Inhibitory effects of casticin on migration of eosinophil and expression of chemokines and adhesion molecules in A549 lung epithelial cells via NF-κB inactivation

Ethnopharmacological relevance

The fruits of Vitex rotundifolia L. have long been used for the treatment of inflammation of the respiratory tract in East Asia.

Aim

To determine if casticin, one of the constituents of Vitex rotundifolia L., has anti-allergic and anti-inflammatory effects in asthma.

Materials and methods

The in vitro anti-inflammatory activity of casticin was studied in A549 human type II-like epithelial lung cells using an eotaxin inhibition assay. Additionally, its effects on eotaxin, regulated on activation normal T cell expressed and secreted (RANTES), vascular cell adhesion molecule (VCAM)-1, and inter-cellular adhesion molecule (ICAM)-1 expression were investigated by real time-polymerase chain reaction (real time-PCR). The inhibition of nuclear factor κB (NF-κB) activity in the presence of casticin was determined by analyzing confocal microscopy images of fluorescence immunocytochemical analysis while the suppression of inhibitory κB (IκB)-α phosphorylation was studied using Western blot analysis. Finally, the inhibitory effect of casticin on eosinophil migration toward prestimulated A549 cell media was measured using the human eosinophilic leukemia cell line.

Results and discussion

Casticin significantly suppressed eotaxin production in cytokine activated A549 lung epithelial cells. Casticin also suppressed the mRNA expression levels of eotaxin, RANTES, VCAM-1, and ICAM-1, which subsequently contributed to the inhibition of eosinophil migration. Furthermore, casticin inhibited IκB-α phosphorylation and nuclear translocation of p65 in A549 cells.

Conclusion

Casiticin inhibited the eosinophil migration and activity of chemokines and adhesion molecules involved in the inflammatory process of asthma by suppressing the NF-κB pathway. These results suggest that casticin has the potential for use in the treatment of allergic asthma.     

蛇葡萄素对免疫细胞的趋化作用

目的:观察蛇葡萄素在一定浓度下对中性粒细胞和单核细胞的趋化作用。方法:分别与趋化因子IL-8、MCP-1作对照,在琼脂糖中进行化学增活和化学趋化实验。结果:蛇葡萄素在25.6μg/m、l51.2μg/m l浓度下,具有显著诱导中性粒细胞和单核细胞产生趋化的作用。浓度为25.6μg/m l的蛇葡萄素与150 ng/m l IL-8或50 ng/m l的MCP-1的增活效应无显著差异(P>0.05)。浓度为12.8μg/m l的蛇葡萄素的趋化效应强于150 ng/m l的IL-8或100 ng/m l的MCP-1(P<0.05)。蛇葡萄素与IL-8及MCP-1对中性粒细胞和单核细胞的趋化作用均存在协同作用(P<0.05)。结论:蛇葡萄素对中性粒细胞和单核细胞均有化学增活和化学趋化效应,且在对免疫细胞的化学增活方面,蛇葡萄素与IL-8及MCP-1均存在协同作用。     

Petasites extract Ze 339 (PET) inhibits allergen‐induced Th2 responses,airway inflammation and airway hyperreactivity in mice

Background: The herbal Petasites hybridus (butterbur) extract (Ze 339, PET) is known to have leukotriene inhibiting properties, and therefore might inhibit allergic diseases. Methods: The effect of PET was investigated in ovalbumin (OVA) immunized BALB/c mice given intranasally together with antigen challenge in the murine model of allergic airway disease (asthma) with the analysis of the inflammatory and immune parameters in the lung. Results: PET given with the antigen challenge inhibited the allergic response. PET inhibited airway hyperresponsiveness (AHR) and eosinophil recruitment into the bronchoalveolar lavage (BAL) fluid upon allergen challenge, but had no effect in the saline control mice. Eosinophil recruitment was further assessed in the lung by eosinophil peroxidase (EPO) activity at a concentration of 100 µg PET. Microscopic investigations revealed less inflammation, eosinophil recruitment and mucus hyperproduction in the lung with 100 µg PET. Diminution of AHR and inflammation was associated with reduced IL‐4, IL‐5 and RANTES production in the BAL fluid with 30 µg PET, while OVA specific IgE and eotaxin serum levels remained unchanged. Conclusion: PET, which has been reported to inhibit leukotriene activity, reduced allergic airway inflammation and AHR by inhibiting the production of the Th2 cytokines IL‐4 and IL‐5, and RANTES. Copyright © 2009 John Wiley & Sons, Ltd.     

