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基于网络药理学和分子对接的山奈酚治疗老年性骨质疏松症机制研究

Research on the Mechanism of Kaempferol for Treating Senile Osteoporosis by Network Pharmacology and Molecular Docking.

作者信息

Tang Fuyu, Zhang Peng, Zhao Wenhua, Zhu Guangye, Shen Gengyang, Chen Honglin, Yu Xiang, Zhang Zhida, Shang Qi, Liang De, Jiang Xiaobing, Ren Hui

机构信息

Guangzhou University of Chinese Medicine, Guangzhou 510405, China.

Liuzhou Hospital of Chinese Medicine (Liuzhou Hospital of Zhuang Medicine), Guangxi Zhuang Autonomous Region, Liuzhou, 545000, China.

出版信息

Evid Based Complement Alternat Med. 2022 Feb 3;2022:6741995. doi: 10.1155/2022/6741995. eCollection 2022.

Abstract

Kaempferol (KP), as a natural anti-inflammatory compound, has been reported to have curative effects on alleviating senile osteoporosis (SOP), which is an inflammation-related musculoskeletal disease, but the molecular mechanisms remain unclear due to scanty relevant studies. We predicted the targets of KP and SOP, and the common targets of them were subsequently used to carry out PPI analysis. Moreover, we adopted GO and KEGG enrichment analysis and molecular docking to explore potential mechanisms of KP against SOP. There were totally 152 KP-related targets and 978 SOP-related targets, and their overlapped targets comprised 68 intersection targets. GO enrichment analysis showed 1529 biological processes ( < 0.05), which involved regulation of inflammatory response, oxidative stress, regulation of bone resorption and remodeling, osteoblast and osteoclast differentiation, etc. Moreover, KEGG analysis revealed 146 items including 44 signaling pathways ( < 0.05), which were closely linked to TNF, IL-17, NF-kappa B, PI3K-Akt, MAPK, estrogen, p53, prolactin, VEGF, and HIF-1 signaling pathways. By means of molecular docking, we found that kaempferol is bound with the key targets' active pockets through some connections such as hydrogen bond, pi-alkyl, pi-sigma, pi-pi Stacked, pi-pi T-shaped, and van der Waals, illustrating that kaempferol has close combination with the key targets. Collectively, various targets and pathways involve in the process of kaempferol treatment against SOP through regulating inflammatory response, oxidative stress, bone homeostasis, etc. Moreover, our study first reported that kaempferol may regulate core targets' expression with involvement of inflammatory response, oxidative stress, and bone homeostasis, thus treating SOP.

摘要

山奈酚(KP)作为一种天然抗炎化合物,已被报道对缓解老年性骨质疏松症(SOP)具有治疗作用,SOP是一种与炎症相关的肌肉骨骼疾病,但由于相关研究较少,其分子机制仍不清楚。我们预测了KP和SOP的靶点,并随后使用它们的共同靶点进行蛋白质-蛋白质相互作用(PPI)分析。此外,我们采用基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析以及分子对接来探索KP抗SOP的潜在机制。共有152个与KP相关的靶点和978个与SOP相关的靶点,它们的重叠靶点包括68个交集靶点。GO富集分析显示1529个生物学过程(P<0.05),涉及炎症反应调节、氧化应激、骨吸收和重塑调节、成骨细胞和破骨细胞分化等。此外,KEGG分析揭示了146项,包括44条信号通路(P<0.05),这些通路与肿瘤坏死因子(TNF)、白细胞介素-17(IL-17)、核因子κB(NF-κB)、磷脂酰肌醇-3激酶-蛋白激酶B(PI3K-Akt)、丝裂原活化蛋白激酶(MAPK)、雌激素、p53、催乳素、血管内皮生长因子(VEGF)和缺氧诱导因子-1(HIF-1)信号通路密切相关。通过分子对接,我们发现山奈酚通过氢键、π-烷基、π-σ、π-π堆积、π-π T形和范德华力等一些连接与关键靶点的活性口袋结合,说明山奈酚与关键靶点有紧密结合。总的来说,各种靶点和通路通过调节炎症反应、氧化应激、骨稳态等参与山奈酚治疗SOP的过程。此外,我们的研究首次报道山奈酚可能通过炎症反应、氧化应激和骨稳态调节核心靶点的表达,从而治疗SOP。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a27d/8831051/2b3c18ee8f8c/ECAM2022-6741995.001.jpg

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