Elucidation of the Underlying Mechanism of Gujian Oral Liquid Acting on Osteoarthritis through Network Pharmacology, Molecular Docking, and Experiment.
Elucidation of the Underlying Mechanism of Gujian Oral Liquid Acting on Osteoarthritis through Network Pharmacology, Molecular Docking, and Experiment.
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DOI：
10.1155/2022/9230784
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发表时间：
2022
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
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骨健口服液是我国传统中药复方，广泛用于治疗骨关节炎。然而，GJ的活性成分和潜在的机制尚未完全阐明。因此，我们通过网络药理学和实验验证来研究GJ对OA的影响，并探讨其潜在的机制。首先，共鉴定了175种生物活性化合物，并在比较GJ和OA的靶标后获得134个重叠靶标。PPI网络分析获得了包括IL 6和AKT 1在内的8个中心靶点。在此基础上，构建了GJ-target-OA网络和蛋白质-蛋白质相互作用（PPI）网络，并进行了GO和京都基因与基因组百科全书（KEGG）途径富集分析。这些结果强调了炎症性肿瘤坏死因子（TNF）作为GJ治疗OA的有希望的信号通路。此外，分子对接也证实了前两个活性化合物与前三个靶基因直接结合。最后，我们在体内和体外验证了GJ对OA的影响。体内实验证实，GJ不仅能显著减轻OA的软骨退变和软骨下骨硬化，而且能降低关节软骨细胞中肿瘤坏死因子-α（TNF-α）和p-p65的表达。此外，GJ含药血清对TNF-α诱导的软骨细胞炎症反应也有一定的保护作用。因此，本研究预测并证实了GJ可能通过调节TNF-α/NF-κ B（NF-κB）信号通路发挥抗炎、抗血小板聚集的作用。
Gujian oral liquid (GJ), a traditional herbal formula in China, has been widely used to treat patients with osteoarthritis (OA). Nevertheless, the active component and potential mechanism of GJ are not fully elucidated. Thus, we investigate the effect of GJ and explore its underlying mechanism on OA through network pharmacology and experimental validation. First, a total of 175 bioactive compounds were identified, and 134 overlapping targets were acquired after comparing the targets of the GJ with those of OA. 8 hub targets, including IL6 and AKT1, were obtained in PPI network analysis. Then, we built up GJ-target-OA network and protein-protein interaction (PPI) network, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The results underlined inflammatory tumor necrosis factor (TNF) as a promising signaling pathway of GJ for OA treatment. Moreover, molecular docking also verified the top two active compounds had direct bindings with the top three target genes. Finally, we verified the effect of GJ on OA in vivo and in vitro. In vivo experiments validated that GJ not only significantly attenuated OA phenotypes including articular cartilage degeneration and subchondral bone sclerosis but also reduced the expressions of tumor necrosis factor-α (TNF-α) and p-p65 in articular chondrocytes. Besides, GJ serum also had a protective effect on chondrocytes against inflammation caused by TNF-α in vitro. Hence, our study predicted and verified that GJ could exert anti-inflammation and anticatabolism effects partially via regulating TNF-α/NF-kappa B (NF-κB) signaling.
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影响因子：
17.1
作者：
Matsuzaki T;Alvarez-Garcia O;Mokuda S;Nagira K;Olmer M;Gamini R;Miyata K;Akasaki Y;Su AI;Asahara H;Lotz MK
通讯作者：
Lotz MK
DOI：
10.1038/nrrheum.2016.136
发表时间：
2016-10
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
Robinson WH;Lepus CM;Wang Q;Raghu H;Mao R;Lindstrom TM;Sokolove J
通讯作者：
Sokolove J
RelA/p65 抑制通过调节炎症、细胞增殖和凋亡来防止肌腱粘附
影响因子：
9
作者：
Chen S;Jiang S;Zheng W;Tu B;Liu S;Ruan H;Fan C
通讯作者：
Fan C
影响因子：
16.6
作者：
Monteagudo S;Cornelis FMF;Aznar-Lopez C;Yibmantasiri P;Guns LA;Carmeliet P;Cailotto F;Lories RJ
通讯作者：
Lories RJ
影响因子：
5.7
作者：
Luo, Yun;Wang, Chong-Zhi;Yuan, Chun-Su
通讯作者：
Yuan, Chun-Su