Scholarlink

<p>Ulcerative colitis is a chronic inflammatory condition of the gastrointestinal tract, and new therapeutic strategies targeting specific molecular pathways are of great interest. This study evaluated the anti-inflammatory effect of epiisopiloturine, an imidazole alkaloid, in acetic acid-induced colitis in mice, with focus on the role of the type M1 muscarinic acetylcholine receptor. Molecular docking revealed a strong binding affinity between epiisopiloturine and this cholinergic receptor subtype (-8.44 ΔG (kcal/mol)). Colitis was induced with 6% acetic acid, followed by treatment with epiisopiloturine (0.01, 0.1 or 1&#xa0;mg/kg, <i>i.p.</i>), dexamethasone (2&#xa0;mg/kg, <i>s.c.</i>), pirenzepine (10&#xa0;mg/kg, <i>i.p</i>.) or vehicle. Epiisopiloturine at 0.1&#xa0;mg/kg significantly reduced macroscopic and histological damage. Biochemical analyses showed decreased myeloperoxidase activity, oxidative stress markers and levels of pro-inflammatory cytokines, cyclooxygenase-2, and inducible nitric oxide synthase. The co-administration of pirenzepine, a selective antagonist of the muscarinic acetylcholine receptor, reversed these protective effects, indicating that this receptor plays a critical role in the mechanism of action of epiisopiloturine. These findings demonstrate that epiisopiloturine exerts a significant anti-inflammatory effect through modulation of the cholinergic system, supporting its potential as a novel therapeutic candidate for the treatment of ulcerative colitis.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Epiisopiloturine Attenuates the Pro-inflammatory Effects of Experimental Colitis Through the M1 Muscarinic Acetylcholine Receptor

  • 期刊论文

  • 发表日期：

    2026年1月3日

查看全文
  • Viviane Pinheiro Alves de Almeida,
  • Tino Marcos Lino da Silva,
  • Diva de Aguiar Magalhães,
  • Ana Clara Coelho da Costa,
  • Fernando Mesquita de Sousa de Lima,
  • Antônio Kleiton de Sousa,
  • Rafael da Silva Prudêncio,
  • Anna Sofia Miranda Loiola Araújo,
  • Kayo Alves Figueiredo,
  • Even Herlany Pereira Alves,
  • Daniel Fernando Pereira Vasconcelos,
  • Daniel Dias Rufino Arcanjo,
  • Carlos Eduardo da Silva Monteiro,
  • Álvaro Xavier Franco,
  • Humberto Barbosa Costa Filho,
  • Pedro Marcos Gomes Soares,
  • José Roberto de Souza de Almeida Leite,
  • Leiz Maria Costa Veras,
  • Tarcisio Vieira de Brito,
  • André Luiz dos Reis Barbosa

摘要

Ulcerative colitis is a chronic inflammatory condition of the gastrointestinal tract, and new therapeutic strategies targeting specific molecular pathways are of great interest. This study evaluated the anti-inflammatory effect of epiisopiloturine, an imidazole alkaloid, in acetic acid-induced colitis in mice, with focus on the role of the type M1 muscarinic acetylcholine receptor. Molecular docking revealed a strong binding affinity between epiisopiloturine and this cholinergic receptor subtype (-8.44 ΔG (kcal/mol)). Colitis was induced with 6% acetic acid, followed by treatment with epiisopiloturine (0.01, 0.1 or 1 mg/kg, i.p.), dexamethasone (2 mg/kg, s.c.), pirenzepine (10 mg/kg, i.p.) or vehicle. Epiisopiloturine at 0.1 mg/kg significantly reduced macroscopic and histological damage. Biochemical analyses showed decreased myeloperoxidase activity, oxidative stress markers and levels of pro-inflammatory cytokines, cyclooxygenase-2, and inducible nitric oxide synthase. The co-administration of pirenzepine, a selective antagonist of the muscarinic acetylcholine receptor, reversed these protective effects, indicating that this receptor plays a critical role in the mechanism of action of epiisopiloturine. These findings demonstrate that epiisopiloturine exerts a significant anti-inflammatory effect through modulation of the cholinergic system, supporting its potential as a novel therapeutic candidate for the treatment of ulcerative colitis.

Graphical Abstract