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ABSTRACT: Aristolochic acid nephropathy is caused by aristolochic acid (AA) and AA-containing herbs. In traditional Chinese medicine, a principle called "Jun-Chen-Zou-Shi" may be utilized to construct a remedial herbal formula that attempts to mitigate the toxicity of the main ingredient. This study used Bu-Fei-A-Jiao-Tang (BFAJT) to test if the compound remedy based on a principle of "Jun-Chen-Zou-Shi" can decrease the toxicity of AA-containing herbs. We compared the three toxicities of AA standard, Madouling (an Aristolochia herb), and a herbal formula BFAJT. AA standard was given for BALB/c mice at a dose of 5 mg/kg bw/day or 7.5 mg/kg bw/day for 10 days. Madouling and BFAJT were given at an equivalence of AA 0.5 mg/kg bw/day for 21 days. Nephrotoxicity was evaluated by metabolomics and histopathology. The urinary metabolomics profiles were characterized by (1)H NMR spectroscopy. The spectral data was analyzed with partial least squares discriminant analysis, and the significant differential metabolites between groups were identified. The result showed different degrees of acute renal tubular injuries, and metabolomics analysis found that the kidney injuries were focused in proximal renal tubules. Both metabolomics and pathological studies revealed that AA standard, Madouling, and BFAJT were all nephrotoxicants. The compositions of the compound remedy did not diminish the nephrotoxicity caused by AA.
Evidence-based Complementary and Alternative Medicine 01/2013; 2013:263757. · 4.77 Impact Factor
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ABSTRACT: This study aimed to determine whether brazilin exhibits anti-inflammatory effects that inhibit T helper cell type II (T(H)2) responses and whether it suppresses allergic inflammation reactions in a murine model of asthma. We found that brazilin inhibited the mRNA and protein expression of interleukin (IL)-4 and IL-5 induced by phorbol myristate acetate (PMA) and cAMP in EL-4 T cells in a dose-dependent manner. Following the intratracheal instillation of brazilin in ovalbumin (OVA)-immunized mice, we found that brazilin-treated mice exhibited decreases in the release of IL-4, IL-5, IL-13, eotaxin-1, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF); inhibited T(H)2 functioning via a decrease in IL-4 production; and exhibited attenuation of OVA-induced lung eosinophilia, airway hyperresponsiveness, and airway remodeling. These results suggest that brazilin exhibits anti-T(H)2 effects both in vitro and in vivo and may possess therapeutic potential for allergic diseases.
Journal of Agricultural and Food Chemistry 08/2012; 60(37):9405-14. · 2.82 Impact Factor
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ABSTRACT: The metabolic profile of the potent hypoglycemic agent, (2S)-pterosin A (1), in rat urine via intragastrical oral administration was investigated. In total, 19 metabolites (M1-M19) were identified. Among these, 16 metabolites were characterized by high-performance liquid chromatography solid-phase extraction-tube transfer-NMR, and seven metabolites were further isolated from the treated urine to enable further structural determination. Twelve of these are new compounds. The phase I metabolites of 1 were formed via various oxidations at positions C-3, C-10, C-12, C-13, or C-1 followed by decarboxylation of C-10 or C-14, and lactonization at C-12/C-14 or C-14/C-12. The phase II metabolites were glucuronide conjugates from the parent compound or phase I metabolites. The major metabolites were found to be (2S)-14-O-glucuronylpterosin A (M9), (2S)-2-hydroxymethylpterosin E (M14), and (±)-pterosin B (M19). Quantitative HPLC analysis of metabolites, based on similar UV absorption and use of the regression equation of 1, indicated that ∼71% 1 was excreted as metabolites in rat urine.
