Mulberroside A mitigates intervertebral disc degeneration by inhibiting MAPK and modulating Ppar-γ/NF-κB pathways.

IF 4.4 3区医学 Q2 IMMUNOLOGY

Journal of Inflammation-London Pub Date : 2024-08-28 DOI:10.1186/s12950-024-00398-7

Tao Xu, Hongqi Zhao, Xuan Fang, Shanxi Wang, Jian Li, Hua Wu, Weihua Hu, Rui Lu

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引用次数: 0

Abstract

Background: Intervertebral disc degeneration (IVDD) is a common spine disease with inflammation as its main pathogenesis. Mulberroside A (MA), isolated from herbal medicine, possesses anti-inflammatory characteristics in many diseases. Whereas, there is little exploration of the therapeutic potential of MA on IVDD. This study aimed at the therapeutic potential of MA on IVDD in vivo and in vitro and the mechanism involved.

Methods: In vitro, western blotting, RT-qPCR, and immunofluorescence analysis were implemented to explore the bioactivity of MA on interleukin-1 beta (IL-1β)-induced inflammation nucleus pulposus cells (NPCs) isolated from Sprague-Dawley male rats. In vivo, X-ray and MRI were applied to measure the morphological changes, and histological staining and immunohistochemistry were employed to investigate the histological changes of intervertebral disc sections on puncture-induced IVDD rat models.

Results: In vitro, MA up-regulated the expression level of anabolic-related proteins (Aggrecan and Collagen II) and decreased catabolic-related proteins (Mmp2, Mmp3, Mmp9, and Mmp13) in IL-1β-induced NPCs. Furthermore, MA inhibits the production of pro-inflammatory factors (Inos, Cox-2, and Il-6) stimulated by IL-1β. Mechanistically, MA inhibited the signal transduction of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) pathways in IL-1β-induced NPCs. Moreover, MA might bind to Ppar-γ and then suppress the NF-kB pathway. In vivo experiment illustrated that MA mitigates the IVDD progression in puncture-induced IVDD model. X-ray and MRI images showed MA restore the disc height and T2-weighted signal intensity after puncturing. H&E and Safranin O/Fast Green also showed MA also alleviated morphological changes caused by acupuncture. In addition, MA reversed the expression level of Mmp13, Aggrecan, Collagen II, and Ppar-γ induced in IVDD models.

Conclusions: MA inhibited degenerative phenotypes in NPCs and alleviated IVDD progression via inhibiting the MAPK and NF-κB pathways; besides, MA suppressed the NF-κB pathway was attributed to activating Ppar-γ, those supported that MA or Ppar-γ might be a potential drug or target for IVDD.

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桑白皮苷 A 可通过抑制 MAPK 和调节 Ppar-γ/NF-κB 通路减轻椎间盘退变。

背景：椎间盘退变（IVDD）是一种常见的脊柱疾病，其主要发病机制是炎症。从中草药中分离出来的桑白皮苷 A（MA）在许多疾病中都具有抗炎特性。然而，目前还很少有研究探讨桑白皮苷 A 对 IVDD 的治疗潜力。本研究旨在探讨 MA 在体内和体外对 IVDD 的治疗潜力及其机制：方法：在体外，采用Western blotting、RT-qPCR和免疫荧光分析方法探讨MA对分离自Sprague-Dawley雄性大鼠的白细胞介素-1β（IL-1β）诱导的炎症性髓核细胞（NPCs）的生物活性。在体内，应用X射线和核磁共振成像测量其形态学变化，并采用组织学染色和免疫组化方法研究穿刺诱导的IVDD大鼠模型椎间盘切片的组织学变化：结果：在体外，MA能上调IL-1β诱导的NPC中合成代谢相关蛋白（Aggrecan和Collagen II）的表达水平，降低分解代谢相关蛋白（Mmp2、Mmp3、Mmp9和Mmp13）的表达水平。此外，MA 还能抑制 IL-1β 刺激的促炎因子（Inos、Cox-2 和 Il-6）的产生。从机制上讲，MA抑制了IL-1β诱导的鼻咽癌中丝裂原活化蛋白激酶（MAPK）和核因子卡巴-B（NF-κB）通路的信号转导。此外，MA可能与Ppar-γ结合，进而抑制NF-kB通路。体内实验表明，在穿刺诱导的IVDD模型中，MA能缓解IVDD的进展。X射线和MRI图像显示，穿刺后MA能恢复椎间盘高度和T2加权信号强度。H&E 和 Safranin O/Fast Green 也显示 MA 也缓解了针刺引起的形态学变化。此外，MA还逆转了IVDD模型中诱导的Mmp13、Aggrecan、胶原蛋白II和Ppar-γ的表达水平：结论：马应龙通过抑制MAPK和NF-κB通路，抑制了NPC的退行性表型，缓解了IVDD的进展；此外，马应龙抑制NF-κB通路是由于激活了Ppar-γ，这些都支持马应龙或Ppar-γ可能是治疗IVDD的潜在药物或靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Inflammation-London IMMUNOLOGY-

CiteScore

7.90

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Journal of Inflammation welcomes research submissions on all aspects of inflammation. The five classical symptoms of inflammation, namely redness (rubor), swelling (tumour), heat (calor), pain (dolor) and loss of function (functio laesa), are only part of the story. The term inflammation is taken to include the full range of underlying cellular and molecular mechanisms involved, not only in the production of the inflammatory responses but, more importantly in clinical terms, in the healing process as well. Thus the journal covers molecular, cellular, animal and clinical studies, and related aspects of pharmacology, such as anti-inflammatory drug development, trials and therapeutic developments. It also considers publication of negative findings. Journal of Inflammation aims to become the leading online journal on inflammation and, as online journals replace printed ones over the next decade, the main open access inflammation journal. Open access guarantees a larger audience, and thus impact, than any restricted access equivalent, and increasingly so, as the escalating costs of printed journals puts them outside University budgets. The unrestricted access to research findings in inflammation aids in promoting dynamic and productive dialogue between industrial and academic members of the inflammation research community, which plays such an important part in the development of future generations of anti-inflammatory therapies.