摘要
目的结合网络药理学预测与动物实验验证的方法探讨青钱柳治疗糖尿病性脂肪肝的作用及机制。方法通过文献检索搜集青钱柳的化学成分,利用SwissADME、SwissTargetPrediction、Super-PRED数据库筛选青钱柳活性成分及作用靶点;检索TTD、DrugBank、DisGeNET数据库获取糖尿病及非酒精性脂肪肝相关靶点,通过韦恩图取交集获得药物与疾病的共同靶点,运用STRING数据库构建蛋白相互作用网络并筛选关键靶点,使用DAVID平台进行GO富集分析和KEGG通路富集分析,使用Cytoscape3.9软件构建活性成分-共同靶点-信号通路网络;建立糖尿病性脂肪肝动物模型并使用青钱柳进行干预,对预测结果中的关键靶点及相关通路进行初步验证。结果青钱柳治疗糖尿病性脂肪肝的关键靶点有15个,其中AKT1发挥重要作用。GO富集分析显示,主要条目包括66个生物过程、2个细胞组分、13个分子功能。KEGG通路富集分析表明,涉及胰岛素抵抗、癌症、阿尔茨海默病、肝炎、脂质和动脉粥样硬化、AGE-RAGE、TNF、HIF-1、PI3K-Akt等信号通路。实验结果显示,青钱柳可降低模型大鼠肝功能指标及血脂、血糖水平,对大鼠肝脏脂肪样病理变化有改善作用,可下调p-PI3K、p-Akt1、p-mTOR蛋白表达,差异均有统计学意义(P<0.05)。结论青钱柳对血糖、血脂、肝功能有调节作用,并可减轻肝脏脂肪样变,从而治疗糖尿病性脂肪肝,其机制可能与抑制PI3K/Akt1/mTOR信号通路以增强自噬有关。
Objective To investigate the effects and mechanism of Cyclocarya paliurus leaves in the treatment of diabetic fatty liver by means of network pharmacological prediction and animal experiments.Methods The chemical constituents of Cyclocarya paliurus leaves were collected from the literature,and SwissADME,SwissTargetPrediction,and Super-PRED databases were used to screen the active components and targets of Cyclocarya paliurus leaves.Diabetes and nonalcoholic fatty liver-related targets were obtained based on TTD,DrugBank and DisGeNET databases,and then the common targets for drugs and diseases were obtained through the intersection of Venn diagrams.The STRING database was used to construct the protein-protein interaction network,and the key targets were screened.GO and KEGG pathway enrichment analysis were performed on DAVID platform.Cytoscape 3.9 software was applied to construct active ingredient-common target-signaling pathway network.An animal model of diabetic fatty liver was established and intervened with Cyclocarya paliurus leaves to preliminarily verify the core targets and related pathways.Results There are 15 key targets involved in the treatment of diabetic fatty liver,among which AKT1 played an important role.GO enrichment analysis showed that the main entries included 66 biological processes,2 cellular components,and 13 molecular functions.KEGG pathway enrichment analysis showed that signaling pathways involving insulin resistance,cancer,Alzheimer disease,hepatitis,lipids and atherosclerosis,AGE-RAGE,TNF,HIF-1,PI3K-Akt signaling pathways.The experimental results showed that Cyclocarya paliurus leaves could decrease liver function indexes,lipid and blood glucose levels in model rats,improve the fatty like pathological changes in the liver,and down-regulate the expressions of p-PI3K,p-Akt1 and p-mTOR,with statistical significance(P<0.05).Conclusion Cyclocarya paliurus leaves can regulate blood glucose,blood lipids,liver function,and reduce hepatic steatosis,thus play the role of treaing diabetic fatty
作者
刘艺璇
吴琴
张亚男
蔡昱哲
李定祥
邓奕辉
LIU Yixuan;WU Qin;ZHANG Yanan;CAI Yuzhe;LI Dingxiang;DENG Yihui(Hunan Province Key Laboratory of Cerebrovascular Disease Prevention and Treatment of Integrated Traditional Chinese and Western Medicine,Hunan University of Chinese Medicine,Changsha 410208,China;Hunan University of Chinese Medicine,Changsha 410208,China)
出处
《中国中医药信息杂志》
CAS
CSCD
2023年第11期52-60,共9页
Chinese Journal of Information on Traditional Chinese Medicine
基金
国家自然科学基金面上项目(81874416)
湖南省科技创新计划(2020RC4050)
湖南省卫生健康委科研课题(D202303067824)
长沙市自然科学基金(kq2208188)
湖南省研究生科研创新项目(CX20220787)。
