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.
Keywords: Metabolomics; Network pharmacology; Transcriptomics; Urinary tract infection; Yinhua Miyanling Tablet.
Copyright © 2024. Published by Elsevier B.V.