Editorial of Special Issue "Molecular Mechanisms of Natural Products and Phytochemicals in Immune Cells and Asthma".

The Special Issue "Molecular Mechanisms of Natural Products and Phytochemicals in Immune Cells and Asthma" in the International Journal of Molecular Sciences includes original research and reviews on the molecular mechanisms of active, natural products (medicinal plants and animal ones) and phytochemicals in vitro and in vivo [...].

Hypericum ascyron L. extract reduces particulate matter-induced airway inflammation in mice.

The consequences of increased industrialization increased the risk of asthma and breathing difficulties due to increased particulate matter in the air. We aim to investigate the therapeutic properties of Hypericum ascyron L. extract (HAE) in airway inflammation and unravel its mechanism of action. We conducted nitric oxide and cell viability assay, real-time PCR and western blot analyses along with in vitro studies. in vivo studies include a model of coal fly ash and diesel exhaust particle (CFD)-induced airway inflammation in mice. HAE reduced coal fly ash (CFA)-induced nitric oxide secretion without exhibiting cytotoxicity in MH-S cells. HAE also reduced the mRNA expression of pro-inflammatory cytokines and reduced the expression of proteins in the NFκB and MAPK pathways. In a mice model of CFD-induced airway inflammation, HAE effectively reduced neutrophil infiltration in bronchoalveolar lavage fluid (BALF) and increased the amount of T cells in the BALF, lungs, and blood while reducing all other immune cell subtypes to reduce airway inflammatory response. CXCL-1, IL-17, MIP-2, and TNF-α expression in the BALF were also reduced. HAE effectively reduced MIP-2 and TNF-α mRNA expression in the lung tissue of mice. In a nutshell, HAE is effective in preventing airway inflammation induced by CFA in MH-S cells, as well as inflammation induced by CFD in mice.

Cryptotympana pustulata Extract and Its Main Active Component, Oleic Acid, Inhibit Ovalbumin-Induced Allergic Airway Inflammation through Inhibition of Th2/GATA-3 and Interleukin-17/RORγt Signaling Pathways in Asthmatic Mice.

Cicadae Periostracum (CP), derived from the slough of Cryptotympana pustulata, has been used as traditional medicine in Korea and China because of its diaphoretic, antipyretic, anti-inflammatory, antioxidant, and antianaphylactic activities. The major bioactive compounds include oleic acid (OA), palmitic acid, and linoleic acid. However, the precise therapeutic mechanisms underlying its action in asthma remain unclear. The objective of this study was to determine the antiasthmatic effects of CP in an ovalbumin (OVA)-induced asthmatic mouse model. CP and OA inhibited the inflammatory cell infiltration, airway hyperresponsiveness (AHR), and production of interleukin (IL)7 and Th2 cytokines (IL-5) in the bronchoalveolar lavage fluid and OVA-specific imunoglobin E (IgE) in the serum. The gene expression of IL-5, IL-13, CCR3, MUC5AC, and COX-2 was attenuated in lung tissues. CP and OA might inhibit the nuclear translocation of GATA-binding protein 3 (GATA-3) and retinoic acid receptor-related orphan receptor γt (RORγt) via the upregulation of forkhead box p3 (Foxp3), thereby preventing the activation of GATA-3 and RORγt. In the in vitro experiment, a similar result was observed for Th2 and GATA-3. These results suggest that CP has the potential for the treatment of asthma via the inhibition of the GATA-3/Th2 and IL-17/RORγt signaling pathways.

The Ethanol Extract of Holotrichia diomphalia Larvae, Containing Fatty acids and Amino acids, Exerts Anti-Asthmatic Effects through Inhibition of the GATA-3/Th2 Signaling Pathway in Asthmatic Mice.

