Meihua Jin

Tianjin Medical University, T’ien-ching-shih, Tianjin Shi, China

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Publications (23)48.63 Total impact

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    ABSTRACT: Our previous study showed that the extract of Inula japonica Thunb (I. japonica) has anti-inflammatory and anti-asthmatic activities. In an attempt to find anti-inflammatory compounds from I. japonica, we recently isolated 1,6α-dihydroxy-4αH-1,10-secoeudesma-5(10),11(13)-dien-12,8β-olide (SE), 6α-isobutyryloxy-1-hydroxy-4αH-1,10-secoeudesma-5(10),11(13)-dien-12,8β-olide (IBSE), and 6α-isovaleryloxy-1-hydroxy-4αH-1,10-secoeudesma-5(10),11(13)-dien-12,8β-olide (IVSE) from the extract of I. japonica, and investigated their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The inhibitory effect of IVSE, SE and IBSE on NO production in LPS-induced RAW264.7 cells was examined using Griess reagent, and the effects of IVSE on the expressions of nitric oxide synthase (iNOS) and its upstream signal proteins including IκB kinase(IKK)/ inhibitor kappa B (IκB)-α/ Nuclear factor κB (NF-κB) and mitogen-activated protein kinases (MAPKs) were investigated by Western blot. Among the 3 compounds isolated, SE, IBSE, and IVSE inhibited NO production at 2.5 μM with 5.1%, 40.4%, and 52.8%, respectively. IVSE displayed the most potent inhibition of NO production. Mechanism analysis indicated that IVSE dramatically decreased the expression of inducible iNOS, reduced the translocation of the NF-κB subunit p65 into the nucleus by interrupting the phosphorylation and degradation of IκB-α, and inhibited the activation of the upstream mediator IKK α/β. Furthermore, our results showed that IVSE inhibited the phoshorylation of MAPKs including extracellular regulated kinases (ERK1/2), c-Jun N-terminal kinases (JNK) and p38. IVSE exhibited anti-inflammatory activity by inhibiting NO production, in which inactivation of NF-κB and MAPKs might be involved. Our results suggest that IVSE might become an anti-inflammatory drug candidate. Copyright © 2015. Published by Elsevier Inc.
    Life Sciences 01/2015; 124. DOI:10.1016/j.lfs.2015.01.008 · 2.30 Impact Factor
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    ABSTRACT: We isolated JEUD-38, a new sesquiterpene lactone from Inula japonica Thunb. JEUD-38 dramatically attenuated lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Consistent with this finding, the protein expression of inducible nitric oxide synthase (iNOS) was blocked by JEUD-38 in a concentration-dependent manner. To elucidate the mechanism, we examined the effect of JEUD-38 on LPS-stimulated nuclear factor-κB (NF-κB) nuclear translocation, inhibitory factor-κB (IκB) phosphorylation, and degradation. JEUD-38 reduced the translocation of p65, via abrogating IκB-α phosphorylation and degradation. In addition, JEUD-38 inhibited LPS-stimulated phosphorylation of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Since iNOS as well as the upstream NF-κB and MAPKs are known to be closely involved in inflammation, these results suggest that JEUD-38 is a promising candidate for prevention and therapy of inflammatory diseases.
    Inflammation 11/2014; 38(3). DOI:10.1007/s10753-014-0056-2 · 1.92 Impact Factor
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    ABSTRACT: Stellettin B was isolated from marine sponge Jaspis stellifera. In vitro antitumor activities were investigated on 39 human cancer cell lines. Stellettin B exhibited highly potent inhibition against the growth of a human glioblastoma cell line SF295, with a GI50 of 0.01 μM. In contrast, stellettin B showed very weak inhibitory activity on normal cell lines including HMEC, RPTEC, NHBE and PrEC, with GI50s higher than 10 μM, suggesting its relatively selective cytotoxicity against human cancer cells compared to normal human cell lines. We then focused on the antitumor activity of this compound on SF295 cells. Flow cytometric analysis indicated that stellettin B induced apoptosis in SF295 cells in a concentration-dependent manner. Further study indicated that stellettin B increased the production of ROS, the activity of caspase 3/7, as well as the cleavage of PARP, each of which is known to be involved in apoptosis. To investigate the molecular mechanism for cell proliferation inhibition and apoptosis induction, effect on the phosphorylation of several signal proteins of PI3K/Akt and RAS/MAPK pathways was examined. Stellettin B inhibited the phosphorylation of Akt potently, with no activity on p-ERK and p-p38, suggesting that inhibition of PI3K/Akt pathway might be involved in the antiproliferative and apoptosis-inducing effect. However, homogenous time-resolved fluorescence (HTRF) assay indicated that stellettin B did not inhibit PI3K activity, suggesting that the direct target might be signal protein upstream of Akt pathway other than PI3K.
