Urinary tract infections (UTIs) are common bacterial infections that represent a severe public health problem. They are often caused by Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumonia), Proteus mirabilis (P. mirabilis), Enterococcus faecalis (E. faecalis), and Staphylococcus saprophyticus (S. saprophyticus). Among these, uropathogenic E. coli (UPEC) are the most common causative agent in both uncomplicated and complicated UTIs. The adaptive evolution of UPEC has been observed in several ways, including changes in colonization, attachment, invasion, and intracellular replication to invade the urothelium and survive intracellularly. While antibiotic therapy has historically been very successful in controlling UTIs, high recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly reduce the efficacy of these treatments. Furthermore, the gradual global emergence of multidrug-resistant UPEC has highlighted the need to further explore its pathogenesis and seek alternative therapeutic and preventative strategies. Therefore, a thorough understanding of the clinical status and pathogenesis of UTIs and the advantages and disadvantages of antibiotics as a conventional treatment option could spark a surge in the search for alternative treatment options, especially vaccines and medicinal plants. Such options targeting multiple pathogenic mechanisms of UPEC are expected to be a focus of UTI management in the future to help combat antibiotic resistance.
The purpose of this study was to elucidate the metabolic action patterns of P. forrestii against rheumatoid arthritis (RA) using metabolomics, and to obtain its potential effective substances for treating RA. First, the therapeutic effects of P. forrestii against RA were confirmed; second, the chemical composition of P. forrestii was analyzed, and 17 prototypes were absorbed into blood; subsequently, plasma metabolomics studies using UPLC-Triple-TOF-MS/MS and GC-MS were performed to disclose the metabolomics alterations in groups, which revealed 38 altered metabolites after drug intervention. These metabolites were all associated with the arthritis pathophysiology process (−log(p) > 1.6). Among them, sorted by variable important in projection (VIP), the metabolites affected (VIP ≥ 1.72) belonged to lipid metabolites. Finally, Pearson’s analysis between endogenous metabolites and exogenous compounds was conducted to obtain potential pharmacological substances for the P. forrestii treatment of RA, which showed a high correlation between five blood-absorbed components and P. forrestii-regulated metabolites. This information provides a basis for the selection of metabolic action modes for P. forrestii clinical application dosage, and potential pharmacological substances that exerted anti-RA effects of P. forrestii were discovered. The study provided an experimental basis for further research on pharmacoequivalence, molecular mechanism validation, and even the development of new dosage forms in the future.
Biancaea decapetala (Roth) O. Deg. (Fabaceae), traditionally used by the Hmong people to treat rheumatoid arthritis (RA), has not been extensively studied for the correlation between its anti-inflammatory activity and its active components. Protosappanoside D (PTD), a new component, has been isolated for the first time from the extract of Biancaea decapetala. This study focused on the anti-arthritic and anti-inflammatory effects of Biancaea decapetala extracts (BDE) and PTD, along with their pharmacokinetic–pharmacodynamic (PK-PD) analysis. In the adjuvant-induced arthritis (AA) rat model, HE staining and cytokine assays showed that BDE alleviated joint damage and reduced inflammatory cytokines, similar to the positive control. In the LPS-induced inflammatory cell model, both BDE and PTD demonstrated anti-inflammatory effects by inhibiting the secretion of inflammatory factors. A PK-PD analysis of BDE in AA rats and inflammatory cells, as well as an analysis of PTD as a monomer, was conducted. The results indicated that PTD had different regulatory effects on cytokines like TNF-α, with a certain lag and sustained effects. These findings suggest the potential of BDE and PTD as treatments for rheumatoid arthritis, though further in vivo studies and clinical trials are needed.