中药复方“别敏”治疗呼吸道变应性疾病作用机制的实验研究

目的：探讨中药复方“别敏”治疗呼吸道变应性疾病的作用机制。方法：将豚鼠分为5组：正常组,模型组,“别敏”高、中、低剂量组。于实验第1天用10%卵蛋白腹腔注射致敏豚鼠,于第15天用5%卵蛋白雾化吸入诱发哮喘发作,观察各组豚鼠引喘潜伏期,外周血、支气管肺泡灌洗液（BALF）中嗜酸性粒细胞和IL-5水平变化,脾淋巴细胞增殖反应及血清皮质酮水平变化。结果：模型组豚鼠外周血和BALF中嗜酸性粒细胞、血清IL-5以及血清皮质酮水平明显高于正常组（P〈0.05）。中药复方“别敏”能够明显延长致敏豚鼠引喘潜伏期（P〈0.05）,抑制外周血及BALF中嗜酸性粒细胞水平升高（P〈0.05）,抑制脾淋巴细胞的增殖反应特别是高剂量组（P〈0.05）,降低血清IL-5水平尤其是高、中剂量组（P〈0.05）。结论：中药复方“别敏”能有效防治呼吸道变应性疾病,其机制可能通过调节淋巴细胞功能,降低IL-5水平,降低气道和外周血嗜酸性粒细胞的数量而起作用。     

疏风止咳汤治疗咳嗽性哮喘的实验研究

目的:探讨疏风止咳汤治疗咳嗽性哮喘的作用机制。方法:参照 Huston 方法建立豚鼠哮喘模型,在成功造模的基础上,选择与气道变应性炎症有密切相关并具有抗气道炎症评价意义的多项指标,实验中检测了气道反应性,支气管肺泡灌洗液(BALF)中细胞总数、嗜酸粒细胞(EOS)绝对值计数、嗜酸性粒细胞阳离子蛋白(ECP)、白介素-4(IL-4)、白介素-5(IL-5)、干扰素-γ(IFN-γ)等的含量变化。结果:(1)疏风止咳汤能够阻断气道炎症的发生、发展过程而降低哮喘豚鼠气道高反应性。(2)疏风止咳汤能够促进 Th_1细胞分泌IFN-γ,抑制 Th_2细胞分泌 IL-4、IL-5等细胞因子,调节 Th_1/Th_2细胞之间的平衡。(3)疏风止咳汤能够降低BALF 中 IL-5水平,抑制 EOS 的分化和增殖及向气道的趋化及浸润;抑制嗜酸粒细胞的激活和减少 ECP 等炎性介质的释放,从而减轻气道变应性炎症。结论:疏风止咳汤治疗咳嗽性哮喘是通过多种途径、多个环节作用于影响疾病的多个靶点,发挥联合协同作用而完成的。     

Astragalus Membranaceus prevents airway hyperreactivity in mice related to Th2 response inhibition

AIM OF THE STUDY: Asthma is recognized as a common pulmonary disease throughout the world. To date, there has been a growing interest in herbal products in Traditional Chinese Medicine, which is considered to be effective to treat asthma. A Chinese herb Astragalus Membranaceus (AM) was found useful in treating allergic diseases. The purpose of this study is to determine whether this herbal injection could suppress allergic-induced AHR and mucus hypersecretion in allergic mice. MATERIALS AND METHODS: A mouse model of chronic asthma was used to investigate AM injection on the airway lesions in compared with glucocorticoids. The study was conducted on mice sensitized and challenged with ovalbumin and the whole body plethsmography was performed to assess AHR. The bronchoalveolar lavage (BAL), histopathology were examined. RESULTS: We found 28-day AM administration significantly decreased inflammatory infiltration and mucus secretion in the lung tissues of allergic mice. 28-day AM administration enhanced Ova-induced decreased IFN-gamma, and the Ova-induced elevations of IL-5 and IL-13 in BALF were prevented by 28-day injection. We also showed 28-day AM injection markedly suppressed increased AHR in allergic mice. CONCLUSIONS: Our results indicate Astragalus Membranaceus has a potential role in treating allergic asthma.     