    Marine Drugs 07/2014; 12(7):4200-4213. DOI:10.3390/md12074200 · 3.51 Impact Factor
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    ABSTRACT: PI3Kγ is known to play an important role in inflammation and immune responses. Mast cells are closely involved in the initiation and regulation of immune responses and allergic inflammatory reactions. AS252424 is a specific PI3Kγ inhibitor. Until now, the anti-inflammatory effect of AS252424 on mast cells has not been reported. In this study, we investigated the anti-inflammatory effects of AS252424 on the inflammatory mediators in activated bone marrow-derived mast cells (BMMCs). AS252424 dramatically attenuated c-Kit ligand (KL)-induced leukotriene C4 (LTC4) generation and degranulation in BMMCs. Downregulating phosphorylation of cytosolic phospholipase A2 (cPLA2) and mitogen-activated protein kinase (MAPK) and inhibition of Ca(2+) liberation in BMMCs might be involved in the anti-inflammatory effects. These results suggested that AS252424 might be considered as a chemical tool or a drug candidate for prevention and therapy of inflammatory disease.
    Inflammation 03/2014; 37(4). DOI:10.1007/s10753-014-9852-y · 1.92 Impact Factor
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    ABSTRACT: Tumor metastasis is the main cause of lethality of prostate cancer, because conventional therapies like surgery and hormone treatment rarely work at this stage. Tumor cell migration, invasion and adhesion are necessary processes for metastasis. By providing nutrition and an escape route from the primary site, angiogenesis is also required for tumor metastasis. Phosphatidylinositol 3-kinases (PI3Ks) are well known to play important roles in tumorigenesis as well as metastasis. ZSTK474 is a specific PI3K inhibitor developed for solid tumor therapy. In the present report, antimetastatic activities of ZSTK474 were investigated in vitro by determining the effects on the main metastatic processes. ZSTK474 exhibited inhibitory effects on migration, invasion and adhesive ability of prostate cancer PC3 cells. Furthermore, ZSTK474 inhibited phosphorylation of Akt substrate-Girdin, and the secretion of matrix metalloproteinase (MMP), both of which were reported to be closely involved in migration and invasion. On the other hand, ZSTK474 inhibited the expression of HIF-1α and the secretion of vascular endothelial growth factor (VEGF), suggesting its potential antiangiogenic activity on PC3 cells. Moreover, we demonstrated the antiangiogenesis by determining the effect of ZSTK474-reduced VEGF on tube formation of human umbilical vein endothelial cells (HUVECs). In conclusion, ZSTK474 was demonstrated to have potential in vitro antimetastatic effects on PC3 cells via dual mechanisms: inhibition of metastatic processes including cell migration, invasion and adhesion, and antiangiogenesis via blockade of VEGF secretion.
    International Journal of Molecular Sciences 07/2013; 14(7):13577-91. DOI:10.3390/ijms140713577 · 2.34 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. DOI:10.1016/j.jep.2012.06.015 · 2.94 Impact Factor
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    ABSTRACT: We previously isolated aaptamine, a benzonaphthyridine alkaloid, from marine sponge Aaptos suberitoids. In this study, we investigated the anti-proliferative effect of aaptamine on chronic myeloid leukemia (CML) K562 cells. Aaptamine inhibited growth of K562 with a GI50 as 10 μM, and arrested cell cycle at G2/M phase. Western blot analysis indicated that aaptamine induced p21 expression in K562 cells. Moreover, p21 promoter was activated by aaptamine treatment in p21 transfected K562 cells. Since K562 is p53 negative, aaptamine was demonstrated to be a p53-independent p21 inducer in CML cells.
