ReferenceID 5127
Dioscin ameliorates murine ulcerative colitis by regulating macrophage polarization
Pharmacol Res
Restoring immune balance by targeting macrophage polarization is a potentially valuable therapeutic strategy for ulcerative colitis (UC). Dioscin is a steroidal saponin with potent anti-inflammatory, immunoregulatory, an
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 5127
- Evidence Id
- 21717
- Core Evidence Id
- 21717
- Source Reference Id
- 3537
- Herb2 Reference Id
- HBREF004334
- Subject Paper Key
- HBIN024134_34343656
- Pubmed Id
- 34343656
- Doi
- 10.1016/j.phrs.2021.105796
- Paper Title
- Dioscin ameliorates murine ulcerative colitis by regulating macrophage polarization
- Paper Abstract
- Restoring immune balance by targeting macrophage polarization is a potentially valuable therapeutic strategy for ulcerative colitis (UC). Dioscin is a steroidal saponin with potent anti-inflammatory, immunoregulatory, and hypolipidemic effects. This study examined the protective effect of Dioscin on UC in mice and explored the underlying mechanisms. Mice were induced colitis by dextran sulfate sodium (DSS) and concurrently treated with Dioscin oral administration. RAW264.7 cells were skewed to M1 macrophage polarization by lipopolysaccharide (LPS) and interferon-gamma (INF-gamma) in vitro, and received Dioscin treatment. The results showed that Dioscin ameliorated colitis in mice, reduced macrophage M1 polarization, but markedly promoted M2 polarization in mice colon. Dioscin inhibited mammalian target rapamycin complex 1 (mTORC1)/hypoxia-inducible factor-1alpha (HIF-1alpha) signaling and restrained glycolysis in RAW264.7; however, it activated mammalian target rapamycin complex 2 (mTORC2)/peroxisome proliferator-activated receptor-gamma (PPAR-gamma) signal and facilitated fatty acid oxidation (FAO). The modulation of mTORs signaling may inhibit M1, but promote M2 polarization. Furthermore, the effect of Dioscin on M2 polarization was neutralized by the FAO inhibitor Etomoxir and the mTORC2 inhibitor JR-AB2-011. In parallel, the inhibitory effect of Dioscin on M1 polarization was mitigated by the mTORC1 agonist L-leucine. Both JR-AB2-011 and L-leucine blocked the therapeutic effect of Dioscin in mice with UC. Therefore, Dioscin ameliorated UC in mice, possibly by restraining M1, while skewing M2 polarization of macrophages. Regulation of mTORC1/HIF-1alpha and mTORC2/PPAR-gamma signals is a possible mechanism by which Dioscin inhibited aerobic glycolysis and promoted FAO of macrophages. In summary, Dioscin protected mice against DSS-induced UC by regulating mTOR signaling, thereby adjusting macrophage metabolism and polarization.
- Journal
- Pharmacol Res
- Publish Year
- 2021
- Experiment Subject
- mouse; raw264.7 cells
- Experiment Type
- Animal Experiment
- Phenotype Related
- Ulcerative Colitis; Colitis
- Paper Title Cn
- Paper Title En
- Dioscin ameliorates murine ulcerative colitis by regulating macrophage polarization
- Bilingual Status
- semi_complete