Location: Diet, Genomics and Immunology Laboratory2018 Annual Report
1a. Objectives (from AD-416):
Obesity is a serious health condition, often associated with grave consequences on several chronic diseases such as diabetes, insulin resistance, cardiovascular disease, hypertension, chronic kidney disease (CKD), and other dysfunctions. U.S. government statistics show nearly two-thirds of U.S. adults are overweight and with half of them considered obese. Therefore, this plan is based on the hypothesis that diets containing phenolics and their natural derivatives help decrease risk factors of hypertension, CKD and their related events via improving obesity and its associated conditions. The objectives of this plan are: Objective 1: Determine the extent to which obesity-induced hypertension can be attenuated by polyphenolic compounds (focusing on caffeic acid, ferulic acid, chlorogenic acids and their natural derivatives) found in grains and vegetables. (NP107, C4, PS 4A) Objective 2: Determine the extent to which obesity-induced impaired kidney function can be attenuated by polyphenolic compounds (focusing on caffeic acid, ferulic acid, chlorogenic acids and their natural derivatives) found in grains and vegetables. (NP107, C4, PS 4A) Objective 3: Determine dietary components and their mechanisms that mitigate the adverse effects of exposure to environmental toxins in both parents and offspring on metabolic diseases such as obesity and diabetes. (NP107, C4, PS 4A, C5, PS 5A)
1b. Approach (from AD-416):
The extent to which obesity-induced hypertension can be reduced by polyphenolic compounds (focusing on caffeic acid, ferulic acid, chlorogenic acids, and their natural derivatives) found in grains and vegetables will be evaluated by attenuating subclinical inflammation and its related events by caffeic acid, ferulic acid, chlorogenic acids, protocatechuic acid, and their natural derivatives found in plants including grains and vegetables in an animal model. Regulation of COX enzymes, NF-kB, peroxynitrite, ox-LDL, p38, MCP-1, IL-6, TNF-alpha, and angiotensin will be investigated as mechanisms of action in-vivo. The extent to which obesity-induced impaired kidney function can be attenuated by polyphenolic compounds (focusing on caffeic acid, ferulic acid, chlorogenic acids, and their natural derivatives) found in grains and vegetables will also be determined via reactive oxygen species (ROS) investigating regulation of AGEs, p38, MCP-1, TGF-beta, EMT, and adiponectin-mediated pathways as mechanisms of action in in vitro models.
3. Progress Report:
Health benefits of the consumption of plant-based products (e.g., fruits, vegetables, tea, cocoa, coffee) are widely recognized, but potential health benefits of their chemicals are still being investigated. We focused on elucidating the potential health effects of safflomide-type phenolic amides (e.g., safflomide, javamide-I/-II) found in cocoa, coffee and other plants. This year, we investigated the potential effects of safflomide analogues and javamide-I/-II on MAP Kinases (e.g., pERK, p38, pJNK) and inflammatory cytokines (e.g., TNF-alpha, IL-2, IL-6, MCP-1) related to subclinical inflammation occurring in atherosclerosis, liver disease and CKD. We demonstrated that safflomide can inhibit inflammatory cytokines such as IL-2, TNF-alpha, IL-6 and MCP-1 in human immune cells (e.g., Jurkat, THP-1 cells) via suppressing MAPKs (e.g., p38). This is new information suggesting that safflomide may suppress, not only MCP-1, but also other inflammatory cytokine conditions associated with diabetes, arthrosclerosis and CKD. We also demonstrated that javamide-I can inhibit TNF-alpha and IL-2 stronger than caffeine in human lymphocytic Jurkat cells. These data suggest that javamide-I may be a potent compound to suppress TNF-alpha and IL-2 production more efficiently than caffeine in lymphocytic cells. Javamide-I/-II are found in coffee products (e.g., coffee beans, ground coffee, espresso, green coffee, milk coffee), but there is little information about their quantities in coffee products. A HPLC method for quantifying javamide-I/-II was developed with an electrochemical detector and the method was found to be useful in differentiating javamides' content in coffee beans (Arabica and Robusta) with excellent reproducibility. Robusta beans contain ~ 60X higher javamides than Arabica beans. This study is the first report on the utility of javamide-I/-II as biomarkers in designating Arabica and Robusta beans. In addition, we conducted the proposed animal study and collected biological samples (e.g., blood, urine, liver, kidney) for biological analyses (e.g., creatinine, GFR, cystatin-C, KIM-1, aldosterone, TGF-beta, RANTES, MCP-1, IL-8). This study will provide information about the potential effects of safflomide and its analogues on subclinical inflammation in arthrosclerosis, cardiovascular disease, liver disease, and CKD.
1. Coffee-derived phytochemical javamide-II suppress inflammatory cytokines (TNF-alpha and IL-2) production. Recent studies suggested positive benefits of coffee consumption on inflammation-related diseases, such as diabetes and fatty liver diseases, where regulation of TNF-alpha production from lymphocytes is critically implicated. Javamide-II is an anti-inflammatory compound found in coffee, but there is limited information about its effect on TNF-alpha production by activated lymphocytes. ARS scientists at the Beltsville Human Nutrition Center, Diet, Genomics and Immunology Laboratory, Beltsville, Maryland, demonstrated that javamide-II can inhibit TNF-alpha and IL-2 more than caffeine in human lymphocytic Jurkat cells. This is the first report suggesting that javamide-II may be a potent compound to suppress TNF-alpha and IL-2 production more efficiently than caffeine in lymphocytic cells, which may contribute to beneficial effects of coffee on inflammation-related diseases.
Park, J.B. 2017. In silico screening and in vitro activity measurement of javamide analogues as potential p38 MAP kinase inhibitors. International Journal of Molecular Sciences. 18(12)pii:E2704. https://doi.org/10.3390/ijms ijms18122704.
Liu, M., Yasmeen, R., Fukagawa, N.K., Yu, L., Kim, Y.S., Wang, T.T. 2017. Dose-dependent responses of I3C and DIM on T-cell activation in the human T lymphocyte Jurkat cell line. International Journal of Molecular Sciences. 18(7). pii: E1409. https://doi.org/10.3390/ijms18071409.