Background. Compound Xueshuantong capsule (CXC) and Hexuemingmu tablet (HXMMT) are two important Chinese patent medicines (CPMs) frequently used to treat proliferative diabetic retinopathy (PDR), especially when complicated with vitreous hemorrhage (VH). However, a network pharmacology approach to understand the therapeutic mechanisms of these two CPMs in PDR has not been applied. Objective. To identify differences in the active ingredients between CXC and HXMMT and to comparatively predict and further analyze the molecular targets shared by these CPMs and PDR. Materials and methods. The differentially expressed messenger RNAs (mRNAs) between normal retinal tissues in healthy individuals and active fibrovascular membranes in PDR patients were retrieved from the Gene Expression Omnibus database. The active ingredients of CXC and HXMMT and the targets of these ingredients were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. The intersections of the CPM (CXC and HXMMT) targets and PDR targets were determined. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed, and the ingredient-target networks, protein-protein interaction networks, and KEGG-target (KEGG-T) networks were constructed. Results. CXC contains 4 herbs, and HXMMT contains 19. Radix salviae is the only herb common to both. CXC had 34 potential therapeutic targets in PDR, while HXMMT had these 34 and 10 additional targets. Both CPMs shared the following main processes: response to reactive oxygen species and oxidative stress, regulation of blood vessel diameter and size, vasoconstriction, smooth muscle contraction, hemostasis, and blood coagulation. The shared pathways included the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, relaxin signaling pathway, and IL-17 signaling pathway. Conclusions. Both CXC and HXMMT include components effective at treating PDR and affect the following main processes: response to reactive oxygen species and oxidative stress, regulation of blood vessels, and blood coagulation. Radix salviae, the only herb common to both CPMs, contains many useful active ingredients. The PDR-CXC and PDR-HXMMT networks shared 34 common genes (RELA, HSPA8, HSP90AA, HSP90AB1, BRCA, EWSR1, CUL7, HNRNPU, MYC, CTNNB1, MDM2, YWHAZ, CDK2, AR, FN1, HUWE1, TP53, TUBB, EP300, GRB2, VCP, MCM2, EEF1A1, NTRK1, TRAF6, EGFR, PRKDC, SRC, HDAC5, APP, ESR1, AKT1, UBC, and COPS5), and the PDR-HXMMT network has 10 additional genes (RNF2, VNL, RPS27, COPS5, XPO1, PARP1, RACK1, YWHAB, and ITGA4). The top 5 pathways with the highest gene ratio in both networks were the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, relaxin signaling pathway, IL-17 signaling pathway, and focal adhesion. Additional pathways such as neuroactive ligand-receptor interaction, chemokine signaling pathway, and AMPK signaling pathway were enriched with HXMMT targets. Thus, HXMMT has more therapeutic targets shared by different active ingredients and more abundant gene functions than CXC, which may be two major reasons why HXMMT is more strongly recommended than CXC as an auxiliary treatment for new-onset VH secondary to PDR. However, the underlying mechanisms still need to be further explored.

中文翻译：

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基于网络药理学的方法比较预测复方血栓通胶囊和和血明目片治疗增殖性糖尿病视网膜病变的活性成分和分子靶点

背景。复方血栓通胶囊（CXC）和和血明目片（HXMMT）是两种重要的中成药（CPMs），常用于治疗增殖性糖尿病视网膜病变（PDR），尤其是并发玻璃体出血（VH）时。然而，尚未应用网络药理学方法来了解这两种 CPM 在 PDR 中的治疗机制。客观。识别 CXC 和 HXMMT 之间活性成分的差异，并比较预测和进一步分析这些 CPM 和 PDR 共有的分子靶点。材料和方法. 从基因表达综合数据库中检索健康个体的正常视网膜组织和 PDR 患者的活性纤维血管膜之间差异表达的信使 RNA (mRNA)。CXC和HXMMT的有效成分和这些成分的靶点是从中药系统药理学数据库中检索出来的。确定了 CPM（CXC 和 HXMMT）目标和 PDR 目标的交集。然后，进行了基因本体论和京都基因和基因组百科全书（KEGG）分析，构建了成分-靶标网络、蛋白质-蛋白质相互作用网络和KEGG-靶标（KEGG-T）网络。结果。CXC 含有 4 种草药，HXMMT 含有 19 种。丹参是两者共同的唯一草药。CXC 在 PDR 中有 34 个潜在的治疗靶点，而 HXMMT 有这 34 个和 10 个额外的靶点。两种 CPM 共享以下主要过程：对活性氧和氧化应激的反应、血管直径和大小的调节、血管收缩、平滑肌收缩、止血和凝血。共享通路包括糖尿病并发症中的AGE-RAGE信号通路、TNF信号通路、松弛素信号通路和IL-17信号通路。结论。CXC 和 HXMMT 都包含有效治疗 PDR 的成分并影响以下主要过程：对活性氧和氧化应激的反应、血管调节和血液凝固。丹参是两种 CPM 共有的唯一草药，含有许多有用的活性成分。PDR-CXC 和 PDR-HXMMT 网络共享 34 个共同基因（RELA、HSPA8、HSP90AA、HSP90AB1、BRCA、EWSR1、CUL7、HNRNPU、MYC、CTNNB1、MDM2、YWHAZ、CDK2、AR、FN1、HUWE1、TP53、TUBB、 EP300、GRB2、VCP、MCM2、EEF1A1、NTRK1、TRAF6、EGFR、PRKDC、SRC、HDAC5、APP、ESR1、AKT1、UBC 和 COPS5），PDR-HXMMT 网络还有 10 个额外基因（RNF2、VNL、RPS27 、COPS5、XPO1、PARP1、RACK1、YWHAB 和 ITGA4）。两个网络中基因比例最高的前5个通路分别是糖尿病并发症中的AGE-RAGE信号通路、TNF信号通路、松弛素信号通路、IL-17信号通路和粘着斑。其他通路如神经活性配体-受体相互作用、趋化因子信号通路和 AMPK 信号通路富含 HXMMT 靶标。因此，与 CXC 相比，HXMMT 具有更多不同活性成分共享的治疗靶点和更丰富的基因功能，这可能是 HXMMT 比 CXC 更强烈推荐作为 PDR 继发新发 VH 的辅助治疗的两个主要原因。然而，其潜在机制仍需进一步探索。