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揭示四妙丸在溃疡性结肠炎中的多方面益处:信号通路、肠道微生物群和脂质代谢的综合分析

Unveiling the multifaceted benefits of Simiao Pill in ulcerative colitis: Integrative analysis of signaling pathways, gut microbiota, and lipid metabolism.

作者信息

Peng XingJu, Zou QiuPing, Yang CanJiao, Pu XingNa, Yang HengLi, Wang Mei, Chen Shuai, Pu ShiBiao, Chen XingLong, He HongPing, Li YanPing

机构信息

College of Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, 650500, China.

College of Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, 650500, China.

出版信息

J Ethnopharmacol. 2025 Apr 25;346:119714. doi: 10.1016/j.jep.2025.119714. Epub 2025 Mar 28.

DOI:10.1016/j.jep.2025.119714
PMID:40158828
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Ulcerative colitis (UC), a chronic idiopathic inflammatory bowel disease, is characterized by a prolonged and recurrent course. The classical Traditional Chinese Medicine (TCM) formula Simiao Pill (SMP) has demonstrated unique and widespread therapeutic effects on diarrhea and other intestinal inflammation. However, its material basis and potential mechanisms of action remain unclear.

AIM OF THE STUDY

This study aims to explore the mechanisms by which SMP alleviates UC, emphasizing its anti-inflammatory properties and its role in regulating gut microbiota.

MATERIALS AND METHODS

The chemical composition of SMP was identified using UPLC-Q-TOF-MS/MS. Network pharmacology and molecular docking were applied to predict potential anti-UC targets and pathways. In vitro models in RAW264.7 cells and an in vivo mouse model induced by dextran sulfate sodium (DSS) were established to evaluate the potential mechanisms using molecular biology techniques. Additionally, gut microbiota changes were analyzed via 16S rRNA sequencing, and metabolic profiling was conducted using UPLC-Q-TOF-MS/MS.

RESULTS

SMP significantly improved UC symptoms by targeting 148 protein-related pathways, including TLR4/PI3K/Akt/NF-κB, a key inflammatory regulator. Molecular docking confirmed strong interactions between SMP compounds and targets. SMP reduced inflammation, restored gut barrier integrity, and modulated gut microbiota and lipid metabolism in UC mice.

CONCLUSIONS

SMP alleviates UC by regulating the TLR4/PI3K/Akt/NF-κB pathway, balancing gut microbiota, and improving lipid metabolism. These findings support SMP's potential as a UC treatment and warrant further clinical exploration.

摘要

民族药理学相关性

溃疡性结肠炎(UC)是一种慢性特发性炎症性肠病,其特点是病程迁延且反复发作。经典的中药方剂四妙丸(SMP)已在腹泻和其他肠道炎症方面显示出独特且广泛的治疗效果。然而,其物质基础和潜在作用机制仍不清楚。

研究目的

本研究旨在探讨四妙丸缓解溃疡性结肠炎的机制,重点关注其抗炎特性及其在调节肠道微生物群中的作用。

材料与方法

采用超高效液相色谱-四极杆飞行时间串联质谱(UPLC-Q-TOF-MS/MS)鉴定四妙丸的化学成分。应用网络药理学和分子对接技术预测潜在的抗溃疡性结肠炎靶点和通路。建立RAW264.7细胞体外模型和葡聚糖硫酸钠(DSS)诱导的小鼠体内模型,运用分子生物学技术评估潜在机制。此外,通过16S rRNA测序分析肠道微生物群的变化,并使用UPLC-Q-TOF-MS/MS进行代谢谱分析。

结果

四妙丸通过靶向148条与蛋白质相关的通路(包括关键炎症调节因子TLR4/PI3K/Akt/NF-κB)显著改善了溃疡性结肠炎症状。分子对接证实了四妙丸化合物与靶点之间有强烈的相互作用。四妙丸减轻了溃疡性结肠炎小鼠的炎症,恢复了肠道屏障完整性,并调节了肠道微生物群和脂质代谢。

结论

四妙丸通过调节TLR4/PI3K/Akt/NF-κB通路、平衡肠道微生物群和改善脂质代谢来缓解溃疡性结肠炎。这些发现支持了四妙丸作为溃疡性结肠炎治疗药物的潜力,值得进一步进行临床探索。

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