基于数据挖掘和网络药理学的栀子防治前列腺增生的用药规律和作用机制及实验验证  

Medication law,mechanism of action and experimental validation of Gardeniae Fructus against prostate hyperplasia based on data mining and network pharmacology

作　　者：杨晶莹 胡毅龙 赵怡楠 岳璐 任翔 苗明三[1,2] YANG Jingying;HU Yilong;ZHAO Yinan;YUE Lu;REN Xiang;MIAO Mingsan(College of Pharmacy,Henan University of Chinese Medicine,Henan Zhengzhou 450046,China;Henan Provincial Collaborative Innovation Centre for R&D of Yu Medicine Industry Chain,Henan Zhengzhou 450046,China)

机构地区：[1]河南中医药大学药学院,河南郑州450046 [2]豫药全产业链研发河南省协同创新中心,河南郑州450046

出　　处：《中国医院药学杂志》2025年第5期546-553,共8页Chinese Journal of Hospital Pharmacy

基　　金：河南省重大专项(编号:231111521200);岐黄学者(编号:国中医药人教函2022-6);河南中医药大学2023年度研究生科研创新能力提升计划(编号:2023KYCX058)。

摘　　要：目的:探索栀子防治前列腺增生(benign prostatic hyperplasia,BPH)的用药规律与作用机制,并进行实验验证。方法:基于数据挖掘筛选古籍记载的含栀子组方,分析组方中与栀子配伍高频中药的用药规律。检索数据库获得栀子的活性成分靶点与BPH的疾病靶点,进行“活性成分-疾病”靶点关联分析。采用雄性昆明小鼠连续28 d颈背部皮下注射丙酸睾酮油溶液(12.5 mg·kg^(-1))复制BPH模型,自造模第8天起阳性对照组,栀子高、中、低剂量组连续灌胃给药21 d。ELISA法检测小鼠血清中E2、T、IL-1β、IL-6、TNF-α、IL-10水平,HE法观察各组小鼠前列腺组织病理变化。结果:符合标准的中药组方中,含栀子的有893首,与栀子配伍的中药频次达9056次,其中高频中药21味(频数≥90);高频中药药性多为寒、微寒,药味主要有苦、辛、甘,多归肺经、脾经、肝经,多为清热药、补虚药、解表药。栀子主要活性成分为槲皮素、异欧前胡素、山柰酚、β-谷甾醇等,核心靶点为SRC、HSP90AA1、AKT1、EGFR等,涉及花生四烯酸代谢、NF-κB信号通路等。动物实验结果表明,栀子可显著降低BPH小鼠血清中E2、IL-1β、IL-6、TNF-α含量(P<0.01),增加IL-10、T水平,减轻前列腺组织病变。结论:该研究证实了栀子具备改善BPH的理论基础、物质基础及药理活性,为栀子改善“淋证涩痛”的核心功效提供了现代研究支撑。OBJECTIVE To explore the medication law and mechanism of action of Gardeniae Fructus(GF)to prevent and control benign prostatic hyperplasia(BPH)and to conduct an experimental validation.METHODS Based on data mining screen⁃ing ancient records containing GF prescription,the medication law of compatibility of frequently used traditional Chinese herbals to GF prescription was analyzed.Active ingredient targets of GF and the disease targets of BPH were searched in online databases,and an active ingredient-disease-target network was created.A BHP model in male Kunming mice was created by subcutaneous injections of testosterone propionate oil solution(12.5 mg·kg^(-1))into the back of the neck for 28 consecutive days.From the 8th day of modeling,oral gavage of low-dose,medium-dose and high-dose GF was given for consecutive 21 days.Serum estradiol(E2),testosterone(T),interleukin-1beta(IL-1β),IL-6,tumor necrosis factor-alpha(TNF-α),and IL-10 were detected by Enzyme-linked immunosorbent assay(ELISA),and the histopathological changes of the prostate gland were observed by hema⁃toxylin and eosin(H&E)staining in the mice in each group.RESULTS Among the eligible Chinese herbal medicine formulas,there were 893 prescriptions containing raw GF.A total of 9056 frequencies of compatibility to raw GF were detected,involving 21 high-frequency Chinese herbal medicines(frequency≥90),and they were mainly cold and slightly cold in drug properties,bit⁃ter,pungent and sweet in the flavour,and mostly attributed to the lung,spleen and liver meridians.Functionally,they were used for clearing up heat,tonifying emptiness,and relieving epidemiology.The main active ingredients of GF consisted of quercetin,isoimperatorin,kaempferol,β-sitosterol,etc.The core targets were proto-oncogene c-Src(SRC),heat shock protein 90α(HSP90AA1),protein kinase B(AKT1),and epidermal growth factor receptor(EGFR),that were mainly enriched in the metabolism of arachidonic acid,and the NF-κB signaling pathway.Animal experiments showed that GF significantly

关 键 词：栀子 前列腺增生 数据挖掘 网络药理学 作用机制 

分 类 号：R965[医药卫生—药理学]