Inhibitory effect of kefiran on ovalbumin-induced lung inflammation in a murine model of asthma

Kefiran is a major component of kefir which is a microbial symbiont mixture that produces jelly-like grains. This study aimed to evaluate the therapeutic availability of kefiran on the ovalbumin-induced asthma mouse model in which airway inflammation and airway hyper-responsiveness were found in the lung. BALB/c mice sensitized and challenged to ovalbumin were treated intra-gastrically with kefiran 1 hour before the ovalbumin challenge. Kefiran significantly suppressed ovalbumin-induced airway hyper-responsiveness (AHR) to inhaled methacholine. Administration of kefiran significantly inhibited the release of both eosinophils and other inflammatory cells into bronchoalveolar lavage (BAL) fluid and lung tissue which was measured by Diff-Quik. Interleukin-4 (IL-4) and interleukin-5 (IL-5) were also reduced to normal levels after administration of kefiran in BAL fluid. Histological studies demonstrate that kefiran substantially inhibited ovalbumin-induced eosinophilia in lung tissue by H&E staining and goblet cell hyperplasia in the airway by PAS staining. Taken above data, kefiran may be useful for the treatment of inflammation of lung tissue and airway hyper-responsiveness in a murine model and may have therapeutic potential for the treatment of allergic bronchial asthma. These two authors made equal contribution to this work.     

Britanin attenuates ovalbumin-induced airway inflammation in a murine asthma model

We previously demonstrated the alleviation of ovalbumin (OVA)-induced airway inflammation by Inulae flos. In the present study, the effects of britanin, a sesquiterpene compound isolated from Inulae flos, were evaluated in an in vivo animal model for anti-asthma activity through observation of airway hyperresponsiveness (AHR), eosinophil recruitment, Th2 cytokine and IgE levels, and lung histopathology. Britanin administration effectively reduced AHR induced by aerosolized methacholine, airway eosinophilia, Th2 cytokines in bronchoalveolar lavage fluids and the supernatant of cultured splenocytes compared with OVA-induced mice. Histological studies showed that increased inflammatory cell infiltration and mucus secretion were reduced by britanin administration. Thus, britanin may have therapeutic potential for treating allergic asthma.     

桔梗的化学成分和抗肿瘤活性研究进展

桔梗作为一种药食两用的植物,具有显著的镇咳祛痰、抗肿瘤、抗氧化及降血糖等作用。迄今为止,从桔梗中共分离得到55种皂苷类化合物,三萜皂苷是其主要的活性成分。本文对近年来桔梗的化学成分研究进展进行了总结,并从诱导肿瘤细胞凋亡、增强机体免疫功能、抑制端粒酶活性、抑制肿瘤细胞浸润与转移以及阻滞细胞周期等方面,对国内外桔梗抗肿瘤活性的研究进展进行了阐述。     

桔梗生长年限和采收期与质量的相关性研究

目的确定桔梗最佳生长年限与最佳采收期。方法蒽酮比色法测定多糖含量;HPLC测定桔梗皂苷D含量;改进的总苷称重法测定总皂苷含量。结果以两年生,9月下旬至11月上旬采收的桔梗质量最佳。结论三种指标具有代表性,能够较全面反映药材质量。     

Isoimperatorin attenuates airway inflammation and mucus hypersecretion in an ovalbumin-induced murine model of asthma

Isoimperatorin (IMP), an active natural furocoumarin, has numerous pharmacologic effects, including anti-inflammatory, analgesic, antispasmodic, and anticancer activities. This study aimed to evaluate the preventive activity of IMP in an ovalbumin (OVA)-induced murine model of asthma and to investigate its possible molecular mechanisms. Female BALB/c mice were sensitized on days 0 and 14 via intraperitoneal injection of 20 μg OVA. On days 21–23 after the initial sensitization, the mice received an airway challenge with OVA (1% w/v in PBS) for 1 h; meanwhile, IMP (10 or 30 mg/kg once daily) was administered by gavage on days 18–23. Our results revealed that IMP significantly lowered the productions of interleukin (IL)-4, IL-5, IL-13, eotaxin, and immunoglobulin (Ig)E in bronchoalveolar lavage fluid (BALF), plasma, or lung tissues. Histological studies showed that IMP inhibited OVA-induced inflammatory cell infiltration and mucus production in the respiratory tract. In addition, pretreatment with IMP suppressed the activation of p38 mitogen-activated protein kinase (p38 MAPK), extracellular-signal-regulated kinases 1/2 (ERK1/2), and nuclear factor-κB (NF-κB). Together, these results suggest that IMP effectively inhibits airway inflammation and mucus hypersecretion by downregulating the levels of Th2 cytokines and inhibiting NF-κB and MAPK pathways.     

