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| Discussion of the mechanism of Qixuan Yijianing in the treatment of Graves disease based on network pharmacology and animal experiments |
| GAO Changjiu1 DING Song1 LU Fang2 LIU Changfeng2 YU Donghua2 LIU Shumin2 |
1.Graduate School, Heilongjiang University of Chinese Medicine, Heilongjiang Province, Harbin 150040, China;
2.Institute of Chinese Medicine, Heilongjiang University of Chinese Medicine, Heilongjiang Province, Harbin 150040, China |
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Abstract Objective To explore the mechanism of Qixuan Yijianing in the treatment of Graves disease (GD) based on network pharmacology and animal experiments. Methods The active constituents and targets of Qixuan Yijianing were detected by traditional Chinese medicine systems pharmacology database and analysis platform, and chemical database, and GD related targets were detected from Genecards, online human Mendelian genetic database, etc. The common targets of drugs and diseases were introduced into STRING platform to construct protein-protein interaction (PPI) network and screen core targets. Cytoscape 3.8.2 software was used to map the drug-active ingredient-target network and screen core components. The core target was enriched by Metascape platform. Forty 6-week-old female BALB/c mice with SPF grade and body weight of (20±2) g were selected, ten of which were set as normal control group, and the remaining 30 were immunized with recombinant adenovirus Ad-TSHR-289 for three times to construct GD model. The mice that modeled successfully were divided into GD model group, Methimazole group, and Qixuan Yijianing group by random number table method, with eight mice in each group. Qixuan Yijianing group was intragastric administration of Qixuan Yijianing 50 g/kg, Methimazole group was intragastric administration of Methimazole Tablets 3.75 mg/kg, normal control group and GD model group were intragastric administration of drinking water of the same volume, once a day. After four weeks of continuous administration, serum vascular endothelial growth factor (VEGF) content was detected by enzyme-linked immunosorbent assay. The expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) in thyroid tissues of the four groups was detected by immunohistochemistry. Results A total of 63 active ingredients with 281 targets and 1 489 targets of GD were obtained. There were 124 targets of drugs and diseases. PPI obtained 21 core targets of signal transduction and transcription activator 3, serine/threonine protein kinase 1, VEGFA, etc. Eighteen core components including luteolin, kaempferol, quercetin, ursolic acid, and β-sitosterol were obtained by drug-target analysis. 954 items of inflammatory response, angiogenesis, and vascular morphogenesis were obtained GO by analysis, and 92 pathways including MAPK, PI3K/AKT, and VEGF were obtained by KEGG analysis. Animal experiments showed that the expression levels of serum VEGF and thyroid PECAM-1 in GD model group were higher than those in normal control group, and those in Qixuan Yijianing group were lower than those in GD model group, the differences were highly statistically significant (P＜0.01). Conclusion Qixuan Yijianing is able to treat GD by regulating MAPK, PI3K/AKT, VEGF, and other signaling pathways to inhibit angiogenesis.
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