2. Academic Validation
  3. Dioscin ameliorates murine ulcerative colitis by regulating macrophage polarization

Dioscin ameliorates murine ulcerative colitis by regulating macrophage polarization

  • Pharmacol Res. 2021 Oct;172:105796. doi: 10.1016/j.phrs.2021.105796.
Mei-Mei Wu 1,  Qiu-Mei Wang 2,  Bao-Yuan Huang 3,  Chu-Tian Mai 4,  Chun-Li Wang 5,  Tian-Tian Wang 6,  Xiao-Jun Zhang 7
Affiliations

Affiliations

  • 1 School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; Clinical Experimental Center, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen 529030, PR China. Electronic address: 905712541@qq.com.
  • 2 School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China. Electronic address: 2293023351@qq.com.
  • 3 School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China. Electronic address: 354204515@qq.com.
  • 4 State Key Laboratory for Quality Research in Chinese Medicines, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau. Electronic address: 514069804@qq.com.
  • 5 Guangxi Botanical Garden of Medicinal Plants, Xiangzhu Ave, Nanning 510663, PR China. Electronic address: 2420224310@qq.com.
  • 6 School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China. Electronic address: 826165151@qq.com.
  • 7 School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China. Electronic address: zhangxj@gzucm.edu.cn.
PMID: 34343656 DOI: 10.1016/j.phrs.2021.105796
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-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.

Keywords

Dioscin; Fatty acid oxidation; Glycolysis; Macrophage polarization; Mammalian target of rapamycin; Ulcerative colitis.

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