Luteoloside Inhibits IL-1β-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration

Lin, Jialiang; Chen, Jiaoxiang; Zhang, Zengjie; Xu, Tianzhen; Shao, Zewei; Wang, Xiaobin; Ding, Yuanzhe; Tian, Naifeng; Jin, Haiming; Sheng, Sunren; Gao, Weiyang; Zhang, Xiaolei; Wang, Xiangyang

doi:10.3389/fphar.2019.00868

Cited by 37 publications

(25 citation statements)

References 50 publications

(75 reference statements)

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“…A recent study pointed that Nrf2 activation could prevent IDD progress via inhibiting excessive apoptosis and inflammatory response. 21 In the present study, we found SA inhibited the IL-1β-induced excessive apoptosis and inflammatory response via the activation of Nrf2 in NP cells. In addition, the results of in vivo results also confirmed our above results that SA do prevent IDD progress.…”

Section: Discussionsupporting

confidence: 55%

<p>Sinapic Acid Inhibits IL-1β-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration</p>

Huang

Zheng

Lin

et al. 2020

JIR

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Background Low back pain (LBP) is a very common condition and leads to serious pain, disability, and price tag all over the world. Intervertebral disk degeneration (IDD) is one of the major reasons that contributed to LBP. The levels of interleukin 1 beta (IL-1β) increase significantly in degenerative disks. IL-1β also accelerates IDD. Sinapic acid (SA) has the effect of anti‐inflammatory, antioxidant and antimicrobial. However, the effect of SA on IDD has never been studied. Therefore, the aim of this study was to figure out whether SA has protective effect on nucleus pulposus (NP) cells and further explore the possible underlying mechanism. Methods The nucleus pulposus (NP) tissues of rats were collected and cultured into NP cells. The NP cells were stimulated by IL-1β and treated with SA. In vitro treatment effects were evaluated by ELISA, Western blot assay, immunofluorescence, TUNEL method and real-time PCR. We conducted percutaneous needle puncture in the rat tail to build intervertebral disk degeneration model and treated rats with SA. In vivo treatment effects were evaluated by hematoxylin and eosin (HE) and safranin O (SO) staining and magnetic resonance imaging (MRI) method. Results Our results showed that SA not only inhibited apoptosis but also suppressed inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS) interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in IL-1β-stimulated NP cells. As to extracellular matrix (ECM), SA could increase collagen II and aggrecan levels and reduce the expression of MMP13 and ADAMTS5 during the stimulation of IL-1β. Furthermore, SA could activate nuclear factor‐erythroid 2‐related factor‐2 (Nrf2) to inhibit nuclear factor κB (NF‐κB) induced by IL‐1β. Nrf2 knockdown partly reduced the protective effect of SA on NP cells. Correspondingly, SA ameliorated IDD by promoting Nrf2 expression. In vivo results also showed that SA could delay the progression of IDD. Conclusion In conclusion, we demonstrated that SA could protect the degeneration of NP cells and revealed the underlying mechanism of SA on Nrf2 activation in NP cells.

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Section: Discussionsupporting

confidence: 55%

<p>Sinapic Acid Inhibits IL-1β-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration</p>

Huang

Zheng

Lin

et al. 2020

JIR

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“…In the present study, CHON-001 cell apoptosis was induced by IL-1β, whereas SNHG16 knockdown significantly decreased the expression of cleaved caspase-3, a proapoptotic protein, in IL-1β-induced CHON-001 cells ( 30 ). Lin et al ( 31 ) reported that luteoloside inhibited IL-1β-induced apoptosis in vitro by inactivating cleaved caspase-3 ( 31 ). The aforementioned results are consistent with the results of the present study, indicating that SNHG16 knockdown inhibited CHON-001 cell apoptosis by downregulating the expression levels of cleaved caspase-3.…”

