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<p>Ulcerative Colitis (UC) is a chronic illness that commonly demands the use of medication, sometimes for long term. In a DSS mouse model, we examined 5-aminosalicylic acid (5ASA) in comparison to a defined polyphenol-rich herbal mixture CSPG: <i>Cirsium japonicum</i>,<i> Scutellaria baicalensis</i>,<i> Paeonia japonica</i>, and <i>Glycyrrhizae radix</i>, using a two-phase approach. In phase 1 (days 1–14, without DSS stimulation), the herbal formula CSPG produced a more gut-friendly preventive profile compared to 5ASA in non-inflammatory condition:Unlike 5-ASA, which decreases microbial diversity as previously reported, CSPG preserved overall diversity and maintained protective taxa such as Ruminococcaceae uncultured ; and reduced inflammatory metabolites (uracil, glyceric acid, succinic acid) more effectively than 5ASA. Next, in phase 2 (days 15–24, with DSS inflammatory stimulation), CSPG matched first-line 5-ASA in suppressing inflammation (reduced colon shortening and procalcitonin). Its PI3K–Akt upregulation—together with NF-κB repression—was associated with more continuous ZO-1/ZO-2/occludin proteins expression and normalization of claudin-2 and MUC1/MUC2/MUC4, indicating barrier-repair capacity, a result supported by in vitro HT-29 experiments. Simultaneously, CSPG corrected DSS-induced dysbiosis more effectively than 5ASA: it increased SCFA-linked taxa (<i>Prevotellaceae UCG-001</i> and <i>Ruminococcus</i>; 5ASA also rose but to a lesser extent), and reduced inflammation-associated groups ( <i>[Eubacterium] siraeum group</i>, and <i>Erysipelotrichaceae</i>). CSPG restored SCFAs and elevated glycine, proline, pyruvate, and myo-inositol, while reducing succinate and uracil—with stronger effects than 5-ASA for pyruvate, myo-inositol, and succinate, and comparable effects for butyrate. Although CSPG is not a single-target, rationally designed drug like 5ASA, it achieved comparable anti-inflammatory and barrier-repair effects and, unlike 5ASA, also improved gut microbiota composition and metabolite profiles, indicating potential advantages for long-term UC management.</p>

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Multi-aspect therapeutic effects of a polyphenolic herbal formulation Cirsium japonicum, Scutellaria baicalensis, Paeonia japonica, and Glycyrrhiza uralensis on ulcerative colitis: inflammation modulation, gut microbiota remodeling, and metabolite profiling

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  • 发表日期：

    2026年1月3日

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  • Cha-Kyung Youn,
  • Sang-Mi Kang,
  • Eun-Ju Kim,
  • Seung-ho Seo,
  • Ju-Yeong Myeong,
  • Huy Hieu Phung,
  • Cong Duc Nguyen,
  • Yanghee You,
  • Hong-Seok Son,
  • Chang-Su Na

摘要

Ulcerative Colitis (UC) is a chronic illness that commonly demands the use of medication, sometimes for long term. In a DSS mouse model, we examined 5-aminosalicylic acid (5ASA) in comparison to a defined polyphenol-rich herbal mixture CSPG: Cirsium japonicum, Scutellaria baicalensis, Paeonia japonica, and Glycyrrhizae radix, using a two-phase approach. In phase 1 (days 1–14, without DSS stimulation), the herbal formula CSPG produced a more gut-friendly preventive profile compared to 5ASA in non-inflammatory condition:Unlike 5-ASA, which decreases microbial diversity as previously reported, CSPG preserved overall diversity and maintained protective taxa such as Ruminococcaceae uncultured ; and reduced inflammatory metabolites (uracil, glyceric acid, succinic acid) more effectively than 5ASA. Next, in phase 2 (days 15–24, with DSS inflammatory stimulation), CSPG matched first-line 5-ASA in suppressing inflammation (reduced colon shortening and procalcitonin). Its PI3K–Akt upregulation—together with NF-κB repression—was associated with more continuous ZO-1/ZO-2/occludin proteins expression and normalization of claudin-2 and MUC1/MUC2/MUC4, indicating barrier-repair capacity, a result supported by in vitro HT-29 experiments. Simultaneously, CSPG corrected DSS-induced dysbiosis more effectively than 5ASA: it increased SCFA-linked taxa (Prevotellaceae UCG-001 and Ruminococcus; 5ASA also rose but to a lesser extent), and reduced inflammation-associated groups ( [Eubacterium] siraeum group, and Erysipelotrichaceae). CSPG restored SCFAs and elevated glycine, proline, pyruvate, and myo-inositol, while reducing succinate and uracil—with stronger effects than 5-ASA for pyruvate, myo-inositol, and succinate, and comparable effects for butyrate. Although CSPG is not a single-target, rationally designed drug like 5ASA, it achieved comparable anti-inflammatory and barrier-repair effects and, unlike 5ASA, also improved gut microbiota composition and metabolite profiles, indicating potential advantages for long-term UC management.