Mangiferin Mitigates Lipopolysaccharide-Induced Lung Injury by Inhibiting NLRP3 Inflammasome Activation

Li, Ning; Xiong, Rui; He, Ruyuan; Liu, Bohao; Wang, Bo; Geng, Qing

doi:10.2147/jir.s304492

Cited by 25 publications

(22 citation statements)

References 30 publications

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“…In addition, it possesses numerous pharmacological activities, such as anti-inflammatory, immunomodulatory and antioxidative effects ( 15 ). In the present study, MAF exerted little to no toxicity on A549 cells but mediated protective effects on cells after H/R injury, which was similar to previous reports that MAF attenuated myocardial ischemia-reperfusion injury and lung injury ( 32 , 33 ). When the concentration of MAF used was <20 µM, H/R injury was protected by MAF in a dose-dependent manner.…”

Section: Discussionsupporting

confidence: 92%

Mangiferin inhibits hypoxia/reoxygenation‑induced alveolar epithelial cell injury via the SIRT1/AMPK signaling pathway

Chen

Huang

2021

Exp Ther Med

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Lung ischemia-reperfusion injury (LIRI) is one of the complications that can occur after lung transplantation and may lead to morbidity and mortality. Mangiferin (MAF) is a naturally occurring glucosyl xanthone that has been documented to possess anti-inflammatory, immunomodulatory and potent antioxidant effects. The purpose of the present study was to investigate the effect of MAF on LIRI using a hypoxia-reoxygenation (H/R) cell model. In the present study, the viability of lung alveolar epithelial cells (A549) and H/R-A549 were detected by MTT assay. ELISA was used to evaluate the expression levels of IL-6 and IL-1β. TUNEL assay and western blotting were used to evaluate the apoptosis. In addition, H/R-A549 cells were treated with sirtinol, which is known inhibitor of sirtuin 1 (SIRT1) activity, to determine the effects of MAF on proteins associated with the SIRT1/5'AMP-activate protein kinase (AMPK) signaling pathway using western blotting. The results showed that 20 µM MAF exerted a protective effect on A549 cells against H/R mediating no clear cytotoxic effects. In terms of inflammation, MAF reduced IL-6, IL-1β, cyclooxygenase-2 and inducible nitric oxide synthase expression, which was accompanied by activation of the SIRT1/AMPK signaling pathway. In addition, compared with those in the group treated with sirtinol, expression of SIRT1, Bcl-2 and AMPK activity were elevated in MAF-treated H/R-A549 cells, whereas the expression of Bax, cleaved caspase-3 and cleaved caspase-9 was suppressed. TUNEL analysis of H/R-A549 cells treated with MAF in combination with sirtinol revealed that treatment with sirtinol blocked the SIRT1/AMPK signaling pathway and increased the apoptosis rate compared with the MAF group. Taken together, results of the present study revealed that MAF could inhibit lung H/R cell injury through the SIRT1/AMPK signaling pathway.

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Section: Discussionsupporting

confidence: 92%

Mangiferin inhibits hypoxia/reoxygenation‑induced alveolar epithelial cell injury via the SIRT1/AMPK signaling pathway

Chen

Huang

2021

Exp Ther Med

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“…85–23, revised in 1996) and also approved by the Animal Care and Use Committee of our hospital (WDRM 20210305). Male C57BL/6 mice (8–10 weeks old) were intratracheally injected with LPS (5 mg/kg in 50 μ L saline) to generate sepsis-induced ALI as we previously described [ 23 , 24 ]. Mice with rmGDF7 treatment were subcutaneously injected with rmGDF7 (25 μ g per mouse) at 24 h before LPS injection, according to a previous study [ 17 ].…”

Section: Methodsmentioning

confidence: 99%

“…To obtain BALF, mice were sacrificed and intratracheally injected with 1.0 mL of precooled phosphate buffer saline (PBS) 3 times. Then, the fluid was collected and centrifuged for 5 min at 1500 rpm at 4°C to obtain cell-free supernatants, which were then used for the analysis of total proteins and cytokines as we previously described [ 23 , 24 ]. Next, the sedimented cell pellets were resuspended in 0.5 mL of PBS and counted with a hemocytometer and Wright-Giemsa staining.…”

Section: Methodsmentioning

confidence: 99%

Growth Differentiation Factor 7 Prevents Sepsis-Induced Acute Lung Injury in Mice

