Five new compounds from the stems of Ephedra equisetina.

Five new compounds were identified from the stems of Ephedra equisetina Bunge. Their structures were elucidated by spectroscopic methods, involving UV, IR, NMR spectrum and HRESIMS analyses. The absolute configuration of compound 2 was proved by comparing their experimental and calculated ECD spectrum. The vitro bioactive assay of all compounds suggested that compound 1, 3, 4, 5 and 6 may have potential anti-asthmatic activities.

Immunomodulatory and anti-inflammatory effects of Aerva lanata in ovalbumin induced allergic asthmatic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Aerva lanata Linn. (A. lanata) is traditionally used for cough, sore throat and asthma. AIM OF STUDY: The aim of the present study was to investigate the immunomodulatory and anti-inflammatory potentials of A. lanata in allergic asthmatic mice. MATERIALS AND METHODS: BALB/c mice were administered with three different (methanol, n-hexane and ethyl acetate) extracts of A. lanata two weeks after immunization with ovalbumin and continued for 7 days. Inflammatory cells count was estimated in blood and broncho-alveolar lavage fluid (BALF). RT-PCR was used to find out mRNA expression levels of inflammatory mediators. GC-MS analysis was also carried out. RESULTS: Among three extracts of A. lanata, ethyl acetate extract ameliorated (p < 0.001) count of inflammatory cells both blood and BALF remarkably. This study indicated that ethyl acetate extract of A. lanata lowered (p < 0.001) the level of inflammatory modulator TNF-α and IgE antibodies. A. lanata reduced (p < 0.001) interleukin 4, 5, 13 and enhanced (p < 0.001) expression levels of AQP1 and AQP5 in asthmatic mice. GC-MS analysis of ethyl acetate fraction indicated the presence of various anti-oxidant phyto-constituents. The groups treated with A. lanata improved inflammatory, goblet cells hyperplasia scoring and alveolar thickening. CONCLUSIONS: The anti-asthmatic effect of A. lanata might be contributed by the suppression of edema, pro-inflammatory cytokines and IgE antibodies, and elevation of aquaporin expression levels, suggesting future study and clinical trials to propose it as a candidate to treat allergic asthma. The anti-oxidant phytochemicals present in A. lanata might be responsible for such potential.

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.

Investigation of antinociceptive, antipyretic, antiasthmatic, and spasmolytic activities of Brazilian Cannabis sativa L. roots in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Many studies are performed with the aerial parts of Cannabis sativa L. (Cannabaceae). However, roots remain poorly studied, despite citations in the scientific literature. The C. sativa roots are indicated for the treatment of pain, inflammation, fever, among other health problems. AIM OF THE STUDY: This study aimed to evaluate the antinociceptive, antipyretic, antiasthmatic, and spasmolytic activities of C. sativa roots in experimental models using mice and rats. MATERIAL AND METHODS: The chemical composition of the aqueous extract of C. sativa roots (AECsR) was evaluated by LC-MS. The antinociceptive activity was assessed in mice by the induction of writhing with acetic acid, paw licking with formalin, and reactivity in the hot plate test. Fever was induced by the administration of a suspension of Saccharomyces cerevisiae in young rats. The asthmatic activity was performed with ovalbumin (OVA)-immunized mice with cellular and histological analysis. Finally, the spasmolytic activity was performed using mice isolated trachea. For in vivo studies, the doses were 12.5, 25, or 50 mg/kg whereas for in vitro, the concentration of AECsR was 729 µg/mL. RESULTS: From the LC-MS data, we identified p-coumaroyltyramine, feruloyltyramine canabissativine in AECsR. The extract promoted a reduction of writhing in all tested doses (12.5, 25, or 50 mg/kg). Similarly, it reduced the pain in the formalin test at doses of 12.5 and 50 mg/kg (first phase) and 12.5 and 25 mg/kg (second phase). In the hot plate test, the doses of 12.5, 25, and 50 mg/kg promoted antinociceptive effect at different times, and the lowest dose maintained its action in the analyzes performed at 60, 90, and 120 min after administration. The anti-inflammatory activity of AECsR was observed in the mouse model of asthma, reducing the total leukocyte count in the bronchoalveolar fluid (BALF) at a dose of 25 mg/kg, as well as reducing eosinophilia in all tested doses (12.5, 25, and 50 mg/kg). Histological analysis of lungs stained with H&E and PAS showed a reduction in the number of inflammatory cells in the perivascular and peribronchial region, as well as reduced mucus production. CONCLUSION: The results suggest that AECsR promotes pain control, either by a central or inflammatory mechanism, and has antiasthmatic activity. However, there was no antipyretic or spasmolytic effect.

