Urinary excretion rate and bioavailability of chlorogenic acid, caffeic acid, p-coumaric acid, and ferulic acid in non-fasted rats maintained under physiological conditions

Kunihiro Kishida,Harumi Matsumoto

doi:10.1016/j.heliyon.2019.e02708

Abstract

Hydroxycinnamic acids (HAs) are one of the major classes of phenolic compounds and epidemiological studies have suggested that they have beneficial health effects. This study aimed to determine the urinary excretion rate of chlorogenic acid, caffeic acid, p-coumaric acid, and ferulic acid in non-fasted rats and to estimate their bioavailability under physiological conditions. Previous studies have primarily used fasted animals, which exhibit severe changes in various physiological processes. Furthermore, the food matrix can affect HA bioavailability. Thus, our studies using non-fasted rats under physiological conditions may allow for a more accurate determination of both the HA urinary excretion rate and the bioavailability of HAs. HAs were successively gavaged to rats at a dose of 40 mg/kg body weight (BW) with a wash-out period of one week. The rats were fed the AIN-93M diet throughout the experiment. The urine was collected at time intervals of 0–6 h, 6–24 h, and 24–48 h after HA administration. Ingested HAs, except chlorogenic acid, were primarily excreted in the urine within 0–6 h as free forms or conjugated (glucuronidated and/or sulfated) forms. The majority of the ingested chlorogenic acid was detected in the urine at 6–24 h or 24–48 h as caffeic acid, p-coumaric acid, ferulic acid, and their conjugates. The total urinary excretion rate (% of the dose) at 48 h was ferulic acid (73.2%) > caffeic acid (61.6%) >p-coumaric acid (54.1%) >> chlorogenic acid (4.9%). The percentages of the conjugates in the urine differed amongst the rats gavaged with the individual HAs (74% for chlorogenic acid, 83% for caffeic acid, 68% for p-coumaric acid, and 96% for ferulic acid), which may be explained by their distinct bioactivities. These data reveal that caffeic acid, p-coumaric acid, and ferulic acid are much more bioavailable than chlorogenic acid, even though they are excreted more rapidly than chlorogenic acid. Our findings may provide additional insight into the health benefits of HAs and how they function in the body.

Highlights

Epidemiological studies have suggested that dietary phenolic compounds from plant products contribute to the prevention of degenerative diseases such as cardiovascular disease and cancer [1, 2, 3]
The results suggest that the majority of ingested caffeic acid, p-coumaric acid, and ferulic acid were absorbed, conjugated, and excreted in the urine within 0–6 h, while chlorogenic acid was poorly absorbed and urinary excretion was detected at 6–24 h and 24–48 h
Konishi et al reported that the intestinal absorption of these Hydroxycinnamic acids (HAs) was mediated by monocarboxylic transporters (MCTs) and plasma HA concentrations were associated with the order of affinity for MCTs [26, 27, 28, 29] Our results are in agreement with these studies except that in our studies caffeic acid exhibited a higher urinary excretion rate than p-coumaric acid

Summary

Introduction

Epidemiological studies have suggested that dietary phenolic compounds from plant products contribute to the prevention of degenerative diseases such as cardiovascular disease and cancer [1, 2, 3]. The antioxidant capacity of dietary phenolic compounds may explain the health benefits since several in vitro studies demonstrated that these compounds protect low-density lipoprotein (LDL) from oxidative modifications [4, 5, 6]. Studies analyzing the antioxidant capacity of phenolic compounds in vivo are controversial, since many of the phenolic compounds are poorly absorbed and metabolized into inactive forms, resulting in low blood concentrations [7]. Specific phenolic compounds exhibit bioactivity in vivo, functioning as inhibitors of NADPH oxidase and 5-lipoxygenase [9, 10]. The majority of phenolic compounds in foods are present as bound forms with low bioaccessibility; they are poorly bioavailable [11, 12, 13, 14]. It is essential to study their bioavailability to assess their bioactive

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