Toll-like receptor 4 is a key regulator of asthma exacerbation caused by aluminum oxide nanoparticles via regulation of NF-κB phosphorylation.

Aluminum oxide nanoparticles (Al2O3 NPs) have recently been reported to cause an inflammatory response in the lungs, and studies are being conducted on their adverse effects, especially in patients with underlying lung diseases such as asthma. However, the underlying mechanism of asthma aggravation caused by Al2O3 NPs remains unclear. This study investigated whether Al2O3 NPs exacerbate ovalbumin (OVA)-induced asthma and focused on the correlation between toll-like receptor 4 (TLR4) signaling and Al2O3 NP-induced asthma exacerbation. Al2O3 NP exposure in asthmatic mice resulted in increased inflammatory cell counts in the lungs, airway hyperresponsiveness, and increased levels of inflammatory cytokines compared with only OVA-induced mice, and excessive secretion of mucus was observed in the airways. Moreover, Al2O3 NP exposure in OVA-induced mice increased the expression levels of TLR4, phospho-nuclear transcription factor-kappa B (p-NFκB), myeloid differentiation factor 88 (MyD88), and phospho-NF kappa B inhibitor alpha (p-IκBα). Furthermore, in the lungs of TLR4 knockout mice exposed to Al2O3 NPs and in a human airway epithelial cell line with down regulated TLR4, the expression levels of MyD88, p-NFκB, and p-IκBα were decreased, and asthma-related allergic responses were reduced. Therefore, we demonstrated that TLR4 is important for aggravation of asthma induced by Al2O3 NPs, and this study provides useful information regarding as yet undiscovered novel target signaling.

Anti-asthmatic effects of Phlomis umbrosa Turczaninow using ovalbumin induced asthma murine model and network pharmacology analysis.

BACKGROUND: Phlomis umbrosa Turczaninow has been used as a tradition herbal medicine for treating various inflammatory diseases. PURPOSE: In present study, we explored the effects of P. umbrosa on asthma induced by ovalbumin (OVA) and elucidated the mechanism via in vivo verification and network pharmacology prediction. METHODS: The animals were intraperitoneally injected OVA on day 1 and 14, followed by OVA inhalation on days 21, 22, and 23. The animals were daily treated P. umbrosa extract (PUE, 20 and 40 mg/kg) by oral gavage from day 18 to day 23. RESULTS: PUE significantly decreased airway hyperresponsiveness, eosinophilia, and the production of inflammatory cytokines and OVA specific immunoglobulin E in animals with asthma, along with a reduction in airway inflammation and mucus secretion in lung tissue. In network analysis, antiasthmatic effects of PUE were closely related with suppression of mitogen-activated protein kinases and matrix metalloproteinases (MMPs). Consistent with the results from network analysis, PUE suppressed the phosphorylation of ERK and p65, which was accompanied by a decline in MMP-9 expression. CONCLUSION: Administration of PUE effectively reduced allergic responses in asthmatic mice, which was associated with the suppressed phosphorylation of ERK and p65, and expression of MMP-9. These results indicate that PUE has therapeutic potential to treat allergic asthma.

Subchronic Toxicity Evaluation of Aluminum Oxide Nanoparticles in Rats Following 28-Day Repeated Oral Administration.

Several studies on the potential adverse effects of aluminum oxide nanoparticles (Al2O3NPs) have reported conflicting results. The present study investigated the potential adverse effects of Al2O3NPs in Sprague-Dawley rats following 28-day repeated oral administration. In addition, we aimed to determine the target organ and no-observed-adverse-effect level (NOAEL) of Al2O3NPs. Al2O3NPs was administered once daily by gavage to male and female rats at dose levels of 0, 500, and 1000 mg/kg/day for 28 days. There were no treatment-related adverse effects as indicated by the clinical signs, body weight, food consumption, urinalysis, ophthalmology, hematology, serum biochemistry, gross pathology, organ weight, and histopathology at all the tested doses. Under the experimental conditions of the present study, 28-day repeated oral administration of Al2O3NPs at doses of up to 1000 mg/kg/day did not induce any treatment-related systemic toxicity in male and female rats. The NOAEL of Al2O3NPs was set at 1000 mg/kg/day in both male and female rats and no target organs were identified.

