Molecular basis of phytochemical-gut microbiota interactions.

Dysbiosis-associated molecular pathology is significantly involved in developing and perpetuating metabolic disorders, disrupting host energy regulation, and triggering inflammatory signaling cascades, insulin resistance, and metabolic dysfunction. Concurrently, numerous phytoconstituents are able to interact with the gut microbiota and produce bioactive metabolites that influence host cellular pathways, inflammation, and metabolic processes. These effects include improved insulin sensitivity, lipid metabolism regulation, and suppression of chronic inflammation, highlighting the therapeutic potential of phytoconstituents against metabolic abnormalities. Understanding this symbiotic relationship and the underlying molecular cascades offers innovative strategies for tailored interventions and promising therapeutic approaches to address the growing burden of metabolic disease.

A novel 5-Fluorocuracil multiple-nanoemulsion used for the enhancement of oral bioavailability in the treatment of colorectal cancer.

5-Fluorouracil (5-FU) is a drug of choice for colorectal-cancer. But oral therapeutic efficacy of 5-FU is restricted due to their very little bioavailability because of poor membrane permeability and GIT-absorption. We have developed a multiple nanoemulsion (w/o/w i.e. 5-FU-MNE) in which 5-FU incorporated to improve their oral-absorption. Globule-size of opt-5-FU-MNE was 51.64 ±â€¯2.61 nm with PDI and ZP 0.101 ±â€¯0.001 and -5.59 ±â€¯0.94, respectively. In vitro 5-FU-release and ex vivo permeation studies exhibited 99.71% release and 83.64% of 5-FU from opt-nanoformulation. Cytotoxic in vitro studies-exhibited that 5-FU in opt-5-FU-MNE was 5-times more potent than 5-FU-S on human-colon-cancer-cell-lines (HT-29). The enhanced Cmax with AUC0-8h with opt-5-FU-MNE was shown extremely significant (p < 0.001) in wistar rat's plasma in the comparison of oral and i.v. treated group of 5-FU-S by PK-observations. Furthermore, opt-5-FU-MNE was showed much more significant (p < 0.001) results as compared to 5-FU-S (free) on cell lines for human colon cancer (HT-29).