    International Journal of Molecular Sciences 12/2011; 12(11):7352-9. DOI:10.3390/ijms12117352 · 2.34 Impact Factor
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    ABSTRACT: Class I PI3 Kinase (PI3K) phosphorylates phosphatidylinositol 4,5-bisphophate (PIP2) to generate the second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3) and therefore plays an important role in fundamental cellular responses such as proliferation. There are four isoforms of class I PI3K which are known to have different functions and relate to various diseases such as cancer and inflammation. Flavonoids are abundant in fruits, vegetables and plant-derived beverages such as tea. So far, various pharmacological effects of flavonoids have been reported. We previously reported that the flavonoid baicalein exhibits potent PI3K-inhibitory activity. Recently we examined the inhibitory activity of eighteen flavonoids against PI3Ka by using an in vitro homogenous time resolved fluorescence (HTRF) kinase assay, and deduced their structure-activity relationships by comparing the activities of the analogues. Our result suggests that the number of hydroxyl groups in the A and B rings might promote the activity, while loss of C2-C3 double bond might reduce the activity. Furthermore, the activity against 4 class I PI3K isoforms of some selected flavonoids was investigated, and the results indicate that the flavonoids seem to exhibit more potent activity on PI3Ka and d isoforms compared with that on PI3Kb and g isoforms.
    Molecules 12/2011; 16(6):5159-67. DOI:10.3390/molecules16065159 · 2.42 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. DOI:10.1007/s12272-011-0911-8 · 1.75 Impact Factor
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    ABSTRACT: The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for treating inflammatory diseases. The effects on OVA-induced asthmatic mice of an Inulae Flos extract (IFE) were evaluated in this study. The anti-asthmatic effects of IFE were determined by observing eosinophil recruitment, airway hyper-responsiveness (AHR), Th2 cytokine and IgE levels, and lung histopathology. The IFE treatment effectively reduced the percentage of eosinophils and Th2 cytokines in the bronchoalveolar lavage fluid (BALF) when compared to the levels in OVA-induced mice. IFE also suppressed AHR induced by aerosolized methacholine in OVA-induced mice. The results of the histopathological studies indicate that inflammatory cell infiltration and mucus hypersecretion were both inhibited by the IFE administration when compared to the effect on OVA-induced mice. The IFE treatment also suppressed the serum IgE levels and decreased Th2 cytokines in the supernatant of cultured splenocytes. These results suggest that IFE may have therapeutic potential against asthma.
    Bioscience Biotechnology and Biochemistry 05/2011; 75(5):871-6. DOI:10.1271/bbb.100787 · 1.21 Impact Factor
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    ABSTRACT: To find anti-inflammatory compounds from the tuberous roots of Dioscorea batatas, we isolated 6-hydroxy-2,4,7-trimethoxyphenanthrene (batatasin I) from the dichloromethane (CH(2)Cl(2)) fraction of this plant. Batatasin I inhibited both the generation of prostaglandin D(2) (PGD(2)), leukotriene C(4) (LTC(4)) and degranulation reaction in mouse bone marrow-derived mast cells (BMMCs). This compound inhibited cyclooxygenase-2 (COX-2) dependent PGD(2) generation in a dose dependent manner, with IC(50) values of 1.78 µM. Western blotting probed with specific anti-COX-2 antibodies showed that the decrease in the quantity of the PGD(2) generation was accompanied by a decrease in the COX-2 protein level. In addition, this compound also inhibited the production of 5-lipoxygenase (5-LOX) dependent LTC(4) in a dose dependent manner (IC(50), 1.56 µM). Batatasin I also inhibited the mast cell degranulation reaction (IC(50), 6.7 µM) in BMMCs. This result indicates that batatasin I could be developed as an anti-inflammatory agent through further investigation.
    Biological & Pharmaceutical Bulletin 01/2011; 34(7):1021-5. DOI:10.1248/bpb.34.1021 · 1.78 Impact Factor
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    ABSTRACT: In this study, luteolin-7-O-glucoside (L7G), an herbal medicine isolated from Ailanthus altissima, inhibited 5-lipoxygenase (5-LOX)-dependent leukotriene C(4) (LTC(4)) production in bone marrow-derived mast cells (BMMCs) in a concentration-dependent manner with an IC(50) of 3.0 µM. To determine the action mechanism of L7G, we performed immunoblotting for cytosolic phospholipase A(2) (cPLA(2)) and mitogen-activated protein kinases (MAPKs) following c-kit ligand (KL)-induced activation of BMMCs with or without L7G. Inhibition of LTC(4) production by L7G was accompanied by a decrease in cPLA(2) phosphorylation, which occurred via the extracellular signal-regulated protein kinase-1/2 (ERK1/2) and p38 and c-Jun N-terminal kinase (JNK) pathways. In addition, L7G also attenuated mast cell degranulation in a dose-dependent manner (IC(50), 22.8 µM) through inhibition of phospholipase Cγ1 (PLCγ1) phosphorylation. Our results suggest that the anti-asthmatic activity of L7G may be mediated in part via the inhibition of LTC(4) generation and mast cell degranulation.