Airway fibrosis in a mouse model of airway inflammation

BALB/c mice were sensitized to ovalbumin by systemic injection and then exposed for up to 8 weeks to ovalbumin aerosols in whole body chambers. A pattern of airway inflammation, mucous cell hypertrophy and hyperplasia, and airway remodeling with submucosal fibrosis was observed as lesions evolved over time. Larger conducting airways were removed from the lungs by microdissection. Airway fibrosis was quantified by direct assay for collagen content, which was significantly increased after 4 and 8 weeks of exposure to ovalbumin aerosol. Based upon PCR analysis of mRNA levels in the airways, most of the newly synthesized collagen was Type I. Relaxin, administered by continuous infusion over the second half of a 4-week exposure to ovalbumin, was able to inhibit the accumulation of collagen in the airways of exposed mice. Thus, stimulation of collagen degradation by an activator of collagen breakdown by matrix metalloproteinases appears to be an effective therapeutic strategy in prevention of airway fibrosis in this animal model. Whole body plethysmography of unrestrained mice indicated functional changes in airway reactivity in the lungs of exposed animals occurring in conjunction with the reported structural changes. This result indicates that the ovalbumin-exposed mouse may be a suitable model for examining structure-function relationships in the lungs of animals with a predictable time course of airway inflammation, remodeling, and fibrosis and for testing potential new drugs for treatment of asthma or chronic bronchitis at a mechanistic level.     

Inhibition of high-mobility group box 1 in lung reduced airway inflammation and remodeling in a mouse model of chronic asthma

The role of high-mobility group box 1 (HMGB1) in chronic allergic asthma is currently unclear. Both airway neutrophilia and eosinophilia and increase in HMGB1 expression in the lungs in our murine model of chronic asthma. Inhibition of HMGB1 expression in lung in ovalbumin (OVA)-immunized mice decreased induced airway inflammation, mucus formation, and collagen deposition in lung tissues. Analysis of the numbers of CD4⁺ T helper (Th) cells in the mediastinal lymph nodes and lungs revealed that Th17 showed greater increases than Th2 cells and Th1 cells in OVA-immunized mice; further, the numbers of Th1, Th2, and Th17 cells decreased in anti-HMGB1 antibody (Ab)-treated mice. In OVA-immunized mice, TLR-2 and TLR-4 expression, but not RAGE expression, was activated in the lungs and attenuated after anti-HMGB1 Ab treatment. The results showed that increase in HMGB1 release and expression in the lungs could be an important pathological mechanism underlying chronic allergic asthma and HMGB1 might a potential therapeutic target for chronic allergic asthma.     

火把花根片对哮喘豚鼠气道炎症的作用

目的探讨火把花根片对哮喘豚鼠气道慢性炎症的作用。方法建立哮喘豚鼠动物模型 :将豚鼠 2 6只随机分为 3组 ,A组为火把花根组 (9只 ) ,B组为地塞米松组 (9只 ) ,C组为哮喘对照组 (8只 ) ,观测豚鼠支气管肺泡灌洗液 (BALF)细胞总数、嗜酸性粒细胞、淋巴细胞、中性粒细胞数量以及蛋白浓度和肺组织病理学的变化。结果A组BALF细胞总数、以嗜酸性粒细胞为主的炎性细胞数量及蛋白浓度均低于C组 (P <0 0 1) ,其肺组织气道慢性炎症表现亦较C组减轻。结论火把花根片可显著抑制哮喘豚鼠的气道慢性炎症     

Mangosteen xanthones mitigate ovalbumin-induced airway inflammation in a mouse model of asthma

α- and γ-Mangostin, which are the major xanthones purified from a Mangosteen, Garcinia mangostana Linn., exhibit a wide range of anticancer, antioxidant, and anti-inflammatory activities. Here, we assessed their therapeutic effects in a mouse model of ovalbumin (OVA)-induced allergic asthma. Animals were treated with α- and γ-mangostins orally for 3 days at doses of 10 and 30 mg/kg daily, 1 h before the OVA challenge. Administration of α- and γ-mangostins significantly reduced the major pathophysiological features of allergic asthma, including inflammatory cell recruitment into the airway, airway hyperresponsiveness (AHR), and increased levels of Th2 cytokines. In addition, α- and γ-mangostins attenuated the increases in phosphoinositide 3-kinase (PI3K) activity, phosphorylation of Akt, and NF-κB in nuclear protein extracts after OVA challenge. In conclusion, α- and γ-mangostin may have therapeutic potential for the treatment of allergic asthma.     

