Naringin protects human nucleus pulposus cells against TNF-α-induced inflammation, oxidative stress, and loss of cellular homeostasis by enhancing autophagic flux via AMPK/SIRT1 activation

Abstract

Activation of the proinflammatory-associated cytokine, tumor necrosis factor-α (TNF-α), in nucleus pulposus (NP) cells is essential for the pathogenesis of intervertebral disc degeneration (IDD). Restoring autophagic flux has been shown to effectively protect against IDD and is a potential target for treatment. The goal of this study was to explore particular autophagic signalings responsible for the protective effects of naringin, a known autophagy activator, on human NP cells. The results showed that significantly increased autophagic flux was observed in NP cells treated with naringin, with pronounced decreases in the inflammatory response and oxidative stress, which rescued the disturbed cellular homeostasis induced by TNF-α activation. Autophagic flux inhibition was detectable in NP cells cotreated with 3-methyladenine (3-MA, an autophagy inhibitor), partially offsetting naringin-induced beneficial effects. Naringin promoted the expressions of autophagy-associated markers via SIRT1 (silent information regulator-1) activation by AMPK (AMP-activated protein kinase) phosphorylation. Either AMPK inhibition by BML-275 or SIRT1 silencing partially counteracted naringin-induced autophagic flux enhancement. These findings indicate that naringin boosts autophagic flux through SIRT1 upregulation via AMPK activation, thus protecting NP cells against inflammatory response, oxidative stress, and impaired cellular homeostasis. Naringin can be a promising inducer of restoration autophagic flux restoration for IDD.

Mesenchymal Stem Cells May Alleviate the Intervertebral Disc Degeneration by Reducing the Oxidative Stress in Nucleus Pulposus Cells

“…Previous studies have shown that autophagy played a protective role against the oxidative stress in degenerative NPCs [ 24 , 30 , 32 ]. In this research, a significantly different autophagy score between NPC/MSC samples and NPC samples was observed ( Figure 6(a) ).…”

“…The correlation analysis between DElncRNAs and hub OSRDEGs was performed, and DElncRNA-OSRDEG pairs with r > 0.95 and p < 0.05 were selected. The targeted miRNAs for 10 hub OSRDEGs were predicted using TargetScan database ( http://www.targetscan.org/vert_80/ ) [ 30 ]. The targeted miRNAs for DElncRNAs were predicted using the ENCORI database ( https://starbase.sysu.edu.cn/ ) [ 28 ].…”

Heat-Killed Enterococcus faecalis Prevents Adipogenesis and High Fat Diet-Induced Obesity by Inhibition of Lipid Accumulation through Inhibiting C/EBP-α and PPAR-γ in the Insulin Signaling Pathway

“…Fan et al reported that EF-2001 remarkably elevated the expressions of p-AMPK and p-ACC in mice and suggested that EF-2001 decreases hepatic lipid accumulation in the DIO model mice via AMPK pathway while improving livers injured by an HFD [ 23 ]. AMPK is an important factor in regulating homeostasis and basal metabolism in mammalian cells [ 48 ]. The AMPK is a protein marker of lipolysis which demonstrates the effects of drugs that induce lipid production in vivo or in vitro and activates lipolysis enzymes (such as HSL, ATGL, and MGL).…”

Loss of WNK1 Suppressed the Malignant Behaviors of Hepatocellular Carcinoma Cells by Promoting Autophagy and Activating AMPK Pathway

“…AMPK loss could cooperate with oncogenic divers to accelerate tumorigenesis in a tissue-specific manner [28]. Activated AMPK modulated a variety of metabolic processes, including autophagy [29,30]. Under energy-deprived conditions, AMPK is activated triggering autophagy [31].…”