In vitro effect of Derris scandens on normal lymphocyte proliferation and its activities on natural killer cells in normals and HIV-1 infected patients

We investigated the effect of Derris scandens hydroalcoholic extract on lymphocyte proliferation, natural killer (NK) cell activity and secretion of IL-2 and IL-4. Lymphocyte proliferative response of normal individuals was significantly increased at concentrations of 10 ng/ml, 100 ng/ml, 1 microg/ml and 5 microg/ml, whereas the response was significantly decreased at 100 microg/ml. D. scandens at the concentrations of 10 ng/ml, 100 ng/ml, 1 microg/ml and 10 microg/ml significantly enhanced the function of NK cells of normal individuals. The NK cell activity of HIV-infected individuals was significantly increased at a concentration of 10 microg/ml. Furthermore, the extract was shown to induce the IL-2 secretion from normal peripheral blood mononuclear cells (PBMC), whereas the IL-4 was not induced in the presence of the D. scandens extract. Our data suggested that the hydroalcoholic extract of D. scandens possesses in vitro immunostimulating activity on human immunocompetent and immunocompromised PBMC.     

Suppression of interleukin (IL)-8 and human beta defensin-2 secretion in LPS-and/or IL-1β-stimulated airway epithelial A549 cells by a herbal formulation against respiratory infections (BNO 1030)

Aim of the study

A special ethanolic-aqueous extract from seven traditional medicinal plants (BNO 1030) has been used for several decades to treat recurrent infections of the respiratory tract. Considering the potential role of interleukin-8 (IL-8) and human beta defensin-2 (hBD-2) in inflammation, we investigated the effect of BNO 1030 on lipopolysaccharide (LPS) from Pseudomonas aeruginosa or IL-1β-induced inflammatory mediators in A549 human type II alveolar epithelial cells.

Materials and methods

A549 cells were stimulated with LPS (100 μg/ml) or IL-1β (50 ng/ml) in the presence of the preparation and the secretion of IL-8 and hBD-2 were measured after 18 h and 24 h in cell free supernatants using enzyme-linked immunosorbent assays (ELISA). Cell viability and cell growth was investigated by propidium iodide uptake and WST-1 assay, respectively.

Results

BNO 1030 inhibited the secretion of IL-8 and hBD-2 at non-cytotoxic concentrations (0.1-100 μg/ml; cell growth inhibitory concentration, 50% (IC₅₀) = 678 ± 87.6 μg/ml). Stimulation by IL-1β led to a 7-fold activation of IL-8 secretion, which was reduced by 37.7 ± 4.1% (p < 0.05) after incubation with 100 μg/ml BNO 1030. Inducible hBD-2 was suppressed by 91.8 ± 15.6% (p < 0.01) at the same concentration of BNO 1030 (IC₅₀ = 0.7 ± 0.1 μg/ml). The 2-fold increase of IL-8 secretion by LPS-stimulated cells was completely abolished at concentration of 50 μg/ml BNO 1030 (IC₅₀ = 5.7 ± 3.6 μg/ml).

Conclusion

BNO 1030 suppressed the secretion of IL-8 and hBD-2 in cultured epithelial A549 cells. These results support its use as a phytotherapeutic product prepared from traditional remedies in inflammatory diseases, especially those affecting the respiratory tract.     

Dual regulatory effect of plant extracts of Forsythia suspense on RANTES and MCP-1 secretion in influenza A virus-infected human bronchial epithelial cells

