The pathogenesis of ulcerative colitis (UC) is associated with inflammation, oxidative stress, and gut microbiota imbalance. Although most researchers have demonstrated the antioxidant bioactivity of the phenolic compounds in plants, their UC-curing ability and underlying mechanisms still need to be further and adequately explored. Herein, we studied the antioxidation–structure relationship of several common polyphenols in plants including gallic acid, proanthocyanidin, ellagic acid, and tannic acid. Furthermore, the in vivo effects of the plant polyphenols on C57BL/6 mice with dextran-sulfate-sodium-induced UC were evaluated and the action mechanisms were explored. Moreover, the interplay of several mechanisms was determined. The higher the number of phenolic hydroxyl groups, the stronger the antioxidant activity. All polyphenols markedly ameliorated the symptoms and pathological progression of UC in mice. Furthermore, inflammatory cytokine levels were decreased and the intestinal barrier was repaired. The process was regulated by the antioxidant-signaling pathway of nuclear-erythroid 2-related factor 2. Moreover, the diversity of the intestinal microbiota, Firmicutes-to-Bacteroides ratio, and relative abundance of beneficial bacteria were increased. An interplay was observed between microbiota regulation and oxidative stress, immunity, and inflammatory response. Furthermore, intestinal barrier repair was found to be correlated with inflammatory responses. Our study results can form a basis for comprehensively developing plant-polyphenol-related medicinal products.
20 November 2022 in CPT: Pharmacometrics & Systems Pharmacology
The pharmacokinetics (PKs) and safety of medications in particular groups can be predicted using the physiologically‐based pharmacokinetic (PBPK) model. Using the PBPK model may enable safe pediatric clinical trials and speed up the process of new drug research and development, especially for children, a population in which it is relatively difficult to conduct clinical trials. This review summarizes the role of pediatric PBPK (P‐PBPK) modeling software in dose prediction over the past 6 years and briefly introduces the process of general P‐PBPK modeling. We summarized the theories and applications of this software and discussed the application trends and future perspectives in the area. The modeling software's extensive use will undoubtedly make it easier to predict dose prediction for young patients.
Background: Rheumatoid arthritis (RA) is a debilitating autoimmune disorder characterized by chronic inflammation and joint damage. Despite advancements in treatment, complete remission remains elusive. Methods: In this study, we introduce a novel lipid nanoparticle formulation co-delivering hydroxychloroquine (HCQ) and siRNA targeting TNF-α (siTNF-α) using microfluidic technology, marking the first use of such a combination for RA therapy. Results: In LPS-stimulated RAW 264.7 cells, the nanoparticles effectively reduced inflammatory markers. When administered via an intra-articular injection in a rat model, they significantly decreased joint inflammation and demonstrated good biological safety. Conclusions: This pioneering approach highlights the potential of lipid nanoparticles as a dual-delivery platform for enhanced RA treatment through targeted intra-articular administration.