Cimicifugae Rhizoma Extract Attenuates Oxidative Stress and Airway Inflammation via the Upregulation of Nrf2/HO-1/NQO1 and Downregulation of NF-κB Phosphorylation in Ovalbumin-Induced Asthma.

Cimicifugae Rhizoma has been used as a medicinal herb for fever, pain, and inflammation in East Asia. We conducted this study because the effect of Cimicifugae Rhizoma extract (CRE) on allergic asthma has not yet been evaluated. To induce allergic airway inflammation, we intraperitoneally injected ovalbumin (OVA) mixed with aluminum hydroxide into mice twice at intervals of 2 weeks (Days 0 and 14) and then inhaled them thrice with 1% OVA solution using a nebulizer (Days 21 to 23). CRE (30 and 100 mg/kg) was administered orally daily for 6 days (Days 18 to 23). The mice showed remarkable reduction in allergic inflammation at 100 mg/kg of CRE, as evidenced by decreased inflammatory cell counts, pro-inflammatory cytokine levels, OVA-specific immunoglobulin E level, airway hyperresponsiveness, and production of mucus. Additionally, these effects were involved with the enhancement of heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase (NQO1), and nuclear factor erythroid 2-related factor 2 (Nrf2) expression and reduction of nuclear factor-κB (NF-κB) phosphorylation and matrix metalloproteinase-9 expression. Our findings indicated that CRE effectively protected against OVA-induced inflammation and oxidative stress via upregulation of the Nrf2/HO-1/NQO1 signaling and downregulation of NF-κB phosphorylation in asthma caused by OVA.

Evaluation of 28-day repeated oral dose toxicity of SUNACTIVE Zn-P240 in rats.

This study was conducted to investigate the potential toxicity of repeated oral dose of SUNACTIVE Zn-P240, a new type of zinc supplement, in Sprague-Dawley rats. SUNACTIVE Zn-P240 was administered once daily by gavage at doses of 0, 500, 1000, and 2000 mg/kg/day for each group over a 28-day period. At 2000 mg/kg/day, there were increases in serum alkaline phosphatase (ALP) and alanine aminotransferase, liver weight, histopathological changes in stomach, liver, and pancreas and decreases in body weight, food consumption, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration, total protein (TP), and albumin. At 1000 mg/kg/day, there was an increase in the serum ALP level and there were decreases in the MCV, MCH, and TP. There were no treatment-related adverse effects in the 500 mg/kg/day group. Under the present experimental conditions, the target organs in rats were determined to be the stomach, pancreas, liver, and erythrocyte and the no-observed-adverse-effect level (NOAEL) in rats was considered to be 500 mg/kg/day.

Effect of Yijin-Tang, an Oriental Traditional Formula, on Allergic Responses Using an Ovalbumin-Induced Murine Asthma Model.

Yijin-tang is an oriental traditional herb used to treat inflammatory diseases. In the present study, we investigated the protective effects of Yijin-tang water extract (YTE) using an ovalbumin- (OVA-) induced asthma model, focusing on the antioxidant and anti-inflammatory properties of the herb. BALB/c mice were intraperitoneally injected with OVA on days 0 and 14 and then challenged with OVA on days 21, 22, and 23. The animals were orally administered YTE (200 and 400 mg/kg) from days 18 to 23, and this was found to significantly decrease airway hyperresponsiveness and release of inflammatory cells, cytokines, and OVA-specific immunoglobulin E in mice with asthma. In addition, YTE was associated with a marked reduction in airway inflammation and mucus production in lung tissue of mice with asthma. Furthermore, YTE suppressed the expression of matrix metalloproteinase-9 and phosphorylation of ERK in the lungs, which in turn led to a reduction in inducible nitric oxide synthases and an elevation in reduced glutathione and heme oxygenase-1. In conclusion, YTE effectively suppressed allergic responses in mice with asthma and the effect was closely related to antioxidant and anti-inflammatory properties of the herb. Our results indicate that YTE may be a potential agent for the treatment of allergic asthma.

Silibinin Attenuates Silica Dioxide Nanoparticles-Induced Inflammation by Suppressing TXNIP/MAPKs/AP-1 Signaling.