Drug metabolism and disposition: the biological fate of chemicals 05/2012; 40(8):1566-74. · 3.74 Impact Factor
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ABSTRACT: Epidemiological studies have shown that there is a strong correlation between atherosclerosis and ambient air pollution. In this study, we found that motorcycle exhaust particles (MEP) induced adhesion between cells of the human monocytic leukemia cell line (THP-1) and human umbilical vein endothelial cells (HUVECs) in a time-and dose-dependent manner. In addition, MEP treatment induced both mRNA and protein expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HUVECs. The IκB degradation and p65 nuclear translocation was found in MEP-treated HUVECs, suggested the involvement of nuclear factor-κB (NF-κB). MEP-induced VCAM-1 and ICAM-1 protein expression was inhibited by NF-κB inhibitor BAY 11-7085. Oxidative stress was also involved in the signaling of VCAM-1 and ICAM-1 expression. MEP treatment caused hydrogen peroxide and superoxide formation. Pretreatment with α-tocopherol could inhibit MEP-induced reactive oxygen intermediates generation and suppressed MEP-induced IκB degradation and adhesion molecules expression. Furthermore, the carbon black (CB) nanoparticles with different diameters could induce VCAM-1 and ICAM-1 protein expression; however, polycyclic aromatic hydrocarbons (PAHs) only increased the expression of ICAM-1 but not that of VCAM-1 in HUVECs. In this study, we found that MEPs could induce ICAM-1 and VCAM-1 expression through oxidative stress and NF-κB activation in HUVECs.
Toxicology in Vitro 01/2012; 26(4):552-60. · 2.78 Impact Factor
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ABSTRACT: The explosive development of nanotechnology has caused an increase in unintended biohazards in humans and in the ecosystem. Similar to particulate matter, nanoparticles (NPs) are strongly correlated with the increase in incidences of cardiovascular diseases, yet the mechanisms behind this correlation remain unclear. Within the testing concentrations of 0.1-10 μg/ml, which did not cause a marked drop in cell viability, zinc oxide NPs (ZnO-NPs) induced intercellular adhesion molecule-1 (ICAM-1) messenger RNA, and protein expression in both concentration- and time-dependent manner in treated human umbilical vein endothelial cells (HUVECs). ZnO-NPs treatment cause the activation of Ras-related C3 botulinum toxin substrate 1 (Rac1)/cell division control protein 42 homolog (Cdc42) and protein accumulation of mixed lineage kinase 3 (MLK3), followed by c-Jun N-terminal kinase (JNK) and transcription factor c-Jun activation. Induction of ICAM-1 and phosphorylation of JNK and c-Jun could be inhibited by either JNK inhibitor SP600125 or Rac guanosine triphosphatase inhibitor NSC23766 pretreatment. In addition, pretreatment with NSC23766 significantly reduced MLK3 accumulation, suggesting the involvement of Rac1/Cdc42-MLK3-JNK-c-Jun signaling in the regulation of ZnO-NPs-induced ICAM-1 expression, whereas these signaling factors were not activated in zinc oxide microparticles (ZnO-MPs)-treated HUVECs. The increase of ICAM-1 expression on ZnO-NPs-treated HUVECs enables leukocytes to adhere and has been identified as an indicator of vascular inflammation. Our data are essential for safety evaluation of the clinical usage of ZnO-NPs in daily supplements, cosmetics, and biomedicines.
Toxicological Sciences 12/2011; 126(1):162-72. · 4.65 Impact Factor
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ABSTRACT: Abstract Understanding tissue biodistribution and clearance of zinc oxide nanoparticles (ZnO-NPs) is necessary for its risk assessment. Both fed and intraperitoneally injected ZnO-NPs (2.5 g/kg) were absorbed into circulation (within 30 min post-dosing), then biodistributed to the liver, spleen, and kidney. Intraperitoneally injected ZnO-NPs remained in serum for 72 h and could more effectively spread to the heart, lung, and testes, whereas the clearance for fed ZnO-NPs in serum began 6 h after oral administration. Compared with zinc oxide microparticles (ZnO-MPs), ZnO-NPs exhibited much higher absorptivity and tissue biodistribution in fed treatment. A greater fraction of fed ZnO-NPs localised in the liver resulted in transient histopathological lesions. However, superoxide generation and cytotoxicity were showed in vitro treatment with ZnO-NPs (above 20 μg/mL). Considering both in vitro and in vivo data, the ZnO-NPs induced acute liver toxicity which was in compliance with its absorption, biodistribution, and clearance.
Nanotoxicology 09/2011; 6:746-56. · 5.76 Impact Factor
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ABSTRACT: To investigate the effects of shikonin on phorbol myristate acetate (PMA) plus cyclic adenosine monophosphate (cAMP)-induced T helper (T(H)) 2 cell cytokine production, and the underlying mechanism.
