Source: NORTH CAROLINA A&T STATE UNIV submitted to NRP
POSTPRANDIAL EFFECTS OF APPLE POLYPHENOLS ON CARBONYL STRESS IN HUMANS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
ACTIVE
Funding Source
Reporting Frequency
Annual
Accession No.
1025306
Grant No.
2021-67017-34205
Cumulative Award Amt.
$499,975.00
Proposal No.
2020-04448
Multistate No.
(N/A)
Project Start Date
Feb 15, 2021
Project End Date
Feb 14, 2026
Grant Year
2021
Program Code
[A1343]- Food and Human Health
Recipient Organization
NORTH CAROLINA A&T STATE UNIV
1601 EAST MARKET STREET
GREENSBORO,NC 27411
Performing Department
Ctr of Excel for Post Harvest
Non Technical Summary
Humans are both endogenously and exogenously exposed to reactive carbonyl species (RCS). It has been suggested that RCS play a critical role in the development of many chronic diseases, such as Alzheimer's disease, cardiovascular disease, and diabetes and diabetic complications. We have demonstrated that polyphenols from apples and other foods have the capacity to efficiently trap RCS in vitro and in mice and therefore inhibit the formation of Advanced Glycation End products (AGEs). However, it is still largely unknown whether this occurs in humans. The goal of this project is to determine the post-prandial effects of apple polyphenols on the kinetic changes of RCS and RCS associated AGEs/Advanced Lipoxidation End products(ALEs) in humans.
Animal Health Component
(N/A)
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
72411101010100%
Knowledge Area
724 - Healthy Lifestyle;

Subject Of Investigation
1110 - Apple;

Field Of Science
1010 - Nutrition and metabolism;
Goals / Objectives
The goal of this project is to determine the post-prandial effects of apple polyphenols on the kinetic changes of reactive carbonyl species (RCS) and RCS associated AGEs/ALEs in humans. Based on our previous and preliminary data, the hypothesis of this project is that apple polyphenols can trap RCS and thus inhibit the accumulation of RCS and AGEs/ALEs in humans. This hypothesis will be tested by the following specific objectives: Objective 1: To study the formation and pharmacokinetics of RCS conjugates of apple polyphenols and their metabolites in humans; Objective 2: To investigate whether apple polyphenols can decrease the post-prandial levels of reactive carbonyl species in humans; Objective 3: To determine whether apple polyphenols can inhibit the post-prandial accumulation of AGEs/ALEs in humans.
Project Methods
1. For Objective 1, we will synthesize the RCS conjugates of apple polyphenols, confirm the formation of RCS conjugates in human samples using LCMS, and develop LCMS methods to quantifyRCS conjugates of apple polyphenols and obtain the kinetic curves.2. For Objective 2, we will use LCMS to quantify RCS in human samples and obtain the kinetic curves.3. For Objective 3, we will synthesize AGEs, devleop LCMS methods to quantify AGEs and obtain their kinetic curves.

Progress 02/15/24 to 02/14/25

Outputs
Target Audience:The target audience comprises members of the general public with an interest in using food as medicine, as well as scientists in academia and industry who specialize in studying bioactive food compounds. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?We trained a postdoc. How have the results been disseminated to communities of interest?We published one research article and gave twopresentations at two different scientific conferences. What do you plan to do during the next reporting period to accomplish the goals?We plan to continue analyze the data generated from this project and submit two manuscripts in 2025.

Impacts
What was accomplished under these goals? For Objective 1, we quantified the levels of apple polyphenols, their metabolites, and the RCS conjugates of apple polyphenols and their metabolites in urine samples. We are writing a manuscript. For Objective 2, we finished the analysis of the plasma RCS levels in the samples collected from the apple feeding study. We did see positive effects from apple intake on postprandial levels of some RCS. We are finalizing the manuscript and plan to submit it by the end of May 2025. For Objective 3, we finalized our AGEs measurement method and the manuscript was published by JAFC.

