Astragaloside IV Alleviates the Experimental DSS-Induced Colitis by Remodeling Macrophage Polarization Through STAT Signaling
Open Access
- 13 September 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic and relapsing intestinal inflammation, which currently lacks safe and effective medicine. Some previous studies indicated that Astragaloside IV (AS-IV), a natural saponin extracted from the traditional Chinese medicine herb Ligusticum chuanxiong, alleviates the experimental colitis symptoms in vitro and in vivo. However, the mechanism of AS-IV on IBD remains unclear. Accumulating evidence suggests that M2-polarized intestinal macrophages play a pivotal role in IBD progression. Here, we found that AS-IV attenuated clinical activity of DSS-induced colitis that mimics human IBD and resulted in the phenotypic transition of macrophages from immature pro-inflammatory macrophages to mature pro-resolving macrophages. In vitro, the phenotype changes of macrophages were observed by qRT-PCR after bone marrow-derived macrophages (BMDMs) were induced to M1/M2 and incubated with AS-IV, respectively. In addition, AS-IV was effective in inhibiting pro-inflammatory macrophages and promoting the pro-resolving macrophages to ameliorate experimental colitis via the regulation of the STAT signaling pathway. Hence, we propose that AS-IV can ameliorate experimental colitis partially by modulating macrophage phenotype by remodeling the STAT signaling, which seems to have an essential function in the ability of AS-IV to alleviate the pathological progress of IBD.This publication has 55 references indexed in Scilit:
- Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6Chi monocyte precursorsMucosal Immunology, 2013
- Efficacy of drugs used in the treatment of IBD and combinations thereof in acute DSS-induced colitis in miceLife Sciences, 2013
- Rebuilding the balance of STAT1 and STAT3 signalings by fusaruside, a cerebroside compound, for the treatment of T-cell-mediated fulminant hepatitis in miceBiochemical Pharmacology, 2012
- JAK and STAT Signaling Molecules in Immunoregulation and Immune-Mediated DiseaseImmunity, 2012
- A Novel Role for Interleukin-27 (IL-27) as Mediator of Intestinal Epithelial Barrier Protection Mediated via Differential Signal Transducer and Activator of Transcription (STAT) Protein Signaling and Induction of Antibacterial and Anti-inflammatory ProteinsOnline Journal of Public Health Informatics, 2012
- Transcriptional regulation of macrophage polarization: enabling diversity with identityNature Reviews Immunology, 2011
- Interleukin-19 protects mice from innate-mediated colonic inflammationInflammatory Bowel Diseases, 2010
- Neutrophil Apoptosis: Relevance to the Innate Immune Response and Inflammatory DiseaseJournal of Innate Immunity, 2010
- Hyaluronan-Mediated Leukocyte Adhesion and Dextran Sulfate Sodium-Induced Colitis Are Attenuated in the Absence of Signal Transducer and Activator of Transcription 1The American Journal of Pathology, 2008
- Role of Stat3 in suppressing anti-tumor immunityCurrent Opinion in Immunology, 2008