SREBP1c‐Mediated Transcriptional Repression of YME1L1 Contributes to Acute Kidney Injury by Inducing Mitochondrial Dysfunction in Tubular Epithelial Cells DOI Creative Commons
Xin Wang, Jie Zhou, Yuzhu Peng

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract Acute kidney injury (AKI) is a prevalent clinical syndrome with high morbidity and mortality. Accumulating studies suggest mitochondrial dysfunction as the typical characteristics key process of AKI, but underlying mechanism remains elusive. The YME1‐like 1 (YME1L1) ATPase, an inner membrane protein, screened identified to be downregulated in renal tubular epithelial cells various mouse models patients AKI. Dramatically, restoration YME1L1 expression significantly alleviates cisplatin‐induced AKI subsequent chronic disease (CKD) through attenuating via maintaining optic atrophy (OPA1)‐mediated energy metabolism homeostasis. Mechanistically, upregulated sterol regulatory element binding transcription factor 1c (SREBP1c) demonstrated responsible for cisplatin‐mediated transcriptional inhibition directly its promoter region. Moreover, methyltransferase‐like 3 (METTL3)‐mediated m6A modification enhances SREBP1c mRNA stability, thereby upregulating expression. Notably, both depletion tubule‐specific overexpression markedly ameliorate transition CKD. Taken together, these findings that METTL3‐mediated upregulation contributes progression CKD disrupting transcriptionally suppressing YME1L1. Targeting SREBP1c/YME1L1 signaling may serve novel therapeutic strategy against

Language: Английский

Functional effects and mechanisms of Phyllanthus emblica fruit and gallic acid on metabolic diseases: Experimental evidence and clinical perspectives DOI

Xiaoling Gou,

Yin Ding,

Yamei Wu

et al.

Food Bioscience, Journal Year: 2024, Volume and Issue: 59, P. 104039 - 104039

Published: April 7, 2024

Language: Английский

Citations

4
Cornelian Cherry (Cornus mas L.) Fruit Extract Lowers SREBP-1c and C/EBPα in Liver and Alters Various PPAR-α, PPAR-γ, LXR-α Target Genes in Cholesterol-Rich Diet Rabbit Model DOI Open Access
Maciej Danielewski, Andrzej Rapak, Angelika Kruszyńska

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1199 - 1199

Published: Jan. 18, 2024

Cornelian cherry (Cornus mas L.) fruits, abundant in iridoids and anthocyanins, are natural products with proven beneficial impacts on the functions of cardiovascular system liver. This study aims to assess compare whether what extent two different doses resin-purified cornelian extract (10 mg/kg b.w. or 50 b.w.) applied a cholesterol-rich diet rabbit model affect levels sterol regulatory element-binding protein 1c (SREBP-1c) CCAAT/enhancer binding α (C/EBPα), various liver X receptor-α (LXR-α), peroxisome proliferator-activated (PPAR-α), receptor-γ (PPAR-γ) target genes. Moreover, aim is evaluate resistive index (RI) common carotid arteries (CCAs) aortas, histopathological changes CCAs. For this purpose, SREBP-1c, C/EBPα, ATP-binding cassette transporter A1 (ABCA1), G1 (ABCG1), fatty acid synthase (FAS), endothelial lipase (LIPG), carnitine palmitoyltransferase 1A (CPT1A), adiponectin receptor 2 (AdipoR2) tissue were measured. Also, lipoprotein (LPL), visceral adipose tissue-derived serine protease inhibitor (Vaspin), retinol-binding 4 (RBP4) The RI CCAs CCAs, indicated. oral administration decreased SREBP-1c C/EBPα both doses. dose 10 increased ABCA1 FAS, CPT1A, RBP4, enhanced ABCG1 AdipoR2. Mitigations atheromatous rabbits' also observed. obtained outcomes compared results our previous works. confirm that fruit may constitute potentially effective product prevention treatment obesity-related disorders.

Language: Английский

Citations

4
Morroniside attenuates podocytes lipid deposition in diabetic nephropathy: A network pharmacology, molecular docking and experimental validation study DOI
Yao Chen,

Ming Chen,

Wenhui Zhu

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 138, P. 112560 - 112560

Published: July 2, 2024

Language: Английский

Citations

4
Insights into the interaction mechanism between morroniside and digestive enzymes by multi-spectroscopy and molecular docking DOI

Liqun Ji,

Li Fei-Fei,

Z.J Wu

et al.

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: 1333, P. 141703 - 141703

Published: Feb. 8, 2025

Language: Английский

Citations

0
Uncovering the mechanism of Huangkui capsule in the treatment of diabetic kidney disease based on network pharmacology and experimental validation DOI Creative Commons
Junhong Liu,

Ziwei Li,

Zongyao Zhang

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 22, 2025

Language: Английский

Citations

0
Iridoid Glycosides in Kidney-Tonifying Chinese medicinal herbs: Mechanisms and Implications for Alzheimer’s Disease Therapy DOI

Yanjie Qu,

Min-Rui Ding,

Mengxue Zhang

et al.

