Department of Clinical Laboratory, Changzhi People's Hospital, Changzhi, China.
Department of Endocrinology and Metabology, The Third Affiliated Hospital of Shandong First Medical University, Jinan, China.
Medicine (Baltimore). 2024 Aug 2;103(31):e39138. doi: 10.1097/MD.0000000000039138.
Xianlinggubao formula (XLGB), is a traditional Chinese compound Medicine that has been extensively used in osteoarthritis and aseptic osteonecrosis, but its curative effect on diabetic osteoporosis (DOP) and its pharmacological mechanisms remains not clear. The aim of the present study was to investigate the possible mechanism of drug repurposing of XLGB in DOP therapy. We acquired XLGB active compounds from the traditional Chinese medicine systems pharmacology and traditional Chinese medicines integrated databases and discovered potential targets for these compounds by conducting target fishing using the traditional Chinese medicine systems pharmacology and Swiss Target Prediction databases. Gene Cards and Online Mendelian Inheritance in Man® database were used to identify the DOP targets. Overlapping related targets between XLGB and DOP was selected to build a protein-protein interaction network. Next, the Metascape database was utilized to enrich the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. In addition, Auto-Dock Vina software was used to verify drug and target binding. In total, 48 hub targets were obtained as the candidate targets responsible for DOP therapy. The anti-DOP effect mediated by XLGB was primarily centralized on the advanced glycation end products (AGEs)-receptor for AGE signaling pathway in diabetic complications and osteoclast differentiation. In addition, AKT serine/threonine kinase 1, tumor necrosis factor, Interleukin-6, vascular endothelial growth factor A and peroxisome proliferator activated receptor gamma, which were considered as potential therapeutic targets. Furthermore, molecular docking results confirm the credibility of the predicted therapeutic targets. This study elucidates that XLGB may through regulating AGEs formation and osteoclast differentiation as well as angiogenesis and adipogenesis against DOP. And this study provides new promising points to find the exact regulatory mechanisms of XLGB mediated anti-DOP effect.
仙灵骨葆方（XLGB）是一种传统的中药复方，已广泛应用于骨关节炎和无菌性骨坏死，但它对糖尿病性骨质疏松症（DOP）的疗效及其药理机制尚不清楚。本研究旨在探讨 XLGB 药物再利用治疗 DOP 的可能机制。我们从中药系统药理学和中药综合数据库中获取了 XLGB 的活性化合物，并通过中药系统药理学和瑞士靶标预测数据库进行靶标捕捞，发现了这些化合物的潜在靶标。基因卡片和在线孟德尔遗传人体内®数据库用于识别 DOP 靶点。从 XLGB 和 DOP 之间选择重叠的相关靶点，构建蛋白质-蛋白质相互作用网络。接下来，使用 Metascape 数据库来丰富基因本体论和京都基因与基因组百科全书途径。此外，使用 Auto-Dock Vina 软件验证药物与靶标结合。共获得 48 个枢纽靶标，作为负责 DOP 治疗的候选靶标。XLGB 介导的抗 DOP 作用主要集中在糖尿病并发症和破骨细胞分化的晚期糖基化终产物（AGEs）-AGE 信号通路受体上。此外，AKT 丝氨酸/苏氨酸激酶 1、肿瘤坏死因子、白细胞介素-6、血管内皮生长因子 A 和过氧化物酶体增殖物激活受体 γ 被认为是潜在的治疗靶点。此外，分子对接结果证实了预测治疗靶点的可信度。本研究表明，XLGB 可能通过调节 AGEs 的形成和破骨细胞分化以及血管生成和脂肪生成来对抗 DOP。本研究为寻找 XLGB 介导的抗 DOP 作用的确切调节机制提供了新的有前途的研究点。
