Data on the mechanism of JPYSTQKL in the treatment of allergic rhinitis

Published: 4 March 2024| Version 1 | DOI: 10.17632/w5wjntyypr.1
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Allergic rhinitis (AR), also known as allergic rhinitis, is an infectious inflammatory reaction involving allergic reactions and inflammatory factors and immune cells in the body, mainly manifested by nasal congestion, runny nose, and itchy nose. AR is the most common allergic disease in the world, and its incidence has been on the rise in recent years. The number of patients worldwide accounts for about 10%-30% of the total population, which seriously affects the work and life of patients. Jianpi Yishentongqiao Keli(JPYSTQKL) is the chief physician of the tutor Zhang Changxi engaged in clinical medicine for many years, accumulated a lot of experience in the treatment of AR, the Yupingfeng powder, Cangerzi powder, Erxian decoction added and reduced to cut.JPYSTQKL is composed of Aconiti Lateralis Radix Praeparata, Leonuri Fructus, Atractylodes Macrocephala Koidz, Epimrdii Herba, Morindae Officinalis Radix, Saposhnikoviae Radix, Magnoliae Flos, Hedysarum Multijugum Maxim, Cicadae Periostracum, Perilla Frutescens, Licorice , etc.With the use of cold and heat, warm tonifying and qi, so that the lung, spleen and kidney three viscera harmonization, a total of spleen and qi, tonifying kidney and Yang, wind clearing work. We investigated the possible effects of JPYSTQKL on AR through network pharmacology and in vivo experiments. In this paper, 30 key targets of JPYSTQKL, including JUN, IL6, TNF, AKT1, TP53, IL-1β, IL-4, CXCL8, and CCL2, were recorded through the MAPK signaling pathway, IL-17 signaling pathway, and TNF signaling pathway has therapeutic effect on AR rats.

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TCMSP platform was used to screen the active ingredients and targets of JPYSTQKL, and AR disease targets were obtained through GeneCards, OMIM and TTD databases. Protein interaction (PPI) network was constructed with STRING platform. GO/ KEGG enrichment analysis was performed using DAVID online database. The JPYSTQKL active ingredient-AR disease target network was constructed by Cytoscape 3.9.1 to predict potential targets. AutoDockVina was used to validate key compounds and core target genes. The AR rat model was established, and 56 healthy male Wistar rats with SPF grade were selected (provided by Experimental Animal Center of Ningxia Medical University). 8 rats were randomly selected as normal control group , and the other 48 rats were established as allergic rhinitis model. The rat model was sensitized by peritoneal injection of sensitization solution (OVA0.3 mg, dissolved in 1ml of normal saline with 30mg of aluminum hydroxide) on the 1st, 3rd, 5th, 7th, 9th, 11th and 13d, once a day, for a total of 7 times. Starting from the 15th day, 50μL of 5%OVA normal saline solution was dropped into each nostril for local enhancement and sensitization of the nasal cavity, once a day for 10 consecutive times. The normal control group received intraperitoneal injection and nasal drip with the same volume of normal saline.The number of nose scratching, sneezing and runny nose of rats were observed and recorded 10min after the last nasal drip. The model was successful when the total score was above 5. 56 SD rats were randomly divided into control group, model group, JPYSTQKL high-dose group, JPYSTQKL medium-dose group, JPYSTQKL low-dose group, blocker SP600125 group and loratadine group . The contents of IL-4, IgE, SIgE and IFN-γ in nasal lavage solution were detected by electron microscopy and ELISA after HE staining, and the expressions of JNK, p-JNK, JUN and p-c-JUN proteins in nasal mucosa were detected by immunohistochemistry and WB. 196 active components, 96 targets and 157 pathways of JPYSTQKL were screened. KEGG enrichment analysis involved immunoinflammatory signaling pathways. It is related to cell proliferation and apoptosis-related signaling pathways, such as MAPK signaling pathway and IL-17 signaling pathway. ELISA results: Compared with Control group, the serum IgE, SIgE and IL-4 levels in Model group were increased, and IFN-γ content was decreased (P < 0.01). Compared with Model group, the contents of IgE, SIgE and IL-4 in all intervention groups were decreased, and the contents of IFN-γ were increased (P < 0.01). WesternBlot detection results: Compared with Control group, the expressions of JNK, c-JUN, P-JNK and P-C-Jun proteins in nasal mucosa of Model group were significantly up-regulated (P < 0.05). Compared with Model group, the protein contents of JNK, c-JUN, P-JNK and P-C-Jun in nasal mucosa of rats in treatment group were significantly decreased (P < 0.05 ).

Institutions

Ningxia Medical University

Categories

Expression Proteomics, Network Pharmacology

Funding

Natural Science Foundation of Ningxia Province

2022A0335

Key Research and Development Program of Ningxia

2023BEG02014

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