α‐Mangostin protects lipopolysaccharide‐stimulated nucleus pulposus cells against NLRP3 inflammasome‐mediated apoptosis via the NF‐κB pathway

Abstract

Intervertebral disc degeneration (IDD) is a common and chronic inflammatory disorder. α‐Mangostin exhibits a novel biological function against inflammation in various inflammatory diseases. Here, we aimed to explore the role of α‐mangostin in IDD using an in vitro cell model. Human nucleus pulposus cells (NPCs) were exposed to lipopolysaccharide (LPS) to induce inflammatory injury. Cell viability of NPCs was determined by CCK‐8 assay. ELISA was performed to examine the production of interleukin (IL)‐1β and IL‐18. Apoptotic cell death in NPCs was detected by TUNEL staining. The expression levels of apoptotic‐associated proteins were detected by western blotting. Nuclear factor‐kappa B (NF‐κB) activation was examined by determining the expression levels of p‐p65, p65, and nuclear p65. Results showed that treatment with α‐mangostin improved the viability of LPS‐treated NPCs. α‐Mangostin treatment also inhibited the LPS‐induced increase in expression levels of NLRP3, ASC and pro‐caspase‐1, as well as the production of IL‐1β and IL‐18 in NPCs. Moreover, treatment with α‐mangostin or NLRP3 inhibitor (MCC950) significantly decreased apoptotic cell death in NPCs, as compared with treatment with LPS. In addition, the expression levels of cleaved caspase‐3 and Bax were decreased, while Bcl‐2 expression was increased in α‐mangostin‐ or MCC950‐treated NPCs. Treatment with α‐mangostin also suppressed LPS‐induced increase of p‐p65/p65 and nuclear p65 levels. Moreover, inhibition of NF‐κB by PDTC aggravated the inhibitory effects of α‐mangostin on NLRP3 inflammasome activation and apoptosis in LPS‐induced NPCs. These findings suggested that α‐mangostin exerted a protective effect on NLRP3 inflammasome‐mediated apoptosis in LPS‐induced NPCs through regulating NF‐κB signaling.

Irisin inhibits NLRP3 inflammasome activation in HG/HF incubated cardiac microvascular endothelial cells with H/R injury

“…Anfibatide could inhibit the expression of NLRP3, ASC, cleaved‐caspase‐1, Bax and cleaved‐caspase‐3, promoted the expression of Bcl‐2 in cerebral ischemia reperfusion in vivo and in vitro, which indicates that anfibatide could alleviate inflammation and apoptosis through inhibiting NF‐kappaB/NLRP3 axis 29 . Alpha‐mangostin exerted a protective effect on NLRP3 inflammasome‐mediated apoptosis in LPS‐induced NPCs through regulating NF‐κB signaling 30 . Our previous studies have demonstrated that the NLRP3 inflammasome is activated in CMECs, which plays a critical role in the pathophysiology of MI/R injury.…”

“…29 Alpha-mangostin exerted a protective effect on NLRP3 inflammasome-mediated apoptosis in LPS-induced NPCs through regulating NF-κB signaling. 30 Our previous studies have demonstrated that the NLRP3 inflammasome is activated in CMECs, which plays a critical role in the pathophysiology of MI/R injury. Furthermore, NLRP3 inflammasome activation is also responsible for vascular endothelial dysfunction in diabetes.…”

Pyroptosis and Intervertebral Disc Degeneration: Mechanistic Insights and Therapeutic Implications

“… 116 , 117 A recent study has demonstrated that α-mangostin treatment inhibits LPS-induced increase of NLRP3, ASC, and pro-Caspase-1 expression, as well as IL-1β and IL-18 production, suggesting α-mangostin exerts a protective effect on LPS-induced NLRP3 inflammasome of NP cells. 102 …”

Pattern recognition receptor signaling and innate immune responses to schistosome infection

“…A recent investigation revealed that NF-kB signaling is required for NLRP3 inflammasome activity (Zhang et al, 2019;. As a transcription factor, NF-kB probably mediates the transcription of pro-IL-1b and pro-IL-8, which are necessary for NLRP3 inflammasome activity (Chen et al, 2022). In addition to NLRP3 inflammasome, schistosome eggs can induce NLRP6 inflammasome activation in DCs, which also results in IL-1b production (Sanches et al, 2020).…”