Additionally, ESM was tested in a rat passive cutaneous anaphylaxis (PCA) reaction assay by oral administration (25 to 100 mg/kg). ESM dose-dependently inhibited the PCA reaction, which was activated by anti-dinirophenyl (DNP) IgE. These results suggested that ESM might be beneficial in regulating various allergic reactions.
    Archives of Pharmacal Research 01/2009; 31(12):1597-603. · 1.54 Impact Factor
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    ABSTRACT: We evaluated the ability of saucerneol D (SD), a tetrahydrofuran-type sesquilignan isolated from Saururus chinensis, to regulate the expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cells. SD consistently inhibited nitric oxide (NO) production in a dose-dependent manner, with an IC(50) of 2.62 microM, and also blocked LPS-induced iNOS expression. SD potently suppressed both the reporter gene expression and DNA-binding activity of nuclear factor-kappaB (NF-kappaB). In addition, SD inhibited IkappaB-alpha degradation in a concentration- and time-dependent manner. SD also inhibited LPS-induced activation of various mitogen-activated protein kinases, including extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH(2)-terminal kinase (JNK). These findings suggest that SD may inhibit LPS-induced iNOS expression by blocking NF-kappaB and MAPK activation.
    International Immunopharmacology 11/2008; 8(10):1395-400. · 2.42 Impact Factor
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    ABSTRACT: Methyl gallate (MG) is a medicinal herbal product that is isolated from Paeonia lactiflora that inhibits cyclooxygenase-2 (COX-2) dependent phases of prostaglandin D2 (PGD2) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with an IC50 values of 17.0 microM. This compound also found inhibited the COX-2-dependent conversion of the exogenous arachidonic acid to PGD2 in a dose-dependent manner with an IC50 values of 19.0 microM, using a COX enzyme assay kit. However, at concentrations up to 80 microM, MG did not inhibit COX-2 protein expression in BMMC, indicating that MG inhibits COX-2 activity directly. Furthermore, MG consistently inhibited the production of leukotriene C4 (LTC4) in a dose dependent manner, with an IC50 value of 5.3 microM. These results demonstrate that MG has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity, which might provide the basis for novel anti-inflammatory drugs.
    Archives of Pharmacal Research 11/2006; 29(10):874-8. · 1.54 Impact Factor

Publication Stats

94 Citations
31.68 Total Impact Points

Institutions

  • 2006–2013
    • Yeungnam University
      • College of Pharmacy
      Asan, South Chungcheong, South Korea
  • 2008
    • University of Alberta
      • Department of Medicine
      Edmonton, Alberta, Canada