Network Pharmacology and Experimental Validation to Reveal the Pharmacological Mechanisms of Liuwei Dihuang Decoction Against Intervertebral Disc Degeneration.
Network Pharmacology and Experimental Validation to Reveal the Pharmacological Mechanisms of Liuwei Dihuang Decoction Against Intervertebral Disc Degeneration.
复制标题
网络药理学和实验验证，以揭示列韦二王汤的药理学机制反对椎间盘变性。
DOI：
10.2147/dddt.s338439
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Wu C
中科院分区：
文献类型：
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作者：
Zhang H;Yao S;Zhang Z;Zhou C;Fu F;Bian Y;Luo H;Li Y;Yan S;Ge Y;Chen Y;Zhan K;Ge Y;Chen Z;Yue M;Li X;Du W;Jin H;Tong P;Ruan H;Wu C
采用网络药理分析结合实验验证的方法，探讨六味地黄汤抗椎间盘退变的药理作用机制。首先，从公共数据库中收集六味地黄汤的活性成分和相关靶点，以及IVDD的相关基因。采用蛋白质相互作用网络（PPI）、基因本体论（GO）和京都基因与基因组百科全书（KEGG）功能富集分析预测LWDHD抗IVDD的核心靶点和作用途径。其次，选择六味地黄汤治疗的小鼠IVDD模型，验证网络药理学预测的主要靶点。通过搜索活性成分靶标和IVDD靶标的交集，共检索到110个与LWDHD和IVDD中30种活性成分的相关靶标相匹配的靶标。PPI网络分析显示，Caspase-3、IL-1β、P53等17个靶点，是中心目标GO和KEGG富集分析表明，细胞凋亡途径富集了多个靶标，并作为体内实验研究验证的靶标。动物实验结果显示，六味地黄汤不仅能恢复IVDD小鼠椎间盘高度的降低和基质代谢的异常降解，还能逆转Bax、Caspase-3、IL-1β、P53的高表达和Bcl-2的低表达，从而抑制IVD组织的凋亡，改善IVDD的进展。本研究采用综合网络药理学方法，预测了六味地黄汤干预IVDD的有效成分和潜在靶点，并对预测信号通路中涉及的主要靶蛋白进行了实验验证，从综合水平上对六味地黄汤治疗IVDD的药理机制有了新的认识。
To explore the pharmacological mechanisms of Liuwei Dihuang Decoction (LWDHD) against intervertebral disc (IVD) degeneration (IVDD) via network pharmacology analysis combined with experimental validation. First, active ingredients and related targets of LWDHD, as well as related genes of IVDD, were collected from public databases. The protein–protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed to predict the core targets and pathways of LWDHD against IVDD. Secondly, the IVDD model of mice treated with LWDHD was selected to validate the major targets predicted by network pharmacology. By searching the intersection of the active ingredient targets and IVDD targets, a total of 110 targets matched the related targets of 30 active ingredients in LWDHD and IVDD were retrieved. PPI network analysis indicated that 17 targets, including Caspase-3, IL-1β, P53, etc., were hub targets. GO and KEGG enrichment analyses showed that the apoptosis pathway was enriched by multiple targets and served as the target for in vivo experimental study validation. The results of animal experiments revealed that LWDHD administration not only restored the decrease in disc height and abnormal degradation of matrix metabolism in IVDD mice but also reversed the high expression of Bax, Caspase-3, IL-1β, P53, and low expression of Bcl-2, thereby inhibiting the apoptosis of IVD tissue and ameliorating the progression of IVDD. Using a comprehensive network pharmacology approach, our findings predicted the active ingredients and potential targets of LWDHD intervention for IVDD, and some major target proteins involved in the predictive signaling pathway were validated experimentally, which gave us a new understanding of the pharmacological mechanism of LWDHD in treating IVDD at the comprehensive level.