Biflavonoid-rich fraction from Daphne pseudomezereum var. koreana Hamaya exerts anti-inflammatory effect in an experimental animal model of allergic asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Daphne pseudomezereum var. koreana Hamaya is distributed in the Gangwon-do of South Korea and is traditionally used to treat chronic inflammatory diseases, including rheumatoid arthritis. AIM OF THE STUDY: We investigated the anti-inflammatory effect of biflavonoid-rich fraction (BF) obtained from an extract of D. pseudomezereum leaves on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and mouse model of ovalbumin (OVA)-induced allergic asthma. MATERIALS AND METHODS: Neochamaejasmin B (NB) and chamaejasmin D (CD) were spectroscopically characterized as major components of BF obtained from the leaves of D. pseudomezereum. RAW264.7 cells pretreated with NB, CD and BF and activated by LPS (500 ng/ml) were used to assess the anti-inflammatory effects of these materials in vitro. To evaluate the protective effect of BF on allergic asthma, female BALB/c mice were sensitized to OVA by intraperitoneal (i.p.) injection and treated with BF by oral administration (15 or 30 mg/kg). RESULTS: Pretreatment with BF inhibited LPS-stimulated nitric oxide (NO), TNF-α and IL-6, and led to upregulation of heme oxygenase-1 (HO-1) in RAW264.7 macrophages. Orally administered BF significantly inhibited the recruitment of eosinophils and the production of IL-5, IL-6, IL-13 and MCP-1 as judged by the analysis of BALF from OVA-induced asthma animal model. BF also decreased the levels of IgE in the serum of asthmatic mice. BF suppressed the influx of inflammatory cells into nearby airways and the hypersecretion of mucus by the airway epithelium of asthmatic mice. In addition, the increase in Penh in asthmatic mice was reduced by BF administration. Furthermore, BF led to Nrf2 activation and HO-1 induction in the lungs of mice. CONCLUSIONS: These data have shown the anti-asthmatic effects of BF, and therefore we expect that BF may be a potential candidate as a natural drug/nutraceutical for the prevention and treatment of allergic asthma.

Therapeutic Potential of Antileukotriene Drug-Camellia sinensis Extract Co-Formulation on Histamine Induced Asthma in Guinea Pigs.

BACKGROUND/OBJECTIVE: To study the therapeutic potential of Antileukotriene drug- Camellia sinensis extract co-formulation on histamine induced asthma in guinea pigs. METHODS: SRSD of Montelukast sodium was prepared by the solvent evaporation method. Lyophilized aqueous extract of Camellia sinensis leaves and SRSD mixture was filled in capsule and the capsule shell was coated to achieve initial release lag time. In vitro and pharmacokinetic study of capsules was performed and compared with commercial tablets. A further role of green tea, as an antioxidant adjunct for asthma management, has been analyzed by lung histology, mast cell count and oxidative stress assay in the serum of control and experimental animals. RESULTS: The drug release from the commercial tablet was immediate and rapid, but capsule has shown an initial 3.5 hr lag time followed by sustained action up to 8 hr. Pharmacokinetic results show that studied formulations are bioequivalent with respect to Cmax and AUC, while rest parameters showed asignificant difference. Mast cells count in lung tissue were increased (p<0.001) in the experimental group along with glycoprotein deposition in asthmatic bronchioles. Levels of SOD and GPX were decreased (p<0.05) while CAT was increased (p<0.04) in the asthma group in comparison to control. CONCLUSION: In the experimental animal model, co-formulation was effective in modulating allergic inflammation and contributing to better control of the inflammatory response. Our findings suggest that Camellia sinensis leaves extract may be used as an adjunct for future improvements in asthma treatment and prevention.

