Puerarin Ameliorates the Ferroptosis in Diabetic Liver Injure Through the JAK2/STAT3 Pathway Inhibition Based on Network Pharmacology and Experimental Validation

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 737 - 757

Published: Feb. 1, 2025

Background: Diabetic liver injury (DLI) is a common complication of diabetes mellitus (DM), which seriously endangers the health diabetic patients. Puerarin, main active component Pueraria lobata , has shown positive effects in lowering blood glucose and lipids, resisting oxidative stress, protecting liver. However, mechanism protective effect Puerarin on DLI remains unclear. Methods: Various databases were used to screen for targets ferroptosis DLI. Protein-protein interaction (PPI) network Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analysis predict key pathways. Molecular docking was interactions between core targets. KK/Upj-Ay/J (KKAy) mice high (HG)-induced AML12 cells study The molecular mechanisms by acts further verified vivo vitro experiments. Results: KEGG indicated that JAK/STAT pathway might be related anti-DLI Puerarin. revealed good affinity JAK2 STAT3. In vivo, (80 mg/kg) reduced body weight, glucose, lipids function KKAy fed high-sugar, high-fat diet. also ameliorated hepatic pathological changes inflammatory responses, attenuated stress iron overload mice. Western blotting results showed could regulate expression proteins JAK2/STAT3 pathway. vitro, (25, 50, 100 μM) increased cell viability decreased steatosis indexes induced HG (30 mm) varying degrees. More importantly, AG490 blocker experiments regulation process dependent Conclusion: conclusion, this may inhibiting treatment Keywords: puerarin, injury, ferroptosis, pathway, pharmacology

Language: Английский

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Broadening horizons: the multifaceted functions of ferroptosis in kidney diseases

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(12), P. 3726 - 3743

Published: Jan. 1, 2023

Ferroptosis is an iron-dependent programmed cell death pattern that characterized by iron overload, reactive oxygen species (ROS) accumulation and lipid peroxidation. Growing viewpoints support the imbalance of homeostasis disturbance metabolism contribute to tissue or organ injury in various kidney diseases triggering ferroptosis. At present, key regulators complicated network mechanisms associated with ferroptosis have been deeply studied; however, its role initiation progression has not fully revealed. Herein, we aim discuss features, ferroptosis, explore emerging roles organelles gather pharmacological progress, systematically summarize most recent discoveries about crosstalk between diseases, including renal carcinoma (RCC), acute (AKI), diabetic disease (DKD), autosomal dominant polycystic (ADPKD), fibrosis, lupus nephritis (LN) IgA nephropathy. We further conclude potential therapeutic strategies targeting for prevention treatment hope this work will provide insight study pathogenesis kidney-related diseases.

Language: Английский

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Targeting ferroptosis as a prospective therapeutic approach for diabetic nephropathy

Annals of Medicine, Journal Year: 2024, Volume and Issue: 56(1)

Published: April 24, 2024

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus, causing substantive threat to the public, which receives global concern. However, there are limited drugs targeting treatment DN. Owing this, it highly crucial investigate pathogenesis and potential therapeutic targets The process ferroptosis type regulated cell death (RCD) involving presence iron, distinct from autophagy, apoptosis, pyroptosis. A primary mechanism associated with iron metabolism, lipid accumulation ROS. Recently, many studies testified significance in kidney tissue under diabetic conditions explored DN therapy. Our review summarized most current between DN, along investigating significant processes different cells, providing novel target option for

Language: Английский

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Ferroptosis in organ fibrosis: From mechanisms to therapeutic medicines

Journal of Translational Internal Medicine, Journal Year: 2024, Volume and Issue: 12(1), P. 22 - 34

Published: Feb. 1, 2024

Abstract Fibrosis occurs in many organs, and its sustained progress can lead to organ destruction malfunction. Although numerous studies on fibrosis have been carried out, underlying mechanism is largely unknown, no ideal treatment currently available. Ferroptosis an iron-dependent process of programmed cell death that characterized by lipid peroxidation. In the past decade, a growing body evidence demonstrated association between ferroptosis fibrotic diseases, while targeting may serve as potential therapeutic strategy. This review highlights recent advances crosstalk fibrosis, discusses ferroptosis-targeted approaches against are being explored.