We used activated EL-4 murine T-lymphoma cells, which produce interleukin (IL)-4 and IL-5, but not interferon (IFN)-γ, as T(H)2 cell-like cells and treated them with PMA+cAMP to investigate the effects of shikonin on T(H)2 cytokines, transcriptional factors, and the related mitogen-activated protein kinase (MAPK)/nuclear factor (NF)-κB signaling pathway.
The data show that shikonin inhibited the PMA+cAMP-induced mRNA and protein expression of IL-4 and IL-5 via the downregulation of GATA-binding protein-3 (GATA-3) and c-musculoaponeurotic fibrosarcoma (Maf) but not T-box expressed in T cells (T-bet). Moreover, shikonin suppressed the phosphorylation of p38, inhibitor of κB (IκB) kinase (IKK)-β and IκB-α, and the subsequent IκB-α degradation induced by PMA+cAMP; however, the PMA+cAMP-induced phosphorylation of extracellular signal-related kinase (ERK), which resulted in minor inhibition and phosphorylation of c-Jun N-terminal kinase (JNK), seemed to be unaffected by shikonin treatment.
This study suggests that downregulation of GATA-3 and c-Maf via the suppression of p38, IKK-β and IκB-α phosphorylation might contribute to the inhibitory effect of shikonin on mitogen-induced IL-4 and IL-5 production in EL-4T cells. Furthermore, shikonin is a potential drug for treating allergic diseases.
Life sciences 09/2011; 89(11-12):364-70. · 2.56 Impact Factor
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ABSTRACT: Shikonin exhibits a wide range of anti-inflammatory actions. Here, we assessed its effects on maturation of murine bone marrow-derived dendritic cells (BM-DCs) and on allergic reactions in a murine model of asthma.
Cultured murine BM-DCs were used to investigate the effects of shikonin on expression of cell surface markers and their stimulation of T-cell proliferation and cytokine production. The therapeutic potential of shikonin was evaluated in a model of allergic airway disease.
Shikonin dose-dependently inhibited expression of major histocompatibility complex class II, CD80, CD86, CCR7 and OX40L on BM-DCs, induced by a mixture of ovalbumin (OVA; 100µg·mL(-1) ) and thymic stromal lymphopoietin (TSLP; 20ng·mL(-1) ). Shikonin-treated BM-DCs were poor stimulators of CD4(+) T lymphocyte and induced lower levels of interleukin (IL)-4, IL-5, IL-13 and tumour necrosis factor (TNF)-α release by responding T-cells. After intratracheal instillation of shikonin in OVA-immunized mice, OVA challenge induced lower IL-4, IL-5, IL-13, TNF-α and eotaxin release in bronchial alveolar lavage fluid, lower IL-4 and IL-5 production in lung cells and mediastinal lymph node cells and attenuated OVA-induced lung eosinophilia and airway hyperresponsiveness.
Shikonin effectively suppressed OVA + TSLP-induced BM-DC maturation in vitro and inhibited allergic inflammation and airway hyperresponsiveness in a murine model of asthma, showing good potential as a treatment for allergic asthma. Also, our model provides a novel platform for screening drugs for allergic diseases.
British Journal of Pharmacology 12/2010; 161(7):1496-511. · 4.41 Impact Factor
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ABSTRACT: New blood vessel formation is necessary for the repair of ischemia-damaged tissues. Endothelial cells produce exogenous and endogenous angiogenic factors in the mediation of angiogenesis and neovasculogenesis during neovascularization. Exposure to environmental pollutants may alter proangiogenic capacity or desensitize the responses of endothelial cells to stimulation by basic fibroblast growth factor and vascular endothelial growth factor. Human umbilical vein endothelial cells (HUVECs) were pretreated with benzo[a]pyrene (B[a]P), the major carcinogenic constituent found in tobacco smoke, for 24 h. Neovasculogenesis, migration, and proliferation were evaluated in solvent-treated and B[a]P-treated HUVECs. Endothelial capillary-like tube formation, cell migration, mitogen-activated protein kinase (MAPK) phosphorylation, and integrin expression were reduced in B[a]P-treated HUVECs with angiogenic factor stimulation, in comparison to solvent-treated HUVECs, although cell proliferation and Akt activation remained unaffected. Inhibition of B[a]P-mediated MAPK and neovasculogenesis was significantly rescued by pretreatment with α-naphthoflavone, an aryl hydrocarbon receptor (AhR) antagonist. The B[a]P-mediated inhibition of neovasculogenesis was also rescued in AhR-silenced HUVECs, suggesting the requirement for AhR in B[a]P-associated effects. B[a]P also inhibited angiogenesis in a chorioallantoic membrane assay. We conclude that B[a]P is a potent inhibitor of angiogenesis, and its effects are mediated via AhR-dependent phenotypic changes in B[a]P-treated HUVECs. These findings contribute to an understanding of the involvement of AhR agonists in vasculotoxicity.
