Nodakenin alleviates renal ischaemia‐reperfusion injury via inhibiting reactive oxygen species‐induced <scp>NLRP3</scp> inflammasome activation

Yuan, Ling; Lin, Xin; Li, Jianchun; Tan, Ruizhi; Zhong, Xia; Wang, Li

doi:10.1111/nep.13781

Cited by 15 publications

(9 citation statements)

References 22 publications

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“…Nod is a coumarin glycoside extracted from umbelliferae roots. In recent years, it has been con rmed that Nod has antibacterial, anti-in ammatory, antispasmodic, and anti brotic effects, and it can improve cognitive function, and alleviate renal ischaemia-reperfusion injury [19,34,55,56] . In this paper, the anticolitis effect of Nod provides new theoretical support for pharmaceutical research of Nod.…”

Section: Discussionmentioning

confidence: 99%

Nodakenin ameliorated TNBS-induced experimental colitis in mice by inhibiting intestinal epithelial cell pyroptosis

Geng

Huang

et al. 2023

Preprint

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Background and Aims Pyroptosis of intestinal epithelial cells is associated with intestinal barrier dysfunction and the intestinal inflammatory symptoms of Crohn's disease (CD). The natural plant monomer, nodakenin (Nod), inhibits NOD-like receptor protein 3 (NLRP3) expression, and this study aimed to evaluate its effect on CD-like colitis, as well as possible mechanisms. Methods Using TNBS intervention mice as CD animal models, the therapeutic effect of Nod on CD-like colitis in mice was explored through disease activity index (DAI) analysis, weight change, histological analysis, inflammatory factor expression and intestinal barrier function. In addition, the direct effect of Nod on the pyroptosis of intestinal epithelial cells was explored by immunofluorescence and western blot detection in LPS-/ATP-induced colon organoid models. Furthermore, through bioinformatics and in vivo and in vitro experimental verification, the potential mechanism by which Nod protects intestinal epithelial cells was explored. Results Nod intervention improved colitis and intestinal barrier function in TNBS-induced mice, as demonstrated by improvements in weight loss, DAI, tissue inflammation score, proinflammatory factor expression, and intestinal permeability. In addition, Nod inhibited the pyroptosis of intestinal epithelial cells in colitis mice and LPS-/ATP-induced colon organoids, as well as the expression of key pyroptosis regulators, such as NLRP3, GSDMD-N, and cleaved-caspase-1. Mechanistically, Nod inhibited the activation of PI3K/Akt signalling a in intestinal epithelial cells in TNBS-induced mice and LPS-/ATP-induced colonic organoids. Conclusions Nod restrained the pyroptosis of intestinal epithelial cells to protect the intestinal barrier of CD-like colitis by inhibiting PI3K/Akt signalling, this may provide a new option for the treatment of Crohn's disease.

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Section: Discussionmentioning

confidence: 99%

Nodakenin ameliorated TNBS-induced experimental colitis in mice by inhibiting intestinal epithelial cell pyroptosis

Geng

Huang

et al. 2023

Preprint

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“…For instance, restraining activation of NLRP3 inflammasome could protect hepatic I/R injury (Xu et al 2020). Inhibiting activation of NLRP3 inflammasome induced by reactive oxygen species also could improve renal I/R injury (Liao et al 2020). These conclusions are consistent with our results that inhibited the expression of NLRP3 and caspase-1 by rapamycin treatment could alleviate lung injury I/R in rats.…”

Section: Discussionmentioning

confidence: 99%

Rapamycin inhibits LOC102553434-mediated pyroptosis to improve lung injury induced by limb ischemia–reperfusion

