Anti-Inflammation and Anti-Pyroptosis Activities of Mangiferin via Suppressing NF-κB/NLRP3/GSDMD Signaling Cascades

Feng, Mei; Wei, Shaoqiang; Zhang, Shidong; Yang, Ying

doi:10.3390/ijms231710124

Cited by 20 publications

(11 citation statements)

References 40 publications

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“…Results from the present study suggested that LPS enhanced the nuclear translocation of NF-κB, as indicated by the elevation of NF-κB levels in the nuclear extract and the increase of NF-κB immunostaining in the nuclei. The present results are consistent with the literature showing that LPS induces the increase in the expression levels of both NF-κB and the NLRP3 inflammasome (46,47). SCM blocked the nuclear translocation of NF-κB induced by LPS.…”

Section: Discussionsupporting

confidence: 93%

Inhibition of LPS‑induced NLRP3 inflammasome activation by stem cell‑conditioned culture media in human gingival epithelial cells

Sun

Wang

2023

Mol Med Rep

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Interleukin (IL)-1β is a pathogenic factor associated with the destruction of periodontal tissue in periodontitis. IL-1β processing is regulated by cytosolic machinery known as the inflammasome. Porphyromonas gingivalis infection and lipopolysaccharide (LPS) have an important role in the destruction of periodontal tissue in periodontitis. P. gingivalis infection and LPS have been reported to activate the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome in human oral cells. Stem cell therapy exhibits anti-inflammatory effects and stem cell-conditioned culture media (SCM) shows similar beneficial effects. The present study tested the hypothesis that SCM inhibits activation of the inflammasome and protects human gingival epithelial cells (GECs) against LPS-induced inflammatory damage. Human GECs were treated with or without LPS plus SCM or control cell media. NLPR3 inflammasome components and inflammatory factors were measured by western blotting and immunofluorescence. The present study revealed that LPS induced an increase in the expression of inflammasome components, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1. Co-immunoprecipitation revealed increased binding of NLRP3 and ASC, and immunofluorescence showed an increased co-localization of ASC and caspase-1, suggesting that LPS stimulated assembly of the NLRP3 inflammasome. SCM inhibited the overexpression and assembly of NLRP3 inflammasome components induced by LPS. Furthermore, SCM blocked the increase in IL-1β production induced by LPS and inhibited the translocation of the inflammatory factor, NF-κB, into the nuclei. Consequently, SCM protected cells against LPS-induced damage, as suggested by the recovery of disturbed E-cadherin staining pattern, which indicates a disruption in epithelial integrity. In conclusion, treatment with SCM may attenuate LPS-induced inflammatory damage in human GECs via inhibition of NLRP3 inflammasome activation, suggesting a potential therapeutic use for SCM.

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Section: Discussionsupporting

confidence: 93%

Inhibition of LPS‑induced NLRP3 inflammasome activation by stem cell‑conditioned culture media in human gingival epithelial cells

Sun

Wang

2023

Mol Med Rep

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“…Autophagy is a conserved degradation process that maintains cellular homeostasis and the clearance of damaged organelles [ 24 ] and is always accompanied by cell apoptosis, which is a complex process that can promote cell survival or cell death [ 22 ]. In non-neuronal cells, autophagy and apoptosis have been shown to be interconnected by several molecular nodes of crosstalk, enabling the coordinated regulation of cell survival during mild stimulation of autophagy or cell death during excess autophagy [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Mangiferin attenuates lipopolysaccharide-induced neuronal injuries in primary cultured hippocampal neurons

