马粟酸通过抑制 PI3K/AKT 和 NF-κB 信号通路缓解椎间盘退变。

Maslinic acid alleviates intervertebral disc degeneration by inhibiting the PI3K/AKT and NF-κB signaling pathways.

机构信息

Department of Orthopedic Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China.

Panyu Hospital of Chinese Medicine, Department of Minimally Invasive Spine Surgery, Guangzhou 511408, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2024 May 25;56(5):776-788. doi: 10.3724/abbs.2024027.

Abstract

Intervertebral disc degeneration (IDD) is the cause of low back pain (LBP), and recent research has suggested that inflammatory cytokines play a significant role in this process. Maslinic acid (MA), a natural compound found in olive plants ( ), has anti-inflammatory properties, but its potential for treating IDD is unclear. The current study aims to investigate the effects of MA on TNFα-induced IDD and in other models. Our findings suggest that MA ameliorates the imbalance of the extracellular matrix (ECM) and mitigates senescence by upregulating aggrecan and collagen II levels as well as downregulating MMP and ADAMTS levels in nucleus pulposus cells (NPCs). It can also impede the progression of IDD in rats. We further find that MA significantly affects the PI3K/AKT and NF-κB pathways in TNFα-induced NPCs determined by RNA-seq and experimental verification, while the AKT agonist Sc-79 eliminates these signaling cascades. Furthermore, molecular docking simulation shows that MA directly binds to PI3K. Dysfunction of the PI3K/AKT pathway and ECM metabolism has also been confirmed in clinical specimens of degenerated nucleus pulposus. This study demonstrates that MA may hold promise as a therapeutic agent for alleviating ECM metabolism disorders and senescence to treat IDD.

摘要

椎间盘退变(IDD)是导致下腰痛(LBP)的原因,最近的研究表明,炎症细胞因子在这一过程中起着重要作用。齐墩果酸(MA)是橄榄植物()中发现的一种天然化合物,具有抗炎特性,但它治疗 IDD 的潜力尚不清楚。本研究旨在探讨 MA 对 TNFα 诱导的 IDD 和其他模型的影响。我们的研究结果表明,MA 通过上调聚集蛋白聚糖和 II 型胶原水平以及下调核基质细胞(NPC)中 MMP 和 ADAMTS 水平来改善细胞外基质(ECM)的失衡并减轻衰老。它还可以阻止大鼠 IDD 的进展。我们进一步发现,MA 通过 RNA-seq 和实验验证,对 TNFα 诱导的 NPCs 中的 PI3K/AKT 和 NF-κB 通路有显著影响,而 AKT 激动剂 Sc-79 消除了这些信号级联。此外,分子对接模拟表明 MA 直接与 PI3K 结合。PI3K/AKT 通路和 ECM 代谢功能障碍也在退变的髓核临床标本中得到了证实。这项研究表明,MA 可能有希望作为一种治疗剂,用于缓解 ECM 代谢紊乱和衰老,以治疗 IDD。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e82/11187486/0b0b0c859f42/ABBS-2023-537-t1.jpg

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