Toosendanin inhibits T-cell proliferation through the P38 MAPK signalling pathway.
Eur J Pharmacol
; 973: 176562, 2024 Jun 15.
Article
en En
| MEDLINE
| ID: mdl-38588767
ABSTRACT
In recent years, immunosuppressants have shown significant success in the treatment of autoimmune diseases. Therefore, there is an urgent need to develop additional immunosuppressants that offer more options for patients. Toosendanin has been shown to have immunosuppressive activity in vitro as well as effects on autoimmune hepatitis (AIH) in vivo. Toosendanin did not induce apoptosis in activated T-cells and affect the survival rate of naive T-cells. Toosendanin did not affect the expression of CD25 or secretion of IL-2 by activated T-cells, and not affect the expression of IL-4 and INF-γ. Toosendanin did not affect the phosphorylation of STAT5, ERK, AKT, P70S6K. However, toosendanin inhibited proliferation of anti-CD3/anti-CD28 mAbs-activated T-cells with IC50 of (10 ± 2.02) nM. Toosendanin arrested the cell cycle in the G0/G1 phase, significantly inhibited IL-6 and IL-17A secretion, promoted IL-10 expression, and inhibited the P38 MAPK pathway. Finally, toosendanin significantly alleviated ConA-induced AIH in mice. In Summary, toosendanin exhibited immunosuppressive activity in vivo and in vitro. Toosendanin inhibits the proliferation of activated T-cells through the P38 MAPK signalling pathway, significantly suppresses the expression of inflammatory factors, enhances the expression of anti-inflammatory factors, and effectively alleviates ConA-induced AIH in mice, suggesting that toosendanin may be a lead compound for the development of novel immunomodulatory agents with improved efficacy and reduced toxicity.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Triterpenos
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Medicamentos Herbarios Chinos
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Linfocitos T
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Proteínas Quinasas p38 Activadas por Mitógenos
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Proliferación Celular
Límite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
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Eur. j. pharmacol
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European journal of pharmacology
Año:
2024
Tipo del documento:
Article