Multicenter Clinical Randomized Controlled Trial and Network Pharmacology Analysis of Zhenzhu Qingyuan Granules for the Treatment of Gastroesophageal Reflux Disease

珍珠青元颗粒治疗胃食管反流病多中心临床随机对照研究及网络药理学分析

Objective To evaluate the clinical efficacy and safety of Zhenzhu Qingyuan Granules through a clinical randomized controlled trial and to analyze the potential action targets and pathways of this formula using network pharmacology.Methods Patients with gastroesophageal reflux disease(GERD)of liver–stomach stagnant heat pattern who met the inclusion and exclusion criteria were randomly divided into the control group and the observation group.The control group received oral rabeprazole,whereas the observation group were given Zhenzhu Qingyuan Granules in addition to the rabeprazole.The treatment duration was 8 weeks.Clinical efficacy was observed in both groups after 8 weeks.Network pharmacology was used to analyze the action targets of ZhenzhuQingyuanGranules and the genes related to GERD,and core targets were inferred.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to explore the potential mechanisms of this formula.Results The clinical research results showed that the total effective rate in the treatment group was 92.68%,compared with 70.00%in the control group,with a statistically significant difference(p<0.05).After treatment,both Chinese medicine syndrome score and endoscopic score improved in both groups compared with before treatment(p<0.05),and the treatment group showed greater improvement than the control group(p<0.05).Network pharmacology identified effective components of Zhenzhu Qingyuan Granules for treating GERD,including quercetin,luteolin,andβ-sitosterol,with potential action targets such as tumor protein 53(TP53),protein kinase B(AKT1),and tumor necrosis factor.Conclusion Zhenzhu Qingyuan Granules can significantly improve clinical symptoms in patients with GERD of liver–stomach stagnated heat pattern,enhance clinical efficacy,and have high safety.This formula may exert therapeutic effects through multiple targets and pathways.

目的:根据临床随机对照研究评估珍珠青元颗粒治疗胃食管反流病(gastroesophageal reflux disease,GERD)的临床疗效及安全性,通过网络药理学分析本方治疗GERD的潜在作用靶点和通路。方法:选取符合纳排标准的肝胃郁热型GERD患者,随机分为对照组和观察组。对照组予雷贝拉唑口服,观察组在对照组基础上加用珍珠青元颗粒治疗GERD口服。疗程均为8周。8周后观察两组临床疗效。通过网络药理学分析珍珠青元颗粒治疗GERD的作用靶点和GERD疾病相关的基因,并推测其核心靶点,对靶点进行GO(gene ontology)和KEGG(kyoto encyclopedia of genes and genomes)富集分析以探究本方潜在的作用机制。结果:临床研究结果显示,治疗组总有效率为92.68%,对照组为70.00%,两组比较差异有统计学意义(P<0.05);治疗后,两组中医证候积分及内镜积分均较治疗前改善(P<0.05),且治疗组均优于对照组(P<0.05)。通过网络药理学方法鉴定出珍珠青元颗粒治疗GERD的有效成分包括槲皮素、木犀草素、β-谷甾醇等,其潜在作用靶点包括肿瘤蛋白53(tumor protein 53,TP53)、蛋白激酶B(protein kinase B,AKT1)、肿瘤坏死因子(tumor necrosis factor,TNF)等。结论:珍珠青元颗粒治疗GERD可明显改善肝胃郁热型GERD患者的临床症状,提高临床疗效,安全性较高。本方可通过多靶点、多通路发挥治疗GERD的作用。