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

Abstract

Ethnopharmacological relevanceYinhua 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 studyTo investigate the mechanism of YMT in treating UTIs through network pharmacology, multi-omics and experimental validation. Materials and methodsClinically, 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. ResultsAfter 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. ConclusionYMT is effective in treating UTI by down-regulating the TLR4/p38MAPK/p65NFκB pathway, thereby providing a scientific basis for its clinical application.