Puerarin attenuates LPS-induced inflammatory injury in gastric epithelial cells by repressing NLRP3 inflammasome-mediated apoptosis

Peng, Zi-Tan; Liu, Hui

doi:10.1016/j.tiv.2022.105350

Cited by 14 publications

(9 citation statements)

References 27 publications

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“…In our previous study (16), we also found melatonin inhibited NLRP3 inflammasome to relieve apoptosis in DCD hearts. In the current study, by measuring the expression of Bax, Bcl-2, Caspase-3, and the number of TUNELpositive nuclei, we can conclude that warm ischemia-reperfusion injury leads to myocardial apoptosis in the DCD hearts, while mcc950 treatment attenuates NLRP3 inflammasome-mediated apoptosis (32).…”

Section: Discussionsupporting

confidence: 48%

Normothermic ex vivo heart perfusion with NLRP3 inflammasome inhibitor Mcc950 treatment improves cardiac function of circulatory death hearts after transplantation

Zeng

Niu

et al. 2023

Front. Cardiovasc. Med.

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BackgroundThe utilization of donation after circulatory death (DCD) hearts can enlarge the donor pool. However, DCD hearts suffer from serious ischemia/reperfusion injury (IRI). Recent studies found that the activation of NLRP3 inflammasome could play a significant role in organ IRI. Mcc950, which is a novel inhibitor of the NLRP3 inflammasome, can be applied to treat various kinds of cardiovascular diseases. Therefore, we hypothesized that the treatment of mcc950 could protect DCD hearts preserved with normothermic ex vivo heart perfusion (EVHP) against myocardial IRI via inhibiting NLRP3 inflammasome in a rat heart transplantation model of DCD.MethodsDonor-heart rats were randomly divided into four groups: Control group; Vehicle group; MP-mcc950 group; and MP + PO-mcc950 group. Mcc950 was added into the perfusate of normothermic EVHP in the MP-mcc950 and MP + PO-mcc950 groups, and was injected into the left external jugular vein after heart transplantation in the MP + PO-mcc950 group. Cardiac functional assessment was performed. The level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-associated protein of donor hearts were evaluated.ResultsThe treatment with mcc950 significantly increased the developed pressure (DP), dP/dtmax, and dP/dtmin of the left ventricular of DCD hearts at 90 min after heart transplantation in both MP-mcc950 and MP + PO-mcc950 groups. Furthermore, mcc950 added into perfusate and injected after transplantation in both MP-mcc950 and MP + PO-mcc950 groups significantly attenuated the level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome compared with the vehicle group.ConclusionsNormothermic EVHP combined with mcc950 treatment can be a promising and novel DCD heart preservation strategy, which can alleviate myocardial IRI via inhibiting NLRP3 inflammasome.

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Section: Discussionsupporting

confidence: 48%

Normothermic ex vivo heart perfusion with NLRP3 inflammasome inhibitor Mcc950 treatment improves cardiac function of circulatory death hearts after transplantation

Zeng

Niu

et al. 2023

Front. Cardiovasc. Med.

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“…In addition, hepatic deprivation of SIRT1 could contribute to cholesterol gallstone formation in mice by decreasing hepatocyte nuclear factor 1α/farnesoid X receptor signaling (Purushotham et al 2012 ). Accumulating evidence has highlighted the alleviatory function of the AMPK / SIRT1 signaling pathway on inflammatory injury of epithelial cells, such as intestinal epithelial cells (Zhang & Wu, 2021 ), pulmonary epithelial cells (Li et al 2019 ) and gastric epithelial cells (Peng & Liu, 2022 ). These studies supported our findings that overexpression of AQP3 ameliorated gallbladder injury by activating the AMPK / SIRT1 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

AQP3-mediated activation of the AMPK/SIRT1 signaling pathway curtails gallstone formation in mice by inhibiting inflammatory injury of gallbladder mucosal epithelial cells

