Huangqi and Danshen improve the chronic nephrotoxicity of Cyclosporin A by regulating lipid metabolism

Phytomedicine, Journal Year: 2025, Volume and Issue: 140, P. 156582 - 156582

Published: Feb. 26, 2025

The clinical application of cyclosporine A (CsA) is limited due to nephrotoxicity. Lipid metabolism disorders play important roles in renal injury, but their role CsA nephrotoxicity not yet clear. Huangqi (Astragalus mongholicus Bunge) and Danshen (Salvia miltiorrhiza (HD) ameliorating the CsA, mechanisms still need be fully clarified. This study innovatively aimed analyse coexpression proteins serum metabolites for identification key pathways targets. provides novel insight into mechanism by which HD ameliorates CsA-induced We utilized intervene both vivo vitro models induced CsA. For experiments, we constructed a network metabolites, was used screen pathways. To validate these findings, knocked down vivo. studies, employed MTT, Transwell, flow cytometry, immunofluorescence assays monitor epithelial-mesenchymal transition (EMT) HK-2 cells. Additionally, electron microscopy Seahorse examine effects on mitochondrial structure function. Furthermore, overexpressed Ppara further confirm improves can improve pathological damage function; regulate blood lipids, inflammation oxidative stress indicators; reduce apoptosis tissues. Joint protein metabolomics analyses revealed that two lipid metabolism-related (the PPAR signalling pathway linoleic acid pathway) were coenriched, involving six differential (Cyp2e1, Cyp4a10, Gk, Lpl, Ppara, Pck1) differentially abundant (alpha-Dimorphecolic 12,13-EpOME). Western blot verify expressed proteins. improved accumulation, as demonstrated transmission (TEM) analysis Oil Red O staining. Knockdown affected expression ACOX1 exacerbated RF. In verification significantly inhibited EMT cells overexpression promoted HD-mediated regulation function, reduced apoptosis, ameliorate through protein-serum coexpression, pathway, metabolism. HD-induced upregulation metabolism, function are mechanisms. Ppara/ACOX1/TGF-β1 axis may an this process. These findings offer potential targets future development therapeutic strategies drugs.

Language: Английский

Time-course cross-species transcriptomics reveals conserved hepatotoxicity pathways induced by repeated administration of cyclosporine A

Toxicology Mechanisms and Methods, Journal Year: 2024, Volume and Issue: 34(9), P. 1010 - 1021

Published: June 27, 2024

Cyclosporine A (CsA) has shown efficacy against immunity-related diseases despite its toxicity in various organs, including the liver, emphasizing need to elucidate underlying hepatotoxicity mechanism. This study aimed capture alterations genome-wide expression over time and subsequent perturbations of corresponding pathways across species. Six data from humans, mice, rats, animal liver tissue, human microtissues, two cell lines exposed CsA toxic dose, were used. The microtissue for 10 d was analyzed obtain dynamically differentially expressed genes (DEGs). Single-time points at 1, 3, 5, 7, 28 different species used provide additional evidence. Using microtissue-based longitudinal design, DEGs that consistently up- or down-regulated captured, well-known mechanism involved elucidated. Thirty changed also altered 28-d rat in-house with concordant expression. Some (e.g.

Language: Английский