黑青稞燕麦营养冲调粉通便和降脂功能的研究及其作用机制预测

Bowel-relaxing and lipid-lowering functions of highland barley-oat nutritious powder and its mechanism of action

目的:考察黑青稞燕麦营养冲调粉(BHOP)的通便和降脂功能,并应用网络药理学预测分析其作用机制。方法:采用盐酸洛哌丁胺建立急性小鼠便秘模型,连续给样14 d后采用小肠墨汁推进试验考察通便功能;采用高脂饲料构建高脂血症大鼠模型。给药后检测胆固醇(CHOL)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)含量。利用TCMSP、TCMIP平台收集和筛选组方活性成分及蛋白靶点,使用UniPort数据库预测并标准化活性成分的蛋白靶点;以便秘和高脂血症为疾病背景在GeneCard数据库获取疾病靶点,将二者进行交集,得到共有核心靶点,在STRING网站中进行蛋白质-蛋白质相互作用(PPI)分析,利用Cytoscape 3.7.1将PPI可视化并计算degree值;使用DAVID数据库对核心靶点进行基因本体(GO)功能及京都基因和基因组百科全书(KEGG)通路富集。结果:与模型对照组比较,BHOP各剂量组小肠墨汁推进率均增加,其中中、低剂量组与模型对照组比较,差异有统计学意义(P<0.05或P<0.01);BHOP高剂量组CHOL和TG水平均较模型对照组低,差异有统计学意义(P<0.05)。从数据库中共收集到46种活性成分,预测出53个核心靶点、198种GO功能条目和64条KEGG信号通路。结论:BHOP具有降脂和通便功能,BHOP中的β-葡聚糖、熊果酸、槲皮素、亚油酸等活性成分可能通过作用于白蛋白、血管内皮生长因子A、过氧化物酶体增殖物激活受体γ、表皮生长因子、白细胞介素-6、肿瘤坏死因子、白细胞介素-1β等靶点介导缺氧诱导因子-1、核因子κB等信号通路发挥降脂和通便功能。

Objective:To investigate the bowel-relaxing and lipid-lowering functions of highland barley-oat nutritious powder(BHOP)and its mechanism of action based on network pharmacology.Methods:Loperamide hydrochloride was used to establish a mouse model of acute constipation,and after 14 consecutive days of administration,small intestinal ink propelling test was used to observe bowel-relaxing function.High-fat feed was used to establish a rat model of hyperlipidemia,and cholesterol(CHOL),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were measured after administration.TCMSP and TCMIP platforms were used to obtain the active components and protein targets of the prescription,and Uniports database was used to predict and standardize the protein targets of active components.GeneCard database was used to obtain the disease targets of constipation and hyperlipidemia,and the intersection of the two groups of disease targets was performed to obtain the common core targets;STRING website was used to perform a protein-protein interaction(PPI)analysis,and Cytoscape 3.7.1 was used to visualize PPI and calculate degree value.DAVID database was used to perform gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results:Compared with the model control group,the BHOP groups had an increase in small intestinal ink propelling rate,with a significant difference between the middle-/low-dose groups and the model control group(P<0.05 or P<0.01).The high-dose BHOP group had significantly lower levels of CHOL and TG than the model control group(P<0.05).A total of 46 active components were obtained from the database,and prediction obtained 53 score targets,198 GO functional terms,and 64 KEGG signaling pathways.Conclusion:BHOP has the lipid-lowing and bowel-relaxing functions,and the active components in BHOP,such asβ-glucan,ursolic acid,quercetin,and linoleic acid,exert the lipid-lowing and bowel-relaxing effects by mediating the signaling pathways including hypoxia-inducible factor-1 and nuclear factor-kappa B via the targets such as albumin,vascular endothelial growth factor A,peroxisome proliferator-activated receptorγ,epidermal growth factor,interleukin-6,tumor necrosis factor,and interleukin-1β.