In this study, we investigated the effects of 95% ethanol (FS-t1), 50% ethanol (FS-t2) and water (FS-w) extracts of Forsythia suspense Vahl (Oleaceae) on the production of regulated on activation, normal T cell expressed and secreted (RANTES) and macrophage chemotactic protein-1 (MCP-1) by influenza A virus (H1N1)-infected human bronchial epithelial cell line A549. Virus infection evoked a markedly enhanced production of RANTES from basal 16 +/- 4 to 1307 +/- 294 pg/ml after 72 h inoculation. At the non-cytotoxic doses (20, 100 and 200 microg/ml), FS-t1, FS-t2 and FS-w exhibited a consistent inhibitory effect on virus-stimulated RANTES secretion in a dose-dependent manner wilh IC(50) of 42 +/- 6, 117 +/- 15 and 232 +/- 28 microg/ml, respectively. H1N1 also stimulated MCP-1 production in A549 cells, however to a less degree, from basal 133 +/- 21 to 391 +/- 98 pg/ml after 72 h viral inoculation. The effects of three extracts on MCP-1 secretion were more complex. FS-t1 displayed both positive and negative effect on virus-stimulated MCP-1 production dependent on the concentrations used. On the other hand, FS-t2 increased virus-induced MCP-1 secretion by 1.4-3.3 times while the third fraction FO-w increased by 2.6-3.7 times. These results suggested that Forsythia suspense consisted of both negative and positive regulatory components on RANTES and MCP-1 secretion in H1N1-infected A549 cells, respectively.     

Matrine attenuates allergic airway inflammation and eosinophil infiltration by suppressing eotaxin and Th2 cytokine production in asthmatic mice

Ethnopharmacological relevance

Matrine has been isolated from Sophora flavescens, and found to show anti-inflammatory effects in macrophages and anti-cachectic effects in hepatomas. The present study investigated whether matrine suppressed eosinophil infiltration and airway hyperresponsiveness (AHR) in mice, and decreased the inflammatory response of tracheal epithelial cells.

Materials and methods

BALB/c mice were sensitized and challenged with ovalbumin to induce allergic asthma in mice. These asthmatic mice were given various doses of matrine by intraperitoneal injection. Additionally, activated human tracheal epithelial cells (BEAS-2B cells) were treated with matrine, and evaluated for levels of proinflammatory cytokines and chemokines.

Results

We found that matrine significantly decreased AHR, and suppressed goblet cell hyperplasia, eosinophil infiltration, and inflammatory response in the lung tissue of asthmatic mice. Matrine also reduced the levels of Th2 cytokines and chemokines in bronchoalveolar lavage fluid, and suppressed OVA–IgE production in serum. Furthermore, matrine treatment of activated BEAS-2B cells decreased production of proinflammatory cytokines and eotaxins, as well as suppressed ICAM-1 expression and thus adhesion of eosinophils to inflammatory BEAS-2B cells in vitro.

Conclusions

Our findings suggest that matrine can improve allergic asthma in mice, and therefore has potential therapeutic potential in humans.     

Inhibition of early and late phase allergic reactions by Euphorbia hirta L

A 95% ethanol extract from whole aerial parts of Euphorbia hirta (EH A001) showed antihistaminic, antiinflammatory and immunosuppressive properties in various animal models. EH A001 inhibited rat peritoneal mast cell degranulation triggered by compound 48/80. It significantly inhibited dextran-induced rat paw edema. EH A001 prevented eosinophil accumulation and eosinophil peroxidase activity and reduced the protein content in bronchoalveolar lavage fluid (BALF) in a 'mild' model of asthma. Moreover, the CD4/CD8 ratio in peripheral blood was suppressed. EH A001 attenuated the release of interleukin-4 (IL-4) and augmented interferon-gamma (IFN-gamma) in ovalbumin-sensitized mouse splenocytes. The results were compared with the effects of known compounds, ketotifen, cetirizine and cyclophosphamide. These findings demonstrated that Euphorbia hirta possessed significant activity to prevent early and late phase allergic reactions.     

Herbal formula FBD extracts prevented brain injury and inflammation induced by cerebral ischemia-reperfusion