Holotrichia diomphalia larvae (HD), a natural product from an insect resource, possesses many pharmacological properties, including anticoagulant, antitumor, anti-inflammatory, and analgesic activity. The major bioactive ingredients include oleic acid, palmitic acid, palmitoleic acid, linoleic acid, proline, and glutamic acid. Although HD is associated with immunoregulatory activities in allergic diseases, the therapeutic mechanisms of the action of HD in allergic diseases have not been investigated. The aim of this study was to evaluate the anti-asthmatic potential of HD in an ovalbumin (OVA)-induced mouse model of allergic asthma. Moreover, the anti-inflammatory potential of HD was examined to identify a plausible mechanism of action of HD in vitro. HD strongly reduced goblet cell hyperplasia, eosinophil infiltration, and reactive oxygen species (ROS), which reduced airway hyperresponsiveness (AHR), inflammation, and the expression of Th2 cytokines (IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF). The expression of IL-5, IL-4, eotaxin-2, lysyl oxidase-like 2 (loxl2), and GATA-binding protein 3 (GATA-3) was attenuated in the lungs. In an in vitro assay, HD exerted immunomodulatory effects through the suppression of Th2 cytokines (IL-5, IL-13), IL-17, and tumor necrosis factor (TNF)-α production through downregulation of GATA-3 expression in EL-4 T cells. These findings suggest that the anti-asthmatic activity of HD may occur through the suppression of Th2 cytokines and total Immunoglobulin E (IgE) production by inhibition of the GATA-3 transcription pathway. Our results suggest that HD may be a potential alternative therapy, or a novel therapeutic traditional medicine, for the treatment of allergic asthma.

The Inhibitory Effect of Nodakenin on Mast-Cell-Mediated Allergic Inflammation Via Downregulation of NF-κB and Caspase-1 Activation.

Nodakenin, a coumarin isolated from the roots of Angelicae gigas, is effective for treating function control disorders, bacterial infections, pain, diarrhea, vitamin E deficiency, and for relaxation of the uterus. The aim of this study was to investigate the antiallergic related inflammatory effects in phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1) or anaphylactic activity in a mouse model. Nodakenin inhibited the mRNA expression and production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß in PMACI-stimulated HMC-1. We also studied the inhibitory effects of nodakenin on the nuclear translocation of nuclear factor kappa B (NF-κB) and activation of caspase-1, inhibitory κB kinase (IKK), and Akt in PMACI-stimulated HMC-1. However, mitogen-activated protein kinase (MAPK) activation was not sufficient to abrogate the stimulus. In addition, administration of nodakenin at 20 mg/kg inhibited histamine release and protected mice against compound 48/80-induced anaphylactic mortality. Furthermore, Nodakenin inhibited the mRNA expression and production of pro-inflammatory cytokines and caspase-1 activation in compound 48/80-induced anaphylactic mice. These results suggest new insight that nodakenin may be a promising antiallergic related inflammatory agent for inflammatory disorders. J. Cell. Biochem. 118: 3993-4001, 2017. © 2017 Wiley Periodicals, Inc.

Degree of Impurity and Carbon Contents in the Grain Size of Mg-Al Magnesium Alloys.

In this study, the tendency of having different grain structures depending on the impurity levels in AZ91 alloys was investigated. Two types of AZ91 alloys were analyzed: commercial-purity AZ91 and high-purity AZ91. The average grain size of the commercial-purity AZ91 alloy and high-purity AZ91 is 320 µm and 90 µm, respectively. Thermal analysis revealed negligible undercooling in the high-purity AZ91 alloy, while undercooling of 1.3 °C was observed in the commercial-purity AZ91 alloy. A CS analyzer was employed to precisely analyze the carbon composition of both alloys. The carbon content of the high-purity AZ91 alloy was found to be 197 ppm, while the commercial-purity AZ91 alloy contained 104 ppm, indicating a difference of approximately 2 times. The higher carbon content in the high-purity AZ91 alloy is believed to be due to the use of high-purity pure Mg in its production (the carbon content of high-purity pure Mg is 251 ppm). To simulate the vacuum distillation process commonly used in the production of high-purity Mg ingots, experiments were conducted to investigate the reaction of carbon with oxygen to produce CO and CO2. XPS analysis and simulation results for activities confirmed the formation of CO and CO2 during the vacuum distillation process. It could be speculated that the carbon sources in the high-purity Mg ingot provide Al-C particles, which act as nucleants for Mg grains in the high-purity AZ91 alloy. Thus, it can be considered the main reason that high-purity AZ91 alloys have a finer grain structure than that of commercial-purity AZ91 alloys.