Silica dioxide nanoparticles (SiONPs) have been applied to several fields, such as drug delivery and gene therapy. However, SiONPs are a constituent of fine dust and can induce excessive inflammatory responses in the lungs via the airways. Silibinin, a major component of silymarin, has been known for its anti-oxidant and anti-inflammatory effects. In the present study, we explored the protective effects of silibinin against SiONPs-induced airway inflammation and explored its underlying mechanism of action, focusing on thioredoxin-interacting protein (TXNIP)/mitogen-activated protein kinases (MAPKs) in vitro and in vivo. In SiONPs-stimulated NCI-H292 airway epithelial cells, silibinin treatment effectively suppressed the elevation of the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß, which was accompanied by the reduction in the expression of TXNIP, MAPKs, and activator protein-1 (AP-1). In SiONPs-treated mice, silibinin administration inhibited the increase in inflammatory cell counts and proinflammatory mediators, and it alleviated airway inflammation by SiONPs exposure. In addition, silibinin administration effectively suppressed the elevation of TXNIP/MAPKs/AP-1 signaling by SiONPs exposure. Taken together, silibinin effectively inhibited SiONPs-induced inflammatory responses, and this effect was closely related to the inhibition of TXNIP/MAPK/AP-1 signaling. These results suggested that silibinin might be useful for reducing pulmonary inflammation induced by SiONPs.

Scrophularia buergeriana attenuates allergic inflammation by reducing NF-κB activation.

BACKGROUND: Scrophularia buergeriana Miq. (Scrophulariaceae) (SB) has been used as an oriental medicine for the treatment of inflammatory diseases, such as neuritis and pharyngolaryngitis. PURPOSE: We explored the therapeutic effects of S. buergeriana ethanol extract (SBE) on airway inflammation in ovalbumin (OVA)-induced asthmatic mice and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. METHODS: Mice were intraperitoneally injected with OVA on days 0 and 14 to elevate the immune response. On days 21 to 23, the mice were challenged with OVA solution and SBE (20 and 40 mg/kg) was administered daily by oral gavage from days 18 to 23. RAW264.7 cells were pretreated with SBE 1 h before LPS stimulation. RESULTS: SBE administration effectively suppressed inflammatory cell infiltration, the expression of interleukin (IL)-5, IL-13, and IL-17, immunoglobulin E, and airway hyperresponsiveness in an OVA-induced allergic asthma model. A reduction in histological alterations, including airway inflammation and mucus hypersecretion, was observed. These effects of SBE were accompanied by a decrease in matrix metalloproteinase-9 (MMP-9) expression and nuclear factor kappa B (NF-κB) phosphorylation. These responses were observed in LPS-stimulated RAW264.7 cells. SBE treatment reduced the mRNA expression of tumor necrosis factor (TNF)-α, IL-6, and MMP-9, and NF-κB phosphorylation, in LPS-stimulated RAW264.7 cells. CONCLUSION: Our results indicated that SBE effectively attenuated airway inflammation in an OVA-induced allergic asthma model. These properties of SBE were thought to be involved in the suppression of NF-κB phosphorylation, suggesting that the material has the potential to regulate the development of allergic asthma.

Scrophularia koraiensis Nakai Attenuates Allergic Airway Inflammation via Suppression of NF-κB and Enhancement of Nrf2/HO-1 Signaling.

Scrophularia koraiensis Nakai (Scrophulariaceae) is a medicinal herb that grows in Korea and which has been widely used to treat fever, edema, neuritis and laryngitis. Hence, we evaluated the anti-inflammatory and antioxidant effects of the ethanol extract (SKE) of S. koraiensis Nakai in an ovalbumin (OVA)-induced mouse model. We injected 20 µg of OVA with 2 mg of aluminum on day 0 and day 14 to induce allergic airway inflammation in six-week-old BALB/c mice, and mice were challenged with 1% OVA by nebulization for 1 h on days 21, 22, and 23. SKE was orally administered at 20 mg/kg and 40 mg/kg from day 18 to 23, and its effects were compared with those of montelukast treatment. SKE significantly reduced proinflammatory cytokines, inflammatory cell counts, immunoglobulin-E, and airway hyperresponsiveness during the OVA-induced allergic airway inflammation model; it also reduced airway inflammation and mucus production. In addition, SKE reduced the OVA-induced nuclear factor kappa B (NF-κB) phosphorylation in lung tissues while enhancing nuclear factor erythroid-derived 2-related factor (Nrf-2) and heme oxygenase-1 (HO-1) expression. In conclusion, SKE showed the protective effects on OVA-induced allergic airway inflammation via the suppression of NF-κB phosphorylation and the enhancement of the Nrf2/HO-1 signaling pathway. These results indicate that SKE is a potential therapeutic agent for allergic airway inflammation.

