Abstract
Coptis chinensis Franch (CCF) is extensively used in the treatment of inflammatory-related diseases. Accumulating studies have previously demonstrated the anti-inflammatory properties of CCF, yet data on its exact targets against urinary tract infections (UTIs) remain largely unknown. Therefore, the present study decodes the potential targets of action of CCF against UTIs by network pharmacology combined with experiment evaluations. Based on the pharmacology network analysis, the current study yielded six core ingredients: quercetin, palmatine (R)-canadine, berlambine, berberine, and berberrubine. The protein–protein interaction network (PPI) was generated by the string database, and then, four targets (IL6, FOS, MYC, and EGFR) were perceived as the major CCF targets using the CytoNCA plug-in. The results of molecular docking showed that the six core constituents of CCF had strong binding affinities toward the four key targets of UTIs after docking into the crystal structure. The enrichment analysis indicated that the possible regulatory mechanisms of CCF against UTIs were based on the modules of inflammation, immune responses, and apoptosis among others. Experimentally, the Escherichia coli (E. coli) strain CFT073 was applied to establish in vivo and in vitro models. In vivo results revealed that the key targets, IL6 and FOS, are significantly upregulated in rat bladder tissues of UTIs, whereas the expression of MYC and EGFR remained steady. Last, in vitro results further confirmed the therapeutic potential of CCF by reducing the expression of IL6 and FOS. In conclusion, IL6 and FOS were generally upregulated in the progression of E. coli–induced UTIs, whereas the CCF intervention exerted a preventive role in host cells stimulated by E. coli, partially due to inhibiting the expression of IL6 and FOS.
Highlights
Urinary tract infections (UTIs) are regarded to be among the most common bacterial infections, affecting 150 million people around the world annually (Sihra et al, 2018; Klein and Hultgren, 2020; Behzadi et al, 2021b)
We first obtained a total of 48 candidate compounds from the traditional Chinese medicine systems pharmacology (TCMSP) database based on the absorption, distribution, metabolism, excretion, and toxicity (ADME/T) values
90 genes which showed potential mediation of these bioactive compounds in the treatment of UTIs were obtained from the TCMSP database
Summary
Urinary tract infections (UTIs) are regarded to be among the most common bacterial infections, affecting 150 million people around the world annually (Sihra et al, 2018; Klein and Hultgren, 2020; Behzadi et al, 2021b). Overuse and misuse of the antibiotics has resulted in the increasing emergence of multidrug resistance (MDR) E. coli strains which have acquired more virulence factors and stronger pathogenicity, threatening the utility of carbapenems as reliable agents for UTIs (Jahandeh et al, 2015; Sihra et al, 2018; Vihta et al, 2018; Behzadi, 2020). Identifying a host-targeted therapy is appealing to provide new options for UTIs and to overcome the resistance of E. coli due to the low mutation rate of host genes compared with bacteria
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