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王瑾源,原茵,董梦雪,谭雅文,吕萌,王洪武,郑纺.基于网络药理学初探金芪降糖片治疗肥胖的作用机制[J].湖南中医药大学学报英文版,2023,43(4):677-686.[Click to copy
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| 基于网络药理学初探金芪降糖片治疗肥胖的作用机制 |
| 王瑾源,原茵,董梦雪,谭雅文,吕萌,王洪武,郑纺 |
| (天津中医药大学中西医结合学院, 天津 301617;津药达仁堂集团股份有限公司隆顺榕制药厂, 天津 300457;天津中医药大学中医学院, 天津 301617) |
| 摘要: |
| 目的 观察金芪降糖片对C57BL/6肥胖模型小鼠的治疗效果，并基于网络药理学预测金芪降糖片治疗肥胖的相关机制。方法 选取30只SPF级雄性C57BL/6小鼠，分为正常组、模型组、金芪降糖片组。正常组饲喂正常饲料，模型组及金芪降糖片组饲喂高脂饲料，模型复制成功后给予药物干预。检测C57BL/6小鼠体质量、血脂水平、体内脂肪含量及肝脏、脂肪组织形态。通过TCMSP数据库与GeneCards数据库筛选金芪降糖片治疗肥胖的活性成分及交集靶点；将交集靶点导入STRING数据库分析靶点间的相互作用；通过Biocondoctor数据库进行GO分析和KEGG通路富集分析。基于网络药理学的预测结果，运用Western blot验证关键信号通路的蛋白表达。结果 与空白组相比，模型组小鼠体质量及血清甘油三酯（triglyceride, TG）、总胆固醇（total cholesterol, TC）、低密度脂蛋白胆固醇（lipoprotein cholesterol, LDL-C）含量均升高（P<0.05），高密度脂蛋白胆固醇（high density lipoprotein cholesterol, HDL-C）含量降低（P<0.05），肝脏组织中脂滴蓄积明显增多，脂肪细胞数目增多、体积增大；与模型组相比，金芪降糖片组小鼠体质量及血清TG、TC、LDL-C含量均降低（P<0.05），HDL-C含量升高（P<0.05），肝脏组织中脂滴蓄积情况改善，脂肪细胞数目减少、体积缩小；Micro-CT结果显示，与空白组相比，模型组小鼠体内白色脂肪及棕色脂肪含量均明显升高（P<0.01），而金芪降糖片可减少两类脂肪含量（P<0.01）。同时，金芪降糖片也可改善肥胖小鼠肝脏与脂肪组织变性。通过网络药理学预测得到金芪降糖片治疗肥胖的55个共同靶点及其79条富集通路。KEGG富集分析得到金芪降糖片治疗肥胖的作用机制可能与流体剪切应力和动脉硬化、糖尿病并发症中的AGE-RAGE信号通路、TNF信号通路、PPARγ信号通路等密切相关。Western blot结果显示，与空白组相比，模型组小鼠脂肪组织中PPARγ信号通路关键蛋白明显上调；与模型组相比，金芪降糖片组小鼠脂肪组织中PPARγ信号通路关键蛋白明显下调。结论 金芪降糖片可有效减轻肥胖小鼠体重、改善血脂异常、降低体内脂肪含量、改善肝脏组织中脂滴蓄积及脂肪组织中脂肪细胞数量及大小，其可能通过PPARγ信号通路治疗肥胖。 |
| 关键词: 金芪降糖片 肥胖 网络药理学 PPARγ信号通路 实验验证 |
| DOI：10.3969/j.issn.1674-070X.2023.04.017 |
| Received:November 02, 2022 |
| 基金项目:天津市教委科研计划项目（2021ZD010）；天津中医药大学中西医结学院研究生创新基金（ZXYCXLX202019）。 |
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| Mechanisms of Jinqi Jiangtang Tablet in treating obesity based on network pharmacology |
| WANG Jinyuan,YUAN Yin,DONG Mengxue,TAN Yawen,LV Meng,WANG Hongwu,ZHENG Fang |
| (Integrated Chinese and Western Medicine College, Tianjin University of Chinese Medicine, Tianjin 301617, China;Shunrong Pharmaceutical Factory, Da Rentang Group Co., LTD. Tianjin 300457, China;Chinese Medicine College, Tianjin University of Chinese Medicine, Tianjin 301617, China) |
| Abstract: |
| Objective To observe the therapeutic effects of Jinqi Jiangtang Tablet on C57BL/6 obese mice, and predict the related mechanism of Jinqi Jiangtang Tablet in treating obesity based on network pharmacology.Methods The total of 30 SPF male C57BL/6 mice were selected and divided into normal group, model group and Jinqi Jiangtang Tablet group. Normal group was fed normal diet, model group and Jinqi Jiangtang Tablet group were fed high-fat diet, and drug intervention was given after successful model replication. Body weight, lipid level, fat content, liver and adipose tissue morphology of C57BL/6 mice were determined. The active ingredients and intersection targets of Jinqi Jiangtang Tablet in treating obesity were screened by TCMSP and GeneCards databases. The intersection targets were imported into STRING database to analyze the interaction between targets. GO analysis and KEGG pathway enrichment analysis were performed with Biocondoctor database. The protein expression of key signaling pathways was verified with Western blot based on the prediction results of network pharmacology.Results Compared with control group, the body weight and serum content of triglyceride (TG), total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in model group were higher (P<0.05) while high density lipoprotein cholesterol (HDL-C) content was lower (P<0.05). The lipid droplet accumulation in liver tissue increased significantly, and the number and volume of adipose cells increased. Compared with model group, the body weight and serum content of TG, TC and LDL-C in Jinqi Jiangtang Tablet group were lower (P<0.05), while HDL-C content was higher (P<0.05). The accumulation of lipid droplets in liver tissue was improved, and the number and volume of adipose cells decreased. Micro-CT showed that compared with control group, the content of white fat and brown fat in model group were significantly higher (P<0.01), while Jinqi Jiangtang Tablet could reduce the content of two kinds of fat (P<0.01). Meanwhile, Jinqi Jiangtang Tablet could improve liver and adipose tissue degeneration in obese mice. The total of 55 common targets and 79 enrichment pathways of Jinqi Jiangtang Tablet for obesity were predicted by network pharmacology. KEGG enrichment analysis showed that the mechanism of action of Jinqi Jiangtang Tablet in the treatment of obesity may be closely related to fluid shear stress and AGE-RAGE signaling pathway, TNF signaling pathway and PPARγ signaling pathway in arteriosclerosis and diabetes complications. Western blot showed that compared with control group, the key proteins of PPARγ signaling pathway in adipose tissue of mice in model group were significantly up-regulated. Compared with model group, the key proteins of PPARγ signaling pathway in adipose tissue of mice in Jinqi Jiangtang Tablet group were significantly down-regulated.Conclusion Jinqi Jiangtang Tablet can effectively reduce the weight of obese mice, improve dyslipidemia, decrease the body fat content, and improve the accumulation of fat drops in liver tissue and the number and size of fat cells in adipose tissue. It may take effects in treating obesity through PPARγ signaling pathway. |
| Key words: Jinqi Jiangtang Tablet obesity network pharmacology PPARγ signaling pathway experimental verification |
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