Jin Qi, Hao Xiao-Feng, Xie Li-Ke, Xu Jing, Sun Mei, Yuan Hang, Wang Shi-Hui, Wu Gai-Ping, Miao Meng-Lu
Surgical Department of Fundus Disease and Trauma, Eye Hospital, China Academy of Chinese Medical Sciences, Beijing 100040, China.
Evid Based Complement Alternat Med. 2020 Nov 2;2020:8878569. doi: 10.1155/2020/8878569. eCollection 2020.
Diabetic retinopathy (DR) includes a series of typical lesions affected by retinal microvascular damage caused by diabetes mellitus (DM), which not only seriously damages the vision, affecting the life's quality of patients, but also brings a considerable burden to the family and society. Membranaceus (AM) is a commonly used medicine in clinical therapy of eye disorders in traditional Chinese medicine (TCM). In recent years, it is also used for treating DR, but the specific mechanism is unclear. Therefore, this study explores the potential mechanism of AM in DR treatment by using network pharmacology.
Based on the oral bioavailability (OB) and drug likeness (DL) of two ADME (absorption, distribution, metabolism, excretion) parameters, Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), Swiss Target Prediction platform, GeneCards, and OMIM database were used to predict and screen the active compounds of AM, the core targets of AM in DR treatment. The Metascape data platform was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the core targets.
24 active compounds were obtained, such as quercetin, kaempferol, and astragaloside IV. There were 169 effective targets of AM in DR treatment, and the targets were further screened and finally, 38 core targets were obtained, such as VEGFA, AKT1, and IL-6. EGFR tyrosine kinase inhibitor resistance, AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, and other metabolic pathways participated in oxidative stress, cell apoptosis, angiogenesis signal transduction, inflammation, and other biological processes.
AM treats DR through multiple compounds, multiple targets, and multiple pathways. AM may play a role in the treatment of DR by targeting VEGFA, AKT1, and IL-6 and participating in oxidative stress, angiogenesis, and inflammation.
糖尿病视网膜病变（DR）包括一系列由糖尿病（DM）引起的视网膜微血管损伤所导致的典型病变，不仅严重损害视力，影响患者生活质量，还给家庭和社会带来相当大的负担。膜荚黄芪（AM）是中医临床治疗眼部疾病常用的一味中药。近年来，其也被用于治疗DR，但具体机制尚不清楚。因此，本研究运用网络药理学探索AM治疗DR的潜在机制。
基于两个药物代谢动力学（吸收、分布、代谢、排泄）参数即口服生物利用度（OB）和类药性（DL），利用中药系统药理学数据库（TCMSP）、瑞士靶点预测平台、基因卡片（GeneCards）和在线孟德尔人类遗传数据库（OMIM）预测并筛选AM的活性成分，即AM治疗DR的核心靶点。利用Metascape数据平台对核心靶点进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。
获得了24种活性成分，如槲皮素、山奈酚和黄芪甲苷IV。AM治疗DR有169个有效靶点，对这些靶点进一步筛选，最终得到38个核心靶点，如血管内皮生长因子A（VEGFA）、蛋白激酶B1（AKT1）和白细胞介素-6（IL-6）。表皮生长因子受体（EGFR）酪氨酸激酶抑制剂耐药性、糖尿病并发症中的晚期糖基化终末产物-晚期糖基化终末产物受体（AGE-RAGE）信号通路、磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-Akt）信号通路等代谢途径参与了氧化应激、细胞凋亡、血管生成信号转导、炎症等生物学过程。
AM通过多种化合物、多个靶点和多条途径治疗DR。AM可能通过靶向VEGFA、AKT1和IL-6并参与氧化应激、血管生成和炎症反应在DR治疗中发挥作用。