Toxicological Sciences 09/2010; 118(2):544-53. · 4.65 Impact Factor
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ABSTRACT: Oxysterols, the major components of oxidized low-density lipoproteins (ox-LDLs), are present in atherosclerotic plaque and are suggested to play an active role in plaque development. The formation of an atherosclerotic lesion occurs through activation of cellular events that include vascular smooth muscle cell (SMC) migration and proliferation. Therefore, we investigated the roles of two common oxysterols, 7-ketocholesterol (7-keto) and cholesterol-5alpha,6alpha-epoxide (alpha-epoxide) on SMCs. Our results showed that 7-keto and alpha-epoxide promoted SMC migration by a chemotactic assay, and induced mitogenic effects by MTT assay and BrdU assay. Specific inhibitors confirmed that MMPs, EGFR and PI3K are involved in oxysterol-induced SMC migration, while EGFR, ERK, Akt, and sphingomyelin/ceramide pathways might play a role in SMC proliferation. More, the co-immunoprecipitation study indicated that 7-keto and alpha-epoxide caused EGFR phosphorylation and there was an interaction between EGFR and PI3K. At protein expression level, Akt and ERK were activated, at messenger RNA level, MMP-2/9 mRNA was transcribed, at enzyme activity level, the MMP-2/9 enzyme activity were increased in SMCs treated with 7-keto and alpha-epoxide according to Western bolt, RT-PCR and a fluorogenic substrate. Taken together, we concluded that 7-keto and alpha-epoxide may be an atherogenic factor by stimulating SMC migration and proliferation.
Toxicology Letters 05/2010; 197(2):88-96. · 3.23 Impact Factor
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ABSTRACT: Aristolochic acids (AAs) are a mixture of structural-related compounds, in which aristolochic acid I (AA I) and aristolochic acid II (AA II) are reported to be correlated with Aristolochic acid nephropathy (AAN). In this work, a rapid and sensitive ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to determine AA I and AA II in herbal products and biological fluids. By using gradient elution with a mobile phase composed of a mixture of 10mM ammonium formate buffer (pH 3.0) and acetonitrile, AAs could be determined within 10 min. Under optimum UHPLC-MS/MS conditions, the limit of detections was 0.14 and 0.26 ng mL(-1) for AA I and AA II, respectively. Run-to-run repeatability and intermediate precision of peak area for AA I and AA II were less than 5.74% relative standard deviation (RSD). Accuracy was tested by spiking 10, 100 and 1000 ng mL(-1) in rat serum and the recoveries were within 76.5-92.9%. Matrix effects were within 78.8-127.7%. The developed method was successfully applied to determine AA I and AA II in several herbal products and to investigate their pharmacokinetic behavior in female Wister rats. The result shows that the developed UHPLC-MS/MS method is efficient, sensitive, and accurate for the determination of AA I and AA II in herbal products and biological samples.
Talanta 03/2010; 80(5):1672-80. · 3.79 Impact Factor
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ABSTRACT: Overuse and abuse of antibiotics can increase the risk of cancer. Chloramphenicol can inhibit both bacterial and mitochondrial protein synthesis, causing mitochondrial stress and decreased ATP biosynthesis. Chloramphenicol can accelerate cancer progression; however, the underlying mechanisms of chloramphenicol in carcinogenesis and cancer progression are still unclear. We found that chloramphenicol can induce matrix metalloproteinase (MMP)-13 expression and increase MMP-13 protein in conditioned medium, resulting in an increase in cancer cell invasion. Chloramphenicol also activated c-Jun N-terminal kinases (JNK) and phosphatidylinositol 3-kinase (PI-3K)/Akt signaling, leading to c-Jun protein phosphorylation. The activated c-Jun protein has been proven to activate binding to the MMP-13 promoter and also upregulate the amount of MMP-13. Both the SP 600125 (JNK inhibitor) and LY 294002 (PI-3K/Akt inhibitor) can inhibit chloramphenicol-induced c-Jun phosphorylation, MMP-13 expression, and cell invasion. Overexpression of the dominant-negative JNK and PI-3K p85 subunit also negate chloramphenicol-induced responses. Other antibiotics that cause mitochondrial stress and a decrease in ATP biosynthesis also induce MMP-13 expression. These findings suggest that chloramphenicol-induced PI-3K/Akt, JNK phosphorylation, and activator protein 1 activation might function as a novel mitochondrial stress signal that result in an increase of MMP-13 expression and MMP-13-associated cancer cell invasion. The findings of this study confirms that chloramphenicol, and other 70S ribosomal inhibitors, should be administered with caution, especially during cancer therapy.