Respiratory protective effects of Korean Red Ginseng in a mouse model of particulate matter 4-induced airway inflammation.

Background: Air pollution has led to an increased exposure of all living organisms to fine dust. Therefore, research efforts are being made to devise preventive and therapeutic remedies against fine dust-induced chronic diseases. Methods: Research of the respiratory protective effects of KRG extract in a particulate matter (PM; aerodynamic diameter of <4 µm) plus diesel exhaust particle (DEP) (PM4+D)-induced airway inflammation model. Nitric oxide production, expression of pro-inflammatory mediators and cytokines, and IRAK-1, TAK-1, and MAPK pathways were examined in PM4-stimulated MH-S cells. BALB/c mice exposed to PM4+D mixture by intranasal tracheal injection three times a day for 12 days at 3 day intervals and KRGE were administered orally for 12 days. Histological of lung and trachea, and immune cell subtype analyses were performed. Expression of pro-inflammatory mediators and cytokines in bronchoalveolar lavage fluid (BALF) and lung were measured. Immunohistofluorescence staining for IRAK-1 localization in lung were also evaluated. Results: KRGE inhibited the production of nitric oxide, the expression of pro-inflammatory mediators and cytokines, and expression and phosphorylation of all downstream factors of NF-κB, including IRAK-1 and MAPK/AP1 pathway in PM4-stimulated MH-S cells. KRGE suppressed inflammatory cell infiltration and number of immune cells, histopathologic damage, and inflammatory symptoms in the BALF and lungs induced by PM4+D; these included increased alveolar wall thickness, accumulation of collagen fibers, and TNF-α, MIP2, CXCL-1, IL-1α, and IL-17 cytokine release. Moreover, PM4 participates induce alveolar macrophage death and interleukin-1α release by associating with IRAK-1 localization was also potently inhibited by KRGE in the lungs of PM4+D-induced airway inflammation model. KRGE suppresses airway inflammatory responses, including granulocyte infiltration into the airway, by regulating the expression of chemokines and inflammatory cytokines via inhibition of IRAK-1 and MAPK pathway. Conclusion: Our results indicate the potential of KRGE to serve as an effective therapeutic agent against airway inflammation and respiratory diseases.

Anti-Inflammatory Effects of Cicadidae Periostracum Extract and Oleic Acid through Inhibiting Inflammatory Chemokines Using PCR Arrays in LPS-Induced Lung inflammation In Vitro.

In this study, we aimed to evaluate the anti-inflammatory effects and mechanisms of CP and OA treatments in LPS-stimulated lung epithelial cells on overall chemokines and their receptors using PCR arrays. In addition, we aimed to confirm those effects and mechanisms in LPS-stimulated lung macrophages on some chemokines and cytokines. In our study, CP treatments significantly inhibited the inflammatory mediators CCL2, CCL3, CCL4, CCL5, CCL6, CCL9, CCL11, CCL17, CCL20, CXCL1, CXCL2, CXCL3, CXCL5, CXCL7, CXCL10, TNF-α, and IL-6, while markedly suppressing NF-κB p65 nuclear translocation and the phosphorylations of PI3K p55, Akt, Erk1/2, p38, and NF-κB p65 in LPS-stimulated lung epithelial cells. CP treatments also significantly decreased the inflammatory mediators CCL2, CCL5, CCL17, CXCL1, and CXCL2, while markedly inhibiting phospho-PI3K p55 and iNOS expression in LPS-stimulated lung macrophages. Likewise, OA treatments significantly suppressed the inflammatory mediators CCL2, CCL3, CCL4, CCL5, CCL8, CCL11, CXCL1, CXCL3, CXCL5, CXCL7, CXCL10, CCRL2, TNF-α, and IL-6, while markedly reducing the phosphorylations of PI3K p85, PI3K p55, p38, JNK, and NF-κB p65 in LPS-stimulated lung epithelial cells. Finally, OA treatments significantly inhibited the inflammatory mediators CCL2, CCL5, CCL17, CXCL1, CXCL2, TNF-α, and IL-6, while markedly suppressing phospho-PI3K p55, iNOS, and Cox-2 in LPS-stimulated lung macrophages. These results prove that CP and OA treatments have anti-inflammatory effects on the inflammatory chemokines and cytokines by inhibiting pro-inflammatory mediators, including PI3K, Akt, MAPKs, NF-κB, iNOS, and Cox-2. These findings suggest that CP and OA are potential chemokine-based therapeutic substances for treating the lung and airway inflammation seen in allergic disorders.