Sophoricoside from Sophora japonica ameliorates allergic asthma by preventing mast cell activation and CD4+ T cell differentiation in ovalbumin-induced mice.

Asthma is a chronic inflammatory lung disorder with continuously increasing prevalence worldwide. Novel strategies are needed to prevent or improve asthma. The aim of this study was to investigate the effects of sophoricoside from Sophora japonica on allergic asthma. The mature seeds of S. japonica contain a large amount of sophoricoside. Sophoricoside reduced allergic and asthmatic symptoms by suppressing airway inflammation and antibody-antigen reaction in mouse models. In particular, sophoricoside suppressed immune cell recruitment into the airway lumens of the lungs and production of pro-inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of ovalbumin (OVA)-induced mice. It also decreased the amounts of histamine and arachidonic acid metabolites released in OVA-induced mice and antibody-antigen stimulated mast cells. In addition, sophoricoside decreased differentiation of naïve CD4+ T cells into T helper type 1 (Th1), Th2, and Th17 cells. Overall, we demonstrated that sophoricoside improved allergic asthma by suppressing mast cell activation and CD4+ T cell differentiation.

Quantitative proteomic profiling of targeted proteins associated with Loki Zupa Decoction Treatment in OVA-Induced asthmatic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Loki Zupa (LKZP) decoction is one of the herbal prescriptions in traditional Uyghur medicine, which is commonly used for treating airway abnormality. However, underlying pathological mechanism and pathways involved has not been well studied. OBJECTIVES: In this paper, we aim to further confirmed the anti-inflammatory and anti-fibrotic role of LKZP decoction in airway, and uncover the passible mechanism involved via comprehensive quantitative proteomic DIA-MS analysis. MATERIALS AND METHODS: Mice asthmatic model was established with sensitizing and challenging with OVA. Lung function, pathological status, and inflammatory cytokines were assessed. Total of nine lung tissues were analyzed using proteomic DIA-MS analysis and 18 lung tissues were subjected to PRM validation. RESULTS: Total of 704 differentially expressed proteins (DEPs) (363 up regulated, 341 down regulated) were quantified in comparison of asthmatic and healthy mice, while 152 DEPs (91 up regulated, 61 down regulated) were quantified in LKZP decoction treated compared to asthmatic mice. Total of 21 proteins were overlapped between three groups. ECM-receptor interaction was significantly enriched and commonly shared between downregulated DEPs in asthma and upregulated DEPs in LKZP decoction treated mice. Total of 20 proteins were subjected to parallel reaction monitoring (PRM) analysis and 16 of which were quantified. At last, two proteins, RMB 10 and COL6A6, were validated with significant difference (P < 0.001) in protein abundance. CONCLUSIONS: Our results suggest that attenuated airway inflammation and fibrosis caused by LKZP decoction may associated with ECM-receptor interaction and RMB 10 and COL6A6 may be targeted by LKZP decoction in OVA-induced asthmatic mice.

