Attenuation of Airway Inflammation and Airway Remodeling in Ovalbumin Asthmatic Rats by Artemisinin through PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

ABSTRACT

ObjectiveTo investigate the molecular mechanism of action of artemisinin in attenuating asthmatic airway inflammation and airway remodeling through the phosphoinositide 3-kinase（PI3K）/protein kinase B（Akt） signaling pathway. MethodFifty male SD rats were randomly divided into blank group， model group， and low-dose， medium-dose， and high-dose groups of artemisinin， with 10 rats in each group. The ovalbumin （OVA）-induced asthma model of the rats was established， and after successful modeling， the blank group and model group received tail vein injection of 1.0 mL·kg-1 normal saline， while the low-dose， medium-dose， and high-dose groups of artemisinin received tail vein injection of 12.5， 25， and 50 mg·kg-1 artemisinin daily for seven days. Airway resistance was measured by the acetylcholine chloride method. Cell number and species changes in the alveolar lavage fluid of each group were determined by flow cytometry. Morphological changes in airway endothelial tissue were determined by the hematoxylin-eosin （HE） staining method. Apoptosis was determined by CytoTox 96 method， and enzyme-linked immunosorbent assay （ELISA） method was used to determine the NOD-like receptor thermal protein domain associated protein 3 （NLRP3） inflammasome， interleukin-1β （IL-1β）， and interleukin-10 （IL-10） expression. Western blot method was used to detect the （p）-PI3K/p-Akt level in the alveolar bronchial tissue of each group. ResultCompared with the blank group， the total number of cells， total number of macrophages， total number of eosinophils， total number of lymphocytes， and total number of neutrophils were significantly higher in the model group （P<0.05）. HE staining showed that the airway mucosa of the rats had obvious edema， and a large number of inflammatory cells were infiltrated （P<0.05）. The rate of apoptosis was significantly higher （P<0.05）， and the levels of the inflammasome NLRP3， IL-1β， and IL-10 increased significantly （P<0.05）. p-PI3K/p-Akt level increased significantly （P<0.05）. Compared with the model group， the total number of cells， total number of macrophages， total number of eosinophils， total number of lymphocytes， and total number of neutrophils were significantly decreased after the intervention of artemisinin at low， medium， and high concentrations （P<0.05）. HE staining showed that the degree of edema of the airway mucosa of the rats was reduced， and the area of the inflammatory cell infiltration was drastically reduced （P<0.05）. The apoptosis rate was significantly reduced （P<0.05）， and the levels of the inflammasome NLRP3， IL-1β， and IL-10 decreased significantly （P<0.05）. p-PI3K/p-Akt level decreased significantly （P<0.05）. ConclusionArtemisinin significantly inhibits NLRP3 inflammasome activation， reduces cellular pyroptosis and inflammatory cell expression， and attenuates airway inflammatory manifestations and airway remodeling in asthmatic rats， which may be related to the regulation of p-PI3K/p-Akt， and the results may provide laboratory insights and basis for the treatment of bronchial asthma with artemisinin.