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<p>Ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), is characterised by oxidative stress (OS), and inflammation with infiltration of macrophages in colonic tissue. Effective remedies are lacking, highlighting the requirement for novel anti-inflammatory compounds with antioxidant properties to prevent UC. An eminent flavonoid sanggenol L (SL) is sequestered from the root bark of <i>Morus alba (Mulberry)</i>. Mulberry extracts are reported as having anti-UC activity. SL exhibited anti-oxidative, anti-diabetic, anti-inflammatory, and anti-cancer activities. Hence, we intended to evaluate the role of SL on dextran sulfate sodium (DSS)-induced oxidative damage, intestinal barrier integrity, and inflammatory signalling. Mice were separated into four sets: normal control, DSS-induced, DSS+SL (25 mg/kg bw), and DSS + SL (50 mg/kg bw). UC was developed to assess body weight, colon length, cytokines, toxicity markers, OS markers, colon, kidney, and liver histopathology, and RT-PCR. Administration of SL (25 and 50 mg/kg bw) reduced the UC-related symptoms such as weight loss, colon shortening, OS, inflammatory mediators, neutrophil infiltration, and histopathological changes in a quantity-related manner. SL recovered the liver and kidney by normalize the levels of AST, ALT, BUN and Cr in serum and colon tissue. SL treatment enhanced mRNAs present in the tight junction (TJ), thus strengthening the membrane integrity of the intestinal epithelial barrier. Furthermore, SL could trigger Nrf2/HO-1 signalling, thus enhancing antioxidant status, while suppressing TLR4/p65 signalling to reduce DSS-induced inflammation and OS in mouse models.</p>

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Sanggenol L Regulates Nrf2/HO-1/p65 Signalling Pathways via Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice

  • 期刊论文

  • 发表日期：

    2026年7月20日

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  • Tao Qi,
  • Yongyong Chen,
  • Shaohua Wang,
  • Periyannan Velu,
  • Vijayalakshmi Annamalai,
  • Kang Wu

摘要

Ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), is characterised by oxidative stress (OS), and inflammation with infiltration of macrophages in colonic tissue. Effective remedies are lacking, highlighting the requirement for novel anti-inflammatory compounds with antioxidant properties to prevent UC. An eminent flavonoid sanggenol L (SL) is sequestered from the root bark of Morus alba (Mulberry). Mulberry extracts are reported as having anti-UC activity. SL exhibited anti-oxidative, anti-diabetic, anti-inflammatory, and anti-cancer activities. Hence, we intended to evaluate the role of SL on dextran sulfate sodium (DSS)-induced oxidative damage, intestinal barrier integrity, and inflammatory signalling. Mice were separated into four sets: normal control, DSS-induced, DSS+SL (25 mg/kg bw), and DSS + SL (50 mg/kg bw). UC was developed to assess body weight, colon length, cytokines, toxicity markers, OS markers, colon, kidney, and liver histopathology, and RT-PCR. Administration of SL (25 and 50 mg/kg bw) reduced the UC-related symptoms such as weight loss, colon shortening, OS, inflammatory mediators, neutrophil infiltration, and histopathological changes in a quantity-related manner. SL recovered the liver and kidney by normalize the levels of AST, ALT, BUN and Cr in serum and colon tissue. SL treatment enhanced mRNAs present in the tight junction (TJ), thus strengthening the membrane integrity of the intestinal epithelial barrier. Furthermore, SL could trigger Nrf2/HO-1 signalling, thus enhancing antioxidant status, while suppressing TLR4/p65 signalling to reduce DSS-induced inflammation and OS in mouse models.