Antiasthmatic effects of hesperidin, a potential Th2 cytokine antagonist, in a mouse model of allergic asthma.

BACKGROUND AND OBJECTIVE: The features of asthma are airway inflammation, reversible airflow obstruction, and an increased sensitivity to bronchoconstricting agents, termed airway hyperresponsiveness (AHR), excess production of Th2 cytokines, and eosinophil accumulation in the lungs. To investigate the antiasthmatic potential of hesperidin as well as the underlying mechanism involved, we studied the inhibitory effect and anti-inflammatory effect of hesperidin (HPN) on the production of Th2 cytokines, eotaxin, IL-17, -OVA-specific IgE in vivo asthma model mice. METHODS: In this paper, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed intratracheally, intraperitoneally, and by aerosol allergen challenges. We investigated the effect of HPN on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production and OVA-specific IgE production in a mouse model of asthma. RESULTS: In BALB/c mice, we found that HPN-treated groups had suppressed eosinophil infiltration, allergic airway inflammation, and AHR, and these occurred by suppressing the production of IL-5, IL-17, and OVA-specific IgE. CONCLUSIONS: Our data suggest that the therapeutic mechanism by which HPN effectively treats asthma is based on reductions of Th2 cytokines (IL-5), eotaxin, OVA-specific IgE production, and eosinophil infiltration via inhibition of GATA-3 transcription factor.

Preparation of Fly Ash/Epoxy Composites and Its Effects on Mechanical Properties.

In this research, a fly ash/epoxy composite was fabricated using fly ash filler classified as industrial waste. The behavior of its mechanical properties was investigated by changing the volume of fly ash to 10, 30 and 50 vol.%. To determine the influence of particle size on the mechanical properties, we used two different sizes of the fly ash, which were separated by sieving to less than 90 µm and 53 µm. To optimize fabrication conditions, the viscosity of the fly ash/epoxy slurry was measured at various temperatures with different fly ash volume fractions. In terms of mechanical properties, tensile strength increased as the amount of fly ash increased, up to a critical point. On the other hand, the compression strength of the composite increased continuously as the amount of fly ash increased. Finally, the fracture surfaces were characterized and correlated with the mechanical properties.

NCM 1921, a Mixture of Several Ingredients, Including Fatty Acids and Choline, Attenuates Atopic Dermatitis in 1-Chloro-2,4-Dinitrobenzene-Treated NC/Nga Mice.

Atopic dermatitis (AD) is a chronic inflammatory skin disease in humans. In this study, we evaluated the effects of a mixture (NCM 1921) of omega-3 butter, omega-3 beef tallow oil, omega-3 lard oil, caprylic acid, lauric acid, choline, and Fe on AD in 1-chloro-2,4-dinitrobenzene (DNCB)-treated NC/Nga mice. NCM 1921 significantly ameliorated the macroscopic and microscopic signs and reduced skin thickness and mast cell incorporation in the skin lesions of mice with DNCB-induced AD. Furthermore, it reduced serum immunoglobulin E levels; reduced the number of IgE-producing B cells, peripheral blood mononuclear cells, white blood cells, and differential white blood cells; and increased the number of lymphocytes. NCM 1921 normalized the total cell number in dorsal skin tissue, the axillary lymph node, and spleen following DNCB exposure and reduced the number of CD23+/B220+ cells in the axillary lymph node and CD3+ cells in dorsal skin tissue. Moreover, it reduced the levels of interleukin (IL)-4 and IL-13 but increased the levels of interferon-γ in anti-CD3-stimulated splenocytes. Immunohistofluorescence staining showed that NCM 1921 treatment significantly increased claudin1, filaggrin, and Sirt1 protein expressions in AD skin lesions. These results suggest that NCM 1921 could be a valuable remedy for the treatment of AD.

