Dongxuan Huang*, Chaowen He*, Dongsheng Huang*, Jianfeng Peng*, Fan Yang*, Yahui Cao*, Xiaohua Luo*, Yili Liao**, #
*Department of Pulmonary and Critical Care Medicine, Shenzhen Longhua District Central Hospital - *Hypertensive Disorders Complicating Pregnancy Diagnosis & Treatment Center, Shenzhen Maternity & Child Healthcare Hospital
Objective: To investigate the effects and mechanisms of deguelin in alleviating asthma-related allergic airway inflammation by inhibiting the NF-κB signalling pathway.
Methods: Forty clean grade mice were selected. A mouse acute asthma model was established by ovalbumin (OVA) sensitisation. The mice were randomly divided a model group, low-dose group (1 mg/kg), high-dose group (4 mg/kg), and dexamethasone group (1 mg/kg), each with 10 rats each. The group was given an intraperitoneal injection of the corresponding drug. Another 10 normal mice were selected as the blank control group. The pathological changes of the lung tissue were observed by HE staining, and bronchoalveolar lavage fluid (BALF) was collected from each group. The ELISA was adopted to detect the inflammatory cells (Eosinophils, lymphocytes, and neutrophils) and inflammatory factors [Interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 13 (IL-13), and immunoglobulin E (IgE)]. Western blot was used to detect the changes of NF-κB P65, p-P65, and IκBα, and the effect and the molecular mechanism of deguelin on the asthma-related inflammatory response were analysed.
Results: Observation under light microscopy showed that inflammatory exudation and inflammatory cell infiltration were reduced after high dose treatment with scrotonin, and inflammatory exudation and inflammatory cell infiltration were most significantly reduced in the dexamethasone group. Compared with the blank control group, the number of eosinophils, lymphocytes, and neutrophils in the BALF of the model group was significantly increased (P<0.05). Compared with the model group, the levels of inflammatory cells in the various dose groups of deguelin were significantly lower (P<0.05). Compared with the blank control group, the levels of IL-4, IL-5, IL-13, and IgE in the BALF of the model group were significantly increased (P<0.05). Compared with the model group, the levels of IL-4, IL-5, IL-13, and IgE were significantly lower in each dose group (P<0.05), and the degree of reduction was more significant with the increase in the dose. Western blot showed that the expression of p-P65 and p-IκBα in the model group was significantly increased compared to the control group, and the expression of IκBα was significantly decreased (P<0.05). The expression of IκBα in the houttuin group was significantly higher than that in the model group (P<0.05), and the levels of p-P65 and p-IκBα were also significantly inhibited.
Conclusion: Deguelin can reduce inflammation and exudation of alveolar wall and infiltration of inflammatory cells, reduce the level of Th2 cytokines, and alleviate asthma-related allergic airway inflammation, which may be involved in the inhibition of the NF-κB signalling pathway and may be an effective asthma treatment drug.
Deguelin, NF-κB signalling pathway, asthma, inflammatory.