Dong

Ying

Liu

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Acute lung injury (ALI) is a life-threatening complication during sepsis and contributes to multiple organ failure and high mortality for septic patients. The present study aims to investigate the role and molecular basis of growth differentiation factor 7 (GDF7) in sepsis-induced ALI. Methods. Mice were subcutaneously injected with recombinant mouse GDF7 Protein (rmGDF7) and then intratracheally injected with lipopolysaccharide (LPS) to generate sepsis-induced ALI. Primary peritoneal macrophages were isolated to further evaluate the role and underlying mechanism of GDF7 in vitro. Results. GDF7 was downregulated in LPS-stimulated lung tissues, and rmGDF7 treatment significantly inhibited inflammation and oxidative stress in ALI mice, thereby preventing LPS-induced pulmonary injury and dysfunction. Mechanistically, we found that rmGDF7 activated AMP-activated protein kinase (AMPK), and AMPK inhibition significantly blocked the anti-inflammatory and antioxidant effects of rmGDF7 during LPS-induced ALI. Further findings revealed that rmGDF7 activated AMPK through a downregulated stimulator of interferon gene (STING) in vivo and in vitro. Conclusion. GDF7 prevents LPS-induced inflammatory response, oxidative stress, and ALI by regulating the STING/AMPK pathway. Our findings for the first time identify GDF7 as a potential agent for the treatment of sepsis-induced ALI.

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“…Pharmacological studies indicate that mangiferin is related to anti-inflammatory, antipyretic, analgesic, antibacterial, immune regulation, hypoglycemic, and antioxidant effects [ 17 ]. For example, mangiferin significantly reduced NO, IL-1β, IL-6, and TNF-α by inhibiting activation of NF-κB in LPS-induced mouse microglia cells [ 18 ], and decreased IL-1β, IL-6, and TNF-α by inhibiting the nuclear translocation of the NF-κB p65 subunit in mononuclear macrophages, and protected mouse lung injury against sepsis [ 19 ]. Meanwhile, mangiferin may interact with TLR4/PI3K/AKT/NFκB signaling to inhibit NLRP3 inflammasome activation and modulate GSDMD-mediated pyroptosis in rats [ 20 ], and it alleviated the histopathology of inflammation and the levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) via inhibiting NF-κB and NLRP3 inflammasome activation in lactating female mice [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

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

Feng

Wei

Zhang

et al. 2022

IJMS

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Mangiferin (MF), a xanthone that extensively exists in many herbal medicines, processes significant activities of anti-inflammation and immunomodulation. The potential regulatory effect and mechanism of mangiferin on cell pyroptosis remain unclear. In this study, mouse bone-marrow-derived macrophages (BMDMs) were stimulated with 1 μg/mL LPS to induce cell pyroptosis and were treated with 10, 50, or 100 μg/mL MF for regulating pyroptosis. The cell supernatants TNF-α, IL-1β, IL-6, and IL-18 were detected by enzyme-linked immunosorbent assay (ELISA); gene expression of TNF-α, IL-1β, IL-6, IL-18, Caspase-1, Caspase-11, and gasdermin D (GSDMD) was tested by real-time polymerase chain reaction (RT-PCR), and protein expression levels of apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), nod-like receptor protein-3 (NLRP3), caspase-1, caspase-11, GSDMD, and NF-κB were detected by Western blot. The results showed that MF significantly inhibited the secretion and gene expression of TNF-α, IL-6, IL-1β, and IL-18 that were elevated by LPS. Moreover, MF significantly suppressed the gene expression of Caspase-1, Caspase-11, and GSDMD, and decreased the protein levels of NLRP3, caspase-1, caspase-11, full-length GSDMD (GSDMD-FL), GSDMD N-terminal (GSDMD-N), and NF-κB. In conclusion, mangiferin has a multi-target regulating effect on inflammation and pyroptosis by inhibiting the NF-κB pathway, suppressing inflammatory caspase-mediated pyroptosis cascades, and reducing GSDMD cleavage in LPS-induced BMDMs.

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Mangiferin Mitigates Lipopolysaccharide-Induced Lung Injury by Inhibiting NLRP3 Inflammasome Activation

Cited by 25 publications

References 30 publications

Mangiferin inhibits hypoxia/reoxygenation‑induced alveolar epithelial cell injury via the SIRT1/AMPK signaling pathway

Mangiferin inhibits hypoxia/reoxygenation‑induced alveolar epithelial cell injury via the SIRT1/AMPK signaling pathway

Growth Differentiation Factor 7 Prevents Sepsis-Induced Acute Lung Injury in Mice

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

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