Toxicological Sciences 03/2010; 116(1):140-50. · 4.65 Impact Factor
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ABSTRACT: p53, can regulate cell apoptosis in both transcription-dependent and -independent manners. The transcription-independent pathway was demonstrated by the translocation of p53 to mitochondria. Our study showed that p53 mitochondrial translocation was found in mitomycin C (MMC)-treated HepG2. The p53 C-terminal domain is clustered with potential nuclear leading sequences and showed strong electrostatic ion-ion interactions with cardiolipin, phosphatidylglycerol and phosphatidic acid in vitro. Disruption of cardiolipin biosynthesis by phosphatidylglycero-phosphate synthase (PGS) or CDP-diacylglycerol synthase 2 (CDS-2) short hairpin RNA (shRNA) transfection eliminated the MMC-induced translocation of mitochondrial p53. The elimination of mitochondrial p53 translocation also reduced Bcl-xL and Bcl-2 mitochondrial distribution. In HEK 293T models with saturated p53 expression, the mitochondrial partition of p53, Bcl-xL, and Bcl-2 obviously decreased in their PGS shRNA- or CDS-2 shRNA-expressing stable clones. In p53-null H1299 models, both the mitochondrial partitions of Bcl-xL and Bcl-2 were strongly reduced in relation to the HEK 293T models. The Bcl-xL mitochondrial partition was elevated in H1299 models expressing pCEP4-p53wt suggesting the direct carrier role of p53 in transporting Bcl-xL to the mitochondria. We also found that the cytosolic pool of Bcl-xL and Bcl-2 remained unaffected in the low-dose MMC treatment but decreased in the high-dose MMC treatment. The cytosolic pool of Bcl-2 and Bcl-xL directly regulated their amounts in p53-dependent mitochondrial distribution. In the low-dose MMC treatment, the increased mitochondrial p53, Bcl-xL, and Bcl-2 could attenuate apoptosis. However, in the high-dose MMC treatment, only the p53 translocated to the mitochondria and resulted in apoptosis progression. On the basis of this study, we thought mitochondrial p53 might regulate apoptosis in a biphasic manner.
Neoplasia (New York, N.Y.) 02/2010; 12(2):150-60. · 5.48 Impact Factor
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ABSTRACT: Oxidized cholesterols belong to a subgroup of oxLDLs which play major roles in atherosclerosis. In order to investigate the contribution of oxysterols from oxLDLs in atherosclerosis, cholesterol-3-beta, 5-alpha, 6-beta-triol (alpha-Triol) was studied in human umbilical vein endothelial cells. We found that alpha-Triol concentration- and time-dependently enhanced COX-2 protein expression and mRNA production followed by PGE(2) generation in human umbilical vein endothelial cells. In addition, alpha-Triol upregulated peNOS(1177) protein phosphorylation and concentration-dependently increased nitric oxide production. eNOS(1177) phosphorylation was abrogated by the PI3K inhibitor, LY294002. In studying the mechanisms involved in alpha-Triol-induced COX-2/PGE(2) production, inhibitors of NOS, PI3K, p38, and NF-kappaB, effectively attenuated COX-2 protein induction and mRNA expression, suggesting that the PI(3)K-Akt-eNOS pathway, p38MAPK, and NF-kappaB are involved in alpha-Triol-induced COX-2 expression, and following increases in p38 and Akt phosphorylation, the concentration-dependent inhibition of COX-2 protein expression by L-NAME further suggested their involvement at the translation level. We concluded that alpha-Triol increases COX-2 mRNA and protein expression via coordination with the PI(3)K-Akt-eNOS pathway and NF-kappaB. Moreover, COX-2 gene expression might be regulated by activated p38 MAPK in another unknown regulation pathway. Our findings also suggested that alpha-Triol might contribute to the effect of induced atherosclerosis in humans through COX-2 production in endothelial cells.
