Trigonella foenum-graecum L. protects against renal function decline in a mouse model of type 2 diabetic nephropathy by modulating the PI3K-Akt-ERK signaling pathway

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

Published: March 18, 2025

Trigonella foenum-graecum L. (HLB) exhibits promising pharmacological properties for the treatment of type 2 diabetic nephropathy (DN). This study aims to enhance understanding HLB's pharmacodynamic effects and elucidate mechanisms underlying its therapeutic potential in DN. The HLB were initially evaluated a murine DN model through oral administration an aqueous extract HLB. primary bioactive constituents subsequently identified using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). Network pharmacology analysis was integrated these data uncover molecular targets Key renal metabolites profiled untargeted metabolomics, followed by metabolic pathway enrichment conducted MetaboAnalyst 6.0 platform, which facilitated identification relevant pathways modulates Finally, quantitative real-time polymerase chain reaction (QRT-PCR) Western blot (WB) techniques employed validate expression levels key genes proteins, thereby confirming Animal experiments indicated that significantly improved blood glucose regulation function while reducing oxidative stress abnormalities lipid metabolism mice. A total 34 compounds 159 as active components metabolomics revealed 61 critical metabolites, among PI3K-Akt-ERK signaling pathway-known be involved diabetes-was highlighted crucial pathway. QRT-PCR WB analyses demonstrated upregulated MAPK1, MAPK3, AKT1, PI3K. These results suggest may alleviate modulating metabolism. Its are likely mediated pathway, along upregulation PI3K expression. lays groundwork further investigations into action

Language: Английский

The RAGE Pathway in Skin Pathology Development: A Comprehensive Review of Its Role and Therapeutic Potential

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13570 - 13570

Published: Dec. 18, 2024

The receptor for advanced glycation end-products (RAGE), a member of the immunoglobulin superfamily, is expressed in various cell types and mediates cellular responses to wide range ligands. activation RAGE triggers complex signaling pathways that drive inflammatory, oxidative, proliferative responses, which are increasingly implicated pathogenesis skin diseases. Despite its well-established roles conditions such as diabetes, cancer, chronic inflammation, contribution pathologies remains underexplored. This review synthesizes current findings on RAGE’s involvement pathophysiology diseases, including psoriasis, atopic dermatitis, lichen planus, focusing inflammatory signaling, tissue remodeling, cancer progression. Additionally, it examines RAGE-modulating treatments investigated dermatological contexts, highlighting their potential therapeutic options. Given significance variety conditions, further research into mediated may uncover new opportunities targeted interventions skin-specific signaling.

Language: Английский