School of Basic Medical Sciences, Shaoyang University, Shaoyang, P.R. China.
College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, P.R. China.
Curr Eye Res. 2022 Oct;47(10):1450-1462. doi: 10.1080/02713683.2022.2108456. Epub 2022 Aug 22.
Age-related macular degeneration (AMD) is the commonest cause of permanent vision loss in the elderly. Traditional Chinese medicine (TCM) has long been used to treat AMD, although the underlying functional mechanisms are not understood. This study aims to predict the active ingredients through screening the chemical ingredients of anti-AMD decoction and to elucidate the underlying mechanisms.
We collected the prescriptions for effective AMD treatment with traditional Chinese medicine and screened several Chinese medicines that were used most frequently in order to compose "anti-AMD decoction." The pharmacologically active ingredients and corresponding targets in this anti-AMD decoction were mined using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Subsequently, the AMD-related targets were identified through the GeneCards database. Network pharmacology was performed to construct the visual network of anti-AMD decoction-AMD protein-protein interaction (PPI). Further, the Autodock software was adopted for molecular docking on the core active ingredients and core targets. The function of core ingredients against oxidative stress and inflammation in retinal pigment epithelial cells was assessed using biochemical assays.
We screened out 268 active ingredients in anti-AMD decoction corresponding to 258 ingredient targets, combined with 2160 disease targets in AMD, and obtained 129 drug-disease common targets. The key core proteins were predominantly involved in inflammation. Furthermore, molecular docking showed that four potential active ingredients (Quercetin, luteolin, naringenin and hederagenin) had good affinity with the core proteins, IL-6, TNF, VEGFA and MAPK3. Quercetin, luteolin and naringenin demonstrated capacities against oxidative stress and inflammation in human retinal pigment epithelial cells.
The data suggests that anti-AMD decoction has multiple functional components and targets in treating AMD, possibly mediated by suppression of oxidative stress and inflammation.
年龄相关性黄斑变性（AMD）是老年人永久性视力丧失的最常见原因。中药（TCM）长期以来一直用于治疗 AMD，尽管其潜在的功能机制尚不清楚。本研究旨在通过筛选抗 AMD 方剂的化学成分来预测活性成分，并阐明其潜在机制。
我们收集了治疗 AMD 的有效中药处方，并筛选了几种最常用的中药，以组成“抗 AMD 方剂”。使用中药系统药理学（TCMSP）数据库挖掘该抗 AMD 方剂中的药理活性成分及其相应靶点。随后，通过基因卡片数据库识别与 AMD 相关的靶点。通过网络药理学构建抗 AMD 方剂-AMD 蛋白-蛋白相互作用（PPI）的可视化网络。进一步采用 Autodock 软件对核心活性成分和核心靶点进行分子对接。采用生化测定评估核心成分对视网膜色素上皮细胞氧化应激和炎症的作用。
我们从抗 AMD 方剂中筛选出 268 种活性成分，对应 258 种成分靶点，结合 AMD 中的 2160 种疾病靶点，得到 129 种药物-疾病共同靶点。关键核心蛋白主要参与炎症。此外，分子对接显示，四种潜在的活性成分（槲皮素、木樨草素、柚皮苷和栀子苷）与核心蛋白 IL-6、TNF、VEGFA 和 MAPK3 具有良好的亲和力。槲皮素、木樨草素和柚皮苷在人视网膜色素上皮细胞中具有抗氧化应激和抗炎作用。
数据表明，抗 AMD 方剂在治疗 AMD 方面具有多种功能成分和靶点，可能通过抑制氧化应激和炎症来实现。
