2. Academic Validation
  3. Toosendanin alleviates dextran sulfate sodium-induced colitis by inhibiting M1 macrophage polarization and regulating NLRP3 inflammasome and Nrf2/HO-1 signaling

Toosendanin alleviates dextran sulfate sodium-induced colitis by inhibiting M1 macrophage polarization and regulating NLRP3 inflammasome and Nrf2/HO-1 signaling

  • Int Immunopharmacol. 2019 Nov;76:105909. doi: 10.1016/j.intimp.2019.105909.
Huining Fan 1,  Wei Chen 1,  Jinshui Zhu 2,  Jing Zhang 3,  Shiqiao Peng 4
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
  • 2 Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: [email protected].
  • 3 Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: [email protected].
  • 4 Department of Endocrinology and metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Disease, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 11001, PR China. Electronic address: [email protected].
PMID: 31520988 DOI: 10.1016/j.intimp.2019.105909
Abstract

Toosendanin (TSN), a triterpenoid extracted from the bark of fruit of Melia toosendan Sieb et Zucc, has been proven to have various biological activities including anti-inflammatory activity. But its effects on experimental colitis remain unreported. Herein, we investigated the role and potential mechanisms of TSN in dextran sulfate sodium (DSS) induced colitis in mice. The results showed that, TSN reduced colitis-associated disease activity index (DAI), shortened colon length, and weakened the pathological damage of the colon tissues in murine colitis models. Further studies disclosed that, TSN inhibited the secretion of proinflammatory cytokines and oxidative stress, and suppressed M1 macrophage polarization and the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome, but upregulated HO-1/Nrf2 expression in murine colitis. In addition, TSN maintained intestinal barrier by regulating zonula occludens-1 (ZO-1) and occludin expression. In conclusion, our findings demonstrated that, TSN alleviates DSS-induced experimental colitis by inhibiting M1 macrophage polarization and regulating NLRP3 inflammasome and Nrf2/HO-1 signaling, and may provide a novel Chinese patent medicine for the treatment of murine colitis.

Keywords

Colitis; Intestinal barrier; Macrophage; NLRP3 inflammasome; Nrf2/HO-1; Toosendanin.

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