Subscriber access provided by University of Sussex Library
Article
Identification of Plasma and Urinary Metabolites and Catabolites Derived from Orange Juice (Poly)phenols: Analysis by High Performance Liquid Chromatography-High Resolution-Mass Spectrometry Gema Pereira-Caro, Iziar A Ludwig, Thelma Polyviou, Dalia Malkova, Ada Garcia, Jose-Manuel Moreno Rojas, and Alan Crozier J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.6b02088 • Publication Date (Web): 24 Jun 2016 Downloaded from http://pubs.acs.org on July 4, 2016
Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of Agricultural and Food Chemistry is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
Page 1 of 41
Journal of Agricultural and Food Chemistry
Identification of Plasma and Urinary Metabolites and Catabolites Derived from Orange Juice (Poly)phenols: Analysis by High Performance Liquid Chromatography-High Resolution-Mass Spectrometry
Gema Pereira-Caro§, Iziar A. Ludwig$, Thelma Polyviou¶, Dalia Malkova¶ , Ada García¶, José Manuel Moreno-Rojas§, and Alan Crozier#*
§Postharvest
Technology and Agrifood Industry Area, Andalusian Institute of Agricultural
and Fishery Research and Training (IFAPA) Alameda del Obispo, Córdoba. Spain. $Department ¶
of Food Technology, Universitat de Lleida, Lleida, Spain
School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Science,
School of Medicine, University of Glasgow, Glasgow, UK #Department
of Nutrition, University of California, Davis, California, USA
1 ACS Paragon Plus Environment
Journal of Agricultural and Food Chemistry
1
ABSTRACT: Orange juice is a rich source of (poly)phenols, in particular the flavanones
2
hesperetin-7-O-rutinoside and naringenin-7-O-rutinoside. Following the acute consumption
3
of 500 mL of orange juice containing 398 µmol of (poly)phenols by 12 volunteers, 0-24 h
4
plasma and urine samples were analysed by targeted high-performance liquid
5
chromatography-high resolution-mass spectrometry in order to identify flavanone
6
metabolites and phenolic acid and aromatic catabolites. A total of 19 flavanone metabolites
7
which comprised di-O-glucuronide, O-glucuronide, O-glucuronyl-sulfate, and sulfate
8
derivatives of hesperetin, naringenin and eriodictyol, and 65 microbial-derived phenolic
9
catabolites, such as phenylpropanoid, phenylpropionic, phenylacetic, benzoic and
10
hydroxycarboxylic acids and benzenetriol and benzoylglycine derivatives, including free
11
phenolics and phase II sulfate, glucuronide and methyl metabolites, were identified or
12
partially identified in plasma and/or urine samples. The data obtained provide a detailed
13
evaluation of the fate of orange juice (poly)phenols as they pass through the gastrointestinal
14
tract, and are absorbed into circulatory systems prior to renal excretion. Potential pathways
15
for these conversions are proposed.
16 17
KEYWORDS: orange juice, flavanones, HPLC-HR-MS identification, urinary and plasma
18
metabolites; phenolic catabolites, bioavailability, humans
19
2 ACS Paragon Plus Environment
Page 2 of 41
Page 3 of 41
Journal of Agricultural and Food Chemistry
20
INTRODUCTION
21
Human intervention trials have provided evidence for the protective effects against chronic
22
diseases of a fruit and vegetable (poly)phenol-rich diet.1,2 Fruit juices represent a further
23
option for consumers to increase their intake of (poly)phenols. In particular, orange juice (OJ)
24
is of interest due to its widespread consumption and high flavanone content, predominantly in
25
the form of hesperetin-7-O-rutinoside and naringenin-7-O-rutinoside3. Epidemiological
26
prospective studies have shown consistent associations between the intake of flavanone-
27
containing citrus fruit and prevention of various types of cancer,4,5,6 and regular consumption
28
of OJ has been linked to improved vascular function.7
29
Among the factors necessary to elucidate the mode of action underlying the potential
30
protective effects of flavanones in humans, is an understanding of the absorption, disposition,
31
metabolism and excretion (aka bioavailability) of flavanones in vivo. Following ingestion, OJ
32
flavanones were, until recently, considered to be poorly bioavailable with only relatively small
33
amounts of the ingested dose entering the systemic circulation, not as the parent compounds
34
but as phase II metabolites, mainly glucuronide and sulfate derivatives, with studies reporting
35
peak plasma concentration ranging from 63 to 1500 nM8,9 and urinary recoveries
