BackgroundPolyphenols, a group of complex naturally occurring compounds, are widely distributed throughout the plant kingdom and are therefore readily consumed by humans. The relationship between their chemical structure and intestinal absorption, transport, and first-pass metabolism remains unresolved, however.MethodsHere, we investigated the intestinal absorption and first-pass metabolism of four polyphenol compounds, apigenin, resveratrol, emodin and chrysophanol, using the in vitro Caco-2 cell monolayer model system and in situ intestinal perfusion and in vivo pharmacokinetic studies in rats, so as to better understand the relationship between the chemical structure and biological fate of the dietary polyphenols.ConclusionAfter oral administration, emodin and chrysophanol exhibited different absorptive and metabolic behaviours compared to apigenin and resveratrol. The differences in their chemical structures presumably resulted in differing affinities for drug-metabolizing enzymes, such as glucuronidase and sulphatase, and transporters, such as MRP2, SGLT1, and P-glycoprotein, which are found in intestinal epithelial cells.
Genistein (4',5,7-trihydroxyisoflavone), a naturally occurring phenolic compound, possesses well-known preventive activity in breast and prostate cancer, cardiovascular diseases, and postmenopausal problems. The aim of this study is to investigate the distribution and dose-dependent absorption, metabolism, and excretion of genistein in rats. Genistein was orally administered to rats at different doses. At various time intervals, blood, bile, and urine samples were collected and incubated with glucuronidase to hydrolyze the glucuronidated genistein. Genistein was detected by HPLC. High levels of glucuronidated genistein were detected in the plasma, bile, and urine after genistein administration. When genistein was administered to rats at 6.25, 12.5, and 50 mg x kg (-1) doses, the AUC (0- t) values for genistein were 23.5, 80.9, and 177.9 mg x min x L (-1); the oral absolute bioavailabilities were 21.9, 33.5, and 19.0%; the AUC (0- t) values of glucuronidated genistein were 173.8, 470.7, and 1721.2 mg x min x L (-1), respectively. The cumulative biliary excretion of genistein respective to each dose was 42.6 +/- 6.5, 75.2 +/- 18.9, and 126.6 +/- 34.8 microg; the cumulative biliary excretion of glucuronidated genistein was 108.5 +/- 35.2, 423.5 +/- 158.3, and 853.7 +/- 320.8 microg for each dose, respectively. The cumulative urinary excretion of genistein was 34.8 +/- 10.8, 187.3 +/- 67.0 and 213.6 +/- 30.6 microg for each dose, respectively; the cumulative levels of glucuronidated genistein excreted in the urine were 217.8 +/- 52.1, 583.1 +/- 106.9, and 1108.4 +/- 88.1 microg, respectively. These results indicated that at high doses absorption, biotransformation, and excretion of genistein occurred in a nonlinear dose-dependent manner. Therefore, the results of these pharmacokinetic studies raise important questions about the therapeutic significance of consuming large quantities of genistein, genistein analogues, or soy-based neutraceuticals.
With the extensive application of doxorubicin (DOX), DOX resistance has become one of the main obstacles to the effective treatment of breast cancer. In this paper, DOX and resveratrol (RES) were co-encapsulated in a modified PLGA nanoparticle (NPS) to overcome the DOX resistance. CLSM results indicated that DOX and RES were simultaneously delivered into the nucleus of DOX-resistant human breast cancer cells by DOX/RES-loaded NPS. Consequently, DOX/RES-loaded NPS showed significant cytotoxicity on MDA-MB-231/ADR cells and MCF-7/ADR cells. Furthermore, DOX/RES-loaded NPS could overcome DOX resistance by inhibiting the expression of drug resistance-related protein such as P-gp, MRP-1 and BCRP, and induce apoptosis through down-regulating the expression of NF-κB and BCL-2. In tumor-bearing mice, DOX/RES-loaded NPS mainly delivered DOX and RES to tumor tissue. Compared with free DOX, DOX/RES-loaded NPS significantly inhibited the DOX-resistant tumor growth in tumor-bearing mice without causing significant systemic toxicity. In a word, DOX/RES-loaded NPS could overcome the DOX resistance and had the potential in the treatment of DOX-resistant breast cancer.
The design, synthesis and biological evaluation of the cationic lipid gene delivery vectors based on cholesterol and natural amino acids lysine or histidine are described. Cationic liposomes composed of the newly synthesized cationic lipids 1a or 1b and neutral lipid DOPE (1,2-dioleoyl-l-α-glycero-3-phosphatidyl-ethanolamine) exhibited good transfection efficiency. pEGFP-N1 plasmid DNA was transferred into 293T cells by cationic liposomes formed from cationic lipids 1a and 1b, and the transfection activity of the cationic lipids was superior (1a) or parallel (1b) to that of the commercially available 3β-[N-(N',N'-dimethylaminoethyl)-carbamoyl] cholesterol (DC-Chol) derived from the same cholesterol backbone with different head groups. Combined with the results of agarose gel electrophoresis, transfection experiments with various molar ratios of the cationic lipids and DOPE and N/P (+/−) molar charge ratios, a more effective formulation was formed, which could lead to relatively high transfection efficiency. Cationic lipid 1a represents a potential agent for the liposome used in gene delivery due to low cytotoxicity and impressive gene transfection activity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.