Source: UNIVERSITY OF ILLINOIS submitted to
IDENTIFICATION AND MECHANISM OF ANTHOCYANINS FROM FOODS [INCLUDING COLORED CORN] WITH ANTIDIABETIC POTENTIAL
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
NEW
Funding Source
Reporting Frequency
Annual
Accession No.
1014457
Grant No.
(N/A)
Project No.
ILLU-698-326
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Jan 8, 2018
Project End Date
Sep 30, 2022
Grant Year
(N/A)
Project Director
De Mejia, E.
Recipient Organization
UNIVERSITY OF ILLINOIS
2001 S. Lincoln Ave.
URBANA,IL 61801
Performing Department
Food Science & Human Nutrition
Non Technical Summary
Corn (Zea mays L.) is the most widely produced grain in the United States. Anthocyanins (ANC) present in colored cornare natural pigments with food colorant potential that exert different health benefits. However there is a gap in knowledge related to the effect of individual ANC in type-2 diabetes (T2DM), a disease that costs more than $245 billion to the U.S. There is also a need forinformation about the relationship of the ANC composition in colored corn and their antidiabetic potential. Furthermore, there is a need to confirm these effects in a more complex biological system, such as an animal model. The first aim of this study looks for the determination of the antidiabetic potential of individual ANC from colored corn in vitro using different dual-cell culture systems. The second aim will establish the relationship between ANC chemical composition of different varieties of colored corn with their antidiabetic potential. A third aim focuses on the confirmation of the antidiabetic potential of ANC from colored corn and the molecular mechanisms involved in an animal model. This research is relevant since it focuses on the use of dietary bioactive components to decrease T2DM, a disease that causes more than 70,000 deaths per year, affecting approximately 13% of the American population.
Animal Health Component
0%
Research Effort Categories
Basic
50%
Applied
50%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
50215101060100%
Knowledge Area
502 - New and Improved Food Products;

Subject Of Investigation
1510 - Corn;

Field Of Science
1060 - Biology (whole systems);
Goals / Objectives
Specific goal #1: Determine the antidiabetic potential of individual anthocyanins from colored corn in vitro. Our working hypothesis is that ANC from colored corn will interact with the novel molecular targets FFAR1 (free fatty acid receptor 1) and GK (glucokinase) in an in vitro model to promote insulin secretion and glucose utilization. Specific goal #2: Establish the relationship between chemical composition of anthocyanin-rich extracts of different varieties of colored corn with their antidiabetic potential. Our working hypothesis is that the antidiabetic molecular mechanisms of various ANC-rich extracts from colored corn varieties will depend on their different ANC composition. Specific goal #3: Confirm the antidiabetic potential of anthocyanins from colored corn and the molecular mechanisms involved in an animal model. Our working hypothesis is that the ANC from colored corn will reduce T2DM in a rat model through the increase of insulin secretion and insulin sensitization to improve glucose utilization. The animal use portion of this objective will not be conducted at the University of Illinois.This part of the research will be performed as a collaboration with the Institute of Neurobiology of the National University of Mexico (UNAM, Campus Juriquilla), with register SAGARPA-SENESICA No. AUT-B-C-0815-024 and the study protocol approved by the Bioethics Committee of University of Queretaro, Queretaro, Mexico.
Project Methods
The project will be divided into three different phases according to our specific goals. In phase I we will assess the efficacy of individual bioactive compounds, including anthocyanins, from foods (including colored corn)to modulate markers related to chronic diseases using innovative in vitro experiments with intestinal, pancreatic, and hepatic dual-cell culture systems. After selecting the most promising compounds based on their bioactivities, we will move to phase II, where the relation of the chemical composition of bioactive-extracts from unique varieties of colored corn with their antidiabetic mechanism of action will be established. Furthermore, in phase III the antidiabetic potential of bioactive compounds from foods, including colored corn, will be confirmed in an animal model of rats, and the mechanisms of action will be established. It is important to clarify that the animal model work will not be performed at the University of Illinois.The proposed research is innovative because it will systematically investigate at the molecular level the role of individual bioactive compounds from foods, including colored corn, in health and wellness as it relates specifically to type-2 diabetes as well as atherosclerosis attenuation or prevention. This proposal offers transformative solutions as it is seeking to understand the role of dietary compounds extracted from foods on chronic diseases using an in vitro dual-cell culture system, an animal model, confocal immunofluorescence microscopy, and molecular docking experiments. These approaches will allow us to better understand the anti-diabetic mechanisms of dietary foods and will determine the long-term potential to ameliorate or prevent their risk. With the knowledge gained from this research, the role of dietary bioactive compounds from foods, including corn, to reduce chronic diseases will be expanded, thus contributing to the field of phytochemicals on human health.