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: 348, P. 119870 - 119870

Published: April 25, 2025

Language: Английский

Citations

0
Regulation of autophagy by the PI3K-AKT pathway in Astragalus membranaceus -Cornus officinalis to ameliorate diabetic nephropathy DOI Creative Commons
Rui Zhang, X Lan, Wenhui Zhu

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: May 13, 2025

Aims and background Autophagy plays an increasingly significant role in diabetic nephropathy (DN), but the mechanism by which autophagy participates DN injury is not well understood. Our previous studies have shown that Astragalus membranaceus - Cornus officinalis (AM-CO) improves lipid metabolism disorders, however, exact of also defined. The aim this study was to investigate therapeutic effects AM-CO on action using lipidomic techniques network pharmacological approaches. Experimental methods vivo experiments were carried out KKAy mice model with intervention AM-CO. Analysis kidney serum samples from treated technology obtain biomarkers for treatment identify main targets associated DN; Analyse potential signalling pathways pharmacology methods. In vitro performed PA-induced HK-2 cells results verified protein blotting immunofluorescence. Results Lipidomic analysis revealed 363 differential metabolites 195 tissue, compared analysed find their common belonging phosphatidylethanolamine (PE) classes, respectively. addition, PE a vital functiona process autophagy. And speculated Calycosin (Cal), major component AM-CO, could ameliorate regulating through modulating PI3K-AKT signaling pathway. showed induce autophagy, increase LC3II expression decrease P62 expression. Meanwhile, Cal inhibit levels p62, PI3K, P-AKT AKT. addition PI3K activator resulted reversal Conclusion conclusion, can pathway its regulation key

Language: Английский

Citations

0
Morroniside Ameliorates High-Fat and High-Fructose-Driven Chronic Kidney Disease by Motivating AMPK–TFEB Signal Activation to Accelerate Lipophagy and Inhibiting Inflammatory Response DOI
Cong Zhang,

Yuquan Xiong,

Yao-Hua Luo

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Studies have substantiated that dietary-fat- and fructose-overconsumption-caused lipid metabolism disorders can trigger renal lipotoxicity to drive the progression of chronic kidney disease (CKD). This study was conducted evaluate efficacy morroniside, a natural active substance extracted from fruit Cornus officinalis, in inhibiting CKD high-fat high-fructose-fed mice. Our results showed histological changes such as fatty degeneration tubular cells, dilatation, glomerular fibrosis, abnormal function kidneys high-fat- mice, which significantly improved after morroniside treatment. Mechanistically, maintained homeostasis inhibited NLRP3 inflammatory vesicle activation by activating AMPKα promote TFEB nuclear translocation-mediated lipophagy. Consistent were observed palmitic acid-induced HK-2 cells. Notably, silencing or both reversed effects promoting lipophagy responses vivo vitro. Therefore, our provides compelling evidence delays AMPK/TFEB-mediated inflammasome activation, suggesting dietary supplementation with morroniside-rich foods (such officinalis) might be an effective strategy for prevention CKD.

Language: Английский

Citations

0
Unveiling the molecular mechanisms of stigmasterol on diabetic retinopathy: BNM framework construction and experimental validation DOI Creative Commons

Hongrong Zhang,

Yufan Li, Qi Xu

et al.

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: May 9, 2025

Background Diabetic retinopathy (DR), one of the most common complications diabetes, severely impacts patients’ quality life. The combined use traditional Chinese medicines Astragalus, Fructus ligustris, and Cornus officinalis has yielded considerable therapeutic effects in clinical DR treatment. Methods In this study, a multimodule framework (BNM) encompassing bioinformatics, network pharmacology, machine learning (ML) based on molecular fingerprints was innovatively developed to thoroughly investigate mechanisms medicine treating DR. Results A total 40 active components 12 core targets were identified. Enrichment analysis identified key pathways such as VEGF signaling pathway, TNF pathway HIF-1 pathway. Prediction models using targets, PPARG, constructed from GEO database validated via immune infiltration docking, revealing that PPARG may be potential target for Moreover, component medicine, stigmasterol, ML model fingerprints. vivo experiments demonstrated stigmasterol can regulate glucose lipid metabolism, improve systemic inflammatory levels, ameliorate ocular vascular changes by modulating expression PPARG. Conclusion BNM suggests an important treatment DR, with its mechanism potentially related VEGF/VEGFR

Language: Английский

Citations

0
The role of CBL family ubiquitin ligases in cancer progression and therapeutic strategies DOI Creative Commons
Jiaqi Ren,

Linlin Lv,

Xufeng Tao

et al.

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

Published: July 26, 2024

The CBL (Casitas B-lineage lymphoma) family, as a class of ubiquitin ligases, can regulate signal transduction and activate receptor tyrosine kinases through various kinase-dependent pathways. There are three members the family: c-CBL, CBL-b, CBL-c. Numerous studies have demonstrated important role in cellular pathways, particularly those involved occurrence progression cancer, hematopoietic development, regulation T cell receptors. Therefore, purpose this review is to comprehensively summarize function regulatory family proteins different human tumors, well progress drug research targeting so provide broader clinical measurement strategy for treatment tumors.

Language: Английский

Citations

2