Dioscin ameliorates murine ulcerative colitis by regulating macrophage polarization
Copyright © 2021. Published by Elsevier Ltd..
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-γ (INF-γ) 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-1α (HIF-1α) signaling and restrained glycolysis in RAW264.7; however, it activated mammalian target rapamycin complex 2 (mTORC2)/peroxisome proliferator-activated receptor-γ (PPAR-γ) 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-1α and mTORC2/PPAR-γ 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.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2021 |
---|---|
Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:172 |
---|---|
Enthalten in: |
Pharmacological research - 172(2021) vom: 15. Okt., Seite 105796 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Wu, Mei-Mei [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 03.03.2022 Date Revised 03.03.2022 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1016/j.phrs.2021.105796 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM328881201 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM328881201 | ||
003 | DE-627 | ||
005 | 20231225203910.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231225s2021 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.phrs.2021.105796 |2 doi | |
028 | 5 | 2 | |a pubmed24n1096.xml |
035 | |a (DE-627)NLM328881201 | ||
035 | |a (NLM)34343656 | ||
035 | |a (PII)S1043-6618(21)00380-7 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Wu, Mei-Mei |e verfasserin |4 aut | |
245 | 1 | 0 | |a Dioscin ameliorates murine ulcerative colitis by regulating macrophage polarization |
264 | 1 | |c 2021 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 03.03.2022 | ||
500 | |a Date Revised 03.03.2022 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2021. Published by Elsevier Ltd. | ||
520 | |a 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-γ (INF-γ) 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-1α (HIF-1α) signaling and restrained glycolysis in RAW264.7; however, it activated mammalian target rapamycin complex 2 (mTORC2)/peroxisome proliferator-activated receptor-γ (PPAR-γ) 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-1α and mTORC2/PPAR-γ 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Dioscin | |
650 | 4 | |a Fatty acid oxidation | |
650 | 4 | |a Glycolysis | |
650 | 4 | |a Macrophage polarization | |
650 | 4 | |a Mammalian target of rapamycin | |
650 | 4 | |a Ulcerative colitis | |
650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
650 | 7 | |a Cytokines |2 NLM | |
650 | 7 | |a Hif1a protein, mouse |2 NLM | |
650 | 7 | |a Hypoxia-Inducible Factor 1, alpha Subunit |2 NLM | |
650 | 7 | |a PPAR gamma |2 NLM | |
650 | 7 | |a Pparg protein, mouse |2 NLM | |
650 | 7 | |a dioscin |2 NLM | |
650 | 7 | |a 3B95U4OLWV |2 NLM | |
650 | 7 | |a Dextran Sulfate |2 NLM | |
650 | 7 | |a 9042-14-2 |2 NLM | |
650 | 7 | |a Mechanistic Target of Rapamycin Complex 1 |2 NLM | |
650 | 7 | |a EC 2.7.11.1 |2 NLM | |
650 | 7 | |a Diosgenin |2 NLM | |
650 | 7 | |a K49P2K8WLX |2 NLM | |
700 | 1 | |a Wang, Qiu-Mei |e verfasserin |4 aut | |
700 | 1 | |a Huang, Bao-Yuan |e verfasserin |4 aut | |
700 | 1 | |a Mai, Chu-Tian |e verfasserin |4 aut | |
700 | 1 | |a Wang, Chun-Li |e verfasserin |4 aut | |
700 | 1 | |a Wang, Tian-Tian |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Xiao-Jun |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Pharmacological research |d 1992 |g 172(2021) vom: 15. Okt., Seite 105796 |w (DE-627)NLM012597384 |x 1096-1186 |7 nnns |
773 | 1 | 8 | |g volume:172 |g year:2021 |g day:15 |g month:10 |g pages:105796 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.phrs.2021.105796 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 172 |j 2021 |b 15 |c 10 |h 105796 |