[关键词]
[摘要]
目的 阐明桑白皮-地骨皮治疗便秘的配伍特点、应用规律并进行药效研究。方法 检索含桑白皮-地骨皮治疗便秘的方剂信息,运用Excel、SPSS Modeler等工具对该药对的剂量、功效、配比进行关联规则与可视化分析。采用网络药理学探讨该药对治疗便秘的潜在作用靶点及机制,并进行药效实验验证。结果 最终筛得含桑白皮-地骨皮药对106首方剂,剂量桑白皮以9 g最多,地骨皮以15 g最多;涉及泻肺平喘、泻热导滞、润肠通便等14种功效。配比以1∶1、0.6∶1为主。网络药理学分析得到桑白皮-地骨皮有效成分17个,成分和疾病交集靶点61个,主要核心靶点为白细胞介素-6(interleukin-6,IL-6)、蛋白激酶B1(protein kinase B,AKT1)等。京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集表明该药对治疗便秘的相关通路为磷脂酰肌醇3-激酶(phosphatidylinositol-3-kinase,PI3K)/蛋白激酶(protein kinase B,AKT)信号通路等。分子对接结果提示,活性成分槲皮素、山柰酚等与靶点蛋白结合活性较强。动物实验表明,桑白皮-地骨皮各剂量组的大鼠粪便含水量均升高,首粒黑便排出时间均缩短,肠道推进率均加快,差异具统计学意义。桑白皮-地骨皮药对可减少大鼠结肠组织炎症细胞浸润,增多杯状细胞;血清中P物质(substance P,SP)、胃动素(motilin,MTL)、5-羟色胺(5-hydroxytryptamine,5-HT)、AKT1、前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase,PTGS2)含量增加,血管活性肠肽(vasoactive intestinal peptide,VIP)、IL-6含量减少,差异具统计学意义。结论 桑白皮-地骨皮功效以泻肺平喘、泻热导滞、润肠通便为主,不同配伍比例可增强或减弱其功效,桑白皮-地骨皮具有治疗便秘的作用。
[Key word]
[Abstract]
Objective To elucidate the compatibility characteristics, application patterns, and pharmacological efficacy of the Sangbaipi (Mori Cortex)-Digupi (Lycii Cortex) medicinal pair in the treating of constipation. Methods Formulas containing Mori Cortex-Lycii Cortex for constipation treatment were systematically retrieved. Tools such as Excel and SPSS Modeler were utilized to perform association rule mining and visualization analyses on the dosage, efficacy, and ratio of the medicinal pair. Network pharmacology approaches were employed to investigate potential therapeutic targets and mechanisms of the medicinal pair in constipation treatment, followed by experimental verification for drug efficacy.Results A total of 106 formulas were screened, with the most frequent dosages being 9 g for Mori Cortex and 15 g for Lycii Cortex. The formulas demonstrated 14 types of efficacy, including clearing lung heat, relieving cough and asthma, and promoting bowel movements. The primary compatibility ratios of the medicinal pair were 1∶1 and 0.6∶1. Network pharmacology analysis identified 17 active components and 61 overlapping targets between the components and diseases, with core targets including interleukin-6 (IL-6) and protein kinase B1 (AKT1). Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis revealed that the phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway was significantly associated with the therapeutic effects of the medicinal pair. Molecular docking results indicated strong binding affinities between active components (e.g., quercetin and kaempferol) and target proteins. Animal experiments demonstrated that all dosage groups of the Mori Cortex-Lycii Cortex pair significantly increased fecal water content, reduced the time to expel the first black stool, and accelerated intestinal propulsion rates. The differences are statistically significant. Additionally, the medicinal pair reduced inflammatory cell infiltration in colon tissue and increased goblet cell counts. Post-treatment serum levels of substance P (SP), motilin (MTL), 5-hydroxytryptamine (5-HT), AKT1, and prostaglandin-endoperoxide synthase (PTGS2) were significantly elevated, while levels of vasoactive intestinal peptide (VIP) and IL-6 were reduced, and the difference was statistically significant. Conclusion The Mori Cortex-Lycii Cortex medicinal pair primarily exerts therapeutic effects by clearing lung heat, relieving cough and asthma, purging heat and removing stagnation and promoting bowel movements. Different compatibility ratios can modulate its efficacy, demonstrating its potential as an effective treatment for constipation.
[中图分类号]
R285
[基金项目]
国家中医药管理局李冀名老中医药专家传承工作室项目(2014);国家中医药管理局李冀全国名中医传承工作室项目(2022);2023年黑龙江省中医药科研项目:基于“肺肠同治”的泻白散对肺炎模型大鼠肠道菌群的调控机制(20230830225018);2022年度黑龙江省卫生健康委科技计划:基于TLR4/NF-κB信号通路探讨泻白散治疗幼龄大鼠肺炎模型的作用机制(20221313050712)