Callicarpa japonica Thunb. ameliorates allergic airway inflammation by suppressing NF-κB activation and upregulating HO-1 expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Callicarpa japonica Thunb., as an herbal medicine has been used for the treatment of inflammatory diseases in China and Korea. MATERIALS AND METHODS: Ultra performance liquid chromatography-photodiode array-quadrupole time-of-flight mass spectrometer (UPLC-PDA-QTof MS) was used to detect the major phenylethanoid glycosides in the C. japonica extract. BALB/c mice were intraperitoneally sensitized by ovalbumin (OVA) (on days 0 and 7) and challenged by OVA aerosol (on days 11-13) to induce airway inflammatory response. The mice were also administered with C. japonica Thunb. (CJT) (20 and 40 mg/kg Per oral) on days 9-13. CJT pretreatment was conducted in lipopolysaccharide (LPS)-stimulated RAW264.7 or phorbol 12-myristate 13-acetate (PMA)-stimulated A549 cells. RESULTS: CJT administration significantly reduced the secretion of Th2 cytokines, TNF-α, IL-6, immunoglobulin E (IgE) and histamine, and the recruitment of eosinophils in an OVA-exposed mice. In histological analyses, the amelioration of inflammatory cell influx and mucus secretion were observed with CJT. The OVA-induced airway hyperresponsiveness (AHR), iNOS expression and NF-κB activation were effectively suppressed by CJT administration. In addition, CJT led to the upregulation of HO-1 expression. In an in vitro study, CJT pretreatment suppressed the LPS-induced TNF-α secretion in RAW264.7 cells and attenuated the PMA-induced IL-6, IL-8 and MCP-1 secretion in A549 cells. These effects were accompanied by downregulated NF-κB phosphorylation and by upregulated HO-1 expression. CONCLUSION: These results suggested that CJT has protective activity against OVA-induced airway inflammation via downregulation of NF-κB activation and upregulation of HO-1, suggesting that CJT has preventive potential for the development of allergic asthma.

Structural characterization and anti-asthmatic effect of α-l-arabino(4-O-methyl-α-d-glucurono)-ß-d-xylan from the roots of Rudbeckia fulgida.

Many native plant biopolymers or derivatives thereof have interesting biological effects and therefore the search for additional biological activities is important to map their overall effects. A low molecular weight (Mw = 7600 g/mol) hemicellulose polymer α-L-arabino(4-O-methyl-α-D-glucurono)-ß-D-xylan (AGX) was isolated from the crushed roots of the Rudbeckia fulgida medicinal plant by alkaline extractions and anion-exchange chromatography. Analysis of neutral sugars revealed a predominance of xylose (82.3 wt%) and arabinose (6.8 wt%), while other neutral sugars were found only in small amounts as contaminants. The uronic acid content in Rudbeckia AGX was determined to be 8.8 wt%. Pharmacological tests showed that Rudbeckia AGX effectively suppressed cough and the initial amplitude of histamine/methacholine-induced bronchoconstriction in healthy OVA-sensitive guinea pigs. In addition, its effect at a dose of 100 mg/kg was similar to or greater than that of the positive control bronchodilator salbutamol and the antitussive codeine agent. These findings support the fact that Rudbeckia AGX could be a suitable candidate for alternative treatment of allergic asthma.

Sojadodamgangki-tang attenuates allergic lung inflammation by inhibiting T helper 2 cells and Augmenting alveolar macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Sojadodamgangki-tang (SDG) is a traditional East-Asian herbal medicine mainly composed of Pinellia ternate (Thunb.) Makino, Perilla frutescens (L.) Britt and 10 kinds of medicinal herbs. It has been used to treat asthma and mucus secretion including lung and bronchi. AIM OF THE STUDY: The aim of this study was to investigate the anti-inflammatory effects of Sojadodamgangki-tang (SDG) on allergic lung inflammation in vitro and in vivo as well as the underlying mechanisms. MATERIALS AND METHODS: We used an ovalbumin (OVA)-induced murine allergic airway inflammation model. Five groups of 8-week-old female BALB/C mice were divided into the following groups: saline control group, the vehicle (allergic) group that received OVA only, groups that received OVA and SDG (200 mg/kg or 400 mg/kg), and a positive control group that received OVA and Dexamethasone (5 mg/kg). In vitro experiments include T helper 2 (TH2) polarization system, murine macrophage cell culture, and human bronchial epithelial cell line (BEAS-2B) culture. RESULTS: SDG administration reduced allergic airway inflammatory cell infiltration, especially of eosinophils, mucus production, Th2 cell activation, OVA-specific immunoglobulin E (IgE), and total IgE production. Moreover, the activation of alveolar macrophages, which leads to immune tolerance in the steady state, was promoted by SDG treatment. Interestingly, SDG treatment also reduced the production of alarmin cytokines by the human bronchial epithelial cell line BEAS-2B stimulated with urban particulate matter. CONCLUSION: Our findings indicate that SDG has potential as a therapeutic drug to inhibit Th2 cell activation and promote alveolar macrophage activation.