Herbal Combinational Medication of Glycyrrhiza glabra, Agastache rugosa Containing Glycyrrhizic Acid, Tilianin Inhibits Neutrophilic Lung Inflammation by Affecting CXCL2, Interleukin-17/STAT3 Signal Pathways in a Murine Model of COPD.

Chronic obstructive pulmonary disease (COPD) is caused by exposure to toxic particles, such as coal fly ash (CFA), diesel-exhaust particle (DEP), and cigarette smoke (CS), leading to chronic bronchitis, mucus production, and a subsequent lung dysfunction. This study, using a mouse model of COPD, aimed to evaluate the effect of herbal combinational medication of Glycyrrhiza glabra (GG), Agastache rugosa (AR) containing glycyrrhizic acid (GA), and tilianin (TN) as active ingredients. GA, a major active component of GG, possesses a range of pharmacological and biological activities including anti-inflammatory, anti-allergic, anti-oxidative. TN is a major flavonoid that is present in AR. It has been reported to have anti-inflammatory effects of potential utility as an anti-COPD agent. The COPD in the mice model was induced by a challenge with CFA and DEP. BALB/c mice received CFA and DEP alternately three times for 2 weeks to induce COPD. The herbal mixture of GG, AR, and TN significantly decreased the number of neutrophils in the lungs and bronchoalveolar lavage (BAL) fluid. It also significantly reduced the production of C-X-C motif chemokine ligand 2 (CXCL-2), IL-17A, CXCL-1, TNF-α, symmetric dimethylarginine (SDMA) in BALF and CXCL-2, IL-17A, CXCL-1, MUC5AC, transient receptor potential vanilloid-1 (TRPV1), IL-6, COX-2, NOS-II, and TNF-α mRNA expression in the lung tissue. Notably, a combination of GG and AR was more effective at regulating such therapeutic targets than GG or AR alone. The histolopathological lung injury was alleviated by treatment with the herbal mixture and their active ingredients (especially TN). In this study, the herbal combinational mixture more effectively inhibited neutrophilic airway inflammation by regulating the expression of inflammatory cytokines and CXCL-2 by blocking the IL-17/STAT3 pathway. Therefore, a herbal mixture of GG and AR may be a potential therapeutic agent to treat COPD.

Effects of a herbal formulation, KGC3P, and its individual component, nepetin, on coal fly dust-induced airway inflammation.

Coal fly dust (CFD)-induced asthma model is used as an ambient particulate matter model of serious pulmonary damage. We aimed to evaluate the effects of a combination of ginseng and Salvia plebeia R. Br extract (KGC-03-PS; KG3P) and its individual components (hispidulin, nepetin and rosmarinic acid) in a CFD-induced mouse model of airway inflammation (asthma). We also evaluated signal transduction by KG3P and its individual components in the alveolar macrophage cell line, MH-S cells. In vitro, KG3P and its individual components inhibited nitric oxide production and expression of pro-inflammatory mediators and cytokines (iNOS, COX-2, IL-1ß, IL-6 and TNF-α) through the NF-κB and MAPK pathways in coal fly ash (CFA)-induced inflammation in MH-S cells. Moreover, in the CFD-induced asthma model in mice, KG3P and its predominant individual component, nepetin, inhibited Asymmetric Dimethyl arginine (ADMA) and Symmetric Dimethyl arginine (SDMA) in serum, and decreased the histopathologic score in the lungs. A significant reduction in the neutrophils and immune cells in BALF and lung tissue was demonstrated, with significant reduction in the expression of the pro-inflammatory cytokines. Finally, IRAK-1 localization was also potently inhibited by KG3P and nepetin. Thus, KG3P extract can be considered as a potent candidate for amelioration of airway inflammation.