Toxicology Letters 08/2009; 190(2):172-8. · 3.23 Impact Factor
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ABSTRACT: The genotoxic potential of podophyllin (PD) was investigated in this study. PD increased bacterial revertants and abnormal chromosomal structures in a concentration-dependent manner, both with and without metabolic activating enzymes, and increased the incidence of micronuclei in imprinted control region mouse reticulocytes. Results from three studied constituents of PD, such as podophyllotoxin, kampferol, and quercetin, suggested that the mutagenic effect of PD was not due to the presence of podophyllotoxin, kampferol, and quercetin and might be related to other components and the formation of reactive oxygen species. The detailed mutagenic mechanisms need further investigation, and the medicinal use of PD needs to be cautioned against.
Drug and Chemical Toxicology 02/2009; 32(1):68-76. · 1.08 Impact Factor
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ABSTRACT: 2-Chloroethanol (2-CE) is a commonly used solvent in industry; unfortunately, severe hypotension is one of main toxic signs during intoxication. Calcium ion modulation is considered to be an important role of vasorelax-ation. The aim of this study is to evaluate either 2-CE or its main metabolite, chloroacetaldehyde (CAA), possible cause of hypotension, by using isolated rat aortic rings. Results revealed that 2-CE caused a weakly relaxation in the phenylephrine (PE) pre-induced endothelium-intact aortic rings. However, its metabolite, CAA induced vasore-laxation and showed dose dependency in endothelium-intact and -denuded aortic rings. The half inhibitory con-centration (IC 50) of 2-CE exceeded 50 mM; meanwhile, the IC 50 values of CAA in the endothelium-intact and -de-nuded aortic rings were 3.3 and 2.7 mM, respectively. The CAA-induced relaxation could be significantly attenu-ated by adding calcium (CaCl 2) and various Ca 2+ channel blockers, dantrolene, nifedipine, and NiCl 2 . Nifedipine presents the most strong inhibition effect among the calcium blockers. In conclusion, it is suggested that the hy-potension effect of 2-CE intoxicated cases may be mainly mediated by its metabolite CAA, and calcium channels are partially involved inducing the vasorelaxation.
Journal of Health Science. 01/2009; 55:525-531.
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ABSTRACT: Shikonin/alkannin (SA) derivatives, analogs of naphthoquinone pigments, are the major components of root extracts of the Chinese medicinal herb (Lithospermum erythrorhizon; LE) and widely distributed in several folk medicines. In the present study, the effect and the underline molecular mechanism of shikonin derivatives isolated from root extracts of Lithospermum euchroma on lipopolysaccharide (LPS)-induced inflammatory response were investigated.
Effects of five SA derivatives, including SA, acetylshikonin, beta,beta-dimethylacrylshikonin, 5,8-dihydroxy-1.4-naphthoquinone, and 1,4-naphthoquinone on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in mouse macrophage RAW264.7 cells were examined.
Data suggested that SA derivatives inhibited LPS-induced NO and PGE(2) production, and iNOS protein expression. RT-PCR analysis showed that SA derivatives diminished LPS-induced iNOS mRNA expression. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in LPS-stimulated RAW 264.7 cells was concentration-dependently suppressed by SA derivatives. SA inhibited NF-kappaB activation by prevention of the degradation of inhibitory factor-kappaB and p65 level in nuclear fractions induced by LPS.
Taken together, these results suggest that the anti-inflammatory properties of SA derivatives might result from inhibition of iNOS protein expression through the downregulation of NF-kappaB activation via suppression of phosphorylation of ERK, in LPS-stimulated RAW 264.7 cells.
