Absorption and Metabolism of Phenolics from Digests of Polyphenol-Rich Potato Extracts Using the Caco-2/HepG2 Co-Culture System

Abstract

The bioactivity of dietary polyphenols depends upon gastrointestinal and hepatic metabolism of secondary microbial phenolic metabolites generated via colonic microbiota-mediated biotransformation. A polyphenol-rich potato extract (PRPE) containing chlorogenic, caffeic, and ferulic acids and rutin was digested in a dynamic multi-reactor gastrointestinal simulator of the human intestinal microbial ecosystem (GI model). Simulated digestion showed extensive degradation of the parent compounds and the generation of microbial phenolic metabolites. To characterize the transport and metabolism of microbial phenolic metabolites following digestion, a co-culture of intestinal Caco-2 and hepatic HepG2 cells was exposed to the PRPE-derived digests obtained from the colonic vessels. Following a 2 h incubation of the digesta with the Caco-2/HepG2 co-cultures, approximately 10–15% of ferulic, dihydrocaffeic, and dihydroferulic acids and 3–5% of 3-hydroxybenzoic, 3-hydroxyphenylpropionic, and coumaric acids were observed in the basolateral side, whereas 3-hydroxyphenylacetic acid, phenylpropanoic acid, and cinnamic acid were not detected. Subsequent HepG2 cellular metabolism led to major increases in ferulic, dihydrocaffeic, 3-hydroxyphenylpropionic, and coumaric acids ranging from 160–370%. These findings highlight the importance of hepatic metabolism towards the generation of secondary metabolites of polyphenols despite low selective Caco-2 cellular uptake of microbial phenolic metabolites.

Chlorogenic acid inhibits proliferation and induces apoptosis in A498 human kidney cancer cells via inactivating PI3K/Akt/mTOR signalling pathway

“…However, little work has been done to clarify the antitumour effects of CA on kidney cancer. Since CA has been verified through in‐vitro and in‐vivo studies that it is highly bioavailable in humans and protects d ‐galactose‐induced kidney injury, we reasonably speculate that CA may possess antitumour activity against RCC. In this study, we firstly report the inhibition effect of CA against RCC cells and reveal the underlying molecular mechanisms.…”

Chlorogenic Acid and Its Microbial Metabolites Exert Anti-Proliferative Effects, S-Phase Cell-Cycle Arrest and Apoptosis in Human Colon Cancer Caco-2 Cells

“…Although such compounds are poorly absorbed [ 22 ], their relatively high concentrations in the gut lumen could exert functional anti-colon cancer effects. There are a limited number of studies regarding the anti-cancer effects of CGA and CA on colon cancer cell lines, including Caco-2 cells.…”

Chlorogenic Acid Improves the Regorafenib Effects in Human Hepatocellular Carcinoma Cells

“…Several studies have demonstrated that CGA shows many biological properties; it is widely accepted that this molecule has several human health benefits, acting as an antibacterial [ 2 ], anti-inflammatory [ 3 ], and antioxidant [ 4 ] agent, as well having hypoglycemic and hypolipidemic [ 5 ] activities. In addition, in vivo and in vitro studies have shown that CGA is highly bioavailable in humans [ 6 , 7 ].…”