Publications

  • Type: Peer Reviewed Journal Articles Status: Published Year Published: 2025 Citation: Wang, W.; Zhu, Y.; Sang, S. Optimization for simultaneous determination of a panel of advanced glycation end products as biomarkers for metabolic diseases. J Agric Food Chem. 2025, 73, 6970-6980.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2024 Citation: Sang, S. Carbonyl stress as a new mechanistic target of dietary flavonoids for prevention of metabolic disorders 268th ACS National Meeting, Denver, CO, August 18-22, 2024
  • Type: Conference Papers and Presentations Status: Published Year Published: 2024 Citation: Yu, J.; Wang, W.; Zhu, Y.; Sang, S. The combination of pharmacokinetic studies and targeted metabolomics as a powerful tool for identifying exposure biomarkers of apple intake 72nd Conference on Mass Spectrometry and Allied Topics, Anaheim, CA, June 2-6, 2024


Progress 02/15/23 to 02/14/24

Outputs
Target Audience:The target audience comprises members of the general public with an interest in using food as medicine, as well as scientists in academia and industry who specialize in studying bioactive food compounds. Changes/Problems:Our first NCE request has been approved. What opportunities for training and professional development has the project provided?We trained one graduate student whose research is to investigate the mechanisms that apple polyphenols trap reactive carbonyl species generated from lipid peroxidation. One of his manuscripts has been published by the Journal of Agricultural and Food Chemistry. How have the results been disseminated to communities of interest?We published one research article and gave four presentations at four different scientific conferences. What do you plan to do during the next reporting period to accomplish the goals?We plan to finish the analysis of apple polyphenols and their RCS conjugates in plasma samples and publishe two manuscripts based on results generated from Objectives 1 and 2 and one manuscript from Objective 3.

Impacts
What was accomplished under these goals? For Objective 1, we quantified the levels of apple polyphenols, their metabolites,and the RCS conjugates of apple polyphenols and their metabolites in urine samples. For Objective 2, we finished the analysis of the plasma RCS levels in the samples collected from the apple feeding study. Wedid see positive effects from apple intake on postprandial levels of some RCS. We are writing two manuscripts based on results generated from Objectives 1 and 2. For Objective 3, we finalized our AGEs measurement method. We are writing a manuscript on our LC/MS AGEs method.?

Publications

  • Type: Journal Articles Status: Published Year Published: 2023 Citation: Djorgbenoo, R.; Wang, W.; Zhu, Y.; Sang, S. Detoxifation of lipid peroxidation aldehyde, 4-hydroxynonenal, by apple phloretin in vitro and in mice. J Agric Food Chem 2023, 71, 10629-10637.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2023 Citation: Djorgbenoo, R.; Wang, W.; Zhu, Y.; Sang, S. Detoxification of lipid peroxidation aldehyde, 4-hydroxynonenal, by flavonoids in apple and grapefruit. 265th ACS National Meeting, Indianapolis, IN, March 26-30, 2023.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2023 Citation: Sang, S. Yu, J.; Wang, W.; Zhu, Y. Postprandial effects of apple polyphenols on carbonyl stress in humans. Nutrition 2023 ASN Annual Conference, Boston, MA, July 21-25, 2023.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2023 Citation: Yu, J.; Zhu, Y.; Wang, W.; Sang, S. Identification of exposure biomarkers for apple consumption by targeted metabolomics approach 266th ACS National Meeting, San Francisco, CA, August 13-17, 2023.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2023 Citation: Djorgbenoo, R.; Zhu, Y.; Wang, W.; Sang, S. Detoxification of lipid peroxidation aldehyde, 4-hydroxynonenal, by flavonoids in apple and grapefruit. IFT Annual Meeting, Chicago, IL, July 16-19, 2023.


Progress 02/15/22 to 02/14/23

Outputs
Target Audience:Target audience includes general public who have interest to food as medicine and scientists in academia and industry who study bioactive food compounds. Changes/Problems:Because the delay of Year 1, we will ask one-year no-cost extension for this project. What opportunities for training and professional development has the project provided?We trained one graduate student whose research is to inviestigate the mechanism that apple polyphenols trap reactive carbonyl species generated from lipid peroxidation. One of his manuscript has been accepted by the Journal of Agriculturaland Food Chemistry. How have the results been disseminated to communities of interest?Three presentations were given at different conferences. What do you plan to do during the next reporting period to accomplish the goals?We plan to publish results found from Aim 1 and complete Aim 2.

