The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, Australia.
J Orthop Surg Res. 2022 Jun 14;17(1):314. doi: 10.1186/s13018-022-03194-2.
Diabetic osteoporosis (DOP) is one of the chronic complications of diabetes mellitus, but without a standardized treatment plan till now. Liuwei Dihuang pill (LDP) has gradually exerted a remarkable effect on DOP in recent years; its specific mechanism is not clear yet.
We adopted network pharmacology approaches, including multi-database search, pharmacokinetic screening, network construction analysis, gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis and molecular docking to elaborate the active components, signaling pathways and potential mechanisms of LDP in the treatment of DOP.
Twenty-seven active ingredients and 55 related disease targets have been found through integrated network pharmacology. Functional enrichment analysis shows that five key active ingredients, including beta-sitosterol, stigmasterol, diosgenin, tetrahydroalstonine, and kadsurenone, may give full scope to insulin secretion estrogen-level raising and angiogenesis in biological process through the pivotal targets. In addition, the underlying effect of PI3K/AKT/FOXO and VEGF pathways is also suggested in the treatment.
Based on systematic network pharmacology methods, we predicted the basic pharmacological effects and potential mechanisms of LDP in the treatment of DOP, revealing that LDP may treat DOP through multiple targets and multiple signaling pathways, which provide evidence for the further study of pharmacological mechanism and broader clinical thinking.
糖尿病性骨质疏松症（DOP）是糖尿病的慢性并发症之一，但目前尚无标准化的治疗方案。近年来，六味地黄丸（LDP）在治疗 DOP 方面逐渐显现出显著效果，但其具体机制尚不清楚。
我们采用网络药理学方法，包括多数据库检索、药代动力学筛选、网络构建分析、基因本体富集分析、京都基因与基因组百科全书通路分析和分子对接，阐述 LDP 治疗 DOP 的活性成分、信号通路和潜在机制。
通过整合网络药理学，发现了 27 个活性成分和 55 个相关疾病靶点。功能富集分析表明，五种关键活性成分，包括β-谷甾醇、豆甾醇、薯蓣皂苷元、四氢巴马汀和川陈皮素，可能通过关键靶点在生物过程中充分发挥胰岛素分泌、雌激素水平升高和血管生成的作用。此外，还提示了 PI3K/AKT/FOXO 和 VEGF 通路的潜在作用。
基于系统的网络药理学方法，我们预测了 LDP 治疗 DOP 的基本药理作用和潜在机制，表明 LDP 可能通过多种靶点和多种信号通路治疗 DOP，为进一步研究药理机制和更广泛的临床思维提供了证据。