Section: Discussionmentioning

confidence: 99%

lncRNA SNHG16 promotes the occurrence of osteoarthritis by sponging miR‑373‑3p

2020

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Osteoarthritis (OA) is a common age-related joint disorder, for which no effective disease-modifying drugs are currently available. Long non-coding RNAs (lncRNAs) are involved in the occurrence of OA. lncRNA small nucleolar RNA host gene 16 (SNHG16) has been reported to regulate inflammation; however, the exact biological function of SNHG16 in OA and its underlying mechanism of action remain unclear. In this study, gene and protein expression levels were detected using reverse transcription-quantitative PCR and western blotting, respectively. Cell apoptosis was analyzed using flow cytometry and ELISA was performed to detect TNF-α levels. The interactions between lncRNA SNHG16 and microRNA (miR)-373-3p were examined using the dual-luciferase reporter assay. lncRNA SNHG16 was upregulated in OA tissue compared with normal joint tissue. The expression levels of collagen II were significantly reduced in OA tissue compared with normal tissue. Similarly, aggrecan expression levels were significantly reduced in IL-1β-treated CHON-001 cells compared with the controls. In addition, the protein expression levels of MMP13 were significantly increased in OA tissues and IL-1β-treated CHON-001 cells compared with the controls. SNHG16 knockdown significantly increased the expression levels of aggrecan, and decreased the expression levels of MMP13, cleaved caspase-3 and p21 in IL-1β-treated CHON-001 cells. In addition, IL-1β induced CHON-001 cell apoptosis, while SNHG16 knockdown decreased IL-1β-induced apoptosis. Furthermore, the luciferase activity assay suggested that SNHG16 negatively regulated miR-373-3p in OA. Finally, the results suggested that the proinflammatory effect of IL-1β on CHON-001 cells was significantly reduced by SNHG16 knockdown. In conclusion, lncRNA SNHG16 knockdown significantly limited the progression of OA by sponging miR-373-3p in vitro, which suggested that SNHG16 may serve as a potential therapeutic target for OA.

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“…A recent in vitro study showed that luteoloside, a flavonoid glycoside, could suppress inflammatory factors, such as TNF-α and IL-6, in IL-1β-primed NP cells through inhibition of the NF-κB signaling cascade. They demonstrated that luteoloside promoted the nuclear factor erythroid 2-related factor 2 (Nrf2) translocation to the nuclei; Nrf2 can act through activation of the Nrf2/HO-1 (heme oxygenase-1) signaling in NP cells and mitigate inflammation by suppressing the NF-κB signaling cascade and by anti-apoptotic function 57 .…”

Section: Small Molecules and Ivd Regenerationmentioning

confidence: 99%

Small molecule-based treatment approaches for intervertebral disc degeneration: Current options and future directions

et al. 2021

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Low back pain (LBP) is a major reason for disability, and symptomatic intervertebral disc (IVD) degeneration (IDD) contributes to roughly 40% of all LBP cases. Current treatment modalities for IDD include conservative and surgical strategies. Unfortunately, there is a significant number of patients in which conventional therapies fail with the result that these patients remain suffering from chronic pain and disability. Furthermore, none of the current therapies successfully address the underlying biological problem - the symptomatic degenerated disc. Both spinal fusion as well as total disc replacement devices reduce spinal motion and are associated with adjacent segment disease. Thus, there is an unmet need for novel and stage-adjusted therapies to combat IDD. Several new treatment options aiming to regenerate the IVD are currently under investigation. The most common approaches include tissue engineering, growth factor therapy, gene therapy, and cell-based treatments according to the stage of degeneration. Recently, the regenerative activity of small molecules (low molecular weight organic compounds with less than 900 daltons) on IDD was demonstrated. However, small molecule-based therapy in IDD is still in its infancy due to limited knowledge about the mechanisms that control different cell signaling pathways of IVD homeostasis. Small molecules can act as anti-inflammatory, anti-apoptotic, anti-oxidative, and anabolic agents, which can prevent further degeneration of disc cells and enhance their regeneration. This review pursues to give a comprehensive overview of small molecules, focusing on low molecular weight organic compounds, and their potential utilization in patients with IDD based on recent in vitro , in vivo, and pre-clinical studies.

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Luteoloside Inhibits IL-1β-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration

Cited by 37 publications

References 50 publications

<p>Sinapic Acid Inhibits IL-1β-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration</p>

<p>Sinapic Acid Inhibits IL-1β-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration</p>

lncRNA SNHG16 promotes the occurrence of osteoarthritis by sponging miR‑373‑3p

Small molecule-based treatment approaches for intervertebral disc degeneration: Current options and future directions

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