Progress 01/08/18 to 09/30/18

Outputs
Target Audience:Members of the target audience included producers, consumers, and the foodindustry. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Participation and networking in scientific meetings: Americal Chemical Society. Division of Agricultural and Food Chemistry. Oral presentation by invitation. August 19, 2018 - Boston Convention and Exhibition Center. American Chemical Society. Division of Agricultural and Food Chemistry. Natural Alternatives to Artificial Food Additives. Oral presentation. August, 23, 2017 - Walter E. Washington Convention Center. American Society for Nutrition (June 9-12, 2018, Boston). How have the results been disseminated to communities of interest?Presentation in scientific meetings: Luna-Vital, D. A and, de Mejia, E.G. 2018. Current evidence of beneficial effects of anthocyanins from colored corn in in vitro models of obesity and diabetes (AGFD 59). In: Health Promoting Food Ingredients. Division of Agricultural and Food Chemistry. Oral presentation by invitation. August 19, 2018 - Boston Convention and Exhibition Center. de Mejia, E. andLuna-Vital, D. 2017. Stabilization of anthocyanins with food pigment potential and their insulin sensitizing effect in adipocytes under inflammatory status (final paper number: AGFD 219) PAPER ID: 2739944. Division of Agricultural and Food Chemistry. Natural Alternatives to Artificial Food Additives. Oral presentation. August, 23, 2017 - Walter E. Washington Convention Center. Luna-Vital, D. and Gonzalez de Mejia, E. 2018. Activation of novel type-2 diabetes markers free fatty acid receptor-1 and glucokinase by anthocyanins from colored corn in vitro. American Society for Nutrition (June 9-12, 2018, Boston). Abstract ID: 435046. What do you plan to do during the next reporting period to accomplish the goals?Continue with the analyses of the samples from the animal study and submit for publication the following manuscripts: Zhang, Q., Luna-Vital, D. and Gonzalez de Mejia, E. 2018. Anthocyanins from colored maize ameliorated the inflammatory paracrine interplay between macrophages and adipocytes through regulation of NF-κB and JNK-dependent MAPK pathways. Luna-Vital, D., Chatham, L., Juvik, J., Singh, V., Somavat, P. and de Mejia, E. 2019. Water soluble phenolics from an improved variety of Apache red maize activated free fatty acid receptor-1 and glucokinase in vitro. Journal of Agricultural and Food Science. Zhang, Q., Gonzalez de Mejia, E., Luna-Vital, Tao, T., Chandrasekaran, S., Chatham, L., Juvik, J., Singh, V. and Kumar, D. 2019. Anthocyanins from colored maize ameliorated the inflammatory paracrine interplay between macrophages and adipocytes through regulation of NF-kB and JNK-dependent MAPK pathways.

Impacts
What was accomplished under these goals? The objective of this study was to evaluate the ability of anthocyanins (ANC) present in purple corn to enhance insulin secretion and hepatic glucose uptake in pancreatic cells and hepatocytes, through activation of the free fatty acid receptor-1 (FFAR1) and glucokinase (GK), respectively. Using a dual-layer cell culture with Caco-2 cells, INS-1E or HepG2 cells were treated with an anthocyanin-rich extract from the pericarp of purple corn (PCW), as well as pure ANC cyanidin-3-O-glucoside (C3G), peonidin-3-O-glucoside, pelargonidin-3-O-glucoside. Delphinidin-3-O-glucoside (D3G) was used for comparative purposes. Semipurified C3G (C3G-P) and condensed forms (CF-P) isolated from PCW were also used. At 100 μM, the pure ANC enhanced glucose-stimulated insulin secretion (GSIS) in INS-1E cells ranging from 18% to 40% (p<0.05) compared to untreated cells. PCW increased GSIS by 51%. D3G was the most effective anthocyanin activating FFAR1 (EC50: 196.6 μM). PCW had activating potential on FFAR1 (EC50: 77 μg/mL). PCW, as well as C3G and D3G increased the expression of FFAR1, PLC, and phosphorylation of PKD, related to the FFAR1-dependent insulin secretory pathway. The treatment with 100 μM of P3G and C3G increased (p<0.05) glucose uptake in HepG2 cells by 19% and 31%. PCW increased the glucose uptake in HepG2 cells by 48%. It was determined that CF-P was the most effective for activating GK (EC50: 39.9 μM) and the PCW extracts had an efficacy of EC50: 44 μg/mL. The ANC in purple corn also reduced AMPK phosphorylation and PEPCK expression in HepG2 cells, known to be related to reduction in gluconeogenesis. It is demonstrated for the first time that dietary ANC can enhance the activity of novel biomarkers FFAR1 and GK and potentially ameliorate type-2 diabetes comorbidities.

Publications

  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Luna-Vital, D.A. and Gonzalez de Mejia, E. 2018. Anthocyanins from purple corn activate free fatty acid-receptor 1 and glucokinase enhancing in vitro insulin secretion and hepatic glucose uptake. PLoS ONE 13(7): e0200449. https://doi.org/10.1371/journal.pone.0200449.