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基于网络药理学和实验验证的臭椿皮治疗溃疡性结肠炎机制研究。

Investigation of the mechanism of Bark of Ailanthus altissima in the treatment of ulcerative colitis based on network pharmacology and experimental verification.

机构信息

The College of Life Sciences, Northwest University, 710069, Xi'an, Shaanxi, China.

Department of Chinese Materia Medica and Natural Medicines, Air Force Medical University, 710032, Xi'an, Shaanxi, China.

出版信息

J Ethnopharmacol. 2025 Jan 30;337(Pt 2):118916. doi: 10.1016/j.jep.2024.118916. Epub 2024 Oct 10.

DOI:10.1016/j.jep.2024.118916
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

The bark of Ailanthus altissima (Mill.) Swingle (BAA), a widely used Chinese medicinal herb in traditional remedies for bowel disorders, has yet to be explored in the context of ulcerative colitis (UC), and its therapeutic mechanisms remain unclear.

AIM OF THE STUDY

This study integrated network pharmacology and experimental validation to investigate the effects and underlying mechanisms of BAA in treating UC.

MATERIALS AND METHODS

First, UPLC-MS/MS analysis was employed to identify the chemical constituents of BAA. Network pharmacology was then applied to analyze the potential mechanisms of BAA based on these identified compounds. Lastly, a dextran sulfate sodium (DSS)-induced UC mouse model was utilized to assess BAA's therapeutic efficacy, with Western blotting performed to examine changes in protein expression within the key pathway influenced by BAA.

RESULTS

UPLC-MS/MS and SwissADME analysis identified 223 active compounds in BAA. Network pharmacology suggested that the PI3K/AKT pathway may serve as a primary mechanism by which BAA exerts its anti-UC effects. In the DSS-induced UC mouse model, BAA significantly mitigated colonic injury, reduced DAI scores, and promoted weight recovery in mice. Additionally, BAA downregulated pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, thereby suppressing inflammatory responses in the colon. Western blot analysis further demonstrated that BAA primarily inhibited the PI3K/AKT pathway in UC mouse colon tissue.

CONCLUSION

This study highlights that BAA effectively reduces colonic inflammation and preserves intestinal mucosal integrity, likely through the inhibition of PI3K/AKT pathway activity, positioning it as a potential treatment for UC.

摘要

民族药理学相关性

臭椿(Mill.)斯旺格尔(BAA)的树皮,一种广泛用于治疗肠道疾病的传统药物的中药,尚未在溃疡性结肠炎(UC)的背景下进行研究,其治疗机制尚不清楚。

研究目的

本研究综合网络药理学和实验验证,研究 BAA 治疗 UC 的作用和潜在机制。

材料和方法

首先,采用 UPLC-MS/MS 分析鉴定 BAA 的化学成分。然后,应用网络药理学分析基于这些鉴定化合物的 BAA 潜在机制。最后,利用葡聚糖硫酸钠(DSS)诱导的 UC 小鼠模型评估 BAA 的治疗效果,采用 Western blot 检测 BAA 影响的关键途径内蛋白表达的变化。

结果

UPLC-MS/MS 和 SwissADME 分析鉴定了 BAA 中的 223 种活性化合物。网络药理学表明,PI3K/AKT 途径可能是 BAA 发挥抗 UC 作用的主要机制。在 DSS 诱导的 UC 小鼠模型中,BAA 显著减轻结肠损伤,降低 DAI 评分,并促进小鼠体重恢复。此外,BAA 下调促炎细胞因子,包括 TNF-α、IL-1β 和 IL-6,从而抑制结肠中的炎症反应。Western blot 分析进一步表明,BAA 主要抑制 UC 小鼠结肠组织中的 PI3K/AKT 途径。

结论

本研究表明 BAA 可有效减轻结肠炎症,保护肠黏膜完整性,可能通过抑制 PI3K/AKT 途径活性,成为 UC 的潜在治疗方法。

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