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.

Shin NR ，Kwon HJ ，Ko JW ，Kim JS ，Lee IC ，Kim JC ，Kim SH ，Shin IS ... -  《-》

Geniposide inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma.

Our group recently reported the strong anti-inflammatory effects of geniposide (Gen), a bioactive iridoid glucoside derived from gardenia jasminoides, in a mouse acute lung injury model. Herein, we hypothesized that Gen might also have potential therapeutic benefits in treatment of asthma, which was tested in a mouse model of ovalbumin (Ova)-induced allergic airway inflammation. Ova-sensitized and -challenged BALB/c mice, as compared with control animals, displayed airway hyperresponsiveness (AHR), bronchoalveolar lavage eosinophilia, mucus hypersecretion, and increased T help 2 (Th2)-associated cytokine and chemokine amounts, as well as serum Ova-specific immunoglobulin E (IgE) level. Being compared with the Ova-induced hallmarks of asthma, intraperitoneal Gen treatment prevented eosinophilic pulmonary infiltration, attenuated the increases in interleukin (IL)-4, IL-5, and IL-13, and reduced eotaxin and vascular cell adhesion molecule 1 (VCAM-1) expression. Also, Gen significantly ameliorated the Ova-driven airway hyperresponsiveness, mucus hypersecretion, and allergen-specific IgE level, which are the cardinal pathophysiological symptoms in allergic airway diseases. In addition, the efficacy of Gen was comparable to that of dexamethasone (Dex), a currently available anti-asthmatic drug. Collectively, our findings reveal that the development of immunoregulatory strategies based on Gen may be considered as an effective adjuvant therapy for allergic asthma.

Deng Y ，Guan M ，Xie X ，Yang X ，Xiang H ，Li H ，Zou L ，Wei J ，Wang D ，Deng X ... -  《-》

Effects of anthraquinones from Cassia occidentalis L. on ovalbumin-induced airways inflammation in a mouse model of allergic asthma.

Cassia occidentalis Linn. is a traditional ayruvedic edible shrub containing anthraquinones (AQs) as the principle active constituents. In folk medicine, it has a variety of uses including treatment of whooping cough ('pertussis') and inflammatory diseases. Despite these applications, limited data are available to validate the effects of C. occidentalis AQs on airways inflammation in asthma. To explore the anti-inflammatory potential of AQs extracted from C. occidentalis using an in vivo model of ovalbumin (OVA)-induced asthma. Extraction and optimization of AQs from C. occidentalis was performed by mechanochemistry. Allergic asthma in BALB/c mice was sensitized and challenged by OVA, and the effects of AQs investigated in a mouse model. OVA-specific IgE concentrations in serum, and Th1/Th2 cytokine (IL-4, IL-5, IL-13 and IFN-γ) concentrations, inflammatory cell counts and classification in bronchoalveolar lavage fluid (BALF) were determined. Histopathological evaluation of lung tissue was performed using hematoxylin and eosin (H&E), and periodic acid-schiff (PAS) staining. Th1/Th2 cytokine mRNA expression was analyzed using the 2-ΔΔCt method. Treatment with AQs decreased inflammatory cell counts and production of Th2 cytokines (IL-4, IL-5 and IL-13) in BALF, and OVA-specific IgE in serum. In contrast,Th1 cytokine IFN-γ production in BALF was promoted. AQs also decreased mRNA expression of Th1/Th2 cytokine in lung tissue. Histological studies demonstrated that AQs substantially inhibited OVA-induced cellular infiltration, mucus hypersecretion and goblet cell hyperplasia in the lung. These findings demonstrated the inhibitory effects of AQs, derived from C. occidentalis, on OVA-induced allergic asthma in mice. The results suggest a promising ethnopharmacological use for AQs in patients with asthma.

Xu W ，Hu M ，Zhang Q ，Yu J ，Su W ... -  《-》

Butylphthalide ameliorates airway inflammation and mucus hypersecretion via NF-κB in a murine asthma model.