Impacts
What was accomplished under these goals? For Objective 1, we have finished the chemical profile of the apples used in the feeding study, the metabolic profile of apple polyphenols including major phase I and microbial metabolites of apple polyphenols and their RCS conjugates, and the development of the quantitative LC/MS method to analyze the levels of apple polyphenols, their metabolites, and the RCS conjugates of apple polyphenols and their metabolites. We are quantifying the levels ofapple polyphenols, their metabolites, and the RCS conjugates of apple polyphenols and their metabolites. For Objective 2, we finished the analysis of the urinary RCS levels in the samples collected from the apple feeding study. We did see some positive effects from apple intake. For Objective 3, we modified our AGEs measurement method by including more than 10 AGEs. Once the method is finalized, we will quantify the AGE levels in the samples from the feeding study.

Publications

  • Type: Journal Articles Status: Accepted Year Published: 2023 Citation: Djorgbenoo, R.; Wang, W.; Zhu, Y.; Detoxifation of lipid peroxidation aldehyde, 4-hydroxynonenal, by apple phloretin in vitro and in mice. J Agric Food Chem (Accepted)
  • Type: Conference Papers and Presentations Status: Published Year Published: 2022 Citation: Alfaro-Viquez, E.; Zhao, Y.; Sang, S. Dietary phloretin and quercetin reduce plasma and tissue methylglyoxal and its glycation products in healthy mice treated with methylglyoxal 264th ACS National Meeting, Chicago, IL, August 21-25, 2022.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2022 Citation: Djorgbenoo, R.; Zhu, Y.; Sang, S. Trapping of lipid peroxidation products - malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE)- by apple flavonoid, phloretin. Association of 1890 Research Directors (ARD) Research Symposium 2022, Atlanta, GA, April 2-5, 2022.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2022 Citation: Djorgbenoo, R.; Zhu, Y.; Sang, S. Trapping effects of lipid peroxidation product  4-hydroxynonenal (4-HNE) - by apple flavonoid, phloretin 264th ACS National Meeting, Chicago, IL, August 21-25, 2022.


Progress 02/15/21 to 02/14/22

Outputs
Target Audience:ordinary people who have interest to healthy living and researchers in the field. Changes/Problems:For Year 1, due to the pandemic, we experienced major challenges to hire a qualified postdoc for this project. In addition, our HR was under-staffed and had difficulty to hire new members, which further delayed the hiringprocess. Currently, we are working with HR to have one of my current members to spend 50% of her effort on this grant until we hire a new postdoc. In the future, we will ask one-year no-cost-extension for this project. What opportunities for training and professional development has the project provided?We trained a graduate student whose research will focus on trapping of lipid peroxidation products by dietary flavonoids. How have the results been disseminated to communities of interest?I gave an oral presentation at thePacifichem 2021 conference. What do you plan to do during the next reporting period to accomplish the goals?For next reporting period, we plan to finish all the proposed research in Aim 1.

Impacts
What was accomplished under these goals? Although we was not able to hire a qualified postdoc during the pandemic, we still made some progress for Aim 1. We searched the the metabolites of the major flavonoids in apple and their corresponding RCS conjugates.

Publications

  • Type: Journal Articles Status: Published Year Published: 2022 Citation: Zhu, Y.; Wang, W.; Huang, Q.; Hu, C.; Sang, S. Metabolic investigation on the interaction mechanism between dietary dihydrochalcone intake and lipid peroxidation product acrolein reduction. Mol Nutr Food Res. 2022, 69, 202101107.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2021 Citation: Sang, S. Impact of bioavailability and biotransformation on translating in vitro acrolein-trapping capacities of dietary polyphenols to in vivo situation Pacifichem 2021 (Virtual), December 16-21, 2021.