Piperine inhibits eosinophil infiltration and airway hyperresponsiveness by suppressing T cell activity and Th2 cytokine production in the ovalbumin-induced asthma model.

OBJECTIVES: This study aimed to investigate the effect of piperine on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production, immunoglobulin E and histamine production in a murine model of asthma. METHODS: Asthma was induced in Balb/c mice by ovalbumin sensitization and inhalation. Piperine (4.5 and 2.25 mg/kg) was orally administered 5 times a week for 8 weeks. At 1 day after the last ovalbumin exposure, airway hyperresponsiveness was determined and samples of bronchoalveolar lavage fluid, lung cells and serum were collected for further analysis. KEY FINDINGS: Piperine-treated groups had suppressed eosinophil infiltration, allergic airway inflammation and airway hyperresponsiveness, and these occurred by suppression of the production of interleukin-4, interleukin-5, immunoglobulin E and histamine. Moreover, polymerase chain reaction products for thymus and activation regulated chemokine from lung cell RNA preparations were decreased in the piperine-treated group compared with control groups, although transforming growth factor-beta products were increased in the piperine-treated group. CONCLUSIONS: The results suggest that the therapeutic mechanism by which piperine effectively treats asthma is based on a reduction of Th2 cytokines (interleukin-4, interleukin-5), eosinophil infiltration, and by marked reduction of thymus and activation regulated chemokine, eotaxin-2 and interleukin-13 mRNA expression (especially transcription of nuclear factor-kappaB dependent genes) in lung tissue, as well as reduced interleukin-4, interleukin-5 and eotaxin levels in bronchoalveolar lavage fluid, and histamine and ovalbumin-specific immunoglobulin E production in serum.

Pinellia ternata, Citrus reticulata, and their combinational prescription inhibit eosinophil infiltration and airway hyperresponsiveness by suppressing CCR3+ and Th2 cytokines production in the ovalbumin-induced asthma model.

BACKGROUND AND OBJECTIVE: This study was aimed to analyse the curative effects of Pinellia ternata, Citrus reticulata, and their combination on airway hyperresponsiveness (AHR) to inhaled methacholine, pulmonary eosinophilic infiltration, Th2 cytokine production, and IgE and histamine production in a murine model of asthma. METHODS: For this purpose, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed intratracheally, intraperitoneally, and by aerosol allergen challenges for 12 weeks. We examined the development of pulmonary eosinophilic accumulation, control of Th2 cytokine, immunoglobulin E (IgE), and histamine productions in a murine model of asthma. RESULTS: Our data suggest that the therapeutic mechanism by which Pinellia ternata, Citrus reticulata, and their combinational prescription effectively treats asthma is based on reductions of eosinophil infiltration, eotaxin receptor (CCR3), histamine, OVA-specific IgE productions in serum, and Th2 cytokines (IL-5, IL-13) by marked reductions of IL-5 and IL-13 mRNA expression in lung tissue. CONCLUSIONS: These findings provide evidence that Pinellia ternata, Citrus reticulata, and their combination play a regulatory role in allergic inflammation and offer therapeutic approaches as novel CCR3 antagonists for treatment asthma. However, it is not clear whether pharmacological activities of prescription composed of two herbs are potentiated due to synergistic effect or additive effect.

KGC3P attenuates ovalbumin-induced airway inflammation through downregulation of p-PTEN in asthmatic mice.