4-Hydroxycinnamic acid suppresses airway inflammation and mucus hypersecretion in allergic asthma induced by ovalbumin challenge.

In this study, we investigated whether 4-hydroxycinnamic acid (HA) has a palliative effect on asthmatic inflammatory responses using a mouse model of ovalbumin (OVA)-induced allergic asthma. The mice were divided into five groups, each consisting of seven females (normal control phosphate-buffered saline); OVA (OVA sensitization/challenge); dexamethasone (DEX, OVA sensitization/challenge + dexamethasone 3 mg/kg); HA-10 and HA-20 OVA sensitization/challenge + HA 10 and 20 mg/kg, respectively). Mice treated with HA showed a reduction in airway hyperresponsiveness and in the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) compared with asthmatic control. HA treatment also reduced the levels of interleukin (IL)-5 and IL-13 in BALF and of OVA-specific immunoglobulin E in the serum compared with asthmatic control. HA treatment relieved airway inflammation and mucus overproduction caused by OVA exposure. Additionally, HA inhibited the increases in levels of nuclear factor kappa B, inducible nitric oxide synthase, and cyclooxygenase-2 that normally occur after OVA exposure. HA treatment also reduced the activity and protein level of matrix metalloproteinase-9. Taken together, HA effectively suppressed asthmatic airway inflammation and mucus production caused by OVA exposure. These findings indicate that HA has the potential to be used as a therapeutic agent for asthma.

Therapeutic Effect of Dipsacus asperoides C. Y. Cheng et T. M. Ai in Ovalbumin-Induced Murine Model of Asthma.

Dipsacus asperoides C. Y. Cheng et T. M. Ai (DA) has been used in China as a traditional medicine to treat lumbar and knee pain, liver dysfunction, and fractures. We explored the suppressive effect of DA on allergic asthma using an ovalbumin (OVA)-induced asthma model. In the asthma model, female Balb/c mice were sensitized to OVA on day 0 and 14 to boost immune responses and then exposed to OVA solution by using an ultrasonic nebulizer on days 21 to 23. DA (20 and 40 mg/kg) was administered to mice by oral gavage on days 18 to 23. Methacholine responsiveness was determined on day 24 using a plethysmography. On day 25, we collected bronchoalveolar lavage fluid, serum, and lung tissue from animals under anesthesia. DA treatment effectively inhibited methacholine responsiveness, inflammatory cell infiltration, proinflammatory cytokines such as interleukin (IL)-5 and IL-13, and immunoglobulin (Ig) E in OVA-induced asthma model. Reductions in airway inflammation and mucus hypersecretion, accompanied by decreases in the expression of inducible nitric oxide synthase (iNOS) and the phosphorylation of nuclear factor kappa B (NF-κB), were also observed. Our results indicated that DA attenuated the asthmatic response, and that this attenuation was closely linked to NF-κB suppression. Thus, this study suggests that DA is a potential therapeutic for allergic asthma.

Modificated Mahuang-Tang, a traditional herbal medicine suppresses inflammatory responses induced by cigarette smoke in human airway epithelial cell and mice.