Language: Английский

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Kidney tea [Orthosiphon aristatus (Blume) Miq.] improves diabetic nephropathy via regulating gut microbiota and ferroptosis

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: June 19, 2024

Introduction Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Due to its complex pathogenesis, new therapeutic agents are urgently needed. Orthosiphon aristatus (Blume) Miq., commonly known as kidney tea, widely used in DN treatment China. However, mechanisms have not been fully elucidated. Methods We db/db mice model and evaluated efficacy tea by measuring fasting blood glucose (FBG), serum inflammatory cytokines, injury indicators histopathological changes. Furthermore, 16S rDNA gene sequencing, untargeted metabolomics, electron microscope, ELISA, qRT-PCR, Western blotting were performed explore which exerted effects. Results Twelve polyphenols identified from extract ameliorated FBG, inflammation mice. Moreover, reshaped gut microbiota, reduced abundance Muribaculaceae , Lachnoclostridium Prevotellaceae_UCG-001 Corynebacterium Akkermansia enriched Alloprevotella Blautia Lachnospiraceae_NK4A136_group . Kidney altered levels metabolites pathways such ferroptosis, arginine biosynthesis mTOR signaling pathway. Importantly, improved mitochondrial damage, increased SOD activity, decreased MDA 4-HNE tissues Meanwhile, this functional upregulated GPX4 FTH1 expression downregulated ACSL4 NCOA4 expression, indicating that it could inhibit ferroptosis kidneys. Conclusion Our findings imply can attenuate development modulating microbiota presents a novel scientific rationale for clinical application tea.

Language: Английский

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Beyond Mortality: Exploring the Influence of Plant Phenolics on Modulating Ferroptosis—A Systematic Review

Antioxidants, Journal Year: 2024, Volume and Issue: 13(3), P. 334 - 334

Published: March 10, 2024

Ferroptosis is a recently discovered type of programmed cell death that mechanistically different from other types such as apoptosis, necroptosis, and autophagy. It characterized by the accumulation intracellular iron, overproduction reactive oxygen species, depletion glutathione, extensive lipid peroxidation lipids in membrane. was ferroptosis interconnected with many diseases, neurodegenerative ischemia/reperfusion injury, cancer, chronic kidney disease. Polyphenols, plant secondary metabolites known for bioactivities, are being extensively researched context their influence on which resulted great number publications showing need systematic review. In this review, an literature search performed. Databases (Scopus, Web Science, PubMed, ScienceDirect, Springer) were searched time span 2017 to November 2023, using keyword “ferroptosis” alone combination “flavonoid”, “phenolic acid”, “stilbene”, “coumarin”, “anthraquinone”, “chalcone”; after selection studies, we had 311 papers 143 phenolic compounds. total, 53 compounds showed ability induce ferroptosis, 110 able inhibit out those compounds, 20 both abilities depending model system. The most shikonin, curcumin, quercetin, resveratrol, baicalin. common modes action modulation Nrf2/GPX4 Nrf2/HO-1 axis iron metabolism.

Language: Английский

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Natural flavonoids act as potent ferroptosis inhibitors and their potentials in the treatment of ferroptosis-associated diseases

Pharmacological Research - Modern Chinese Medicine, Journal Year: 2024, Volume and Issue: 10, P. 100377 - 100377

Published: Jan. 26, 2024

Ferroptosis, an iron-dependent cell death characterized by lethal lipid peroxidation, has been involved in the pathogenesis of various diseases, such as ischemia/reperfusion injury, neurodegenerative and inflammatory disorders. Pharmacological inhibition ferroptosis represents a promising strategy for treatment above diseases. Flavonoids, class natural products found medicinal plants functional foods, are known numerous activities, especially newly discovered anti-ferroptotic activity. Our review aims to expand our understanding flavonoids' activity on multiple biological systems highlight importance utilizing flavonoids ferroptosis-associated A systematic literature search was conducted using Google Scholar, PubMed, Web Science, ScienceDirect, Springer Link. The following keywords: flavonoids, products, ferroptosis, mechanism, available information comprehensively studied compiled. We recent advances molecular mechanisms its roles diverse further systematically summarize inhibitory underlying suggest that ROS accumulation labile Fe2+ availability well activation Nrf2 signaling responsible inhibition. also discuss their clinical applications ferroptosis-related Taken together, exhibit prospect This is expected not only facilitate design development flavonoid-based inhibitors, but diseases therapies.

Language: Английский

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Augmenter of liver regeneration knockout aggravates tubular ferroptosis and macrophage activation by regulating carnitine palmitoyltransferase‐1A‐induced lipid metabolism in diabetic nephropathy

Acta Physiologica, Journal Year: 2024, Volume and Issue: 240(7)

Published: May 20, 2024

Ferroptosis is a novel type of programmed cell death that performs critical function in diabetic nephropathy (DN). Augmenter liver regeneration (ALR) exists the inner membrane mitochondria, and inhibits inflammation, apoptosis, oxidative stress acute kidney injury; however, its role DN remains unexplored. Here, we aimed to identify ALR ferroptosis induction macrophage activation DN.

Language: Английский

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Protective effect of vitexin against high fat-induced vascular endothelial inflammation through inhibiting trimethylamineN-oxide-mediated RNA m6A modification

Food & Function, Journal Year: 2024, Volume and Issue: 15(13), P. 6988 - 7002

Published: Jan. 1, 2024

A high-fat diet (HFD) is a major risk factor for cardiovascular disease.

Language: Английский

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Macrophage co-culture promotes cell reprogramming and prevents ferroptosis in aging fibroblasts for neurodegeneration therapy

Journal of Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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