The aim of this work was to verify neuroprotective and anti-inflammatory properties of FBD, a herbal formula composed of Poria cocos, Atractylodes macrocephala and Angelica sinensis, in ICR mice subjected to repetitive 10 min of common carotid arteries occlusion followed 24 h reperfusion. Intragastrical pretreatment with supercritical carbon dioxide extract (FBD-CO(2), 37.5 mg/kg) twice daily for 3.5 d, significantly reduced Evans Blue influx, neuron specific enolase (NSE) efflux, brain infarction (all p<0.05), also inhibited polymorphonuclear leukocytes (PMNs) infiltration (p<0.001), suppressed secretion of tumor necrosis factor (TNF)-alpha in blood (p<0.05), interleukin (IL)-1beta and IL-8 in brain (both p<0.01), and down-regulated cerebral expression of phosphor-IkappaB-alpha and phosphor-nuclear factor kappa-B (NF-kappaB), whether coupled with aqueous extract (FBD-H(2)O, 150 mg/kg) or not. Moreover, FBD-CO(2) (0.1-10 microg/ml) inhibited 0.1 microM phorbol myristate acetate-evoked oxidative burst in rat PMNs, 20 ng/ml TNF-alpha-triggered PMNs adhesion to ECV304 endothelial cells, and PMNs neurotoxicity to PC12 neuron-like cells as well as NSE release (IC(50) 1.30, 0.98, 0.24 and 0.82 microg/ml, respectively). Our study demonstrated that FBD-CO(2) prevented brain ischemia/reperfusion injury, at least in part, by limiting PMNs infiltration and neurotoxicity mediated by TNF-alpha, IL-1beta and IL-8, via inhibition on NF-kappaB activation.     

In vitro anti-allergic activities of a newly concocted traditional Chinese medicine--the wheeze-relief formula

Asthma is one of the most common chronic diseases worldwide. Western medications such as glucocorticoids are effective therapeutic agents but may be associated with side effects. Traditional Chinese medicine (TCM) has been used for treating allergic diseases with observable clinical benefits. The present study investigated whether a novel TCM concoction, the wheeze-relief formula (WRF), possesses in vitro anti-allergic activities. We measured the effects of WRF on the release of eosinophil cationic protein (ECP) by human eosinophils using fluorescence enzyme immunoassay, expression of chemokine receptor CCR3 and adhesion molecule CD49d on eosinophils using immunophenotyping, cytokine induction from peripheral blood mononuclear cells (PBMC) using cytometric bead array (CBA), and the gene expression of cytokines and cytokine receptors using cDNA expression array. Results demonstrated that WRF dose-dependently and significantly: (1) suppressed ECP release from eosinophils activated with granulocyte macrophage-colony stimulating factor (GM-CSF) and platelet activating factor (PAF); (2) inhibited the expression of CCR3 and CD49d on PAF-activated eosinophils; and (3) attenuated the production of tumor necrosis factor alpha and gene expression of IL-2 receptor chain alpha (CD25) on house dust mite (Der p 1) activated PBMC. The above results suggest a possible anti-allergic role of WRF and provide a biochemical basis for further clinical trial on human subjects.     

Regulatory effect of atopic allergic reaction by Carpopeltis affinis

Carpopeltis affinis Okamura (CA, Halymeniaceae) has long been used as therapeutics for various allergic diseases in Korea. The precise effects of CA in experimental models, however, have remained unknown. We studied the effects of a methanol extract of CA on atopic allergic reaction. Histamine content was measured by the o-phthalaldehyde spectrofluorometric procedure. Cytokines were measured by a modified enzyme-linked immunosorbent assay. Cytotoxicity was determined by the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. CA significantly inhibited the histamine release and beta-hexosaminidase release from rat peritoneal mast cells. CA also inhibited interleukin-8 and tumor necrosis factor-alpha secretion from the phorbol 12-myristate 13-acetate and A23187-induced HMC-1 cells (human mast cell line). 48 h exposure to CA (1.0, 10, and 100 microg/ml) had little effect on HMC-1 cell viability. Our results suggest that CA has an inhibitory effect on mast cell-dependent allergic reaction and thus may be useful in the treatment of atopic dermatitis.     

Effect of Kuwanon G Isolated from the Root Bark of Morus alba on Ovalbumin‐induced Allergic Response in a Mouse Model of Asthma

