Absorptive interactions of concurrent oral administration of (+)-catechin and puerarin in rats and the underlying mechanisms

Abstract

Aim: (+)-Catechin and puerarin are polyphenol and flavonoid, respectively, in green tea and foodstuffs. They exhibit potent antioxidant activity and are widely used for treating cardiocerebrovascular diseases. The aim of this work was to investigate the potential interactions between (+)-catechin and puerarin following concurrent oral administration in rats, and their absorption mechanisms in Caco-2 cell monolayers. Methods: Pharmacokinetic studies were conducted in male rats received (+)-catechin (140 mg/kg, po) and/or puerarin (200 mg/kg, po). The cell uptake and transport behavior in Caco-2 cell monolayers and the interactions of the two compounds were analyzed. Results: When (+)-catechin and puerarin were administered concurrently, the AUC 0-12 h and C max values of puerarin were 2.48-fold and 3.91-fold, respectively, as large as those of puerarin alone; the AUC 0-12 h and C max values of (+)-catechin were decreased to 57.62% and 77.55%, respectively, compared with those of (+)-catechin alone. In Caco-2 cell monolayers, (+)-catechin (300 and 600 μmol/L) significantly increased the cell uptake and transport of puerarin, whereas puerarin (300 and 600 μmol/L) significantly decreased the cellular uptake and transport of (+)-catechin. Furthermore, both cyclosporine A (P-glycoprotein inhibitor) and MK-571 (MRP-2 inhibitor) significantly increased the cellular uptake and transport of (+)-catechin and puerarin. Conclusion: Concurrent oral administration of (+)-catechin and puerarin significantly increased the absolute oral bioavailability of puerarin, but decreasing that of (+)-catechin. The competitive efflux of (+)-catechin and puerarin by P-glycoprotein and MRP-2 might lead to this interaction during their absorption process in the small intestine.

Phytochemicals Mediate the Expression and Activity of OCTN2 as Activators of the PPARγ/RXRα Pathway

“…( Xing et al, 2011 ; Chen et al, 2012 ; Guo et al, 2013 ). Pharmacokinetic studies were conducted in male rats received puerarin (200 mg/kg, po) and the plasma concentrations (C max ) reached 2.47 μM ( Su et al, 2016 ). Puerarin may act as a chemopreventive and/or chemotherapeutic agent in colon cancer cells HT-29 and hepatocellular carcinoma cell SMMC-7721 by reducing cell viability and inducing apoptosis through bcl-2/caspase3 or mitochondria-dependent pathway ( Yu and Li, 2006 ; Zhang et al, 2014 ).…”

Catechin and Procyanidin B2 Modulate the Expression of Tight Junction Proteins but Do Not Protect from Inflammation-Induced Changes in Permeability in Human Intestinal Cell Monolayers

“…Despite their many limitations, in vitro cell models still represent a useful tool to predict the effects mediated by natural compounds on several functional end points, such as epithelial barrier permeability. In particular, polarized Caco-2 cell monolayers, alone or in co-culture with goblet-like cells, have been widely used for the investigation of polyphenol adsorption by the intestinal epithelium [28,29,30]. Other studies have exploited the same cell culture system to study the effects mediated by natural compounds on gut function upon inflammatory insults [20,31].…”

Insight into Polyphenol and Gut Microbiota Crosstalk: Are Their Metabolites the Key to Understand Protective Effects against Metabolic Disorders?

“…The important question in the context of nutrition is whether polyphenols behave similarly when evaluated as single compounds as when assessed in complex mixtures [ 93 , 94 ]. Su et al [ 92 ] partially answered this question by showing that, in Caco-2 cells, (+)-catechin significantly enhanced the cellular uptake and transport of the isoflavone daidzein-8- C -glucoside, whereas this compound significantly abated that of (+)-catechin, and that inhibition of efflux pumps increased their uptake. Although valuable for screening polyphenol bioavailability, caution should be used when interpreting the data obtained from the Caco-2 cellular model in terms of predictability.…”

“…Inflammatory and OxS processes were particularly studied. For example, (3′4′-dihydroxyphenyl)-γ-valerolactone significantly decreased TNFα-induced NF-kB transcriptional activity in HepG2 cells [ 92 ]. Furthermore, a decrease was noted in nitrous oxide production and inducible nitrous oxide synthase expression in the murine macrophage RAW264.7 cells and freshly isolated human monocytes, both treated with (δ-(3,4-dihydroxyphenyl)-γ-valerolactone) a metabolite of the maritime pine bark Pycnogenol [ 233 ].…”