Andrographolide prevents human nucleus pulposus cells against degeneration by inhibiting the NF‐κB pathway

Abstract

Intervertebral disc degeneration (IDD) is among the most common spinal disorders, pathologically characterized by excessive cell apoptosis and production of proinflammatory factors. Pharmacological targeting of nucleus pulposus (NP) degeneration may hold promise in IDD therapy, but it is limited by adverse side effects and nonspecificity of drugs. In this study, we used a natural compound, andrographolide (ANDRO), which has been widely used to intervene inflammatory and apoptotic diseases in the investigation of NP degeneration based on IDD‐patients‐derived NP cells by lipopolysaccharide (LPS) treatment for the preservation of degeneration. The results showed that LPS maintained the degeneration status of NP cells as evidenced by a high apoptosis rate and the expression of degenerative and inflammatory mediators after LPS treatment. ANDRO reversed the effects of LPS‐caused degeneration of NP cells and maintained the phenotype of NP cells, as demonstrated by flow cytometry, degenerative mediators (ADAMTS4 and ADAMTS5), inflammatory factors (COX2, PGE2, MMP‐13, and MMP‐3), biomarkers of NP cells (SOX9, ACAN, and COL2A1) expressions, and glycosaminoglycan secretion. We also found the involvement of the nuclear factor kappa‐light‐chain‐enhancer of the activated B cells (NF‐κB) pathway in ANDRO treatment, indicating that ANDRO prevented the LPS‐preserved degeneration of NP cells by inhibiting the NF‐κB pathway. This study may provide a reference for clinic medication of IDD therapy.

Procyanidin B3 alleviates intervertebral disc degeneration via interaction with the TLR4/MD‐2 complex

“…Pan and his colleagues found that serum level of LPS and LBP are strongly related with severity of IVDD grades . Meanwhile, accumulating evidence demonstrated that LPS treatment in cells activated TLR4/NF‐κB signalling axis, which dominates the downstream inflammatory‐related and catabolic‐related genes expression . Therefore, we used LPS to mimic IVDD progression.…”

“…8 Meanwhile, accumulating evidence demonstrated that LPS treatment in cells activated TLR4/ NF-κB signalling axis, which dominates the downstream inflammatory-related and catabolic-related genes expression. 13,29 Therefore, we used LPS to mimic IVDD progression. And our cell experiment results showed that LPS activated TLR4/MyD88 and NF-κB signalling, increased secretion and generation of ADAMTS-5, MMP-13, TNFa, iNOS, IL-6 and COX-2, accelerating ECM breakdown in NP cells.…”

Gene expression profile of lipopolysaccharide‑induced apoptosis of nucleus pulposus cells reversed by syringic acid

“…Subsequently, lPS (Sigma-aldrich; Merck KGaa) or Syra (Sigma-aldrich; Merck KGaa) ( Fig. 2a) were added at a final concentration of 0, 0.001, 0.01, 0.1, 1, 10 and 100 µg/ml for lPS (12,13), and 0, 200, 400 and 600 µM/ml for Syra. after 3 days, 10 µl ccK-8 reagent was added to each well and cultured for a further 2 h. Subsequently, the plate was transferred into a microplate reader (BioTek instruments, inc.), and the absorbance at 450 nm was detected.…”

GABARAP Suppresses EMT and Breast Cancer Progression Via the AKT/mTOR Signaling Pathway

“…Multiple pathways, including mTOR, PI3K/AKT and NF-κB signaling, are involved in GABARAP-regulated autophagy, inflammation and angiogenic activity [8][9][10][11][12][13]. To further verify how GABARAP regulates EMT, we measured AKT/mTOR, NF-κB and ERK/MAPK signaling in breast cancer cells.…”

“…GABARAP, located at 17p13.1, is a 14 kDa cytoplasmic protein that is a member of the autophagy-related protein 8 (Atg8) family and shows a high degree of sequence homology with the autophagy marker light chain 3 (LC3) [7]. Most studies have reported that GABARAP plays a crucial role in modulating the level of autophagy [8][9][10]. For example, Kabeya et al stated that GABARAP binds to autophagic vesicles in a manner similar to that of LC3 and may also be involved in the formation of autophagosomes [11].…”