Absorption properties and effects of caffeic acid phenethyl ester and its p-nitro-derivative on P-glycoprotein in Caco-2 cells and rats

Abstract

Context: Caffeic acid phenethyl ester (CAPE), isolated from honeybee propolis, has pharmacological applications. A synthesized CAPE derivative, p-nitro-caffeic acid phenethyl ester (CAPE-NO 2 ), showed similar activities with CAPE. The pharmacological activities of CAPE and CAPE-NO 2 are related to their absorption properties. Objective: To understand the pharmacokinetic profiles of CAPE and CAPE-NO 2 in rats and investigate the absorption mechanisms and effects on P-glycoprotein in Caco-2 cells. Materials and methods: The pharmacokinetic profiles of CAPE and CAPE-NO 2 were obtained after oral administration (10 mg/kg) to rats. Transport studies of CAPE and CAPE-NO 2 (5, 10, 20 lM) were performed in Caco-2 cell model. P-gp activities were assayed by rhodamine 123 cellular retention. Expression of P-gp was determined after the cells were administrated with CAPE and CAPE-NO 2 (5, 20 lM) for 48 and 72 h. Results: The AUC (0Àt) of CAPE-NO 2 (3239.9 ± 352 ng  h/mL) was two-time greater than CAPE (1659.6 ± 152 ng  h/mL) in rats. The P app values of CAPE and CAPE-NO 2 were (4.86 ± 0.90)  10 À6

Anti-colon cancer effect of caffeic acid p-nitro-phenethyl ester in vitro and in vivo and detection of its metabolites

“…However, there were no metabolites detected in tumours, implying that CAPE and CAPE- p NO 2 were transformed to other compounds in tumours and need to be further studied in the future. Additionally, according to the pharmacokinetic analysis of CAPE and CAPE- p NO 2 in rats, the half-lives (t 1/2 ) of these compounds were 4.2 h and 20.9 h, respectively, and the area under concentration-time curve (AUC all ) values were 1659 and 3239, respectively, indicating that the bioavailability of CAPE- p NO 2 was higher than that of CAPE, and the metabolic processes of CAPE and CAPE- p NO 2 would be different 46 . The most of above metabolites are inactive excrement of CAPE or CAPE- p NO 2 , and there are no literatures reported the anti-cancer effect of these metabolites detected in this study, the results of LC-MS/MS provided a basis for further study to explore the compounds to against colon cancer with stronger effect only.…”

Caffeic Acid Phenethyl Ester Assisted by Reversible Electroporation—In Vitro Study on Human Melanoma Cells

“…The membrane permeability is an important factor in drug absorption. Gou et al’s studies showed that CAPE transport across the cell membrane is limited, which is likely due to the p -glycoprotein overexpression [ 18 ]. It is the main efflux pump for a variety of chemicals, which play an important role in the absorption and distribution of many polyphenolic compounds, including CAPE [ 19 ].…”

Protection of CAPE-pNO2 Against Chronic Myocardial Ischemia by the TGF-Β1/Galectin-3 Pathway in Vivo and in Vitro

“…CAPE was purchased from Meilun Biotechnology (Dalian, China), CAPE-pNO 2 was synthesized, characterized and detected as described in previous study [25] (purity > 99.0%). Vitamin D3 and lipopolysaccharide (LPS) were purchased from Mairuida Technology (Beijing, China).…”

“…CAPE was purchased from Meilun Biotechnology (Dalian, China), CAPE-pNO 2 was synthesized, characterized and detected as described in previous study [25] (purity > 99.0% . Antibodies against galectin-3 (Gal-3), B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), caspase 3, nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), transforming growth factor β1 (TGF-β1), mothers against decapentaplegic homolog 2 (Smad2), collagen I (Col-I), collagen III (Col-III), matrix metalloproteinase-9 (MMP-9), phosphatidylinositol 3-kinase (PI3K), β-actin, horseradish peroxidase (HRP)-conjugated goat anti-rabbit secondary antibody and Cy3-conjugated goat anti-rabbit lgG(H + L) were purchased from Proteintech Group Inc (Wuhan, China).…”