Astragaloside IV regulates differentiation and induces apoptosis of activated CD4+ T cells in the pathogenesis of experimental autoimmune encephalomyelitis.

Abstract

CD4+ T cells, especially T-helper (Th) cells (Th1, Th2 and Th17) and regulatory T cells (Treg) play pivotal role in the pathogenesis of multiple sclerosis (MS), a demyelinating autoimmune disease occurring in central nervous system (CNS). Astragaloside IV (ASI, CAS: 84687-43-4) is one of the saponins isolated from Astragalus membranceus, a traditional Chinese medicine with immunomodulatory effect. So far, whether ASI has curative effect on experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and how it affects the subsets of CD4+ T cells, as well as the underlying mechanism have not been clearly elucidated. In the present study, ASI was found to ameliorate the progression and hamper the recurrence of EAE effectively in the treatment regimens. It significantly reduced the demyelination and inflammatory infiltration of CNS in EAE mice by suppressing the percentage of Th1 and Th17 cells, which was closely associated with the inhibition of JAK/STAT and NF-κB signaling pathways. ASI also increased the percentage of Treg cells in spleen and CNS, which was accompanied by elevated Foxp3. However, in vitro experiments disclosed that ASI could regulate the differentiation of Th17 and Treg cells but not Th1 cells. In addition, it induced the apoptosis of MOG-stimulated CD4+ T cells probably through modulating STAT3/Bcl-2/Bax signaling pathways. Together, our findings suggested that ASI can modulate the differentiation of autoreactive CD4+ T cells and is a potential prodrug or drug for the treatment of MS and other similar autoimmune diseases.

• Authors: Liu Yang, Faping Xing, Xinyan Han, Qi Li, Hui Wu, Hailian Shi, Zhifei Wang, Fei Huang, Xiaojun Wu
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 362 Pg. 105-115 (01 01 2019) ISSN: 1096-0333 [Electronic] United States
• PMID: 30385269 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018. Published by Elsevier Inc.

Chemical References

• NF-kappa B
• STAT Transcription Factors
• Saponins
• Triterpenes
• astragaloside A
• Janus Kinases

Topics

• Animals
• Apoptosis (drug effects)
• CD4-Positive T-Lymphocytes (drug effects, immunology, metabolism)
• Cell Differentiation (drug effects)
• Encephalomyelitis, Autoimmune, Experimental (immunology, metabolism)
• Female
• Janus Kinases (metabolism)
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• STAT Transcription Factors (metabolism)
• Saponins (pharmacology)
• Triterpenes (pharmacology)