Tracheal relaxation through calcium channel blockade of Achillea millefolium hexanic extract and its main bioactive compounds.

ETHNOPHARMACOLOGICAL IMPORTANCE: Achillea millefolium L. (Asteraceae) is used for the treatment of respiratory diseases, diabetes, and hypertension. AIM: to explore its tracheal relaxant properties and clarify its functional mechanism of action on smooth muscle cells, which allow us to propose it as a potential anti-asthmatic drug. MATERIAL AND METHODS: organic and hydro-alcoholic extracts from A. millefolium were obtained by macerations, then their relaxing effect on ex vivo isolated rat trachea rings was determined. Most active extract (hexanic extract, EHAm) was studied to determine its functional mechanism of action using synergic, antagonist and inhibitor agents related with the contraction/relaxation process of the smooth muscle. Also, EHAm was subjected to bio-guided fractionation by open-column chromatography (on silica gel) using cyclohexane-EtOAc (80:20) in an isocratic way to isolate main bioactive compounds. RESULTS: organic and hydro-alcoholic extracts showed relaxant effect in a concentration-response dependent manner, being EHAm the most active. The functional mechanism of action indicates that EHAm induced a non-competitive antagonism to the muscarinic receptors ; in addition, the NO/cGMP pathway is involved in the relaxation process of the tracheal smooth muscle. However, the most important mechanism of action showed by EHAm was related with the calcium channel blockade influx into the smooth muscle cells. On the other hand, epimeric sesquiterpene lactones leucodin (1) and achillin (2) were isolated and purified, which are responsible for the observed smooth muscle relaxant activity of the extract. CONCLUSION: hexanic extract of A. millefollium induced a significant relaxant effect on tracheal rat rings by calcium channel blockade and NO release.

Eriobotrya japonica leaf extract attenuates airway inflammation in ovalbumin-induced mice model of asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Eriobotrya japonica leaves has a very long history of medicinal use as an anti-inflammatory and antitussive agent for bronchial inflammation. AIM OF THE STUDY: The aim of this study was to evaluate the anti-inflammatory activities of Eriobotrya japonica (EJ) leaf water extract in an ovalbumin (OVA)-induced murine asthma model and human tracheal smooth muscle cell (HTSMC). MATERIALS AND METHODS: Mice were sensitized by intra peritoneal OVA and challenged with nebulized OVA. EJ extract was administered orally at various dose. Bronchoalveolar lavage fluid (BALF) was quantified for nitric oxide (NO), eosinophil peroxidase (EPO), interleukin (IL)-4, IL-13 level and immunoglobulin (Ig) E was quantified in serum. Lung tissue sections were stained with hematoxylin and eosin for assessment of inflammatory cell infiltration whereas mucus production and goblet cell hyperplasia were studied by periodic acid schiff staining. Western blot was done for analysis of pERK1/2 expression and NFκB translocation in HTSMC whereas iNOS and COX-2 expression in RAW264.7 cell. RESULTS: EJ significantly reduced the levels of BALF's NO, EPO, MMPs, IL-4, IL-13, and serum IgE. It also decreases inflammatory cell infiltration and mucus production. EJ also attenuated the proliferation of HTSMC, inhibits overexpression of ERK 1/2 and translocation of NFκB in HTSMC as well as iNOS and COX-2 expression in RAW 264.7 cell. CONCLUSION: Present study suggest that, EJ effectively protects against allergic airway inflammation thus possessing potential therapeutic option for allergic asthma management.

