Absorption and Transport Characteristics and Mechanisms of Carnosic Acid

SIMPLE SUMMARY: Carnosic acid (CA), a phenolic diterpenoid mainly found in rosemary and sage, has been reported to possess various health-beneficial activities. However, detailed information about the absorption characteristics and mechanisms of CA and its tissue distribution still remains unclear. It has been well-recognized that the absorption, transport, and metabolism of dietary bioactive compounds are closely related to their biological functions. Herein, a mouse study and Caco-2 cell monolayer model of the intestinal epithelial barrier were used to understand the absorption and transport characteristics of CA. First, we determined the tissue distribution of CA in mice following oral gavage at a physiologically relevant dose. We found that CA was bioavailable systemically and present locally in the digestive tract, especially in the cecum and colon. Next, in Caco-2 cell monolayers, CA exhibited a moderate permeability and was subjected to mild efflux. Moreover, the apparent permeability coefficient of CA transported across Caco-2 cell monolayers was significantly changed when the inhibitors of specific active transporter and passive diffusion were added, suggesting that the absorption and transport of CA involved both passive and active transportation. The present study is an important first step towards understanding the absorption, transport, and metabolic mechanisms of CA. ABSTRACT: Carnosic acid (CA) is a phenolic diterpenoid mainly found in rosemary and sage. CA has been reported to possess health-beneficial effects in various experimental settings. Herein, a mouse experiment and Caco-2 single-cell model were used to understand the absorption and transport characteristics of CA. First, we determined the tissue distribution of CA in mice, following an oral gavage at a physiologically relevant dose. We found that CA was bioavailable systemically and present locally in the digestive tract, especially in the cecum and colon. Next, we thought to characterize the absorption and transport of CA in the Caco-2 cell monolayer model of the intestinal epithelial barrier. In the Caco-2 cell model, CA exhibited a moderate permeability and was subjected to a mild efflux. Moreover, the apparent permeability coefficient (P(app)) of CA transported across Caco-2 cell monolayers was significantly changed when the inhibitors of specific active transporter and passive diffusion were added to cells, suggesting that the absorption and transport of CA involved both passive and active transportation. The present study is an important first step towards understanding the absorption, transport, and metabolic mechanisms of CA. This could provide the scientific basis for developing CA-containing functional foods or dietary supplements with improved bioavailability.