Wang,

Zhang,

Zhou

et al. 2023

Mol Med

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Background Inflammatory injury of gallbladder mucosal epithelial cells affects the development of cholelithiasis, and aquaporin 3 (AQP3) is an important regulator of inflammatory response. This study reports a mechanistic insight into AQP3 regulating gallstone formation in cholelithiasis based on high-throughput sequencing. Methods A mouse model of cholelithiasis was induced using a high-fat diet, and the gallbladder tissues were harvested for high-throughput sequencing to obtain differentially expressed genes. Primary mouse gallbladder mucosal epithelial cells were isolated and induced with Lipopolysaccharides (LPS) to mimic an in vitro inflammatory injury environment. Cell biological phenotypes were detected by TdT-mediated dUTP Nick-End Labeling (TUNEL) assay, flow cytometry, Cell Counting Kit-8 (CCK-8) assay, and Trypan blue staining. In addition, enzyme linked immunosorbent assay (ELISA) determined the production of inflammatory factors in mouse gallbladder mucosa. Results Whole-transcriptome sequencing data analysis identified 489 up-regulated and 1007 down-regulated mRNAs. Bioinformatics analysis revealed that AQP3 was significantly down-regulated in mice with cholelithiasis. AQP3 might also confer an important role in LPS-induced gallbladder mucosal injury. Overexpression of AQP3 activated the AMPK (adenosine monophosphate-activated protein kinase) / SIRT1 (sirtuin-1) signaling pathway to reduce LPS-induced inflammatory injury of the gallbladder mucosa epithelium, thereby ameliorating gallbladder damage and repressing gallstone formation in mice. Conclusion Data from our study highlight the inhibitory role of AQP3 in gallbladder damage and gallstone formation in mice by reducing inflammatory injury of gallbladder mucosal epithelial cells, which is achieved through activation of the AMPK/SIRT1 signaling pathway.

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“…These bioactive substances derived from Flos Puerariae and Semen Hoveniae may have therapeutic efficacy in inflammation-related diseases. For example, puerarin, one of the main flavonoids found in PHE, can attenuate lipopolysaccharide (LPS)-induced inflammatory injury in gastric epithelial cells by repressing the AMPK/SIRT1/NLRP3 signaling pathway ( Peng and Liu, 2022 ). Kakkalide, separated from Pueraria lobata , significantly inhibited LPS-stimulated NF-κB activation and TNF-α expression in macrophages and suppressed TNBS-induced colitis in mice ( Jang et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Flos Puerariae-Semen Hoveniae medicinal pair extract ameliorates DSS-induced inflammatory bowel disease through regulating MAPK signaling and modulating gut microbiota composition

Chen

Zhang

et al. 2022

Front. Pharmacol.

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Background: Inflammatory bowel disease (IBD) is a global gastrointestinal disease characterized by relapsing and remitting inflammatory conditions. Flos Puerariae (the flower of Pueraria lobata [Willd.] Ohwi and P. thomsonii Benth.) and Hovenia dulcis Thunb. (Rhamnaceae) are traditional Chinese medicines. This medicinal pair has been used to treat various diseases due to its excellent anti-oxidant and anti-inflammatory activity. However, the effects of extracts from these plants on dextran sulfate sodium (DSS)-induced colitis have not been investigated; further study is needed to improve the understanding of their mechanisms of action and potential applications.Methods: The chemical constitution of extracts from Flos Puerariae and Semen Hoveniae (PHE) was analyzed using UPLC-LTQ-Orbitrap-MS/MS. The protective effects of PHE on mice with DSS-induced colitis were evaluated through assessment of body weight loss, disease activity index (DAI) score, colon length shortening, and pathological changes. The levels of inflammatory cytokines were determined by ELISA and RT-qPCR. Biomarkers of oxidative stress (ROS, CAT, SOD, MDA, and T-AOC) were analyzed using biochemical kits. The expression of MAPK proteins was determined by Western blotting analysis. Gut microbiota were analyzed via 16S rRNA sequencing.Results: Chemical composition analysis indicated that PHE contains various bioactive compounds, including puerarin, kakkalide, tectoridin, and genistin. The findings from this study suggest that PHE could effectively modulate histopathological score, inflammatory cell infiltration, and inflammatory factor secretion. Notably, PHE ameliorated oxidative stress by inhibiting activation of the MAPK pathway, leading to decreased inflammatory mediators and restored antioxidant enzyme activity. Furthermore, PHE treatment regulated the composition of the gut microbiota by increasing the abundance of benign bacteria, such as Akkermansia, and reducing the abundance of harmful bacteria, such as Proteobacteria.Conclusion: The findings from this study demonstrate the mechanism underlying the amelioration of DSS-induced intestinal oxidative stress by PHE and its positive impact on the restoration of the composition of gut microbiota.

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Puerarin attenuates LPS-induced inflammatory injury in gastric epithelial cells by repressing NLRP3 inflammasome-mediated apoptosis

Cited by 14 publications

References 27 publications

Normothermic ex vivo heart perfusion with NLRP3 inflammasome inhibitor Mcc950 treatment improves cardiac function of circulatory death hearts after transplantation

Normothermic ex vivo heart perfusion with NLRP3 inflammasome inhibitor Mcc950 treatment improves cardiac function of circulatory death hearts after transplantation

AQP3-mediated activation of the AMPK/SIRT1 signaling pathway curtails gallstone formation in mice by inhibiting inflammatory injury of gallbladder mucosal epithelial cells

Flos Puerariae-Semen Hoveniae medicinal pair extract ameliorates DSS-induced inflammatory bowel disease through regulating MAPK signaling and modulating gut microbiota composition

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