BACKGROUND: The roots of Korean red ginseng (Panax ginseng C.A.Mey.; KGC) have been used as an herbal supplement to enhance vital energy and immune capacity. Salvia plebeia R.Br. has been used to treat inflammatory diseases. PURPOSE: The aim of this study was to examine the anti-asthmatic effects of a mixture of Korean red ginseng and Salvia plebeia R.Br. (KGC3P), its component nepetin, and their modes of action in alleviating ovalbumin (OVA)-induced asthma in mice. METHOD: BALB/c mice were sensitized with OVA then subjected to intratracheal, intraperitoneal, and aerosol challenges. KGC3P and nepetin were administered orally for four weeks. Airway hyperresponsiveness (AHR), OVA-specific IgE levels, and Th2 cytokine- and gene expression levels in bronchoalveolar lavage fluid (BALF) and splenocytes were measured. Histological and immune cell subtype analyses were performed. PTEN and Akt phosphorylation levels were also evaluated. RESULTS: KGC3P reduced OVA-induced AHR, serum IgE levels, histological changes, and eosinophils infiltration but also the absolute number of immune cell subtypes including CD3+/CD4+, CD3+/CD8+, CD4+/CD69+, and Gr-1+/CD11b+ in the lungs, BALF, and mesenteric lymph nodes (MLN). KGC3P also lowered the Th2 cytokines IL-4, IL-5, and IL-13 in the BALF and splenocytes and downregulated the IL-4, IL-13, IL-17, TNF-α, and MUC5AC genes in the lung. KGC3P upregulated the peroxisome proliferator-activated receptor (PPAR)γ gene but downregulated the p-Akt and p-PTEN phosphorylation. Similar results were obtained with nepetin treatment. CONCLUSION: KGC3P and nepetin are anti-asthmatic because they reduce various immune cells such as eosinophils and Th2 cell as well as Th2 cytokines. These mechanisms may be accompanied by the regulation of PPARγ expression and the PTEN pathway. Taken together, our results indicate that KGC3P and nepetin may potentially prevent and treat asthma.

Effects of radix adenophorae and cyclosporine A on an OVA-induced murine model of asthma by suppressing to T cells activity, eosinophilia, and bronchial hyperresponsiveness.

The present study is performed to investigate the inhibitory effects of Radix Adenophorae extract (RAE) on ovalbumin-induced asthma murine model. To study the anti-inflammatory and antiasthmatic effects of RAE, we examined the development of pulmonary eosinophilic inflammation and inhibitory effects of T cells in murine by RAE and cyclosporine A (CsA). We examined determination of airway hyperresponsiveness, flow cytometric analysis (FACS), enzyme-linked immunosorbent assay (ELISA), quantitative real time (PCR), hematoxylin-eosin staining, and Masson trichrome staining in lung tissue, lung weight, total cells, and eosinophil numbers in lung tissue. We demonstrated how RAE suppressed development on inflammation and decreased airway damage.

Luteolin attenuates airway inflammation by inducing the transition of CD4+CD25- to CD4+CD25+ regulatory T cells.

Regulatory T cells play an important role in autoimmunity and have been shown to exert anti-inflammatory effects in allergic asthma. Mouse model of airway inflammation was used to examine the suppressive activity of luteolin-induced CD4+CD25+ regulatory T cells (Tregs) in vivo. In this study, BALB/c mice were sensitized with ovalbumin antigen (OVA) by aerosol challenge. Then, various biological processes were examined, including airway eosinophilia; mucus hypersecretion; elevation of OVA-specific IgE, expression of Th2 cytokines and chemokine levels; expression of eotaxin 2 and CCR3; and airway hyper responsiveness (AHR). Luteolin significantly inhibited OVA-induced increase in immune cell and eosinophil counts as well as IL-4, IL-5, IL-13, and eotaxin levels in bronchoalveolar lavage fluid (BAL Fluid). Luteolin and cyclosporine A (CsA) which was a positive control also substantially reduced OVA-specific IgE levels, eotaxin 2 levels, and CCR3 expression in BAL Fluid. In contrast, luteolin significantly increased IL-10 and IFN-γ protein levels, as well as IL-10 and TGF-ß1 mRNA expression in the lung. In vitro studies showed that the number of luteolin-induced CD4+CD25+ Treg (iTreg) cells was higher, with elevated levels of TGF-ß1 and foxp3 mRNA expression in lungs tissue. Transfer of iTreg cells into OVA-sensitized mice reduced AHR, eosinophil recruitment, eotaxin, IgE, and Th2 cytokine expressions, and increased IFN-γ production in BAL Fluid after allergen challenge. Furthermore, adoptive transfer of iTreg cells prevented disease in a CD25-depleted mouse asthma model. Luteolin via induction of foxp3 and CD4+CD25+ Treg cells may represent a new strategy in the development of therapies for managing asthma.

