目的 借助网络药理学方法并结合动物实验预测鼻敏康颗粒治疗变应性鼻炎的分子机制。 方法 借助TCMSP、OMIM、GeneCards、TTD、DrugBank、PharmGKB数据库筛选鼻敏康颗粒的活性成分靶点及变应性鼻炎靶点；运用R语言软件对药物和疾病靶点映射取交集；采用Cytoscape 3.8.0软件、STRING数据库构建交集靶点PPI网络，并进行网络拓扑学分析；利用DAVID数据库进行GO功能富集和KEGG通路富集分析，并对主要活性成分与关键靶点进行分子对接验证。将32只大鼠按随机数字表法分为空白组8只和造模组24只。造模组大鼠经卵清蛋白诱导建立变应性鼻炎模型。将造模成功的24只SD大鼠按随机数字表法分为模型组、西药组、鼻敏康颗粒组，每组8只。西药组灌胃氯雷他定药液1 mg/kg，鼻敏康颗粒组灌胃鼻敏康颗粒药液4.1 g/kg，空白组与模型组大鼠灌胃等体积的生理盐水，1次/d，连续2周。观察并记录30 min各组大鼠鼻炎症状，采用HE染色观察大鼠鼻黏膜病理改变，ELISA法检测大鼠血清中IL-17、IL-6水平，Western blot法测定大鼠鼻黏膜组织中TNF、STAT3蛋白表达。 结果 预测到鼻敏康颗粒治疗变应性鼻炎靶点41个，PPI网络拓扑学分析得到TNF、STAT3等核心靶点，GO生物过程涉及药物反应、炎症反应、细胞因子反应等，KEGG通路主要富集于Th17细胞分化、脂质和动脉粥样硬化、IL-17、Toll样受体等通路。分子对接结果显示，主要活性成分与关键靶点结合活性良好。动物实验表明，鼻敏康颗粒可改善变应性鼻炎大鼠鼻炎症状，下调血清IL-17、IL-6表达，抑制TNF-α、STAT3蛋白表达。 结论 鼻敏康颗粒可通过多个活性成分、多靶点、多通路治疗变应性鼻炎，其机制可能与调控Th17细胞分化通路相关蛋白有关。 Objective To predict the molecular mechanism of Biminkang Granules in the treatment of allergic rhinitis using network pharmacological methods combined with animal experiments. Methods Active component targets and allergic rhinitis targets were screened from TCMSP, OMIM, GeneCards, TTD, DrugBank and PharmGKB databases R language software was used to map the intersection of drug and disease targets Cytoscape software and String platform were used to construct intersection target PPI network and conduct network topology analysis DAVID platform was used to perform GO enrichment and KEGG pathway analysis, and perform molecular docking verification on the main active components and key targets. 32 rats were divided into a blank group of 8 and a model group of 24 using a random number table method. Model rats were induced by ovalbumin to establish an allergic rhinitis model. 24 SD rats that were successfully modeled and were randomly divided into model group, Western medicine group, and Biminkang Granules group using a random number table method, with 8 rats in each group. The Western medicine group was gavaged with 1 mg/kg of loratadine solution, the Biminkang Granules group was gavaged with 4.1 g/kg of Biminkang Granules solution, and the blank group and model group rats were gavaged with the same volume of physiological saline once a day for 2 consecutive weeks. The symptoms of rhinitis in each group of rats for 30 minutes were observed and recorded, and the pathological changes of the rat nasal mucosa were observed using HE staining. ELISA method was used to detect the levels of IL-17 and IL-6 in rat serum, and Western blot method was used to determine the expressions of TNF and STAT3 proteins in rat tissues. Results A total of 41 target proteins of BiMinKang Dranule in the treatment of allergic rhinitis were predicted, and TNF, STAT3 and other core target proteins were obtained by PPI network topology analysis. The biological process of GO involved drug response, inflammatory response, cytokine response, etc.KEGG enrichment is involved in Th17 cell differentiation, lipid and atherosclerosis, IL-17, toll-like receptor and other pathways. Molecular docking results indicated that the main active components had good binding activity to key target proteins.Animal experiments showed that BiMinKang Dranule could improve the inflammatory symptoms of allergic rhinitis rats, down-regulate the expression of IL-17 and IL-6 in blood, and inhibit the expression of TNF and STAT3 proteins. Conclusion Biminkang Granules can treat allergic rhinitis through multiple active components, multiple target proteins and multiple pathways, and the mechanism may be related to the regulation of Th17 cell differentiation pathway related proteins.
Discussion on mechanism of modified Biminkang Granules in treatment of allergic rhinitis based on network pharmacology and experimental verification
Objective To predict the molecular mechanism of Biminkang Granules in the treatment of allergic rhinitis using network pharmacological methods combined with animal experiments. Methods Active component targets and allergic rhinitis targets were screened from TCMSP, OMIM, GeneCards, TTD, DrugBank and PharmGKB databases R language software was used to map the intersection of drug and disease targets Cytoscape software and String platform were used to construct intersection target PPI network and conduct network topology analysis DAVID platform was used to perform GO enrichment and KEGG pathway analysis, and perform molecular docking verification on the main active components and key targets. 32 rats were divided into a blank group of 8 and a model group of 24 using a random number table method. Model rats were induced by ovalbumin to establish an allergic rhinitis model. 24 SD rats that were successfully modeled and were randomly divided into model group, Western medicine group, and Biminkang Granules group using a random number table method, with 8 rats in each group. The Western medicine group was gavaged with 1 mg/kg of loratadine solution, the Biminkang Granules group was gavaged with 4.1 g/kg of Biminkang Granules solution, and the blank group and model group rats were gavaged with the same volume of physiological saline once a day for 2 consecutive weeks. The symptoms of rhinitis in each group of rats for 30 minutes were observed and recorded, and the pathological changes of the rat nasal mucosa were observed using HE staining. ELISA method was used to detect the levels of IL-17 and IL-6 in rat serum, and Western blot method was used to determine the expressions of TNF and STAT3 proteins in rat tissues. Results A total of 41 target proteins of BiMinKang Dranule in the treatment of allergic rhinitis were predicted, and TNF, STAT3 and other core target proteins were obtained by PPI network topology analysis. The biological process of GO involved drug response, inflammatory response, cytokine response, etc.KEGG enrichment is involved in Th17 cell differentiation, lipid and atherosclerosis, IL-17, toll-like receptor and other pathways. Molecular docking results indicated that the main active components had good binding activity to key target proteins.Animal experiments showed that BiMinKang Dranule could improve the inflammatory symptoms of allergic rhinitis rats, down-regulate the expression of IL-17 and IL-6 in blood, and inhibit the expression of TNF and STAT3 proteins. Conclusion Biminkang Granules can treat allergic rhinitis through multiple active components, multiple target proteins and multiple pathways, and the mechanism may be related to the regulation of Th17 cell differentiation pathway related proteins.
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