Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
Phytomedicine. 2024 Dec;135:156167. doi: 10.1016/j.phymed.2024.156167. Epub 2024 Oct 19.
Visceral hypersensitivity is a therapy-resistant hallmark of irritable bowel syndrome (IBS). Many IBS patients' symptoms develop following an acute colitis, and most report that stress worsens symptoms. STW 5-II, a combination of six herbal extracts, is a clinically proven treatment for IBS, but the mechanism is uncertain. Here, we employ two well-characterized rodent models to test the hypothesis that STW 5-II attenuates chronic colonic hypersensitivity.
Separate cohorts of male rats were used for each model of colonic hypersensitivity. The first model used repeated water avoidance stress (1hr/day for 10 days), while the second model used intracolonic trinitrobenzene sulfonic acid to induce a short-lived colitis followed by post-inflammatory visceral hypersensitivity. Both models used sham treatment controls. Colonic sensitivity was quantified as the number of abdominal contractions to graded pressures (20-60 mmHg) of isobaric colorectal distension (CRD). Phosphorylation of extracellular signal-regulated kinase (pERK) was assessed via immunohistochemistry in the brain, spinal cord, and dorsal root ganglion (DRG). STW 5-II (10 ml/kg, p.o.) or vehicle (p.o.) was administered for 7 days, prior to CRD and pERK expression.
Rats exposed to either model developed significant colonic hypersensitivity. Both models enhanced CRD-evoked pERK in DRGs, spinal cord, and brain. STW 5-II decreased colonic hypersensitivity and reduced CRD-evoked brain, spinal, and DRG pERK.
Both models induced colonic hypersensitivity and enhanced pERK expression. STW 5-II inhibited colonic hypersensitivity and decreased noxious neuronal activation in both models, which could explain its clinically proven efficacy in relieving visceral hypersensitivity-related symptoms in IBS.
内脏敏感性是肠易激综合征（IBS）的一种治疗抵抗标志。许多 IBS 患者的症状是在急性结肠炎后发展而来的，大多数患者报告说压力会使症状恶化。STW 5-II 是一种由六种草药提取物组成的组合药物，已被临床证明可用于治疗 IBS，但机制尚不清楚。在这里，我们使用两种经过充分验证的啮齿动物模型来测试 STW 5-II 减轻慢性结肠高敏感性的假设。
分别使用雄性大鼠的两个队列进行每个结肠高敏感性模型的研究。第一个模型使用重复的水回避应激（每天 1 小时，持续 10 天），而第二个模型使用三硝基苯磺酸诱导短暂的结肠炎，然后引起炎症后内脏高敏感性。这两个模型都使用假手术对照组。结肠敏感性通过等压结直肠扩张（CRD）的分级压力（20-60mmHg）下的腹部收缩次数来量化。通过免疫组织化学评估大脑、脊髓和背根神经节（DRG）中的细胞外信号调节激酶（pERK）磷酸化。在 CRD 和 pERK 表达之前，给予 STW 5-II（10ml/kg，po）或载体（po）治疗 7 天。
暴露于任一模型的大鼠均发展出明显的结肠高敏感性。两种模型均增强了 DRG、脊髓和大脑中 CRD 诱发的 pERK。STW 5-II 降低了结肠高敏感性并减少了 CRD 诱发的大脑、脊髓和 DRG pERK。
两种模型均诱导结肠高敏感性并增强 pERK 表达。STW 5-II 抑制结肠高敏感性并减少两种模型中有害神经元的激活，这可以解释其在缓解 IBS 相关内脏高敏感性症状方面的临床疗效。
