专利中药复方治疗功能性便秘的用药规律及机制研究

Medication Rule and Mechanism of Patented Chinese Herbal Compounds in the Treatment of Functional Constipation

目的探讨专利中药复方治疗功能性便秘(functional constipation)的用药规律及作用机制。方法检索国家知识产权局中国专利公布公告网中治疗功能性便秘的中药复方专利,运用Excel表和中医传承计算平台进行用药频数统计、关联分析、聚类分析等;通过网络药理学方法探讨核心高频药组治疗功能性便秘的作用靶点及机制,最后进行分子对接验证。结果纳入中药复方专利72项,涉及中药262味,高频药物为白术(26次,36.11%)、甘草(24次,33.33%)等;以补虚、理气、清热、泻下、化湿和活血化瘀药为主;核心高频药物组是肉苁蓉-当归-白术;核心高频药物组肉苁蓉-当归-白术治疗功能性便秘的主要活性成分可能为槲皮素、β-谷甾醇、豆甾醇等,主要靶点为蛋白激酶B1(AKT1)、热休克蛋白90AA1(HSP90AA1)、MYC、缺氧诱导因子1亚基α(HIF1A)、肿瘤抑制因子P53(TP53)和细胞周期蛋白1(CCND1)等,主要的作用通路为磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)、糖基化终产物(AGE)/糖基化终产物受体(RAGE)、丝裂原活化蛋白激酶(MAPK)、肿瘤坏死因子(TNF)、白细胞介素(IL)-17、缺氧诱导因子(HIF)-1信号通路等。结论专利中药复方主要通过补虚、理气、清热、泻下、化湿和活血化瘀治疗功能性便秘,核心高频药组肉苁蓉-当归-白术可能通过恢复肠道动力、调节肠道菌群、抑制炎症反应等作用治疗功能性便秘。

Objective To explore the medication rule and mechanism of patented Chinese herbal compound in the treatment of functional constipation(FC).Methods The Chinese herbal compounds for the treatment of FC were retrieved from the website for patent announcement of the China National Intellectual Property Administration.Excel table and Traditional Chinese Medicine Inheritance Computing System(TCMICS)were used for frequency statistics,association analysis and cluster analysis.The target and mechanism of core high-frequency drug combination in the treatment of FC were explored by network pharmacology method.Finally,the molecular docking technology was used to verify drug and target binding.Results A total of 72 patented Chinese herbal compounds were included,involving 262 Chinese medicinals.High-frequency drugs were Atractylodis Macrocephalae Rhizoma(26 times,36.11%),Glycyrrhizae Radix(24 times,33.33%).The main effect of high-frequency medicine is to supplement deficiency,regulate qi,clear heat,purge,remove dampness,promote blood circulation and remove blood stasis.The core high-frequency medicine combination is Cistanches Herba-Angelicae Sinensis Radix-Atractylodis Macrocephalae Rhizoma.The main active components of the core high-frequency drug combination in the treatment of FC may be quercetin,β-sitosterol and stigmasterol.The main targets were protein kinase B1(AKT1),heat shock protein 90AA1(HSP90AA1),MYC,hypoxia-inducible factor-1alpha(HIF1A),tumor protein 53(TP53)and cyclin D1(CCND1).The key pathways are phosphatidylinositol 3-kinase(PI3K)/Akt,advanced glycation end products(AGE)/receptor for advanced glycation end products(RAGE),mitogen activated protein kinase(MAPK),tumor necrosis factor(TNF),interleukin(IL)-17 and HIF-1 signaling pathway.Conclusion The patented Chinese herbal compounds are mainly used to treat FC through supplementing deficiency,regulating qi,clearing heat,purging,removing dampness,promoting blood circulation and removing blood stasis.The core high-frequency drug combination(Cistanches Herba-Angelicae Sinensis Radix-Atractylodis Macrocephalae Rhizoma)may treat FC by restoring intestinal motility,regulating intestinal flora and inhibiting inflammation.