Tan,

Liang,

et al. 2024

Aging

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Mangiferin, a naturally occurring potent glucosylxanthone, is mainly isolated from the Mangifera indica plant and shows potential pharmacological properties, including anti-bacterial, anti-inflammation, and antioxidant in sepsis-induced lung and kidney injury. However, there was a puzzle as to whether mangiferin had a protective effect on sepsis-associated encephalopathy. To answer this question, we established an in vitro cell model of sepsis-associated encephalopathy and investigated the neuroprotective effects of mangiferin in primary cultured hippocampal neurons challenged with lipopolysaccharide (LPS). Neurons treated with 20 μmol/L or 40 μmol/L mangiferin for 48 h can significantly reverse cell injuries induced by LPS treatment, including improved cell viability, decreased inflammatory cytokines secretion, relief of microtubule-associated light chain 3 expression levels and several autophagosomes, as well as attenuated cell apoptosis. Furthermore, mangiferin eliminated pathogenic proteins and elevated neuroprotective factors at both the mRNA and protein levels, showing strong neuroprotective effects of mangiferin, including anti-inflammatory, anti-autophagy, and anti-apoptotic effects on neurons in vitro .

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“… 93 Activation of NLRP3/caspase-1/GSDMD signaling induces secretion of factors such as IL-18 and IL-1β, which activate the NF-κB signaling cascade that mediates inflammation and pyroptosis, causing tissue damage. 94 , 95 Therefore, it was hypothesized that YSHXD can inhibit inflammatory response, reduce kidney injury and delay RF by interfering with pyroptosis. We investigated this hypothesis using a UUO-induced rat model of fibrosis and also in the HK-2 cell fibrosis model.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology Analysis and Machine-Learning Models Confirmed the Ability of YiShen HuoXue Decoction to Alleviate Renal Fibrosis by Inhibiting Pyroptosis

Feng,

Luo,

et al. 2023

DDDT

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Purpose YiShen HuoXue decoction (YSHXD) is a formulation that has been used clinically for the treatment of renal fibrosis (RF) for many years. We aimed to clarify therapeutic effects of YSHXD against RF and potential pharmacological mechanisms. Materials and Methods We used network pharmacology analysis and machine-learning to screen the core components and core targets of YSHXD against RF, followed by molecular docking and molecular dynamics simulations to confirm the reliability of the results. Finally, we validated the network pharmacology analysis experimentally in HK-2 cells and a rat model of RF established by unilateral ureteral ligation (UUO). Results Quercetin, kaempferol, luteolin, beta-sitosterol, wogonin, stigmasterol, isorhamnetin, baicalein, and dihydrotanshinlactone progesterone were identified as the main active components of YSHXD in the treatment of unilateral ureteral ligation-induced RF, with IL-6, IL1β, TNF, AR, and PTGS2 as core target proteins. Molecular docking and molecular dynamics simulations further confirmed the relationship between compounds and target proteins. The potential molecular mechanism of YSHXD predicted by network pharmacology analysis was confirmed in HK-2 cells and UUO rats. YSHXD downregulated NLRP3, ASC, NF-κBp65, Caspase-1, GSDMD, PTGS2, IL-1β, IL-6, IL-18, TNF-α, α-SMA and upregulated HGF, effectively alleviating the RF process. Conclusion YSHXD exerts important anti-inflammatory and anti-cellular inflammatory necrosis effects by inhibiting the NLRP3/caspase-1/GSDMD-mediated pyroptosis pathway, indicating that YSHXD represents a new strategy and complementary approach to RF therapy.

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Anti-Inflammation and Anti-Pyroptosis Activities of Mangiferin via Suppressing NF-κB/NLRP3/GSDMD Signaling Cascades

Cited by 20 publications

References 40 publications

Inhibition of LPS‑induced NLRP3 inflammasome activation by stem cell‑conditioned culture media in human gingival epithelial cells

Inhibition of LPS‑induced NLRP3 inflammasome activation by stem cell‑conditioned culture media in human gingival epithelial cells

Mangiferin attenuates lipopolysaccharide-induced neuronal injuries in primary cultured hippocampal neurons

Network Pharmacology Analysis and Machine-Learning Models Confirmed the Ability of YiShen HuoXue Decoction to Alleviate Renal Fibrosis by Inhibiting Pyroptosis

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