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黄芩苷通过调节鸟氨酸脱羧酶1/核因子κB通路和氧化应激减轻慢性急性应激诱导的大鼠肠易激综合征样症状。

Baicalein alleviates chronic acute stress-induced irritable bowel syndrome-like symptoms in rats via modulating the ODC1/NF-κB pathway and oxidative stress.

作者信息

Lin Han, Lv Yunlong, Liu Huacheng, Lin Zheng, Zhu Ning, Huang Bingwu

机构信息

Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, People's Republic of China.

Department of Cardiology, The Third Affiliated Hospital of Shanghai University (Wenzhou People's Hospital), The Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, No. 299 Guan Road, Wenzhou, 325000, Zhejiang Province, People's Republic of China.

出版信息

Biochem Biophys Res Commun. 2025 May 20;771:152058. doi: 10.1016/j.bbrc.2025.152058.

Abstract

BACKGROUND

As a persistent gastrointestinal disorder, irritable bowel syndrome (IBS) influences the gut-brain connection, leading to abdominal pain and altered bowel irregularities. Baicalein, a flavonoid extracted from Scutellaria baicalensis, is frequently utilized in anti-inflammatory treatments. This study aimed to explore baicalein's effectiveness in mitigating IBS symptoms triggered by both chronic and acute stress (CAS) and to uncover its fundamental mechanisms.

METHODS

Sprague-Dawley rats were employed to develop an IBS rat model by inducing CAS for five weeks. Each rat was randomly allocated to one of four experimental groups: model (M), low-dose baicalein (L), high-dose baicalein (H), and control (C). Baicalein was orally administered throughout the experiment. Behavioral assessments were conducted, including forced swimming, marble-burying, intestinal motility, and visceral sensitivity tests. Colonic tissues were collected for histopathological examination, evaluation of oxidative stress (MDA and SOD levels), and analysis of inflammatory cytokines, and ODC1/NF-κB pathway activation using Western blot assay, ELISA, and immunofluorescence.

RESULTS

Baicalein treatment notably ameliorated IBS-like symptoms, such as fecal pellet output and AWR scores, by alleviating stress-induced behavioral changes. Baicalein bolstered antioxidant defenses through boosting SOD activity and lowering MDA levels. Moreover, baicalein inhibited inflammatory responses, targeting IL-6, IL-1β, and TNF-α, while suppressing the expression of ODC1 and restraining NF-κB p65 phosphorylation within the colon. These results indicate that baicalein modulates oxidative stress and inflammation in CAS-associated IBS.

CONCLUSION

Baicalein demonstrates protection against CAS-induced IBS by diminishing intestinal inflammation, oxidative damage, and visceral hypersensitivity via suppression of the ODC1/NF-κB pathway. These findings underscore baicalein's potential as a therapeutic approach for IBS.

摘要

背景

作为一种持续性胃肠道疾病,肠易激综合征(IBS)影响肠脑联系,导致腹痛和肠道功能紊乱。黄芩素是从黄芩中提取的一种黄酮类化合物,常用于抗炎治疗。本研究旨在探讨黄芩素缓解慢性和急性应激(CAS)引发的IBS症状的有效性,并揭示其基本机制。

方法

采用Sprague-Dawley大鼠,通过诱导CAS五周建立IBS大鼠模型。将每只大鼠随机分配到四个实验组之一:模型组(M)、低剂量黄芩素组(L)、高剂量黄芩素组(H)和对照组(C)。在整个实验过程中口服给予黄芩素。进行行为评估,包括强迫游泳、埋大理石、肠道蠕动和内脏敏感性测试。收集结肠组织进行组织病理学检查、氧化应激评估(丙二醛和超氧化物歧化酶水平)、炎症细胞因子分析以及使用蛋白质印迹分析、酶联免疫吸附测定和免疫荧光法分析鸟氨酸脱羧酶1/核因子κB通路激活情况。

结果

黄芩素治疗通过减轻应激诱导的行为变化,显著改善了IBS样症状,如粪便颗粒排出量和腹壁撤离反射评分。黄芩素通过提高超氧化物歧化酶活性和降低丙二醛水平增强抗氧化防御。此外,黄芩素抑制炎症反应,作用于白细胞介素-6、白细胞介素-1β和肿瘤坏死因子-α,同时抑制结肠内鸟氨酸脱羧酶1的表达并抑制核因子κB p65磷酸化。这些结果表明黄芩素调节CAS相关IBS中的氧化应激和炎症。

结论

黄芩素通过抑制鸟氨酸脱羧酶1/核因子κB通路减轻肠道炎症、氧化损伤和内脏超敏反应,从而对CAS诱导的IBS具有保护作用。这些发现强调了黄芩素作为IBS治疗方法的潜力。

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