Cordycepin ameliorates kidney injury by inhibiting gasdermin D‐mediated pyroptosis of renal macrophages through nuclear factor kappa‐B

Journal of Biochemical and Molecular Toxicology, Journal Year: 2024, Volume and Issue: 38(9)

Published: Aug. 29, 2024

Abstract To explain the effect and mechanism of cordycepin (COR) in resisting acute kidney injury (AKI). Network pharmacology was employed to analyze correlations between COR, AKI, pyroptosis, as well action target COR. A mouse model AKI established by ischemia reperfusion (IRI), after treatment with renal function, tissue inflammatory cytokine levels, pyroptosis‐related signals were detected mice. In in‐vitro experiments, damage macrophages caused oxygen‐glucose deprivation model, pyroptosis indicators levels assayed COR treatment. pharmacological analysis revealed that nuclear factor kappa‐B (NF‐κB) primary could inhibit inflammation during IRI inhibiting NF‐κB‐mediated gasdermin D cleavage. When NF‐κB inhibited, weakened. lower cytokines, whose associated NF‐κB. Our study finds can play an anti‐inflammatory role progression through which represents its nephroprotective mechanism.

Language: Английский

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Spectroscopic Relationship between XOD and TAOZHI Total Polyphenols Based on Chemometrics and Molecular Docking Techniques

Molecules, Journal Year: 2024, Volume and Issue: 29(18), P. 4288 - 4288

Published: Sept. 10, 2024

Xanthine oxidase (XOD) is a key enzyme that promotes the oxidation of xanthine/hypoxanthine to form uric acid, and accumulation acid leads hyperuricaemia. The prevalence gout caused by hyperuricaemia increasing year year. TAOZHI (TZ) can be used for treatment rheumatic arthralgia due qi stagnation blood stasis contains large number polyphenolic components. aim this study was investigate relationship between chromatograms XOD inhibition 21 batches TZ total polyphenol extract samples. Chemometric methods such as grey correlation analysis, bivariate partial least squares regression were identify active ingredient groups in extracts TZ, which validated using molecular docking techniques. content contained did not differ significantly, all showed inhibitory effects on XOD. Spectroeffect analysis effect activity result synergistic multiple components, component screened inhibit F2 (4-O-Caffeoylquinic acid), F4, F10 (naringenin). results binding energies nine dockings lower than −7.5 kcal/mol, modes included hydrogen bonding, hydrophobic forces, salt bridges, π-staking, small molecules might exert their pharmacological through residue sites amino acids, threonine, arginine, leucine. This provides some theoretical basis development utilisation polyphenols.

Language: Английский

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Taohong Siwu Decoction Ameliorates Abnormal Uterine Bleeding Via Inhibiting Acsl4-Mediated Ferroptosis

Published: Jan. 1, 2024

Language: Английский

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METTL3, m6A modification, and EGR1: interplay affecting myocardial I/R injury outcomes

Cell Biology and Toxicology, Journal Year: 2024, Volume and Issue: 41(1)

Published: Dec. 20, 2024

The occurrence of severe myocardial ischemia/reperfusion (I/R) injury is associated with the clinical application reestablishment technique for heart disease, and understanding its underlying mechanisms currently an urgent issue. Prior investigations have demonstrated potential enhancement MIRI through EGR1 suppression, although precise regulatory pathways require further elucidation. core focus this investigation to examine molecular regulates mitophagy-mediated cell pyroptosis impact on MIRI. Cardiomyocyte hypoxia/reoxygenation (H/R) models mouse I/R were used investigate involvement in regulating injury. research outcomes that under H/R conditions, expression was upregulated inhibited JAK2/STAT3 pathway, leading enhanced mitophagy disrupted mitochondrial fusion/fission dynamics, ultimately resulting pyroptosis. Further revealed upregulation mediated by methyltransferase like 3 (METTL3)-mediated m6A modification mRNA depended binding insulin growth factor 2 mrna protein (IGF2BP2) N6-methyladenosine (m6A) site enhance stability. In vivo animal experiments confirmed METTL3 IGF2BP2 suppressed activation janus kinase (JAK2) /signal transducer activator transcription (STAT3) thereby inhibiting mitophagy, disrupting promoting pyroptosis, exacerbating

Language: Английский

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