Identification of Active Compounds and Mechanism of Huangtu Decoction for the Treatment of Ulcerative Colitis by Network Pharmacology Combined with Experimental Verification

网络药理学结合实验验证对黄土汤治疗溃疡性结肠炎的有效成分及作用机制进行鉴定

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作者:Wenwen Chen #, Lin He #, Lian Zhong, Jiayi Sun, Lilin Zhang, Daneng Wei, Chunjie Wu

Conclusion

HTD treatment can alleviate the colonic inflammation via inhibiting MMPs including MMP1, MMP3 and MMP9.

Methods

Firstly, the chemical compounds of HTD were qualitatively identified based on Q Exactive Orbitrap LC-MS/MS, and their potential targets were predicted through SwissTargetPrediction. Secondly, the differential expressed genes (DEGs) in colon tissues of UC patients and normal controls were retrieved from the GEO database. Thirdly, the overlapping targets of DEGs and the predicted targets were obtained and subjected to GO and KEGG analysis. Finally, the key targets in the most significantly enriched pathway were verified by in vivo experiment, and the protein and mRNA expressions of matrix metalloproteinase-1 (MMP1), MMP3, MMP7, MMP9 and MMP12 were determined by immunohistochemistry (IHC), Western blotting (WB) and quantitative real-time-PCR (qRT-PCR).

Results

A total of 47 compounds were identified and 29 overlapping targets were obtained from HTD extract. The most significantly enriched pathway of overlapping targets involved was MMP. HTD improved the pathological damage in colon tissues of DSS-induced UC model and significantly decreased the serum levels of IL-1β and IL-6. The protein and mRNA expressions of MMP1, MMP3 and MMP9 in colon tissues were significantly decreased after HTD treatment.

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