The root bark of Morus alba L. (Mori Cortex Radicis; MCR) is traditionally used in Korean medicine for upper respiratory diseases. In this study, we investigated the antiasthmatic effect of kuwanon G isolated from MCR on ovalbumin (OVA)‐induced allergic asthma in mice. Kuwanon G (1 and 10 mg/kg) was administered orally in mice once a day for 7 days during OVA airway challenge. We measured the levels of OVA‐specific IgE and Th2 cytokines (IL‐4, IL‐5, and IL‐13) in the sera or bronchoalveolar lavage (BAL) fluids and also counted the immune cells in BAL fluids. Histopathological changes in the lung tissues were analyzed. Kuwanon G significantly decreased the levels of OVA‐specific IgE and IL‐4, IL‐5, and IL‐13 in the sera and BAL fluids of asthma mice. Kuwanon G reduced the numbers of inflammatory cells in the BAL fluids of asthma mice. Furthermore, the pathological feature of lungs including infiltration of inflammatory cells, thickened epithelium of bronchioles, mucus, and collagen accumulation was inhibited by kuwanon G. These results indicate that kuwanon G prevents the pathological progression of allergic asthma through the inhibition of lung destruction by inflammation and immune stimulation. Copyright © 2014 John Wiley & Sons, Ltd.     

In vitro anti-inflammatory and anti-oxidative effects of Cinnamomum camphora extracts

Cinnamomum camphora Sieb (Lauraceae) has long been prescribed in traditional medicine for the treatment of inflammation-related diseases such as rheumatism, sprains, bronchitis and muscle pains. In this study, therefore, we aimed to investigate the inhibitory effects of Cinnamomum camphora on various inflammatory phenomena to explore its potential anti-inflammatory mechanisms under non-cytotoxic (less than 100 microg/ml) conditions. The total crude extract (100 microg/ml) prepared with 80% methanol (MeOH extract) and its fractions (100 microg/ml) obtained by solvent partition with hexane and ethyl acetate (EtOAc) significantly blocked the production of interleukin (IL)-1 beta, IL-6 and the tumor necrosis factor (TNF)-alpha from RAW264.7 cells stimulated by lipopolysaccharide (LPS) up to 20-70%. The hexane and EtOAc extracts (100 microg/ml) also inhibited nitric oxide (NO) production in LPS/interferon (IFN)-gamma-activated macrophages by 65%. The MeOH extract (100 microg/ml) as well as two fractions (100 microg/ml) prepared by solvent partition with n-butanol (BuOH) and EtOAc strongly suppressed the prostaglandin E(2) (PGE(2)) production in LPS/IFN-gamma-activated macrophages up to 70%. It is interesting to note that hexane, BuOH and EtOAc extracts (100 microg/ml) also inhibited the functional activation of beta1-integrins (CD29) assessed by U937 homotypic aggregation up to 70-80%. Furthermore, EtOAc and BuOH extracts displayed strong anti-oxidative activity with IC(50) values of 14 and 15 microM, respectively, when tested by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and xanthine oxide (XO) assays. Taken together, these data suggest that the anti-inflammatory actions of Cinnamomum camphora may be due to the modulation of cytokine, NO and PGE(2) production and oxidative stress, and of the subfractions tested, the EtOAc extract may be further studied to isolate the active anti-inflammatory principles.     

High eosinophil cationic protein level in asthmatic patients with "heat" Zheng

In traditional Chinese medicine (TCM), the imbalance of yin and yang is one of the basic pathogeneses of a disease. Preponderance of yang leads to "heat" manifestations including thirst, dryness of the throat, dark scanty urine and constipation. Treatment of asthma in TCM is based on the differentiation of "heat" Zheng according to the manifestations. Some of the patients with allergic asthma also present typical "heat" manifestations. To investigate the essence of "heat" manifestation in asthma, we measured the serum level of eosinophil cationic protein (ECP) in asthmatic patients. ECP usually represents the activation of eosinophils which are the main effectors in late allergic reactions. Our results demonstrated that asthmatic patients with "heat" manifestations had higher serum ECP levels, compared to those without "heat" manifestations (34.3 +/- 4 microg/l versus 15.3 +/- 3 microg/l). However, total immunoglobulin B (IgE), and the eosinophil count in peripheral blood did not show any difference between the "heat" and "non-heat" groups. Therefore, we conclude that ECP in asthmatic patients plays an important role in the development of "heat" manifestations as diagnosed by TCM.     