    Biological & Pharmaceutical Bulletin 01/2011; 34(7):1032-6. DOI:10.1248/bpb.34.1032 · 1.78 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. DOI:10.1016/j.fct.2010.07.048 · 2.61 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. DOI:10.1016/j.jep.2010.08.002 · 2.94 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. DOI:10.1248/bpb.33.1 · 1.78 Impact Factor
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    ABSTRACT: This study was conducted to demonstrate the inhibitory effect of saucerneol G (SG), a new lignan, isolated from the aerial part of Saururus chinensis (Saururaceae) on lipopolysaccharide (LPS)-stimulated matrix metalloproteinase-9 (MMP)-9 inductions in RAW 264.7 cells. Aimed at evaluating the mechanism of action by which SG inhibits the LPS-mediated induction of MMP-9, the effects of SG on nuclear factor-κB (NF-κB) DNA binding activity, NF-κB-dependent reporter gene activity, inhibitory factor-κB (IκB) phosphorylation, degradation and p65 nuclear translocation were assessed. SG profoundly suppressed the DNA binding activity and the reporter gene activity as well as translocation of NF-κB p65 subunit. Furthermore, SG also dose dependently inhibited LPS-stimulated activation of mitogen-activated protein kinases (MAPKs). These findings suggest that SG may inhibit LPS-stimulated MMP-9 induction by blocking NF-κB and MAPKs activation.
    Biological & Pharmaceutical Bulletin 01/2010; 33(12):1944-8. DOI:10.1248/bpb.33.1944 · 1.78 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. · 1.78 Impact Factor
  • Biological & Pharmaceutical Bulletin 01/2009; 32(9):1500-1503. DOI:10.1248/bpb.32.1500 · 1.78 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. DOI:10.1016/j.intimp.2008.05.009 · 2.71 Impact Factor
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    ABSTRACT: Ym1 and Ym2 (Ym1/2) are chitinase-like proteins and we reported previously that IL-4 induced Ym1/2 in mouse bone marrow-derived mast cells. In the present study, ovalbumin-induced asthmatic mice were used to investigate the effect of glucocorticoids on Ym1/2 expression. Ym1/2 were highly induced in bronchoalveolar lavage fluid (BALF) and the lung. Ym1/2 expression was completely inhibited by dexamethasone (Dex) in BALF and weakly inhibited in the lung. Primary cultured macrophages were used to investigate the inhibition of Ym1/2 expression at the cellular level. Although Dex pretreatment inhibited the Ym1/2 expression level in an animal model, it did not reduce IL-4 induction of Ym1/2 expression in vitro. Next, we tested whether Dex blocks IL-4 induced STAT6 signaling and found that it had no inhibitory effect on the phosphorylation level of STAT6 in macrophages. The luciferase reporter assay also revealed that Dex did not inhibit IL-4 induction of Ym1/2 promoter activity. These results indicate that the inhibitory effect of Dex on Ym1/2 protein expression in the murine model of asthma does not involve the STAT6 signaling pathway.
    Biological & Pharmaceutical Bulletin 10/2008; 31(9):1663-6. DOI:10.1248/bpb.31.1663 · 1.78 Impact Factor

Publication Stats

155 Citations
48.63 Total Impact Points


  • 2011–2015
    • Tianjin Medical University
      • School of Pharmacy
      T’ien-ching-shih, Tianjin Shi, China
  • 2013
    • School of Pharmaceutical Sciences of Shandong
      Chi-nan-shih, Shandong Sheng, China
  • 2008–2012
    • Yeungnam University
      • College of Pharmacy
      Gyeongsan, Gyeongsangbuk-do, South Korea