Review on the Use of Cell Cultures to Study Metabolism,Transport, and Accumulation of Flavonoids: From Mono‐Cultures to Co‐Culture Systems

The aim of this review is to provide a comprehensive discussion on the various human/animal cell‐based models used to study the absorption, transport, and metabolism of flavonoids. Flavonoids are plant‐based bioactive compounds that have been extensively investigated for their active role in health alleviation and disease prevention. For this purpose, cell lines isolated from various human and animal tissues have been routinely used as an in vitro model to assess the bioavailability and bioactivity of these compounds. This paper reviews for the first time various transporters (SLCT, SGLT, bilitranslocase, and ABC transporters), metabolic routes (deglycosylation, glucuronidation, sulfation, and deconjugation), and accumulation of flavonoids in different cell lines commonly used in flavonoid research. Also, the use of co‐culture systems to study flavonoid bioactivity will be discussed. To date, no definite mono‐culture or co‐culture formulation has been generally accepted to be the most accurate representation of the in vivo situation. Therefore, further investigation and improvement of cell‐based in vitro models for flavonoid research merit further investigation.