Berberine prevents human nucleus pulposus cells from IL‑1β‑induced extracellular matrix degradation and apoptosis by inhibiting the NF‑κB pathway

Abstract

Intervertebral disc degeneration (IDD) is widely considered to be one of the main causes of lower back pain, which is a chronic progressive disease closely related to inflammation, nucleus pulposus (NP) cell apoptosis and extracellular matrix (ECM) degradation. Berberine (BBR) is an alkaloid compound with an anti-inflammatory effect and has been reported to exert therapeutic action in several inflammatory diseases, including osteoarthritis. Therefore, it was hypothesized that BBR may have a therapeutic effect on IDD through inhibition of the inflammatory response. The aim of the present study was to evaluate the influence of BBR on IDD in interleukin (IL)-1β-treated human NP cells in vitro. The results showed that BBR attenuated the upregulation of ECM-catabolic factors [matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-4 and ADAMTS-5], and the downregulation of ECM-anabolic factors (type II collagen and aggrecan) following stimulation of the human NP cells with IL-1β. Treatment with BBR also protected human NP cells from IL-1β-induced apoptosis, as determined by western blotting and flow cytometry. Mechanistically, the IL-1β-stimulated degradation of IκBα, and the phosphorylation and translocation of nuclear factor (NF)-κB p65 were found to be attenuated by BBR, indicating that NF-κB pathway activation was suppressed by BBR in the IL-1β-treated human NP cells. The results of the experiments revealed a therapeutic potential of BBR for the prevention or treatment of IDD.

Effects of the NF‑κB/p53 signaling pathway on intervertebral disc nucleus pulposus degeneration

“…NF-κB is involved in organ and tissue degradation ( 27 – 29 ). p65 belongs to the NF-κB family and it has been widely reported to be associated with IDD ( 30 – 33 ), with p-p65 serving a crucial role during IDD as a marker of NF-κB activation ( 32 – 35 ). The p53 gene is associated with cell senescence and death ( 36 , 37 ), and its expression is significantly increased in rat models of IDD under weightlessness circumstances ( 38 ).…”

Berberine regulates the Notch1/PTEN/PI3K/AKT/mTOR pathway and acts synergistically with 17-AAG and SAHA in SW480 colon cancer cells

“…Berberine (BBR) is a natural product first isolated from the bark of Zanthoxylon clava herculis Linne (Rutaceae) in 1826, it is used clinically for diarrhoea and gastroenteritis. BBR was reported to have a variety of other pharmacological effects such as antitumor (Farooqi et al 2019;Gao et al 2019;Mohammadinejad et al 2019;Yao et al 2019), antidiabetic and hipolipidemic (Lan et al 2015;Sahebkar and Watts 2017;Ma et al 2018), diminishing liver fibrosis (Feng et al 2009), neuroprotective (Pirmoradi et al 2019), anti-inflammatory (Lu et al 2019) and antioxidant (Kazaz et al 2020). Colon cancer, the third most prevalent cancer worldwide, is increasing in individuals less than 50 years old (Siegel et al 2019).…”

Upregulated lnc‑HRK‑2:1 prompts nucleus pulposus cell senescence in intervertebral disc degeneration

“…Among these, ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) and microfibrillar-associated protein 5 (MFAP5) were of interest. ADAMTS5 is one of the major proteolytic enzymes involved in ecM degradation and serves a vital role in this process (48,49). MFAP5 is an ECM glycoprotein that has been demonstrated to be involved in ECM remodeling (50).…”