ArticleFrontiers in pharmacology2025
Dose-dependent immunotoxic mechanisms of celastrol via modulation of the PI3K-Akt signaling pathway.
Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Celastrol Activates HSF1 to Enhance Regulatory T Cells Function and Ameliorate Intestinal Inflammation.Biomolecules · 2025Article
- Photoprotective Effects of Quercetin and Hesperidin in Polymorphous Light Eruption: A Comparative Study with Alpha-Glucosylrutin.Current issues in molecular biology · 2025Article
- Potential active ingredients and mechanisms of Shufeitie ointment in the treatment of chronic obstructive pulmonary disease by integrating transdermal chemistry and network pharmacology.Frontiers in medicine · 2025Article
- Celastrol attenuates diabetic kidney disease progression by repressing senescence of renal tubular epithelial cells.Frontiers in aging · 2025Article
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Authors and funding
11 authors.
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Abstract
Ethnopharmacological relevance: Celastrol, a bioactive compound from Materials and methods: An integrative approach combining network toxicology, molecular docking, and experimental biology identified molecular targets in celastrol-induced immune dysfunction. Network toxicology mapped key pathways, and molecular docking predicted interactions with immune-related proteins. High-dose celastrol (10 mg/kg) was administered to C57BL/6J mice, followed by a histopathological analysis of the thymus and spleen. RNA-Seq evaluated gene expression in immune pathways, and IHC/mIHC validated PI3K-Akt signaling pathway protein expression. Results: Network toxicology identified the PI3K-Akt signaling pathway as a key target of celastrol's immunotoxic effects. High-dose celastrol caused histopathological damage in the thymus and spleen, including lymphocyte depletion and immune cell infiltration. RNA-Seq showed upregulation of critical genes in the PI3K-Akt signaling pathway (Egfr, Pik3c, Akt3), linked to cell proliferation and survival. IHC confirmed increased expression of EGFR, AKT, PIK3, and mTOR, with decreased PTEN. mIHC revealed elevated macrophage activation and inflammation. In contrast, low-dose celastrol suppressed PI3K-Akt signaling by downregulating mTOR, indicating dose-dependent modulation of immune function. Conclusion: Our study demonstrates the dose-dependent immunotoxic effects of celastrol, which is toxic in high doses caused by activation of the PI3K-Akt signaling pathway, while low doses offer protection by blocking this signaling pathway. These findings emphasize the importance of dose selection in therapeutic and safety contexts, enhancing understanding of celastrol's biological effects and its clinical potential in immune-related diseases.
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