Dissecting and Evaluating the Therapeutic Targets of Coptis Chinensis Franch in the Treatment of Urinary Tract Infections Induced by Escherichia coli

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.

Coptidis rhizoma and evodiae fructus against lipid droplet deposition in nonalcoholic fatty liver disease‐related liver cancer by AKT

“…These results suggested that they were the most important active compounds, especially quercetin, contributing to the therapeutic effects of the coptidis rhizoma and evodiae fructus on NAFLD-related liver cancer. Quercetin has been found in coptidis rhizoma and evodiae fructus in various studies (Chang et al, 2022;Liu et al, 2016;Luo et al, 2021;Zeng et al, 2011;Zheng et al, 2021). Studies have demonstrated that quercetin reduces AKT phosphorylation and improves diet-induced dysregulation of lipid metabolism genes in mice with NAFLD through PI3K/ AKT pathway (Pisonero-Vaquero et al, 2015).…”

Distinct immune and inflammatory response patterns contribute to the identification of poor prognosis and advanced clinical characters in bladder cancer patients

“…Three bladder samples of carcinomas and adjacent normal tissues were obtained from BLCA patients who underwent surgery at Guangzhou Medical University’s Second Affiliated Hospital (GZhmu2.cohort) without preoperative immunotherapy or chemotherapy. RNA extraction and qRT-PCR were conducted as previously described ( 22 , 23 ). The PCR primers are described in Supplementary Table 2 .…”

“…All images were observed by a tissue scanner (PathScope 4s, DigiPath, NV, USA) to observe the inflammatory and immune histological changes of bladder tissues. The corresponding score system was performed as previously described ( 22 , 23 ).…”

“…The primary antibodies: CD247 (1:200), TLR2 (1:200), c-MYC (1:500), IL10 (1:200), and FN1 (1:200) were obtained from Proteintech (Rosemont, IL, USA) and were applied for IHC. IHC was conducted as previously described ( 22 , 23 ). For each IHC-tissue section, five random visual fields were selected for determination.…”

Allicin suppressed Escherichia coli-induced urinary tract infections by a novel MALT1/NF-κB pathway

“…The injection was repeated after 4 hours as previously described. 23,24 Rats were treated with allicin intraperitoneally once per day for 1, 3, and 7 days post-injection. The usage method of allicin in the present study was selected based on previous in vivo studies.…”