基于网络药理学及动物实验探讨欧李类黄酮成分抗骨质疏松作用  

Anti-osteoporosis effect of flavonoids from Cerasus humilis based on network pharmacology and animal experiments

作　　者：王瑶 徐春晖 张芳荣 陈方会 杜俊民 WANG Yao;XU Chunhui;ZHANG Fangrong;CHEN Fanghui;DU Junmin(College of Chinese Medicine and Food Engineering,Shanxi University of Chinese Medicine,Jinzhong 031619)

机构地区：[1]山西中医药大学中药与食品工程学院,晋中030619

出　　处：《安徽农业大学学报》2023年第2期356-363,共8页Journal of Anhui Agricultural University

基　　金：山西省科技厅重点研发项目(201703D221028-2)和校级项目(2020PY-ZH-05)共同资助。

摘　　要：为了定性分析欧李果实中的类黄酮成分,通过动物实验研究欧李类黄酮抗骨质疏松作用,并基于网络药理学探讨其作用机制。采用液相色谱-质谱联用法,对欧李果实类黄酮粉末进行成分分析,建立维甲酸小鼠骨质疏松模型,检测小鼠血清中Ca、StrACP、AKP、MDA、T-SOD等含量及股骨长度等物理指标。利用Swiss和PubMed挖掘活性成分靶点信息,通过GeneCards、OMIM、TTD和PharmGKB数据库得到骨质疏松相关靶点信息,将成分靶点和骨质疏松靶点取交集。使用STRING建立蛋白质-蛋白质相互作用(PPI)网络。使用DAVID对欧李果实类黄酮治疗骨质疏松作用靶点进行KEGG通路分析,绘制KEGG富集分析高级气泡图。利用Cytoscape软件构建欧李果实类黄酮治疗骨质疏松“活性成分-靶点”网络图。结果表明:欧李果实类黄酮粉末正离子模式下共检测到50种活性成分;在小鼠骨质疏松模型中,欧李类黄酮显著提高血清钙和AKP水平,增强T-SOD活性,降低MDA含量及StrACP水平;基于网络药理学分析得到欧李果实类黄酮治疗骨质疏松作用前5位KEGG通路主要是催乳素信号通路、内分泌抵抗、C型凝集素受体信号通路、甲状腺激素信号通路和血小板活化通路。SRC和PIK3R1参与上述5个途径,其中,程度最高的靶向基因是PIK3R1。可见欧李果实类黄酮可以改善维甲酸引起的小鼠骨质疏松,其可能与SRC、PIK3R1等靶基因有关。To study the anti-osteoporosis effect of flavonoids from Cerasus humilis fruit by animal experiment and explore its mechanism based on network pharmacology,HPLC-MS was used to analyze the components of flavonoids powder from C.humilis fruit.The osteoporosis model of retinoic acid mice was established to detect the contents of Ca,StrACP,AKP,MDA,T-SOD in serum and physical indexes such as femur length.Swiss and PubMed were used to mine the target information of active components.The information of osteoporosis-related targets was obtained through GeneCards,OMIM,TTD and PharmGKB databases,and the component targets and osteoporosis targets were intersected.STRING was used to establish protein-protein interaction(PPI)networks.DAVID was used to analyze the KEGG pathway of flavonoids from C.humilis fruit in the treatment of osteoporosis,and the high-level bubble diagram of KEGG enrichment analysis was plotted.Cytoscape software was used to construct the“active ingredient-target”network diagram of flavonoids from C.humilis fruit in the treatment of osteoporosis.As results,a total of 50 active components were detected in the positive ion mode of flavonoids powder from C.humilis fruit.In the osteoporosis model of mice,the contents of serum calcium and AKP were significantly increased,the activity of T-SOD was enhanced,and the content of MDA and the level of StrACP were decreased.Based on network pharmacology analysis,the top five KEGG pathways in the treatment of osteoporosis by flavonoids from C.humilis fruit were mainly prolactin signaling pathway,endocrine resistance,C-type lectin receptor signaling pathway,thyroid hormone signaling pathway,and platelet activation pathway.SRC and PIK3R1 were involved in these five pathways,and the target gene with the highest degree was PIK3R1.In conclusion,flavonoids can improve the osteoporosis induced by retinoic acid in mice,which may be related to target genes such as SRC and PIK3R1.

关 键 词：欧李 类黄酮 抗骨质疏松 网络药理学 

分 类 号：R282.71[医药卫生—中药学] S662.309.9[医药卫生—中医学]