BACKGROUND: Cigarette smoke (CS) is a major contributor to the high incidence of chronic obstructive pulmonary disease (COPD) featured as chronic inflammation and airway obstruction. Mahuang-Tang is a traditional polyherbal mixture composed of four different herbs. It is widely used in Asia as a remedy for allergic reaction and inflammation. PURPOSE: We investigated the effects of a modificated Mahuang-Tang water extract (MTWE) against airway inflammation caused by CS and lipopolysaccharide (LPS) in mice and cigarette smoke condensate (CSC)-stimulated NCI-H292 cells. METHODS: CS exposed to animals for 1 h per day from day 1 to day 7 and treated with LPS intranasally on day 4. One hour before CS exposure, animals were received MTWE (50 or 100 mg/kg) by oral gavage. Inflammatory cell count and cytokines levels were measured in the bronchoalveolar lavage fluid. Expression levels of matrix metalloprotease-9 (MMP-9) and extracellular signal-regulated kinase (Erk) were analyzed by western blotting. RESULTS: MTWE markedly decreased the neutrophil and other inflammatory cell counts in the bronchoalveolar lavage fluid and reduced proinflammatory mediators as evidenced by the decreases in inflammatory cell recruitment in lung tissue. Furthermore, MTWE meaningfully declined MMP-9 expression and reduced the Erk phosphorylation, caused by the CS and LPS exposure. In in vitro experiments, MTWE suppressed the elevated expression of proinflammatory cytokines induced by CSC treatment. MTWE reduced Erk phosphorylation and MMP-9 expression in CSC-stimulated H292 cells. CONCLUSION: Overall, MTWE effectively inhibited the pulmonary inflammation and MMP-9 expression caused by the CS and LPS exposure, which was closely involved in suppression of Erk phosphorylation. These results suggest that MTWE possesses a potential for the treatment of COPD.

S-Allyl cysteine reduces eosinophilic airway inflammation and mucus overproduction on ovalbumin-induced allergic asthma model.

S-Allyl cysteine (SAC) is an active component in garlic and has various pharmacological effects, such as anti-inflammatory, anti-oxidant, and anti-cancer activities. In this study, we explored the suppressive effects of SAC on allergic airway inflammation induced in an ovalbumin (OVA)-induced asthma mouse model. To induce asthma, BALB/c mice were sensitized to OVA on days 0 and 14 by intraperitoneal injection and exposed to OVA from days 21 to 23 using a nebulizer. SAC was administered to mice by oral gavage at a dose of 10 or 20 mg/kg from days 18 to 23. SAC significantly reduced airway hyperresponsiveness, inflammatory cell counts, and Th2 type cytokines in bronchoalveolar lavage fluid induced by OVA exposure, which was accompanied by reduced serum OVA-specific immunoglobulin E. In histological analysis of the lung tissue, administration of SAC reduced inflammatory cell accumulation into lung tissue and mucus production in airway goblet cells induced by OVA exposure. Additionally, SAC significantly decreased MUC5AC expression and nuclear factor-κB phosphorylation induced by OVA exposure. In summary, SAC effectively suppressed allergic airway inflammation and mucus production in OVA-challenged asthmatic mice. Therefore, SAC shows potential for use in treating allergic asthma.

Preventive Effect of Garlic Oil and Its Organosulfur Component Diallyl-Disulfide on Cigarette Smoke-Induced Airway Inflammation in Mice.

Garlic (Allium sativum) has traditionally been used as a medicinal food and exhibits various beneficial activities, such as antitumor, antimicrobial, hypolipidemic, antiarthritic, and hypoglycemic activities. The aim of this study was to explore the preventive effect of garlic oil (GO) and its organosulfur component diallyl disulfide (DADS) on cigarette smoke (CS)-induced airway inflammation. Mice were exposed to CS daily for 1 h (equivalent to eight cigarettes per day) for two weeks, and intranasally instilled with lipopolysaccharide (LPS) on day 12 after the initiation of CS exposure. GO and DADS were administered to mice by oral gavage, both at rates of 20 and 40 mg/kg, for 1 h before CS exposure for two weeks. In the bronchoalveolar lavage fluid, GO and DADS inhibited the elevation in the counts of inflammatory cells, particularly neutrophils, which were induced in the CS and LPS (CS + LPS) group. This was accompanied by the lowered production (relative to the CS + LPS group) of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α. Histologically, GO and DADS inhibited the CS- and LPS-induced infiltration of inflammatory cells into lung tissues. Additionally, GO and DADS inhibited the phosphorylation of extracellular signal-regulated kinase and the expression of matrix metalloproteinase-9 in the lung tissues. Taken together, these findings indicate that GO and DADS could be a potential preventive agent in CS-induced airway inflammation.