meso-Dihydroguaiaretic acid attenuates airway inflammation and mucus hypersecretion in an ovalbumin-induced murine model of asthma

meso-Dihydroguaiaretic acid (MDGA), which is a dibenzylbutane lignin isolated from the ethyl acetate fraction of Saururus chinensis, has various biological activities, including anti-oxidative, anti-inflammatory, anti-bacterial, and neuroprotective effects. However, no report has examined the potential anti-asthmatic activity of MDGA. In this study, we evaluated the protective effects of MDGA on asthmatic responses, particularly airway inflammation and mucus hypersecretion in an ovalbumin (OVA)-induced murine model of asthma. Intragastric administration of MDGA significantly lowered the productions of interleukin (IL)-4, IL-5, IL-13, tumor necrosis-α (TNF-α), eotaxin, monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), and immunoglobulin (Ig)E in bronchoalveolar lavage fluid (BALF), plasma, or lung tissues. Histological studies showed that MDGA inhibited OVA-induced inflammatory cell infiltration and mucus production in the respiratory tract. Moreover, MDGA markedly attenuated the OVA-induced activations of nuclear factor kappa B (NF-κB), extracellular-signal-regulated kinases 1/2 (ERK1/2), and p38 mitogen-activated protein kinase (p38 MAPK). Together, these results suggest that MDGA effectively inhibits airway inflammation and mucus hypersecretion by downregulating the levels of T helper 2 (Th2) cytokines, chemokines, and adhesion molecules, and inhibiting the activations of NF-κB and MAPKs.     

Protocatechuic acid suppresses ovalbumin-induced airway inflammation in a mouse allergic asthma model

Protocatechuic acid (PCA) has been isolated from the leaves of ilex chinenses and has numerous pharmacologic effects, including anti-inflammatory and antitumoral activities. This study aims to evaluate the antiasthma activity of PCA and investigate its possible molecular mechanisms. BALB/c mice were sensitized and challenged to ovalbumin (OVA).Then mice were intraperitoneally (i.p.) injected with PCA 1 h before OVA challenge. We found that PCA treatment at 15 or 30 mg/kg significantly decreased OVA-induced airway hyper-responsiveness (AHR) to inhaled methacholine. Type 2 helper T cell (Th2) cytokines in bronchoalveolar lavage (BAL) fluid, such as interleukin-4 (IL-4), interleukin 5 (IL-5) and interleukin-13 (IL-13), and serum OVA-specific immunoglobulin E (IgE) levels, were also reduced by PCA. Moreover treatment with PCA markedly decreased the number of inflammatory cells in BALF and attenuated OVA-induced mRNA expression of CCl11, CCR3, Muc5ac, acidic mammalian chitinase (AMCase), chitinase 3-like protein 4 (Ym2) and E-selectin in lung tissues, lung histopathological studies showed that PCA inhibited inflammatory cell infiltration and mucus hypersecretion compared with the OVA-induced mice group. We then investigated the possible molecular mechanisms which might be implicated in PCA activity. Our results suggested that the protective effect of PCA might be mediated by the inhibition of the extracellular signal-regulated protein kinase (ERK), p38 Mitogen-activated protein kinase (MAPK) phosphorylation and the nuclear factor-κB (NF-κB) activation.     

Skullcapflavone II inhibits ovalbumin-induced airway inflammation in a mouse model of asthma

Skullcapflavone II is a flavonoid derived from Scutellaria baicalensis, a widely used herbal medicine in anti-inflammatory and anticancer therapy in Korea. Skullcapflavone II antagonized the bradykinin receptor more potently than any of the other flavonoids derived from this plant. Here, we were investigated its therapeutic effects in a mouse model of ovalbumin (OVA)-induced allergic asthma. Administration of skullcapflavone II significantly reduced airway hyperresponsiveness (AHR), airway eosinophilia, Th2 cytokine production, and increased transforming growth factor-β1 (TGF-β1) levels in bronchoalveolarlavage (BAL) fluids and lungs from OVA-sensitized and -challenged mice. Skullcapflavone II administration also significantly suppressed subepithelial collagen deposition and goblet cell hyperplasia, elevated Smad7 expression and suppressed pSmad2/3 levels. Collectively, these findings indicate that skullcapflavone II, a potential bradykinin antagonist, reduced the major pathophysiological features of allergic asthma, at least in part by acting on TGF-β1/Smad signaling pathways. Thus, skullcapflavone II may have therapeutic potential for the treatment of allergic asthma.     

