Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Orthopedics, Civil Aviation General Hospital, No. 1, Gaojing Street, Chaoyang District, Beijing 100123, China.
Comput Intell Neurosci. 2023 May 28;2023:7091407. doi: 10.1155/2023/7091407. eCollection 2023.
Intervertebral disc degeneration (IDD) poses a grim public health impact. Duhuo Jisheng Decoction (DJD), a traditional Chinese medicine formula, has recently received significant attention for its efficacy and safety in treating IDD. However, the pathological processes of IDD in which DJD interferes and molecular mechanism involved are poorly understood, which brings difficulties to the clinical practice of DJD for the treatment of IDD. This study systematically investigated the underlying mechanism of DJD treatment of IDD. Network pharmacology approaches were employed, integrating molecular docking and random walk with restart (RWR) algorithm, to identify key compounds and targets for DJD in the treatment of IDD. Bioinformatics approaches were used to further explore the biological insights in DJD treatment of IDD. The analysis identifies AKT1, PIK3R1, CHUK, ALB, TP53, MYC, NR3C1, IL1B, ERBB2, CAV1, CTNNB1, AR, IGF2, and ESR1 as key targets. Responses to mechanical stress, oxidative stress, cellular inflammatory responses, autophagy, and apoptosis are identified as the critical biological processes involved in DJD treatment of IDD. The regulation of DJD targets in extracellular matrix components, ion channel regulation, transcriptional regulation, synthesis and metabolic regulation of reactive oxygen products in the respiratory chain and mitochondria, fatty acid oxidation, the metabolism of Arachidonic acid, and regulation of Rho and Ras protein activation are found to be potential mechanisms in disc tissue response to mechanical stress and oxidative stress. MAPK, PI3K/AKT, and NF-B signaling pathways are identified as vital signaling pathways for DJD to treat IDD. Quercetin and Kaempferol are assigned a central position in the treatment of IDD. This study contributes to a more comprehensive understanding of the mechanism of DJD in treating IDD. It provides a reference for applying natural products to delay the pathological process of IDD.
椎间盘退行性病变（IDD）对公共健康造成了严重影响。独活寄生汤（DJD）作为一种中药方剂，因其在治疗 IDD 方面的疗效和安全性而受到广泛关注。然而，DJD 干预 IDD 的病理过程及其涉及的分子机制尚不清楚，这给 DJD 临床治疗 IDD 带来了困难。本研究系统地研究了 DJD 治疗 IDD 的潜在机制。采用网络药理学方法，整合分子对接和随机游走重启动（RWR）算法，鉴定 DJD 治疗 IDD 的关键化合物和靶点。利用生物信息学方法进一步探讨 DJD 治疗 IDD 的生物学见解。分析确定 AKT1、PIK3R1、CHUK、ALB、TP53、MYC、NR3C1、IL1B、ERBB2、CAV1、CTNNB1、AR、IGF2 和 ESR1 为关键靶点。确定对机械应激、氧化应激、细胞炎症反应、自噬和细胞凋亡的反应为 DJD 治疗 IDD 的关键生物学过程。DJD 靶点对细胞外基质成分、离子通道调节、转录调节、呼吸链和线粒体中活性氧产物的合成和代谢调节、脂肪酸氧化、花生四烯酸代谢以及 Rho 和 Ras 蛋白激活的调节的调控被认为是椎间盘组织对机械应激和氧化应激反应的潜在机制。MAPK、PI3K/AKT 和 NF-B 信号通路被确定为 DJD 治疗 IDD 的重要信号通路。槲皮素和山奈酚被分配在治疗 IDD 中的核心地位。本研究有助于更全面地了解 DJD 治疗 IDD 的机制。它为应用天然产物延缓 IDD 病理进程提供了参考。
