Diurnal rhythmicity in biological processes involved in bioavailability of functional food factors

Abstract

In the past few decades, many types of functional factors have been identified in dietary foods; for example, flavonoids are major groups widely distributed in the plant kingdom. However, the absorption rates of the functional food factors are usually low, and many of these are difficult to be absorbed in the intact forms because of metabolization by biological processes during absorption. To gain adequate beneficial effects, it is therefore mandatory to know whether functional food factors are absorbed in sufficient quantity, and then reach target organs while maintaining beneficial effects. These are the reasons why the bioavailability of functional food factors has been well investigated using rodent models. Recently, many of the biological processes have been reported to follow diurnal rhythms recurring every 24 h. Therefore, absorption and metabolism of functional food factors influenced by the biological processes may vary with time of day. Consequently, the evaluation of the bioavailability of functional food factors using rodent models should take into consideration the timing of consumption. In this review, we provide a perspective overview of the diurnal rhythm of biological processes involved in the bioavailability of functional food factors, particularly flavonoids.

Keywords: bioavailability; diurnal rhythmicity; flavonoids; functional food factors; rodents.

Fig. 1

The negative feedback loop responsible for circadian rhythm.

Fig. 2

Diurnal gene expression profiles of clock genes related to the negative feedback loop, xenobiotic transporter, regulation of absorption in duodenum mucosa in mice. Male C57BL/6 mice (4 weeks old) were acclimatized for 4 weeks in the animal-care room, which was controlled at 23 ± 1°C and 60% humidity under a 12 h light/12 h dark cycle with ad libitum food consumption. Mice were anesthetized with ether at ZT0, 6, 12, 18, and 24 (0). ”ZT” is an abbreviation of Zeitgeber time, with ”ZT0” indicating the period when the light came on. Thus, the light period was from ZT0 to ZT12, and the dark period was from ZT12 to ZT24 (0). The duodenum (5 cm length from the stomach) was removed and the mucosa harvested. Total RNA was extracted and individual gene expression analyzed using quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR, PRISM7000, Applied Biosystems, Foster City, CA) according to our previous methods.⁽⁷⁰⁾ All primers used in this study were obtained from Applied Biosystems. (A) main clock pathway: Bmal1 (Assay ID, Mm00500226_m1), Clock (Mm_00455950_m1), Per1 (Mm_00501813_m1), Per2 (Mm_00478113_m1), Cry1 (Mm_00514392_m1); (B) xenobiotic transporter P-glycoprotein: Mdr1a (Mm_00440761_m1); and (C) regulation of absorption: Sglt1 (Mm_00451203_m1), Glut5 (Mm_ 00900311_m1), Pept1 (Mm_00453524_m1). This experiment was performed in accordance with the guidelines of the University of Shizuoka, Japan, for the Care and Use of Laboratory Animals, based on those of the American Association for Laboratory Animal Science. Individual abbreviations are summarized at the legends of Table 1. Mean bottom values are set at 1.0, and each data point indicates the mean ±  SE (n = 5). The open bar at the bottoms indicates the light period (inactive phase), and the closed bar the dark period (active phase).

Fig. 3

Effects of administration period on gastric emptying time after oral administration of bilberry anthocyanin in mice. Male C57BL/6 mice (6 weeks old) were acclimatized for 2 weeks in the animal-care room with free access to tap water and purified diet. After 12 h of fasting, bilberry extracts obtained from Wakasa Seikatsu Co. Ltd., (Kyoto, Japan) were orally administrated in amounts of 100 mg/kg body weight at ZT0 or ZT12. Animals were anesthetized with ether at individual time points, and the gastrointestinal tract was dissected into stomach and ileum (5 cm length from the blind gut). Tissue specimens were immersed immediately into 5 ml of 10% ice-cold citric acid, and then thoroughly dissected. After mixing at 2,500 rpm for 5 min, the sample solution was centrifuged at 3,000 rpm for 10 min, and 1.5 ml of the supernatant was evaporated to dryness using a centrifugal concentrator. The residue was dissolved in 300 µL of methanol containing 0.5% trifluoroacetic acid and was subjected to high performance liquid chromatography analysis according to our previous method.⁽⁷⁾ This experiment was performed in accordance with the guidelines of the University of Shizuoka, Japan, for the Care and Use of Laboratory Animals, based on those of the American Association for Laboratory Animal Science. Data indicate mean ± SD (n = 5) of total anthocyanins in the stomach (A) and ileum (B) at individual time points. The open bar indicates the administration at ZT0, and the closed bar was at ZT12. *Significant differences vs same time point after the treatment at ZT0 (p<0.05, Fisher-PLSD analysis). B, before the treatment at ZT0 or ZT12; ud, under the detection limits.