Myxopyrum serratulum ameliorates airway inflammation in LPS-stimulated RAW 264.7 macrophages and OVA-induced murine model of allergic asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Myxopyrum serratulum A. W. Hill. (Oleaceae) is a traditionally used Indian medicinal plant for the treatment of cough, asthma and many other inflammatory diseases. AIM OF THE STUDY: In this study, the protective effects of M. serratulum on airway inflammation was investigated in ovalbumin (OVA)-induced murine model of allergic asthma and lipopolysaccharide (LPS)-stimulated inflammation in RAW 264.7 murine macrophages, and the possible mechanisms were elucidated. MATERIALS AND METHODS: The phytochemicals present in the methanolic leaf extract of M. serratulum (MEMS) were identified by reverse phase high performance liquid chromatography (RP-HPLC) analysis. In vitro anti-inflammatory activity of MEMS were evaluated by estimating the levels of nitric oxide (NO), reactive oxygen species (ROS) and cytokines (IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-12, IL-17A, IFN-γ, TNF-α, G-CSF and GM-CSF) in LPS-stimulated RAW 264.7 macrophages. In vivo anti-asthmatic activity of MEMS was studied using OVA-induced murine model. Airway hyperresponsiveness (AHR), was measured; total and differential cell counts, eosinophil peroxidase (EPO), prostaglandin E2 (PGE2), NO, ROS, and cytokines (IL-4, IL-5 and IL-13), were estimated in bronchoalveolar lavage fluid (BALF). Serum total IgE level was measured; and the histopathological changes of lung tissues were observed. The expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in lung tissue homogenates were detected by Western blot. RESULTS: The chromatographic analysis of MEMS identified the presence of gallic acid, protocatechuic acid, catechin, ellagic acid, rutin, p-coumaric acid, quercetin, naringenin and apigenin. MEMS (125 and 250 µg/mL) dose-dependently reduced the levels of NO, ROS and pro-inflammatory cytokines in LPS-stimulated RAW 264.7 macrophages. MEMS (200 and 400 mg/kg, p.o.) significantly (p < 0.05) alleviated AHR; number of inflammatory cells, EPO, PGE2, NO, ROS, and cytokines (IL-4, IL-5 and IL-13) in BALF; serum total IgE and the histopathological changes associated with lung inflammation. Western blot studies showed that MEMS substantially suppressed COX-2 and iNOS protein expressions in the lung tissues of OVA-sensitized/challenged mice. CONCLUSIONS: The present study corroborates for the first time the ameliorative effects of MEMS on airway inflammation by reducing the levels of oxidative stress, pro-inflammatory cytokines and inhibiting COX-2, iNOS protein expressions, thereby validating the ethnopharmacological uses of M. serratulum.

Comparing the Protection Imparted by Different Fraction Extracts of Garlic (Allium sativum L.) against Der p-Induced Allergic Airway Inflammation in Mice.

Garlic (Allium sativum L.) has been used extensively as a food ingredient and medicinally, but the effect on asthmatic airway inflammation has not been studied in detail. We accordingly explored the protective effects exerted by various garlic fraction extracts against airway inflammation with Dermatophagoides pteronyssinus (Der p)-induced allergic asthma in vivo and in vitro. Garlic extraction was realized using n-hexane, dichloromethane, ethylacetate, n-butanol, and water in sequence to obtain different fraction extracts. Mice were orally administered different fractions (80 mg/kg) daily for four weeks. The histological results showed that the water fraction could ameliorate lung-based goblet cell hyperplasia, inflammatory cell infiltration, and mucus hypersecretion. The water fraction extracts decreased IgE and IgG1, and they decreased inflammatory cells as quantified in bronchoalveolar lavage fluid (BALF); however, they increased IgG2a in serum. Moreover, the water fraction extracts increased IFN-γ and IL-12 (both constituting Th1 cytokines) in BALF, but they reduced IL-13, -4, and -5 (all constituting Th2 cytokines), and also inhibited the expression of IL-1ß, IL-6, and TNF-α. The water fraction also inhibited the PI3K/Akt/NF-κB signal pathways in A549 cells. These findings suggest that water fraction extracts of garlic have a clear anti-inflammatory effect on Der p-induced allergic asthma.