Anti-asthmatic effect of schizandrin on OVA-induced airway inflammation in a murine asthma model

Asthma comprises a triad of reversible airway obstruction, bronchial smooth muscle cell hyperreactivity to bronchoconstrictors, and chronic bronchial inflammation. Clinical and experimental findings have established eosinophilia as a sign of allergic disorders. In the present investigation, we evaluated the anti-asthmatic effects of schizandrin and its underlying mechanisms in an in vivo murine asthmatic model. To accomplish this, female BALB/c mice were sensitized and challenged with ovalbumin (OVA), and examined for the following typical asthmatic reactions: increased numbers of eosinophils and other inflammatory cells in bronchoalveolar lavage fluid (BALF); production of Th1 cytokines (such as tumor necrosis factor (TNF)-α in BALF); production of Th2 cytokines (such as interleukin IL-4 and IL-5) in BALF; presence of total and OVA-specific immunoglobulins (Ig)E in serum; presence of oxidative stress; hyperplasia of goblet cells in the lung; and marked influx of inflammatory cells into the lung. Our results collectively show that schizandrin exerts profound inhibitory effects on accumulation of eosinophils into the airways and reduces the levels of IL-4, IL-5, IFN-γ, and TNF-α in BALF. Additionally, schizandrin suppresses the production of reactive oxygen species (ROS) in a dose-dependent manner, and inhibits goblet cell hyperplasia and inflammatory cell infiltration in lung tissue. Thus, schizandrin has anti-asthmatic effects, which seem to be partially mediated by reduction of oxidative stress and airway inflammation, in a murine allergic asthma model. These results indicate that schizandrin may be an effective novel therapeutic agent for the treatment of allergic asthma.     

Susceptibility to ovalbumin-induced airway inflammation and fibrosis in inducible nitric oxide synthetase-deficient mice: mechanisms and consequences

In a previous study, we showed that BALB/c mice demonstrate significant increases in accumulation of airway collagen after 4 weeks of exposure to ovalbumin aerosol. In the current study we examined the response to ovalbumin aerosol of a different strain of mice, C57BL/6, and compared this response to an otherwise isogenic C57BL strain (iNOS(-/-)) in which the gene for inducible nitric oxide synthetase (iNOS) had been knocked out. We hypothesized that C57BL mice, a Th-1-responsive strain, would be relatively resistant to ovalbumin exposure compared with our previous observations in the BALB/c strain, a Th-2 responder. Our results are consistent with this hypothesis, especially with respect to the accumulation of collagen in the airways of the mice exposed to ovalbumin and increased airway reactivity to challenge with methacholine, as measured by the Penh response. Since NO participates in multiple signal transduction pathways, there was no a priori reason to predict whether iNOS(-/-) mice would be more or less susceptible to allergen-induced airway inflammation than their parental wild-type strain. Responses to ovalbumin exposure of the Th-1-responsive C57BL animals were significantly less (or slower) than those we observed with the iNOS(-/-) mice. Significant increases in airway collagen content were seen only after 6 weeks of exposure of the C57BL mice, as contrasted with 4 weeks in the iNOS(-/-) animals. At each time point examined, Penh values for the iNOS(-/-) mice were significantly increased, while no increases were observed with the C57BL strain. Thus, the iNOS(-/-) mice are more susceptible to ovalbumin-induced airway inflammation and fibrosis than the C57BL strain, giving results intermediate between the previous observations in BALB/c mice and our current findings in C57BL animals with the various assays performed. We also asked whether the effects of knocking out the iNOS gene were exerted before or after the release of TGF-beta(1) by eosinophils and other effector cells in the lung. We measured the response of C57BL and iNOS(-/-) mice to direct intratracheal challenge with TGF-beta(1). There was no apparent response of C57BL mice to TGF-beta(1) at 4 or 11 days after TGF-beta(1) challenge, as evaluated by bronchoprovocation testing. On the other hand, the observed Penh values were significantly greater in iNOS(-/-) mice that had also received TGF-beta(1) 4 days previously. These results strongly support the hypothesis that the increased sensitivity of iNOS(-/-) mice to ovalbumin is at least partially dependent on pathways that come into play subsequent to the release of TGF-beta(1) by effector cells in the lungs of mice exposed to ovalbumin aerosol.     

