Targeting Metabolic Diseases with Celastrol: A Comprehensive Review of Anti-Inflammatory Mechanisms and Therapeutic Potential

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119560 - 119560

Published: Feb. 1, 2025

Language: Английский

Exploring the interplay between adipokine-mediated celastrol target genes and T cells in diabetic nephropathy: a mendelian randomization-based causal inference

Diabetology & Metabolic Syndrome, Journal Year: 2025, Volume and Issue: 17(1)

Published: March 18, 2025

Diabetic nephropathy (DN) is influenced by dysregulated adipokines, which play a key role in inflammation, immune responses, and lipid metabolism. However, the precise molecular mechanisms linking adipokine dysregulation, cell infiltration, metabolic reprogramming DN remain poorly understood. Celastrol, bioactive regulator, has been shown to mitigate renal immune-inflammatory damage inhibiting PI3K/Akt/NF-κB signaling pathway. Yet, its specific impact on adipokine-mediated responses metabolism unclear. This study aims elucidate interplay between target genes investigate how celastrol modulates these interactions. Gene expression profiles of patients were obtained from GEO datasets (GSE30122 GSE30528) analyzed for differentially expressed (DEGs) using limma package. set variation analysis (GSVA) was conducted assess pathways, while Mendelian randomization (MR) Pearson correlation evaluated association DEGs adipokines. Immune infiltration IOBR R package (MCP-counter xCell methods), followed MR DN-related responses. Celastrol identified SEA database. A total 70 intersecting identified. GSVA revealed that brown beige adipocyte differentiation pathways downregulated, adipocyte-related upregulated (p < 0.05). demonstrated adiponectin negatively associated with (OR = 0.77, P 0.005), whereas leptin 1.92, 0.016) resistin 1.43, 0.001) positively associated. Three genes, MAGI2, FGF9, THBS2 linked risk T infiltration. correlated 0.51, 6.7e-06), FGF9 -0.8, 2.2e-16) MAGI2 0.75, 1.3e-13) correlated. 22 including THBS2, Our findings reveal progression through adipokine-immune crosstalk, emerging as regulatory genes. These insights provide new avenues biomarker discovery therapeutic implications development DN.

Language: Английский

Chestnut Nonstarch Polysaccharides Enhance Intestinal Barrier Integrity and Modulate Gut Microbiota to Ameliorate DSS-Induced Colitis in Mice

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

Published: April 22, 2025

This study investigated the biological activity of chestnut nonstarch polysaccharide (CNP) after removing starch. CNP was isolated from chestnut, with its monosaccharide composition identified as rhamnose, mannose, fructose, glucuronic acid, ribose, and galacturonic acid. Animal experiments showed that can significantly alleviate inflammatory response induced by dextran sodium sulfate (DSS) in a murine model ulcerative colitis (UC). alleviates mice boosting antioxidant enzymes, reducing pro-inflammatory cytokines, increasing anti-inflammatory strengthening intestinal barrier via tight junction proteins, suppressing inflammation through PI3K/NF-κB pathway. Results 16S rDNA sequencing demonstrated intake improved richness gut microbial community. These findings suggest exerts protective effect against DSS-induced enhancing integrity, mitigating oxidative stress, regulating cytokine levels, restoring balance. The results this highlight important application value development functional foods.

Language: Английский