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基于网络药理学的鹰嘴豆芽素 A 治疗骨质疏松症的作用机制研究

Mechanisms underlying the therapeutic effects of isoflavones isolated from chickpea sprouts in treating osteoporosis based on network pharmacology.

机构信息

Clinical Medicine Institute, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China; Department of Trauma Orthopaedics, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China; Key Laboratory of High Incidence Disease Research in Xinjiang(Xinjiang Medical University), Ministry of Education, Urumqi, 830011, Xinjiang, China; Xinjiang Clinical Research Centre for Orthopaedics, Urumqi, 830011, Xinjiang, China.

Department of Trauma Orthopaedics, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China; Key Laboratory of High Incidence Disease Research in Xinjiang(Xinjiang Medical University), Ministry of Education, Urumqi, 830011, Xinjiang, China; Xinjiang Clinical Research Centre for Orthopaedics, Urumqi, 830011, Xinjiang, China.

出版信息

Biochem Biophys Res Commun. 2023 Sep 3;671:26-37. doi: 10.1016/j.bbrc.2023.05.090. Epub 2023 May 29.

Abstract

Osteoporosis is a systemic bone disease that is caused by multiple factors that lead to an imbalance in bone metabolism. Isoflavones can prevent and treat osteoporosis by regulating bone metabolism through a variety of pathways. The germination of chickpeas can significantly increase their isoflavone contents. However, the use of isoflavones isolated from chickpea sprouts (ICS) to prevent and treat osteoporosis by regulating bone metabolism has not been widely studied. In vivo experimental studies in ovariectomized rats showed that ICS significantly improved femoral bone mineral density (BMD) and trabecular structure, with effects similar to raloxifene. Furthermore, the chemical composition of ICS as well as the targets and signalling pathways its regulates in the prevention and treatment of osteoporosis were predicted by network pharmacological studies. ICS with drug-like properties were identified by Lipinski's 5 principles, and intersecting targets of isoflavones with osteoporosis were identified. The overlapping targets were analysed by PPI, GO and KEGG analyses, and the possible key targets, signalling pathways and biological processes by which ICS treats osteoporosis were predicted; the prediction results were verified by molecular docking technology. The results showed that ICS could play an important role in the treatment of osteoporosis through "multicomponent, multitarget and multipathway" mechanisms, and the MAKP, NF-kB and ER-related signalling pathways may be important pathways by which ICS regulates osteoporosis; these findings provide a new theoretical basis for further experimental studies.

摘要

骨质疏松症是一种由多种因素引起的全身性骨骼疾病,导致骨代谢失衡。异黄酮可以通过多种途径调节骨代谢,从而预防和治疗骨质疏松症。鹰嘴豆发芽可以显著提高其异黄酮含量。然而,通过调节骨代谢用鹰嘴豆芽异黄酮(ICS)来预防和治疗骨质疏松症的应用尚未得到广泛研究。在去卵巢大鼠的体内实验研究中,ICS 显著改善了股骨骨密度(BMD)和小梁结构,效果类似于雷洛昔芬。此外,网络药理学研究预测了 ICS 的化学成分以及其在预防和治疗骨质疏松症中的调节靶点和信号通路。通过 Lipinski 的 5 个原则确定了具有类药性的 ICS,并确定了与骨质疏松症相关的异黄酮的交集靶点。通过 PPI、GO 和 KEGG 分析对重叠靶点进行分析,并预测了 ICS 治疗骨质疏松症的可能关键靶点、信号通路和生物学过程;通过分子对接技术验证了预测结果。结果表明,ICS 可以通过“多成分、多靶点和多途径”机制在骨质疏松症的治疗中发挥重要作用,MAPK、NF-κB 和 ER 相关信号通路可能是 ICS 调节骨质疏松症的重要途径;这些发现为进一步的实验研究提供了新的理论依据。

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