Absorption and Bioavailability of Artepillin C in Rats after Oral Administration

Abstract

Artepillin C (AC), an active ingredient of Brazilian propolis, permeates intact across Caco-2 cells by transcellular passive diffusion. The permeation of AC across Caco-2 cells is as efficient as that of phenolic acids and the microbial metabolites of poorly absorbed polyphenols, which are actively absorbed by the monocarboxylic acid transporter (MCT) (Biochim. Biophys. Acta 2005, 1713, 138-144). Here, the absorption of orally administered AC in rats has been studied to evaluate its pharmacokinetics and bioavailability in vivo in comparison with those of p-coumaric acid (CA), a substrate of MCT. Rats were given 100 micromol/kg of body weight of AC or CA, and blood was subsequently collected from the portal vein and abdominal artery. AC, CA, and their metabolites were quantified by coulometric detection using HPLC-ECD. The serum concentration of intact AC and CA in the portal vein peaked at 5-10 min after administration, with a C(max) of 19.7 micromol/L for AC and 74.8 micromol/L for CA. The area under the curve (AUC) for intact AC and CA in the portal vein was calculated from the serum concentration as 182.6 and 3057.3 micromol.min.L(-1), respectively. The absorption efficiency of CA was about 17-fold higher than that of AC. Furthermore, the bioavailability of CA was about 278-fold higher than that of AC, and the ratio of AUC in the abdominal artery to AUC in the portal vein was 0.04 and 0.70, for AC and CA, respectively. Thus, AC is likely to be more susceptible to hepatic elimination than is CA. The bioactive compound of AC in vivo should be investigated further.

Induction of caspase-dependent apoptosis in melanoma cells by the synthetic compound (E)-1-(3,4-dihydroxyphenethyl)-3-styrylurea

“…Specifically, phenolic acids can be absorbed through the intestine by an active transport system whereupon they can prevent oxidative stress (18,19). In addition, compounds containing one or more aromatic hydroxyl groups replace α-tocopherol as a chain-breaking anti-oxidant and restore reduced glutathione as a protective agent in cells (15).…”

Dry powder formulation with α-glycosyltransferase-treated stevia for the effective absorption of hydrophobic bioactive compounds in crude drugs

“…3b). The AUC of the propolis/Stevia-G (1/10) was 6.4-fold that of the EEP-SPD, suggesting the dramatic enhancement of oral absorption of artepillin C by the preparation of propolis/Stevia-G (1/10) with Stevia-G. Artepillin C has been reported to be readily incorporated into cells and released to the basolateral side via passive transcellular diffusion [15,17]. As shown Fig.…”

“…The rats were fasted for 1 day before the experiments and were anesthetized using diethyl ether. EEP-SPD, the physical mixture of EEP-SPD/Stevia-G (1/10 w/w), and propolis/Stevia-G (1/10) were orally administered (50 mg/kg solid content of propolis) using an oral dosing syringe after dispersion in 50% propylene glycol as reported by Konishi et al [17]. Blood samples (600 μl) were taken from the jugular vein at 10, 20, 30, 45, 60, 120 and 240 min after administration.…”

“…Even though the active compounds in propolis have shown marvelous therapeutic effects in vitro, it is not clear that propolis is effective after oral administration. However, there have been few researches concerning the absorption properties of the active compounds in propolis [16,17].…”

Non-Involvement of the Human Monocarboxylic Acid Transporter 1 (MCT1) in the Transport of Phenolic Acid

“…[4][5][6][7][8] We have also established that the absorption characteristics of these compounds in the Caco-2 cell line are correlated with their absorption efficiency and bioavailability in vivo. [9][10][11] Furthermore, the microbial metabolites of poorly absorbed parent polyphenols are also thought to be absorbed and distributed by MCT, in a similar way to phenolic acids. 12,13) These observations highlight the physiological impact of MCTmediated absorption and distribution in humans, which involves specific transport systems that act not only on phenolic acids but also on microbial metabolites of poorly absorbed polyphenols or dietary fibers having biological activity, which are referred to as ''metabonutrients.''…”