Galgeun-tang Attenuates Cigarette Smoke and Lipopolysaccharide Induced Pulmonary Inflammation via IκBα/NF-κB Signaling.

Galgeun-tang water extract (GGWE) is used to treat various diseases such as the common cold, eczema and asthma in China and Korea. In this study, we investigated the anti-inflammatory effect of GGWE using a cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced induced pulmonary inflammation mouse model. The mice were exposed to CS for a total of seven days (eight cigarettes per day for 1 h) and LPS was administered intranasally to mice on day 4. GGWE was administered by oral gavage at doses of 50 mg/kg or 100 mg/kg 1 h before exposure to CS. GGWE decreased inflammatory cell counts, and expression of inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) in bronchoalveolar lavage fluid (BALF) from mice exposed to CS and LPS. GGWE reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the phosphorylation of inhibitor of kappa-B subunit alpha (IκBα) and nuclear factor kappa-B (NF-κB) in CS- and LPS-exposed mice. Histological examinations revealed that GGWE suppressed inflammatory cell infiltration into lung tissue compared to untreated CS- and LPS-exposed mice. In conclusion, GGWE effectively suppressed CS- and LPS-induced pulmonary inflammation. Our results indicate that GGWE may be used as a protective drug to control pulmonary inflammation diseases such as chronic obstructive pulmonary disease.

Protective effect of water extract of guibi-tang against pulmonary inflammation induced by cigarette smoke and lipopolysaccharide.

Water extract of guibi-tang (GB), a traditional Chinese, Japanese, and Korean herbal medicine, is used to treat memory impairment, insomnia, and peptic ulcers. The aim of this study was to investigate the protective effects of GB on pulmonary inflammation induced by cigarette smoke (CS) and lipopolysaccharide (LPS). C57BL/6 mice were used to develop a pulmonary inflammation model by exposing them to CS for 1 h per day for 7 days. LPS was intranasally administered to mice under mild anesthesia on day 5. GB was administered 1 h before CS exposure at doses of 50 or 100 mg/kg for 7 days. Our results showed that GB suppressed the CS and LPS induced elevation in inflammatory cell counts in the bronchoalveolar lavage fluid (BALF), with significant reductions in protein, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 levels. Histological studies revealed that GB decreased the inflammatory cell infiltration into lung tissue caused by CS- and LPS-exposure. GB also significantly decreased the CS and LPS-induced expression of inducible nitric oxide synthase (iNOS) in the lung tissue. Taken together, GB effectively attenuated airway inflammation caused by CS and LPS. These results indicate that GB is a potential therapeutic herbal formula for pulmonary inflammatory disease.

Genipin inhibits allergic responses in ovalbumin-induced asthmatic mice.

Genipin is a natural compound isolated from the fruit of Gardenia jasminoides with various pharmacological effects. In this study, we investigated whether genipin effectively alleviates allergic responses in a murine model of ovalbumin (OVA)-induced asthma. The mice were administered an intraperitoneal injection of OVA on day 0 and 14 to boost the immune response; genipin was then administered from day 18 to 23 by oral gavage. On days 21 to 23, mice were OVA-challenged using am ultrasonic nebulizer, and airway hyperresponsiveness (AHR) was determined on day 24 by plethysmography. Genipin significantly reduced the inflammatory cell count in bronchoalveolar lavage fluids (BALF) and AHR, which were accompanied by lower interleukin-5 (IL-5), IL-13 and OVA-specific immunoglobulin (Ig) E levels in the BALF or serum from OVA-induced asthmatic mice. In histology, genipin significantly decreased airway inflammation and mucus hypersecretion in OVA-induced asthmatic mice. Additionally, genipin inhibited OVA-induced increases in the expression of inducible nitric oxide synthase and cyclooxygenase-2 proteins. Further, genipin reduced the activity and protein levels of matrix metalloproteinase-9 in lung tissue from OVA induced asthmatic mice. Overall, genipin effectively alleviated the asthmatic inflammatory response in an OVA-induced asthmatic model. Therefore, our results suggest that genipin has therapeutic potential for treating asthma.

