ABSTRACT
Aim To investigate the efficacy of arctigenin on airway inflammation in a mouse model of asthma and the mechanism related to the SIRT1/NLRP3 signaling pathway. Methods Forty female BALB/c mice of clean grade were selected and divided into control group, OVA model group and ATG group (5, 10 and 20 mg · kg
ABSTRACT
The study is to investigate the effect of glaucocalyxin A (GLA) on mast cell-mediated anaphylaxis. The animal welfare and experimental process of this experiment followed the regulations of the Animal Ethics Committee of Yanbian University. BALB/c mice were used in the animal experiment and randomly divided into five groups, control group, model group, and GLA low, medium, and high dose groups (10, 20, and 40 mg·kg-1). Mice were sensitized by intradermal injection of anti-dinitrophenyl-immunoglobulin E (DNP-IgE) into the ears and challenged with a mixture of DNP-human serum albumin (HSA) and 4% evans blue into the tail veins to prepare an animal skin passive cutaneous anaphylaxis (PCA) model, which was collected from both ears for measurement of dye staining and histology. Rat peritoneal mast cells (RPMCs) were used in the cell experiment and divided into control, IgE + antigen (Ag), and IgE + Ag + GLA groups to determine histamine release as well as calcium influx levels. High-affinity IgE receptor (FcεRI)-mediated signaling pathway proteins and HMGB1/TLR4/NF-κB (high mobility group box 1/toll like receptor 4/nuclear transcription factor kappa B) signaling proteins were detected by Western blot. The results of animal experiments suggest that GLA inhibits PCA, reduces evans blue dye exudation, and reduces ear inflammation and ear thickness in mice. The results of cellular experiments suggested that GLA could reduce histamine release and calcium influx, and inhibit tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-13, and IL-1β production; Western blot results showed that GLA inhibited FcεRI-mediated phosphorylation levels of spleen tyrosine kinase (Syk), Lck/Yes novel tyrosine kinase (Lyn), tyrosine kinase Fyn (Fyn), growth-factor receptor-bound protein 2 (Gab2), and phospholipase C (PLC) γ1, while GLA inhibited HMGB1/TLR4 signaling pathway to limit NF-κB p65 nuclear metastasis. The results indicate that GLA inhibits mast cell degranulation and attenuates allergic inflammation through the HMGB1/TLR4/NF-κB signaling pathway.
ABSTRACT
Objective: To investigate the therapeutic effect of glaucocalyxin A(GLA)on airway inflammation in a mouse mod- el of ovalbumin(OVA)-induced asthma and whether the mechanism is associated with the HMGB1/TLR4/NF-κB signaling pathway. Methods: Forty BALB/c mice were divided into 5 groups(8 mice in each group):control group, OVA model group, GLA-L group (10 mg/kg), GLA-H group(40 mg/kg)and dexamethasone group(1 mg/kg). HE and PAS staining were used to observe the inflammatory infiltration and the number of goblet cells in mouse lung tissue;Diff-Quick staining was used to count various cell types in mouse bronchoalveolar lavage fluid(BALF);ELISA was used to detect the content of inflammatory and pro-inflammatory cytokines in mouse BALF;Western blotting(WB)was used to detect the expression of HMGB1, TLR4, MyD88, NF-κB(nuclear)and NF-κB(cytosol)in lung tissue;immunohistochemistry was used to detect the expression level of HMGB1, TLR4 and NF-κB p65 protein in mouse lung tissue. Results: GLA reduced inflammatory cell exudation and goblet cell proliferation in OVA-induced asthmatic model;GLA treatment significantly decreased eosinophils, neutrophils and lymphocytes in BALF of asthmatic mice, and reduced the levels of pro-inflammatory cytokines(P<0.05);WB results showed that GLA inhibited the protein expression of HMGB1, TLR4, MyD88 and NF-κB(nuclear)(P<0.05);immunohistochemistry results showed that GLA reduced the expression of HMGB1, TLR4 and NF-κB p65 protein in lung tissue(P<0.05). Conclusion: GLA could ameliorate the OVA-induced airway inflammation in asthmatic mice, possibly via interfering in the HMGB1/TLR4/NF-κB signaling pathway.