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基于网络药理学、多组学和分子生物学的综合策略阐明银花泌炎灵片治疗尿路感染的作用机制。

Elucidation of the mechanism of the Yinhua Miyanling Tablet against urinary tract infection based on a combined strategy of network pharmacology, multi-omics and molecular biology.

机构信息

Department of Pathogeny Biology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China.

Department of Histology & Embryology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China.

出版信息

J Ethnopharmacol. 2025 Jan 30;337(Pt 1):118835. doi: 10.1016/j.jep.2024.118835. Epub 2024 Sep 16.

DOI:10.1016/j.jep.2024.118835
PMID:39293704
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Yinhua Miyanling Tablet (YMT), a traditional Chinese medicine consisting of 10 herbs, has been widely used clinically to treat urinary tract infections (UTIs), however, its therapeutic mechanism is not fully understood.

AIM OF THE STUDY

To investigate the mechanism of YMT in treating UTIs through network pharmacology, multi-omics and experimental validation.

MATERIALS AND METHODS

Clinically, blood and urine samples from YMT-treated UTI patients were collected for transcriptomic and metabolomic analyses. Computationally, compounds that are related to YMT were obtained from the databases, relevant targets were identified, and UTI-related targets were analyzed to determine the core signaling pathways. Subsequently, an integrated approach combining multi-omics and network pharmacology assisted in identifying the key pathways underlying therapeutic effects of YMT on UTI. Finally, a mouse model of UTI was established using uropathogenic Escherichia coli (UPEC), and the therapeutic mechanism of YMT on UTI was validated by ELISA, qRT-PCR and Western blotting.

RESULTS

After taking YMT, patients showed reduced levels of urinary bacteria, white blood cells, and serum inflammatory factors (CRP, IL-6 and TNF-α). Multi-omics analysis combined with network pharmacology demonstrated that YMT significantly inhibited the TLR/MAPK/NFκB signaling pathway. In vivo experiments confirmed that YMT attenuated UPEC-induced pathological changes in bladder structural, reduced the expression of bladder proteins (TLR4, MyD88, p-p38 MAPK and p-p65 NFκB), increased protein expression of IκB-α, and attenuated the release of inflammatory factors (TNF-α, IL-6 and IL-1β) in mice.

CONCLUSION

YMT is effective in treating UTI by down-regulating the TLR4/p38MAPK/p65NFκB pathway, thereby providing a scientific basis for its clinical application.

摘要

民族药理学相关性

银花泌炎灵片(YMT)是一种由 10 种草药组成的中药,已广泛用于临床治疗尿路感染(UTIs),但其治疗机制尚不完全清楚。

研究目的

通过网络药理学、多组学和实验验证研究 YMT 治疗 UTIs 的机制。

材料与方法

临床上,从 YMT 治疗的 UTI 患者中采集血液和尿液样本进行转录组学和代谢组学分析。通过计算机获取与 YMT 相关的化合物,鉴定相关靶点,并分析与 UTI 相关的靶点,以确定核心信号通路。随后,结合多组学和网络药理学的综合方法,确定 YMT 治疗 UTI 的关键通路。最后,使用尿路致病性大肠杆菌(UPEC)建立 UTI 小鼠模型,通过 ELISA、qRT-PCR 和 Western blot 验证 YMT 治疗 UTI 的机制。

结果

服用 YMT 后,患者尿液中的细菌、白细胞和血清炎症因子(CRP、IL-6 和 TNF-α)水平降低。多组学分析结合网络药理学表明,YMT 显著抑制 TLR/MAPK/NFκB 信号通路。体内实验证实,YMT 减轻了 UPEC 诱导的膀胱结构病理性变化,降低了膀胱蛋白(TLR4、MyD88、p-p38MAPK 和 p-p65 NFκB)的表达,增加了 IκB-α 的蛋白表达,并减轻了炎症因子(TNF-α、IL-6 和 IL-1β)在小鼠体内的释放。

结论

YMT 通过下调 TLR4/p38MAPK/p65NFκB 通路治疗 UTI 有效,为其临床应用提供了科学依据。

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