Synthesis, antiasthmatic, and insecticidal/antifungal activities of allosamidins.

Allosamidins come from the secondary metabolites of Streptomyces species, and they have the pseudotrisaccharide structures. Allosamidins are chitinase inhibitors that can be used to study the physiological effects of chitinases in a variety of organisms. They have the novel antiasthmatic activity and insecticidal/antifungal activities. Herein, the synthesis and activities of allosamidins were summarized and analyzed.

Evaluation of the anti-asthmatic and antitussive potentials of methanol leaf extract of Napoleona vogelii in rodents.

Napoleona vogelii is used in ethnomedicine for the treatment of asthma and cough. This study evaluated antiasthmatic and antitussive properties of its methanol leaf extract (NVE) in rodents. Phytochemical screening was conducted using established methods. Acute oral toxicity test was done in mice and guinea pigs. Ovalbumin (OA)-sensitized guinea pigs were orally pretreated with 100, 200 or 400 mg/kg/day of NVE or 0.5 mg/kg/day of salbutamol for 14 days before exposure to 0.2% histamine aerosol. Latency to preconvulsive dyspnea (PCD), tracheal fluid volume (TFV), flow rate (FR), and tracheal morphometry (TM) were evaluated. Tracheal rings from sensitized guinea pigs were tested in organ baths for antispasmodic and spasmolytic effects. Citric acid and ammonium hydroxide cough models were used to evaluate antitussive effects in guinea pigs and mice respectively. Tannins, alkaloids, flavonoids, and phenolic substances were found in NVE. LD50 values in mice and guinea pigs were greater than 5000 mg/kg. NVE caused a significant (P < 0.05) increase in the latency to PCD and a decrease in TFV in the group treated with 200 mg/kg. TM indicated a reduction in airway narrowing in NVE-treated groups. The presence of NVE significantly attenuated responses of tracheal rings to carbachol. Its addition to carbachol precontracted rings resulted in significant relaxation. Emax for calcium concentration-response was significantly (P < 0.01) decreased in the presence of NVE. Cough bouts dose-dependently decreased significantly (P < 0.05) in guinea pigs and mice. We conclude that NVE seems safe and possesses anti-asthmatic effect that involves inhibition of calcium influx. It also has antitussive properties that may be peripherally mediated.

Discovery of ß2- adrenoceptor agonists in Curcuma zedoaria Rosc using label-free cell phenotypic assay combined with two-dimensional liquid chromatography.

Traditional Chinese Medicines (TCMs) have been widely used in clinical practice, and provided a rich source for discovering new drug leads. However, efficient identification of active molecules responsible for the therapeutic effects of complex TCMs is still highly challenging. Here, we combined label-free cell phenotypic assay with two dimensional liquid chromatography (2DLC) to identify potential ß2-adrenoceptor (ß2-AR) agonists related to anti-asthmatic effect of Curcuma zedoaria Rosc (C.zedoaria), a commonly used TCM. The ethyl acetate extract of C.zedoaria was first fractionated into 26 fractions. Label-free cell phenotypic profiling was then used to locate the active sites. Orthogonal second-dimensional (D2) separation was performed on two fractions displaying agonistic effect at the ß2-AR, combined with screening of the D2 fractions to track the activity. Finally, this approach led to the isolation of three known diarylheptanoids, among which diarylheptanoid b exhibited the most potent agonistic activity with an EC50 value of 5.93 µM. This result was further demonstrated through the chemical synthesis of diarylheptanoid b. It is the first time to discover that diarylheptanoids could activate the ß2-AR, which may be responsible for the anti-asthmatic effect of C.zedoaria observed traditionally and in clinical application. This study also demonstrates the potential of this integrated strategy for identifying active ingredients and determining the basis of therapeutic materials in complex TCMs.

