Effects of Fasting and Phoenix dactylifera on the Expression of Major Drug- Metabolizing Enzymes in the Mouse Livers.

AIMS: This study aimed to investigate the effects of consuming Phoenix dactylifera and fasting on the mRNA expression of major hepatic drug-metabolizing enzymes in mice. METHODS: Phoenix dactylifera ethanolic extract was analyzed using LC-MS/MS. We used forty-two male Balb/c mice, which were treated with low (300 mg/kg) and high (2583 mg/kg) doses of Phoenix dactylifera and fasted for 24 hours, two weeks, and one month. Then, we analyzed the expression of cyp3a11, cyp2c29, cyp2d9, and ugt2b1 using real-time polymerase chain reaction assay. In addition, we assessed the relative liver weights of the mice and the hepatic phathohistological alterations. RESULTS: We found that Phoenix dactylifera ethanolic extract contained 38 phytochemical compounds, mainly kaempherol, campesterol, lutein, apigenin, genistein, and isoquercetin. Fasting significantly upregulated the mRNA expression of several drug-metabolizing enzymes in a time-dependent manner and we showed that consuming the low dose of Phoenix dactylifera significantly upregulated the expression of drug-metabolizing enzymes more than the high dose. The results of the histological examinations and relative liver weight showed that fasting and consuming of Phoenix dactylifera did not cause any toxicological alterations in the liver of the mice. CONCLUSION: It is concluded from this study that fasting and consuming of Phoenix dactylifera upregulated the mRNA expression of major drug-metabolizing enzymes in mouse livers. These findings may explain, at least partly, the variation of drug response during fasting in the month of Ramadan and would direct future clinical studies in optimizing the dosing of pharmacotherapeutic regimen.

Assessment of persistent antimicrobial and anti-biofilm activity of p-HEMA hydrogel loaded with rifampicin and cefixime.

Catheter-associated urinary tract infections (CAUTIs) are nosocomial infections causing more than one million hospital cases annually. The progress of CAUTIs leads to severe health complications. Infections result in blockage of the medical device due to biofilm formation, which necessitates the replacement of the device. The objective of this study is to improve urological biomaterials to minimize microbial growth and reduce the incidence of CAUTIs. Challenges from mixed biofilm are crucial and need to be addressed in the development of new coating materials. Herein, an investigation highlighted the reduction of mixed biofilm overgrowth and attachment tendency on poly-2-hydroxyethyl methacrylate (p-HEMA) surface by loading the hydrogel with rifampicin (RIF), cefixime trihydrate (CFX), and combined ratios of RIF and CFX. Mixed biofilm-formation ability in (3:1) RIF: CFX-loading p-HEMA (F6) surface showed best tendency to resist form biofilm. Persistent antimicrobial activity increased in p-HEMA loaded with combined ratios of RIF and CFX surface compared to p-HEMA alone, antimicrobial activity lasted for 8 days. All fabricated films exhibited %cell viability higher than 75% on HEK 293 cells. The addition of RIF and CFX may improve the duration of urological device employment before replacement.

Synthesis, Structural Characterization and Docking Studies of Sulfamoyl- Phenyl Acid Esters as Dipeptidyl Peptidase-IV Inhibitors.

BACKGROUND: Diabetes mellitus is a major worldwide health concern that has several serious complications including retinopathy, neuropathy, nephropathy and macrovascular diseases. OBJECTIVE: Dipeptidyl peptidase-IV (DPP-IV) inhibitors, gliptins, are a new class of antidiabetic agents that potentiate the action of incretins in decreasing the blood glucose levels. METHODS: In the present study, synthesis and characterization of a series of ten N4-sulfonamido-acrylic and phthalamic acid methyl esters (3a-e and 5a-e) were achieved. RESULTS: In vitro anti-DPP-IV activity of the synthesized compounds was evaluated, where compound 3b demonstrated the best activity with a % inhibition of 41.7 at 10 µM concentration and an IC50 of 23.9 µM. Moreover, Glide docking experiments revealed that our targeted compounds accommodate the binding site of DPP-IV and tend to form H-bonding with the backbones of R125, E206, S209, D545, K554, W629, Y631, and G632. CONCLUSION: Modeling findings recommend the attachment of bulky hydrophobic group on the ester side of the structure in addition to harboring extra aromatic rings that might be beneficial for better binding interaction and biological activity.