Journal of Ethnopharmacology 10/2008; 120(2):264-71. · 3.01 Impact Factor
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ABSTRACT: Evidence indicates that environment pollutants from fossil fuel combustion compromise the immune system by enhancing allergic reactions and damaging the respiratory tract. This study was performed to investigate the effects of motorcycle exhaust particles (MEP), a major air pollutant especially in the urban areas of Taiwan, on allergen-induced airway inflammatory reactions in lab animals. BALB/c mice were intratracheally instilled with ovalbumin (OVA), MEP, or phosphate-buffered saline, 3 times every 2 wk. Airway hyperresponsiveness was measured in unrestrained mice by barometric plethsmography. Bronchoalveolar lavage fluid (BALF) and serum from treated animals were collected for cytokine and antibody determination by enzyme-linked immunosorbent assay (ELISA). Lung tissue stained with hematoxylin/eosin was examined. Data showed that MEP augmented OVA-induced airway inflammation; characterized by infiltration of eosinophils and neutrophils in BALF and lung tissue inflammation. The combination of OVA and MEP markedly increased interleukin-4 (IL-4), interleukin-5 (IL-5), and tumor necrosis factor-alpha (TNF-alpha) protein levels in BALF. In addition, MEP also augmented OVA-induced rise in OVA-specific immunoglobulin (Ig) G1 and IgE and airway hyperresponsiveness. Pretreated lavage cells with mitogen-activated protein kinase (MAPK) inhibitors showed that TNF-alpha release was significantly inhibited. This study found that MEP augmented antigen-induced allergic airway inflammation and airway hyperresponsiveness through a Th2-dominant pathway.
Journal of Toxicology and Environmental Health Part A 02/2008; 71(6):405-12. · 1.83 Impact Factor
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ABSTRACT: Various formulations of agricultural chemicals, including solutions, wettable powders, and emulsifiable concentrates, contain adjuvants of solvents and surfactants in addition to active ingredients. Among these formulations, herbicides are among the most commonly used pesticides globally. Some pesticides have been demonstrated to cause severe circulatory failure in poisoned humans. To clarify the potential risk of herbicides and their adjuvants influence on the cardiovascular system, four technical grade (TG) herbicides and their end products (EP), including paraquat, glyphosate, glufosinate, and atrazine, as well as their formulated adjuvants isopropylamine (IPA), polyoxyethylene alkylether sulfate (AES), ethyl acetate (EA), xylene, petrolium-170 (P-170), and solvesso-100 (S-100), were assessed to determine their effects on isolated rat aorta and heart. The results revealed that the vasorelaxation effects of the herbicide EPs exceeded those of TGs, and atrazine produced more significant vasorelaxation in rat aortas than the other herbicides tested. The formulated adjuvants of IPA did not affect the aorta; however, AES, EA, xylene, P-170 and S-100 caused significant vasorelaxation. Herbicide EPs-induced vasorelaxation was generally endothelium-dependent. Furthermore, the TG and EP of paraquat, and the TG of glufosinate and glyphosate were found to have no effect on the isolated heart. However, the normal twitch tensions of the isolated heart were significantly inhibited by EPs of glyphosate and glufosinate, and by TG and EP of atrazine. Although, the adjuvants of IPA appeared unaffected, however, AES, EA, xylene, P-170 and S-100 caused complete inhibition and contraction on the isolated hearts. These results indicated that the adjuvants of herbicides might enhance hypotension and contributed to cardiovascular disorders during intoxication.
Toxicology in Vitro 07/2007; 21(4):595-603. · 2.78 Impact Factor
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ABSTRACT: The effects of aporphines and secoaporphines on glucose uptake by isolated intestinal brush-border membrane vesicles (BBMV) or basolateral membrane vesicles (BLMV) and glucose absorption during in situ intestinal perfusion were studied. Of the tested compounds, N-allylsecoboldine was the most potent glucose uptake inhibitor, with IC50 values of 159 microM and 121 microM, respectively, for uptake by BBMV and BLMV. While thaliporphine competitively inhibited glucose uptake by both membrane preparations, inhibition by N-allylsecoboldine was competitive using BBMV and noncompetitive using BLMV. In addition, N-allylsecoboldine significantly reduced both glucose absorption during in situ intestinal perfusion and blood glucose levels in the oral glucose tolerance test. The results demonstrate that levels of both aporphines and secoaporphines achievable by oral administration have an inhibitory effect on intestinal glucose uptake and suggest that the hypoglycemic effects of these compounds merit attention.
Life Sciences 07/2006; 79(2):144-53. · 2.53 Impact Factor