Metabolaid® Combination of Lemon Verbena and Hibiscus Flower Extract Prevents High-Fat Diet-Induced Obesity through AMP-Activated Protein Kinase Activation.

Lemon verbena (Lippia citriodora) has been used as a food spice, cosmetic, and in traditional medicine formulations to treat asthma and diabetes in South America and Southern Europe. Hibiscus flower (Hibiscus sabdariffa L.) is used in traditional Chinese medicine in the form of a tea to treat hypertension and inflammation. In the present study, we examined the synergistic effects of a formula of Metabolaid® (MetA), a combination of lemon verbena and hibiscus-flower extracts, on obesity and its complications in high-fat-diet (HFD)-induced obese mice. The results showed that MetA decreased body weight, white adipose tissue (WAT), and liver weight. Additionally, serum and hepatic lipid profiles, glucose levels, glucose tolerance, and cold-induced thermogenesis were significantly improved. Appetite-regulating hormones adiponectin and leptin were significantly increased and decreased, respectively, while the inflammatory-related factors tumor necrosis factor (TNF)-α and interleukin (IL)-6 were downregulated by MetA. Adipogenesis-activating gene expression was decreased, while increased thermogenesis-inducing genes were upregulated in the WAT, correlating with increased phosphorylation of AMPK and fatty-acid oxidation in the liver. Taken together, these results suggest that MetA decreased obesity and its complications in HFD mice. Therefore, this formula may be a candidate for the prevention and treatment of obesity and its complications.

Fritillaria cirrhosa, Anemarrhena asphodeloides, Lee-Mo-Tang and cyclosporine a inhibit ovalbumin-induced eosinophil accumulation and Th2-mediated bronchial hyperresponsiveness in a murine model of asthma.

Asthma is a chronic inflammatory disorder of the airways characterized by excess production of Th2 cytokines and eosinophil accumulation in the lungs. Fritillaria cirrhosa, Anemarrhena asphodeloides and Lee-Mo-Tang are well-known herbs used in oriental medicine for the treatment of asthma and bronchial inflammation. To clarify the anti-asthmatic effects of Fritillaria cirrhosa bulbus, Anemarrhena rhizoma and Lee-Mo-Tang, we examined the development of pulmonary eosinophilic accumulation, control of Th2 cytokine, immunoglobulin E (IgE) and histamine productions in a murine model of asthma. Eosinophil cell proliferation was performed by [(3)H]thymidine uptake, eosinophilic accumulation. Cell counts in bronchoalveolar lavage fluid were investigated by means of fluorescence activated cell sorter analysis and control of Th2 cytokine, IgE and histamine productions were investigated by RT-PCR and ELISA. Moreover, lung tissue was histologically analysed. The suppressive effects of Fritillaria cirrhosa bulbus, Anemarrhena rhizoma and Lee-Mo-Tang on eosinophil recruitment and airway inflammation were demonstrated throughout the reduction of eosinophil numbers. This result correlated with a marked reduction IL-5, IL-13 and IL-4 levels in the bronchoalveolar lavage fluid. Ovalbumin-specific IgE levels were also decreased in serum. Fritillaria cirrhosa bulbus, Anemarrhena rhizoma and Lee-Mo-Tang have deep inhibitory effects on airway inflammation by suppression of Th2 cytokines (IL-4, IL-5 and IL-13), IgE, histamine production, reduction eosinophilic accumulation and increase of interferon-gamma production.