高效液相色谱－蒸发光散射检测器法测定复方桔梗止咳片中桔梗皂苷D含量

目的建立测定复方桔梗止咳片中桔梗皂苷D含量的高效液相色谱－蒸发光散射检测器（HPLC—ELSD）法。方法色谱柱采用Agilent C18柱（150mm×4．6mm,5μm）,以乙腈-水（25：75）为流动相,流速为0．7mL／min;ELSD检测器漂移管温度为90℃,载气1．8Bar;进样量为10μL;柱温为30℃。结果桔梗皂苷D质量浓度线性范围为125．08—1250．8mg／L（r=0．9998）,平均加样回收率为98．60％,RSD=1．00％（n=6）。结论该方法简便、重复性好,可用于测定复方桔梗止咳片中桔梗皂苷D的含量。     

氨茶碱辅助糖皮质激素对支气管哮喘患者气道炎症的改善作用研究

目的 探讨氨茶碱辅助糖皮质激素对支气管哮喘患者气道炎症的改善作用.方法 选取2014年2月至2015年3月我院呼吸内科收治的60例支气管哮喘患者为研究对象,采用抽签随机法均分为观察组和对照组,对照组给予糖皮质激素治疗,观察组在对照组基础上联合氨茶碱辅助治疗.观察治疗后两组临床疗效及气道炎症指标[白细胞介素-5(IL-5)、白细胞介素-10(IL-10)、肿瘤坏死因子(TNF-α)].结果 治疗后观察组总有效率较对照组显著高(86.67％ vs.63.33％;P＜0.05).两组治疗后IL-5、IL-10、TNF-α分别均较治疗前显著降低,且观察组IL-5[(9.82±3.82) pg/ml]、IL-10[(9.60±3.98) pg/ml]、TNF-α[(9.85±3.01) pg/ml]分别均较对照组显著降低,差异均有统计学意义(P＜0.05).结论 氨茶碱辅助糖皮质激素对支气管哮喘患者临床疗效显著,对患者气道炎症的改善作用显著,值得临床推广应用.     

Comparative evaluation of anti-inflammatory properties of thymoquinone and curcumin using an asthmatic murine model

This study was designed to compare the inhibitory effects of thymoquinone (TQ) and curcumin (CMN) on the biological changes associating asthma. TQ appeared to exhibit greater inhibitory effects on the aggregation of inflammatory cells in bronchoalveolar lavage (BAL) fluid and in lung tissues. We also measured the effects of the two agents on serum IgE and the changes in the mRNA levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1). Serum IgE was significantly decreased by TQ and CMN with TQ being more potent. Also, TQ showed superior inhibitory effects on iNOS and TGF-β1. Meanwhile, CMN was more potent in inhibiting mRNA expression of TNF-α. These results suggest that TQ is more potent in inhibiting the inflammatory changes associating asthma. On the other hand, CMN was a less potent inhibitor of all measured parameters, despite its superior inhibitory effect on TNF-α mRNA levels.     

