ABSTRACT
Aberrant activation of NLRP3 inflammasome in colonic macrophages strongly associates with the occurrence and progression of ulcerative colitis. Although targeting NLRP3 inflammasome has been considered to be a potential therapy, the underlying mechanism through which pathway the intestinal inflammation is modulated remains controversial. By focusing on the flavonoid lonicerin, one of the most abundant constituents existed in a long historical anti-inflammatory and anti-infectious herb
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Due to its safety, convenience, low cost and good compliance, oral administration attracts lots of attention. However, the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointestinal tract. One of the critical and most overlooked factors is the symbiotic gut microbiota that can modulate the bioavailability of oral drugs by participating in the biotransformation of oral drugs, influencing the drug transport process and altering some gastrointestinal properties. In this review, we summarized the existing research investigating the possible relationship between the gut microbiota and the bioavailability of oral drugs, which may provide great ideas and useful instructions for the design of novel drug delivery systems or the achievement of personalized medicine.
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Microbes inhabiting the intestinal tract of humans represent a site for xenobiotic metabolism. The gut microbiome, the collection of microorganisms in the gastrointestinal tract, can alter the metabolic outcome of pharmaceuticals, environmental toxicants, and heavy metals, thereby changing their pharmacokinetics. Direct chemical modification of xenobiotics by the gut microbiome, either through the intestinal tract or re-entering the gut enterohepatic circulation, can lead to increased metabolism or bioactivation, depending on the enzymatic activity within the microbial niche. Unique enzymes encoded within the microbiome include those that reverse the modifications imparted by host detoxification pathways. Additionally, the microbiome can limit xenobiotic absorption in the small intestine by increasing the expression of cell-cell adhesion proteins, supporting the protective mucosal layer, and/or directly sequestering chemicals. Lastly, host gene expression is regulated by the microbiome, including CYP450s, multi-drug resistance proteins, and the transcription factors that regulate them. While the microbiome affects the host and pharmacokinetics of the xenobiotic, xenobiotics can also influence the viability and metabolism of the microbiome. Our understanding of the complex interconnectedness between host, microbiome, and metabolism will advance with new modeling systems, technology development and refinement, and mechanistic studies focused on the contribution of human and microbial metabolism.
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OBJECTIVE: To establish an isobutyryl derivatization combined with UPLC-MS/MS method for the quantitative analysis of 5-aminosalicylic acid (5-ASA) in human urine. METHODS: Urine sample was analyzed by UPLC-MS/MS after pretreatment with isobutyryl derivatization and precipitation with acetonitrile. The separation was performed on the ACQUITY UPLC BEH-C18 column (2.1 mm×100 mm,1.7 μm) at 40 ℃ with injection volume of 3 μL. The mobile phase was acetonitrile-5 mmol•L-1 ammonium formate containing 0.075% formic acid (20:80) at a flow rate of 0.4 mL•min-1. Electrospray ionization (ESI) source was applied and operated in multiple reaction monitoring (MRM) mode with negative ionization using the transitions of m/z 222.0→178.1 and m/z 206.1→162.0 for isobutyl 5-ASA and isobutyl 3-amino benzoic acid (3-ABA, IS), respectively. RESULTS: The method was specific and sensitive. It exhibited good linearity over the concentration of 0.100-30.0 μg•mL-1 for 5-ASA with the LLOQ of 0.100 μg•mL-1, extraction recovery of 101.7%-115.4% and normalized matrix factor of 1.000-1.025. The intra- and inter-day precisions were both less than 15%. CONCLUSION: The method is specific, simple, accurate and stable for quantitative analysis of 5-ASA in human urine.
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OBJECTIVE: To develop an LC-MS/MS method for determination of mesalazine and its metabolite, N-Ac-5-ASA, in rat plasma, urine and colon for the pharmacokinetic study of mesalazine and N-Ac-5-ASA in rats.
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The present work carries an analytical method development of prednisolone and 5- amino salicylic acid in tablet dosage form. The method is based upon Q – absorption ratio method for the simultaneous determination of the prednisolone and 5-amino salicylic acid. Both the drugs are widely used for bacterial cure and are recommended for the patients with mild to moderate inflammation of the digestive tract. Ulcerative colitis and crohn’s disease are the target disorders which are treated by both drug candidates. Absorption ratio method is used for the ratio of the absorption at two selected wavelength one of which is the iso-absorptive point and other being the λmax of one of the two components. Prednisolone and 5-ASA shows their iso-absorptive point at 283 nm in ethanol and 0.1N HCl respectively. The second wavelength used is 302 nm which is the λmax of 5-ASA in 0.1N HCl. The linearity was obtained in the concentration range of 1-10 μg/ml for prednisolone and 5-ASA. This method was applied to all pharmaceutical dosage form because there is no excipients interference between them. The results have been validated by recovery studies.
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No abstract available.
Subject(s)
Colitis, Ulcerative , Diagnosis , Diarrhea , Inflammatory Bowel Diseases , UlcerABSTRACT
SASP, 5-ASA, 4ASA are effectivedrugs for ulcerative colitis. They contain the same structure, but their action modes are different. The precise mechanism of salicylates are unclear. SASP,5-ASA inhibit inflammatory mediators, but 4ASA has no effect on PG or LT. 5-ASA has a strong force to scavenge the reactive oxygen metabolites. 4-ASA is weak in this aspect. The salicylates influence the function of several cy-tokines at different degree, such as IL-1, IL-6, IL-2, INF-a, TNF-r, GM-CSF, etc, probably bypreventing the binding of cytokine and receptor, or decreasing some cytokine synthesis and liberation. SASP inhibits neutrophilial cell degrandulation, releases lysosome and other enzymes, and changes the activity of lymphacyte. The salicylates also effect nitric oxide synthesis,adhesion molecules and the intestine permeability.