Zhao Xin, He Meng-Jiao, Zhao Meng, Li Hao-Ran, Zhuang Zi-Ming, Xing Yue, Zhang Xue-Lan, Zhao Pan
Medical School, Shandong Xiehe University, Jinan, 250109, PR China; Department of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China.
Department of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China.
J Ethnopharmacol. 2025 Apr 25;346:119661. doi: 10.1016/j.jep.2025.119661. Epub 2025 Mar 20.
Polygala tenuifolia Willd. (pharmacologically termed Polygalae Radix, PR), a nootropic botanical in traditional Chinese medicine, demonstrates anxiolytic and cognitive-enhancing properties with two millennia of documented therapeutic applications. Long-term or large-dose use of crude Polygalae Radix (CPR) causes intestinal injury, which could be reduced by use of Glycyrrhiza uralensis Fisch. (licorice) decoction-boiled Polygalae Radix. However, the effects of boiling CPR with licorice decoction on reducing intestinal mucosal barrier injury have not been studied.
Our research mainly focused on the alleviating effects and underlying mechanism of CPR after boiling with licorice decoction on intestinal mucosal barrier injury in rats.
SD rats were orally administered CPR and licorice decoction-boiled PR (LPR) extracts respectively for 15 consecutive days. Subsequently, levels of pro-inflammatory cytokines and immunoglobulins were measured, and histopathological changes in intestinal tissues were examined. The mRNA expression levels of pro-inflammatory cytokines were evaluated by qRT-PCR. The expression difference of TLR4/NF-κB signaling pathway key protein and tight junction (TJ) protein were evaluated using Western blotting and immunohistochemistry.
Processing PR with licorice decoction significantly ameliorated the downregulation of intestinal TJ proteins (occludin, claudin-1, and ZO-1) and elevated serum lipopolysaccharide levels induced by CPR. It alleviated the suppression of intestinal immunoglobulin A, serum immunoglobulin A and immunoglobulin G levels caused by CPR while mitigating intestinal mucosal injury and inflammatory responses. Additionally, processing PR with licorice decoction inhibited CPR-triggered upregulation of TLR4, NF-κB p65, p-NF-κB p65, and p-κBα proteins expression, while preventing IκBα downregulation in intestinal tissues. Furthermore, it significantly suppressed the upregulation of interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) mRNA expression while concurrently inhibiting the secretion levels of these pro-inflammatory cytokines in small intestine.
Our experimental data suggest that licorice decoction boiling effectively prevents CPR-induced reductions in TJ proteins and immunoglobulins expression, alleviates intestinal mucosal barrier injuries, and mediates these effects through suppression of TLR4/NF-κB signaling pathway activation and subsequent production of IL-6, IL-8, and TNF-α.
远志（药理学上称为远志根，PR）是一种传统中药中的益智植物，已有两千年的治疗应用记录，具有抗焦虑和增强认知的特性。长期或大剂量使用生远志根（CPR）会导致肠道损伤，而使用甘草汤煮远志根可减轻这种损伤。然而，甘草汤煮远志根对减轻肠黏膜屏障损伤的作用尚未得到研究。
我们的研究主要聚焦于甘草汤煮远志根对大鼠肠黏膜屏障损伤的缓解作用及潜在机制。
将SD大鼠分别连续15天口服给予CPR和甘草汤煮远志根（LPR）提取物。随后，检测促炎细胞因子和免疫球蛋白水平，并检查肠道组织的组织病理学变化。通过qRT-PCR评估促炎细胞因子的mRNA表达水平。使用蛋白质免疫印迹法和免疫组织化学评估TLR4/NF-κB信号通路关键蛋白和紧密连接（TJ）蛋白的表达差异。
用甘草汤处理远志根可显著改善CPR诱导的肠TJ蛋白（闭合蛋白、 Claudin-1和ZO-1）下调以及血清脂多糖水平升高。它减轻了CPR引起的肠道免疫球蛋白A、血清免疫球蛋白A和免疫球蛋白G水平的抑制，同时减轻了肠黏膜损伤和炎症反应。此外，用甘草汤处理远志根可抑制CPR触发的TLR4、NF-κB p65、p-NF-κB p65和p-κBα蛋白表达上调，同时防止肠道组织中IκBα下调。此外，它还显著抑制白细胞介素（IL）-6、IL-8和肿瘤坏死因子-α（TNF-α）mRNA表达上调，同时抑制小肠中这些促炎细胞因子的分泌水平。
我们的实验数据表明，甘草汤煮远志根可有效防止CPR诱导的TJ蛋白和免疫球蛋白表达降低，减轻肠黏膜屏障损伤，并通过抑制TLR4/NF-κB信号通路激活以及随后产生IL-6、IL-8和TNF-α来介导这些作用。
