Mechanism of Yupingfeng San Against Allergic Rhinitis Through ROS/NLRP3/Caspase-1 Signaling Pathway / 中国实验方剂学杂志

ABSTRACT

ObjectiveTo investigate the therapeutic effect of Yupingfeng San on allergic rhinitis （AR） and its effect on Reactive oxygen species （ROS）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3）/cysteinyl aspartate specific proteinase-1 （Caspase-1） pathway. MethodSPF mice were randomly divided into control group， model group， loratadine group （0.9 mg·kg-1）， and low， medium， and high dose Yupingfeng San groups （6， 12， 24 mg·kg-1）， with 10 mice in each group. The control group was given routine feeding， and the other groups were intraperitoneally injected with ［ovalbumin（OVA） + Al（OH）₃ + phosphate buffer solution（PBS）］ suspension once every other day for seven consecutive times. After seven days， 10% OVA solution was instilled in the nose， two times each day for seven consecutive days. After successful modeling， each administration group was intraperitoneally injected with different doses of Yupingfeng San Decoction， and the control group and model group were intraperitoneally injected with an equal volume of normal saline. Symptoms of sneezing， scratching， and runny nose were recorded and scored daily. The levels of ovalbumin specific immunoglobulin E （OVA-sIgE）， histamine， eosinophil cationic protein （ECP）， prostaglandin D2 （PGD2）， interleukin-1β （IL-1β）， interleukin-18 （IL-18）， interleukin-4 （IL-4）， and γ interferon （IFN-γ） in nasal lavage solution and serum of mice were detected by enzyme-linked immunosorbent assay （ELISA）. The damage status of the nasal mucosa was observed by hematoxylin-eosin （HE） staining. The number of goblet cells in the nasal mucosa of mice was observed by periodic acid-Schiff （PAS） staining. The expression of NLRP3 protein in the nasal mucosa of mice was detected by immunohistochemistry. Western blot was used to detect the expressions of NLRP3， cleaved Caspase-1， and cleaved gasdermin D （GSDMD） proteins in the nasal mucosa. The test kit was used to detect the changes in ROS in the nasal cavity of mice in each group. ResultCompared with the control group， the nasal symptoms of the model group were significantly aggravated， and the levels of inflammatory factors OVA-sIgE， histamine， ECP， PGD2， IL-1β， IL-18， and IL-4 in serum and nasal lavage solution were increased （P<0.05，P<0.01）. The levels of IFN-γ were decreased （P<0.05，P<0.01）. The histopathological score， goblet cell number， and ROS content were significantly increased （P<0.01）， and the expressions of pyrodeath-related proteins NLRP3， cleaved Caspase-1， and cleaved GSDMD were increased （P<0.01）. Compared with the model group， the nasal symptoms of the loratadine group and Yupingfeng San groups were significantly relieved， and the levels of inflammatory factors OVA-sIgE， histamine， ECP， PGD2， IL-1β， IL-18， and IL-4 in serum and nasal lavage solution were decreased （P<0.05，P<0.01）. The levels of IFN-γ were increased （P<0.05，P<0.01）. The histopathological scores， goblet cell number， and ROS content were significantly decreased （P<0.05，P<0.01）， and the expressions of pyrodeath-related proteins NLRP3， cleaved Caspase-1， and cleaved GSDMD were decreased （P<0.05，P<0.01）. Compared with the loratadine group， the curative effect of the high dose Yupingfeng San group was further increased （P<0.05，P<0.01）. ConclusionYupingfeng San has a therapeutic effect on AR， and its specific effect may be related to the inhibition of ROS/NLRP3/Caspase-1-induced cell pyroptosis.