Activation of resin with controllable ligand density via catalytic oxa-Michael addition and application in antibody purification.

This article reported a new strategy for resin activation with divinyl sulfone using catalytic oxa-Michael addition in a controllable manner. By screening a variety of organocatalysts, PPh3 and DMAP stand out with high catalytic efficiency in aprotic solutions. X-ray photoelectron spectroscopy (XPS) analysis indicates high reaction efficiency and less side reactions than traditional aqueous reactions, resulting in high activation density. A maximum activation density of 157.5 ±â€¯1.2 µmol/g resin was achieved in 12 h using PPh3 as catalyst, which is 1.5 times higher than the traditional aqueous reactions. Followed by conjugation with a chromatographic ligand, i.e., 4-mercaptoethyl pyridine (MEP), the resin is capable of antibody purification. Using IgG and BSA as model proteins, adsorption isotherms and dynamic binding behavior of the resin samples were investigated. A higher affinity and dynamic binding capacity of IgG was observed on resins with higher ligand density. Finally, the resin samples were applied to the purification of a therapeutic monoclonal antibody from cell culture supernatant. The recovery of the resin samples with high ligand density are 70% higher than those of the commercial resin (MEP HyperCel). Moreover, our method achieves a controllable chromatographic ligand density by varying reaction times, which is useful to clarify the density-affinity relationship and improve process-scale antibody purification.

Anti-asthmatic effects of volatile organic compounds from Chamaecyparis obtusa, Pinus densiflora, Pinus koraiensis, or Larix kaempferi wood panels.

Asthma is a common chronic inflammatory disease in which lung airways narrow and produce extra mucus. Numerous medications, such as steroids, are used to prevent or control asthmatic symptoms, but side effects are associated with those medications. There are reports of anti-inflammatory, antibacterial, and antiparasitic effects of terpene, a volatile organic compound (VOC) in conifers. VOCs easily enter a gaseous form, and wood products are good sources of VOCs. However, only a few studies have been conducted on the effect on asthma of VOCs emitted by wood. In this study, we examined the effects of VOCs diffused from wood panels on ovoalbumin (OVA)-induced asthma in a mouse model. The mice were intraperitoneally sensitized with 10 µg of OVA with aluminum hydroxide on days 0, 7, and 14. From day 21 to day 26, the mice were challenged with 2% OVA intranasally for 30 min. For VOC treatment, asthma model mice were placed in polyacrylamide chambers containing wood panels of Chamaecyparis obtusa, Pinus densiflora, Pinus koraiensis, or Larix kaempferi. On day 27, serum, lung tissue, and bronchoalveolar lavage fluids were prepared for H&E staining, qRT-PCR, ELISA, and Diff-Quik staining, as appropriate. OVA treatment induced hypertrophy of the bronchiolar wall. The budesonide group and all four of the wood panel-exposed groups showed less thickening of the bronchiolar wall and downregulated transcriptional expressions of cytokines such as interleukin-4 (IL-4) and interleukin-13 (IL-13). The serum tumor necrosis factor-α (TNF-α) mRNA expression level was significantly decreased only in the C. obtusa group, but the serum IL-4 levels were decreased in all wood panel treatment groups. Diff-Quik staining of bronchoalveolar lavage fluids revealed a decrease in the number of granulocytes in all wood panel treatment groups. The results suggest that VOCs from C. obtusa, P. densiflora, P. koraiensis and L. kaempferi produce antiasthmatic effects by regulating the production of IL-4, IL-9, IL-13, TNF-α.