et al. 2021

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Limb ischemia reperfusion (I/R) triggers local or systemic injury, and whether the process is mediated by pyroptosis remains unclear, we aimed to explore whether pyroptosis was involved in the process of rapamycin alleviating lung injury induced by I/R and investigate the molecular mechanisms. The histopathology of lung injury induced by I/R was confirmed by hematoxylin-eosin (HE) staining, and malondialdehyde (MDA), superoxide dismutase (SOD), and the expression of pyroptosis related molecules were detected. RNA sequencing was used to mine key long non-coding RNAs (lncRNAs). The model of lipopolysaccharide (LPS)-induced L2 cell damage was also used to explore the effect and mechanism of rapamycin on lncRNA. Rapamycin treatment alleviated I/R-induced lung histopathologically injury and increased the concentration of MDA while decreased activity of SOD and expression of NLRP3, Caspase-1, interleukin-1β (IL-1β), and IL-18 in rat. A total of 63 differentially expressed lncRNAs (DElncRNAs) were identified from IR + Rap group compared with IR group, and these DElncRNAs were mainly involved in cell adhesion molecules (CAMs) and endocytosis pathway. The lncRNA LOC102553434 and its target gene MMP9 were most significantly up-regulated in I/R-injured rat. In vitro experiments showed that LPS induction caused a significant increase in LOC102553434, MMP9, IL-1β, and IL-18 in L2 cells, but rapamycin treatment significantly reversed the effects. After interfering with the expression of LOC102553434 in the LPS-injured cells pretreated with rapamycin, cell proliferation significantly increased, and the expression of MMP, NLRP3 and caspase-1 were significantly decreased. Rapamycin protects the lung from limb I/R injury by regulating LOC102553434 expression and inhibiting pyroptosis pathway. LOC102553434 plays a role in promoting pyroptosis and thus provides a target for clinical treatment of I/R-induced lung injury.

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“…Mouse TECs were isolated and cultured as our previously described (Liao et al, 2021). In brief, renal cortex was carefully obtained from mice (approximately 21 days) and incubated with PBS containing 1% BSA, 0.1% collagenase V (Sigma, USA) under the water bath at 37°C for 15 min.…”

Section: Methodsmentioning

confidence: 99%

“…MTT assay was determined as mentioned previously (Li et al, 2018; Liao et al, 2021). Briefly, 5 × 10 3 cells were seeded and incubated in 96‐well plates overnight.…”

Section: Methodsmentioning

confidence: 99%

Tectorigenin protects against unilateral ureteral obstruction by inhibiting Smad3‐mediated ferroptosis and fibrosis

Yang

Zhu

et al. 2021

Phytotherapy Research

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Renal tubular epithelial cell (TEC) injury and fibrosis are the key factors of the pathogenesis of chronic kidney disease. Here, we reported that tectorigenin is effectively protected against obstructive nephropathy established by unilateral ureteral obstruction (UUO). In vivo, tectorigenin administration significantly alleviated the deteriorations of renal functions including blood urea nitrogen and creatinine. Meanwhile, results from the histology suggested that renal injury characterized by tubular cell damage and fibrosis lesions of kidneys in UUO group were markedly attenuated following tectorigenin treatment. Mechanistically, we found that tectorigenin treatment greatly inhibited Smad3 phosphorylation, and the transcription and protein level of Nox4, a newly identified direct downstream molecule of Smad3 and a modulator of ferroptosis, while it indirectly restored the expression of glutathione peroxidase 4, a negative regulator of ferroptosis. Consistent with in vivo studies, treatment with tectorigenin also suppressed the ferroptosis induced by erastin/RSL3 and fibrosis stimulated by transforming growth factor β1 (TGF‐β1) in primary renal TECs. What is more, treatment with ferroptosis inhibitor, ferrostatin‐1, also impeded TGF‐β1 stimulated the profibrotic effects in TECs, indicating that tectorigenin may relieve fibrosis by inhibiting ferroptosis in TECs. In addition, tectorigenin treatment exhibited a similar tendency, which inhibited Smad3 activation, and the docking analysis revealed that tectorigenin docked well into the Smad3 binding cavity with strong binding affinity (−7.9 kcal/mol). Thus, this study deciphers the protective effect of tectorigenin against obstructive nephropathy through inhibiting Smad3‐mediated ferroptosis and fibrosis.

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Nodakenin alleviates renal ischaemia‐reperfusion injury via inhibiting reactive oxygen species‐induced NLRP3 inflammasome activation

Cited by 15 publications

References 22 publications

Nodakenin ameliorated TNBS-induced experimental colitis in mice by inhibiting intestinal epithelial cell pyroptosis

Nodakenin ameliorated TNBS-induced experimental colitis in mice by inhibiting intestinal epithelial cell pyroptosis

Rapamycin inhibits LOC102553434-mediated pyroptosis to improve lung injury induced by limb ischemia–reperfusion

Tectorigenin protects against unilateral ureteral obstruction by inhibiting Smad3‐mediated ferroptosis and fibrosis

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