Glaucocalyxin A attenuates allergic responses by inhibiting mast cell degranulation through HMGB1/TLR4/NF-κB signaling pathways
10.16438/j.0513-4870.2020-0960
- VernacularTitle:蓝萼甲素通过抑制HMGB1/TLR4/NF-κB信号通路减轻肥大细胞脱颗粒引起的过敏反应
- Author:
Yi-hua PIAO
1
,
2
;
Yi-lan SONG
3
,
4
;
Zhi-guang WANG
5
,
6
;
Jing-zhi JIANG
3
,
4
;
Li LI
3
,
4
;
Chang XU
3
,
4
;
Ying PIAO
3
,
7
;
Hong-mei PIAO
5
,
6
;
Guang-hai YAN
3
,
4
Author Information
1. Department of Critical Care Medicine, Hospital of Yanbian University, Yanji 133000, China
2. Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji 133002, China
3. Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji 133002, China
4. Department of Anatomy, College of Medicine, Yanbian University, Yanji 133002, China
5. Department of Anatomy, College of Medicine, Yanbian University, Yanji 133002, China
6. Respiratory and Critical Care Medicine, Hospital of Yanbian University, Yanji 133000, China
7. Department of Emergency Medicine, Hospital of Yanbian University, Yanji 133000, China
- Publication Type:Research Article
- Keywords:
glaucocalyxin A;
high mobility group box 1;
toll-like receptor 4;
nuclear transcription factor kappa B;
mast cell degranulation
- From:
Acta Pharmaceutica Sinica
2021;56(1):201-207
- CountryChina
- Language:Chinese
-
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.