Artemisia argyi attenuates airway inflammation in ovalbumin-induced asthmatic animals.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia argyi is a traditional herbal medicine in Korea and commonly called as mugwort. It is traditionally used as food source and tea to control abdominal pain, dysmenorrhea, uterine hemorrhage, and inflammation. AIM OF THE STUDY: We investigated the effects of A. argyi (TOTAL) and dehydromatricarin A (DA), its active component on ovalbumin (OVA)-induced allergic asthma. MATERIALS AND METHODS: The animals were sensitized on day 0 and 14 by intraperitoneal injection of OVA with aluminum hydroxide. On day 21, 22 and 23 after the initial sensitization, the animals received an airway challenge with OVA for 1h using an ultrasonic nebulizer. TOTAL (50 and 100mg/kg) or DA (10 and 20mg/kg) were administered to mice by oral gavage once daily from day 18-23. Airway hyperresponsiveness (AHR) was measured 24h after final OVA challenge. RESULT: TOTAL and DA treated animals reduced inflammatory cell counts, cytokines and AHR in asthmatic animals, which was accompanied with inflammatory cell accumulation and mucus hypersecretion. Furthermore, TOTAL and DA significantly declined Erk phosphorylation and the expression of MMP-9 in asthmatic animals. CONCLUSION: In conclusion, we indicate that Total and DA suppress allergic inflammatory responses caused by OVA challenge. It was considered that A. argyi has a potential for treating allergic asthma.

HemoHIM, a herbal preparation, alleviates airway inflammation caused by cigarette smoke and lipopolysaccharide.

HemoHIM, herbal preparation has designed for immune system recovery. We investigated the anti-inflammatory effect of HemoHIM on cigarette smoke (CS) and lipopolysaccharide (LPS) induced chronic obstructive pulmonary disease (COPD) mouse model. To induce COPD, C57BL/6 mice were exposed to CS for 1 h per day (eight cigarettes per day) for 4 weeks and intranasally received LPS on day 26. HemoHIM was administrated to mice at a dose of 50 or 100 mg/kg 1h before CS exposure. HemoHIM reduced the inflammatory cell count and levels of tumor necrosis factor receptor (TNF)-α, interleukin (IL)-6 and IL-1ß in the broncho-alveolar lavage fluid (BALF) induced by CS+LPS exposure. HemoHIM decreased the inflammatory cell infiltration in the airway and inhibited the expression of iNOS and MMP-9 and phosphorylation of Erk in lung tissue exposed to CS+LPS. In summary, our results indicate that HemoHIM inhibited a reduction in the lung inflammatory response on CS and LPS induced lung inflammation via the Erk pathway. Therefore, we suggest that HemoHIM has the potential to treat pulmonary inflammatory disease such as COPD.

Protective effect of HwangRyunHaeDok-Tang water extract against chronic obstructive pulmonary disease induced by cigarette smoke and lipopolysaccharide in a mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: Hwangryunhaedok-tang is an oriental herbal formula treated to cure inflammation and gastric disorders in China, Japan, and Korea. We explored the protective effects of Hwangryunhaedok-tang water extract (HRWE) against airway pathophysiological changes caused by cigarette smoke (CS) and lipopolysaccharide (LPS) in a mouse. MATERIALS AND METHODS: We performed quantitative analyses of five marker components, namely geniposide, baicalin, coptisine, plamatine, and berberine, using high-performance liquid chromatography. Animals were received CS exposure (1h per day) for 7 days. LPS was administered intranasally on day 4. Mice were received HRWE at dose of 100 or 200mg/kg for 1h before CS exposure. RESULTS: Treatment with HRWE significantly suppressed the increased inflammatory cell count induced by CS and LPS exposure. In addition, reduction in IL-6, TNF-α and IL-1ß in broncho-alveolar lavage fluid (BALF) was observed after HRWE treatment. HRWE not only decreased inflammatory cell infiltration in lung, but also decreased the expression of iNOS, NF-κB and matrix metallopeptidase (MMP)-9 in lung tissues. CONCLUSION: This study showed that HRWE can attenuate respiratory inflammation caused by CS and LPS exposure. Therefore, HRWE has potential for treating airway inflammatory disease.