Butylphthalide (NBP) is a phthalide compound contained in Angelicae Sinensis Radix which is one of the most widely used traditional Chinese medicines. This study aims to explore the therapeutic effect of NBP on airway inflammation, mucus hypersecretion and their possible mechanism in asthma mice. BALB/c mice were sensitized and challenged with ovalbumin (OVA) for establishment of asthma model and then treated with NBP during day 22-77. The pulmonary function of the mice was determined, and the pathology of lung tissue and goblet cell hyperplasia were observed through analyzing inflammation scores and goblet cell percentage, respectively. Cytokine IL-4, IL-8, IL-13 and tumor necrosis factor-alpha (TNF-α) in bronchoalveolar lavage fluid (BALF) and total immunogloblin E (T-IgE) and OVA-specific IgE in serum were examined by enzyme-linked immunosorbent assay (ELISA). The expressions of Mucin 5AC (Muc5ac) and nuclear transcription factor-kappa B (NF-κB) in lung tissues were evaluated by immunohistochemistry, western blot and real-time polymerase chain reaction (RT-PCR). The results show that 50 mg/kg NBP significantly reduced OVA-induced increase in inflammation scoring, goblet cell percentage and mucus secretion of airway tissue, and improved the pulmonary function. NBP could also decrease IL-4, IL-8 IL-13, and TNF-α in BALF and T-IgE and OVA-specific IgE in serum. The expression of Muc5ac and NF-κB in lung tissue was significantly down-regulated after NBP treatment. This study suggested that NBP may effectively inhibit airway inflammation and mucus hypersecretion in asthma by modulating NF-κB activation.

Wang Z ，Yao N ，Fu X ，Wei L ，Ding M ，Pang Y ，Liu D ，Ren Y ，Guo M ... -  《-》

A semisynthetic diterpenoid lactone inhibits NF-κB signalling to ameliorate inflammation and airway hyperresponsiveness in a mouse asthma model.

Andrographolide (AGP) and 14-deoxy-11,12-didehydroandrographolide (DDAG), two main diterpenoid constituents of Andrographis paniculata were previously shown to ameliorate asthmatic symptoms in a mouse model. However, due to inadequacies of both compounds in terms of drug-likeness, DDAG analogues were semisynthesised for assessment of their anti-asthma activity. A selected analogue, 3,19-diacetyl-14-deoxy-11,12-didehydroandrographolide (SRS27), was tested for inhibitory activity of NF-κB activation in TNF-α-induced A549 cells and was subsequently evaluated in a mouse model of ovalbumin (OVA)-induced asthma. Female BALB/c mice, 6-8weeks old were sensitized on days 0 and 14, and challenged on days 22, 23 and 24 with OVA. Compound or vehicle (3% dimethyl sulfoxide) was administered intraperitoneally 1h before and 11h after each OVA aerosol challenge. On day 25, pulmonary eosinophilia, airway hyperresponsiveness, mucus hypersecretion, inflammatory cytokines such as IL-4, -5 and -13 in BAL fluid, gene expression of inflammatory mediators such as 5-LOX, E-selectin, VCAM-1, CCL5, TNF-α, AMCase, Ym2, YKL-40, Muc5ac, CCL2 and iNOS in animal lung tissues, and serum IgE were determined. SRS27 at 30μM was found to suppress NF-κB nuclear translocation in A549 cells. In the ovalbumin-induced mouse asthma model, SRS27 at 3mg/kg displayed a substantial decrease in pulmonary eosinophilia, BAL fluid inflammatory cytokines level, serum IgE production, mucus hypersecretion and gene expression of inflammatory mediators in lung tissues. SRS27 is the first known DDAG analogue effective in ameliorating inflammation and airway hyperresponsiveness in the ovalbumin-induced mouse asthma model.

Lim JC ，Goh FY ，Sagineedu SR ，Yong AC ，Sidik SM ，Lajis NH ，Wong WS ，Stanslas J ... -  《-》