1,8-桉油精对卵白蛋白致哮喘豚鼠的气道高反应性和炎症的抑制作用

目的探讨1,8-桉油精(1,8-cineol)对哮喘豚鼠肺功能的改善作用及其机制。方法豚鼠第0天和第7天ip给予0.5ml含卵白蛋白(OVA)20μg的氢氧化铝凝胶致敏,28d后OVA攻击制备哮喘模型。观察豚鼠OVA攻击后1h,1,8-桉油精10,30和100mg.kg-1对豚鼠吸入OVA后1,2,3,4,10,20和30min时气道阻力(Raw)和肺顺应性(Cdyn)变化及支气管肺泡灌洗液(BALF)中白细胞数和细胞分类的影响,并测量豚鼠肺组织中嗜酸细胞阳离子蛋白(ECP)、白细胞介素4(IL-4)、IL-8和肿瘤坏死因子α(TNF-α)的含量。观察豚鼠OVA攻击后17h再吸入乙酰甲胆碱(MCh)后,1,8-桉油精10,30和100mg.kg-1对Raw和Cdyn及BALF中白细胞数和细胞分类的影响,并测量豚鼠肺组织中ECP,IL-4,IL-8和TNF-α的含量。结果与正常对照组比较,豚鼠OVA攻击后1h,在4min时模型组Raw达到高峰;与模型组比较,1,8-桉油精30和100mg.kg-1明显抑制Raw增加(P<0.05);在3min时模型组Cdyn达到高峰,与模型组比较,1,8-桉油精10,30和100mg.kg-1均能明显抑制Cdyn降低(P<0.05);模型组豚鼠肺组织ECP,IL-4和TNF-α含量明显高于正常对照组(P<0.05);1,8-桉油精100mg.kg-1组ECP,IL-4和TNF-α含量均明显低于模型组(P<0.05),模型组与正常对照组豚鼠肺组织IL-8含量无明显差异。与模型组比较,1,8-桉油精100mg.kg-1能明显减少BALF中白细胞数和嗜酸性粒细胞比例(P<0.05)。致敏豚鼠OVA攻击17h后,模型组豚鼠Raw与正常对照组比较显著升高(P<0.05),模型组豚鼠Cdyn与正常对照组比较有显著性差异(P<0.01),1,8-桉油精100mg.kg-1对MCh引起的Raw的增加有明显的抑制作用,1,8-桉油精10,30和100mg.kg-1对MCh引起的Cdyn降低有明显的改善作用;与模型组相比,1,8-桉油精100mg.kg-1能明显减少BALF中白细胞数和中性粒细胞比例,降低肺组织ECP,IL-8和TNF-α含量(P<0.01);模型组与正常对照组豚鼠肺组织IL-4含量无明显差异;1,8-桉油精30mg.kg-1也能降低哮喘豚鼠肺组织中ECP和TNF-α含量(P<0.01)。结论在哮喘急性发作时,1,8-桉油精通过减少嗜酸性粒细胞,下调嗜酸性粒细胞的活性,从而抑制了哮喘的急性发作。在哮喘迟发相阶段,1,8-桉油精可通过下调IL-8水平,降低TNF-α活性,从而抑制或改善由IL-8水平升高导致的中性粒细胞聚集于支气管肺泡而直接引起的哮喘加重和持续状态。     

磷酸酰肌醇-3激酶抑制剂对小鼠气道炎症影响的实验研究

目的观察磷酸酰肌醇-3激酶（P13K）抑制剂LY294002对卵白蛋白诱导哮喘小鼠气道炎症的影响。方法Balb／c小鼠30只，采用随机数字表法分为3组，每组10只：LY294002处理组、卵白蛋白组、正常对照组。通过卵白蛋白多次腹腔注射致敏和反复雾化激发，建立哮喘小鼠模型。末次抗原激发后48h收集支气管肺泡灌洗液和骨髓标本，计数细胞总数和嗜酸性粒细胞，并行肺组织学检查。结果与卵白蛋白组比较，LY294002处理组支气管肺泡灌洗液中细胞总数及嗜酸性粒细胞绝对数明显减少（P〈0．05）：肺组织中细支气管、血管周围嗜酸性粒细胞浸润得到控制，气道黏液分泌减少。结论P13K特异性抑制剂LY294002对卵白蛋白致敏的哮喘小鼠气道炎症具有抑制作用。     

Protective effects of pyrrolidine dithiocarbamate against airway inflammation in the ovalbumin-induced mouse model

Pyrrolidine dithiocarbamate (PDTC) is known to exert anti-tumor and anti-inflammatory effects. However, the effects of PDTC against airway inflammation and its underlying mechanisms have not been reported. In the present study, we examined the protective effects of PDTC in a murine model of asthma induced by ovalbumin. PDTC reduced the number of infiltrating inflammatory cells in concert with reduced eosinophil peroxidase (EPO) activity in bronchoalveolar lavage fluid. In parallel, PDTC decreased airway hyperresponsiveness in a dose dependent manner. All these effects were correlated with heme oxygenase-1 (HO-1) mRNA and protein induction, and reversed by ZnPP, a HO-1 inhibitor. In addition, PDTC reduced the secretion of Th(2) cytokines such as IL-4 and IL-5, whereas ZnPP blocked the inhibitory effects of PDTC on Th(2) cytokine secretion. These results suggest that PDTC protects against airway inflammation at least in part via HO-1 induction, and that inhibitory action on Th(2) cytokines may be associated with the protective mechanism of PDTC.