Inhibitory activity of Chrysanthemi sibirici herba extract on RBL-2H3 mast cells and compound 48/80-induced anaphylaxis

The effects of extracts from various oriental medicinal herbs on mast cell-mediated allergic reaction were investigated. Among them, Chrysanthemi sibirici herba ethanol extract exerted the potent inhibitory activity on antigen-induced degranulation in RBL-2H3 mast cells. Chrysanthemi sibirici herba dose-dependently inhibited DNP-BSA or compound 48/80-induced degranulation in RBL-2H3 mast cells, with IC(50) values of approximately 49 microg/ml and 76 microg/ml, respectively. This extract strongly suppressed compound 48/80-induced systemic anaphylaxis by 48.7% at a dose of 300 mg/kg in mice. Chrysanthemi sibirici herba also inhibited the expression of TNF-alpha and the activation of the MAP kinase, ERK1/2, which is critical for the production of inflammatory cytokines in mast cells, as indicated by the suppression of activating phosphorylation of ERK1/2. These results lead us to conclude that Chrysanthemi sibirici herba may be used clinically to treat various allergic diseases.     

Effects of cryptoporus polysaccharide on rat allergic rhinitis associated with inhibiting eotaxin mRNA expression

Aqueous extract from the fruiting body of Cryptoporus volvatus has been reported to present anti-tumor, anti-allergy, anti-inflammation and immunomodulatory activities. However, the effect mechanisms of anti-allergy and anti-inflammation are poorly understood. The aim of study is to evaluate whether Cryptoporus polysaccharides (CP) extracted from fruiting body of Cryptoporus volvatus decrease the development of nasal symptoms, airway hyperresponsiveness (AHR) to methacholine (MCh) and the infiltration of eosinophils in nasal mucosa in rat model of allergic rhinitis, and investigate a possible action mechanism of CP by detecting the expression of eotaxin mRNA in nasal mucosa and lung tissues. Rats were immunized with ovalbumin and consecutive topical antigen instillation was performed. Repeated intranasal ovalbumin challenge caused rhinitis symptom, AHR to MCh, eosinophil infiltration and histological alterations into the nasal mucosa and increase of eotaxin mRNA expression in nasal mucosa and lung tissue were examined. Pretreatment with CP 3, 9 and 27 mg kg(-1) (ig) decreased the numbers of sneezing 27.4%, 38.4% and 44.3% and nasal rubbing 27.5%, 34.9% and 47.7% comparison with model group, respectively. CP caused a dose-related inhibition of MCh-induced AHR. CP 27 mg kg(-1) decreased the expression of eotaxin mRNA in the nasal mucosa by 35%. These results suggest CP can relieve the symptom, eosinophil infiltration and injury of tissue in nasal mucosa and lung tissue and AHR of allergic rhinitis in rats. Its action mechanism may be associated with the decrease of eotaxin mRNA expression.     

Antiproliferative and antimetastatic effects of the ethanolic extract of Phellinus igniarius (Linnearus: Fries) Quelet

AIM OF THIS STUDY: Phellinus igniarius (Linnearus: Fries) Quelet (Phellinus igniarius) has been used in oriental countries for treatment of various diseases including cancer. However, it is unclear how Phellinus igniarius exerts anticancer effects. MATERIALS AND METHODS: In this study the ethanolic extract from the fruiting body of Phellinus igniarius (EEPI) was used to evaluate the antiproliferative and antimetastatic effects in human hepatocarcinoma SK-Hep-1 cells and rat heart vascular endothelial cells (RHE cells). RESULTS: We found that EEPI inhibited the proliferation of both cell lines in a dose-dependent manner, and the IC50 values at 48 h were 72 and 103 microg/ml for SK-Hep-1 cells and RHE cells, respectively. EEPI at non- or sub-cytotoxic concentrations (25-100 microg/ml) markedly inhibited the migration and invasion of SK-Hep-1 cells. EEPI added at 25 microg/ml significantly decreased the secretion of matrix metalloproteinase-2 (MMP-2) (49%, p<0.01) and vascular endothelial growth factor (VEGF) (13%, p<0.05) in SK-Hep-1 cells. EEPI at 25 microg/ml completely inhibited matrigel-induced tube formation in RHE cells. Importantly, EEPI (25 or 50 microg/ml) in combination with oxaliplatin (Oxa) or 5-flurouracil (5-FU) synergistically inhibited the proliferation of SK-Hep-1 cells. CONCLUSION: These results demonstrate the antiproliferative and antimetastatic effects of EEPI in vitro and the potential of EEPI as an adjuvant for chemotherapy.