Location: Diet, Genomics and Immunology Laboratory2017 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 worldwide, and health benefits of their chemicals are relatively well-documented. However, there is very little information regarding the beneficial health effects of safflomide-type phenolic amides (e.g., safflomide, javamide-I/-II found in cocoa, coffee and other plants) on subclinical inflammation, which is an underling cause for initiating/developing CVD, hypertension, liver disease and chronic kidney disease (CKD). As a continuing research effort, this year, we investigated the potential effects of safflomide and javamide-I/-II on pathological events related to subclinical inflammation occurring in cardiovascular disease, liver disease and CKD. Javamide-I/-II are found in coffee/cocoa-related products (e.g., regular coffee, decaf, espresso, green coffee, milk coffee, cocoa), and safflomide and its derivatives are found in Carthamus tinctorius, Centaurea cyanus, Arachis hypogaea, Coffea sp., Ipomoea obscura, and Theobroma cacao. However, there is currently no information about their potential effects on inflammatory cytokines in CVD, hypertension, fat liver disease and CKD. In the study, we found that safflomide could decrease MCP-1 expression and increase adiponectin in rats fed a high fat diet. The data suggest that safflomide may alleviate subclinical inflammation associated with CVD, hypertension, liver disease and CKD in the obese by lowering MCP-1 and increasing adiponectin in rats. Since the javamide-I/-II found in coffee/cocoa have very similar chemical structures to safflomide, we also investigated potential effects of javamides on inflammatory cytokines. Javamide-I/-II could suppress the expression of MCP-1 and other inflammatory cytokines in vitro, which play crucial roles in tubulointerstitial inflammation in CVD, hypertension, liver disease and CKD. Therefore, we further conducted the proposed animal study and collected biological samples (e.g., blood, urine, liver, kidney) for biological analyses (e.g., creatinine, cystatin-C, KIM-1, aldosterone, TGF-beta, RANTES, MCP-1, IL-8, GFR). This study will provide information about the potential effects of safflomide and javamide-I /-II found in coffee, cocoa and other plants on subclinical inflammation in arthrosclerosis, cardiovascular disease, live disease, and CKD.
1. Numerous reports indicate that coffee/cocoa consumption (3-4 cups per a day) may have beneficial effects on diabetes, liver disease, CVD and some types of inflammation. A recent report suggested that javamide-I/-II found in coffee/cocoa may have strong anti-inflammatory activity, necessitating steadfast method to measure the amounts of javamides in coffee/cocoa products. Therefore, a simplified HPLC method was developed with an electrochemical detector in order to quantify javamides in coffee/cocoa products. The developed HPLC method could detect javamide-I/-II in excellent peak resolutions, great reproducibility and low detection limits. This study is the first report about developing a combined HPLC/electrochemical detector method which can be utilized in measuring the amounts of javamide-I/-II robustly in coffee/cocoa samples with great accuracy, reproducibility and electrochemical profiling.
Park, J.B. 2016. Javamide-I-O-methyl ester increases p53 acetylation and induces cell death via activating caspase 3/7 in monocytic THP-1 cells. Phytomedicine. 23(13):1647-1652. doi: 10.1016/j.phymed.2016.10.004.
Park, J.B., Wang, T.T. 2017. Methyl (E)-(3,4-dihydroxyphenyl)acryloyl)tryptophanate can suppress MCP-1 expression by inhibiting p38 MAP kinase and NF-kB in LPS-stimulated differentiated THP-1 cells. European Journal of Pharmacology. 8(10):149-155.. https://doi.org/10.1016/j.ejphar.2017.07.006.
Delgado, J.A., Weyers, S.L., Dell, C.J., Harmel, R.D., Kleinman, P.J., Sistani, K.R., Leytem, A.B., Huggins, D.R., Strickland, T.C., Kitchen, N.R., Meisinger, J.J., Del Grosso, S.J., Johnson, J.M., Balkcom, K.S., Finley, J.W., Fukagawa, N.K., Powell, J.M., Van Pelt, R.S. 2016. USDA Agricultural Research Service creates Nutrient Uptake and Outcome Network (NUOnet) Journal of Soil and Water Conservation. 71(6):147A-148A. https://doi.org/10.2489/jswc.71.6.147A.
Holmen, B.A., Rakavina, B., Kasumba, J., Fukagawa, N.K. 2017. Reactive oxidative species formation and unregulated particulate emissions from blended diesel and biodiesel light-duty engine emissions. Energy and Fuels. doi: 10.1021/acs.energyfuels.7b00698.