About

Dr. Dragan Milenkovic is an Associate Professor in the Department of Food, Bioprocessing and Nutrition Sciences at North Carolina State University. His research focuses on demonstrating the health effects of polyphenols and polyphenol-rich foods on vascular function and the prevention of cardiovascular, metabolic, and neurodegenerative diseases. He employs multi-genomic approaches, including epigenetics, transcriptomics, proteomics, and metabolomics, along with in-silico docking studies to evaluate interactions between polyphenol metabolites and cell signaling proteins. His system biology approach aims to identify variability in responsiveness to micronutrient intake, considering factors such as gender, age, health status, and genetic polymorphism, to advance precise nutrition. His projects utilize translational research involving in-vitro studies, animal models, and clinical trials.

Research topics

• Political Science
• Computer Science
• Computer Security
• Botany
• Biochemistry
• Psychology
• Social psychology
• Biology
• Library science
• Food science
• Biotechnology
• World Wide Web
• Chemistry
• Law

Selected publications

• Chronic consumption of (poly)phenol-rich foods exerts multigenomic modification of genes linked to cardiometabolic health in postmenopausal women

  Food Research International · 2026-04-16

  article
  PublisherDOI

• Nutrigenomic influence of a curcumin-supplemented high glycemic diet on hippocampal microvasculature in male C57BL/6J mice

  Frontiers in Nutrition · 2026-02-03

  articleOpen accessSenior author

  Introduction Curcumin, a dietary polyphenol primarily derived from turmeric, has potent antioxidant and anti-inflammatory capabilities against diet-related chronic diseases. A high glycemic diet (HGD) has been shown to contribute to cognitive decline and dysfunction of murine brain microvasculature. The goal of our study was to elucidate the multi-genomic effects of curcumin on hippocampal microvessels in mice during consumption of a high glycemic diet. Methods Male C57BL/6J mice were fed a low glycemic diet (LGD, 12% sucrose/weight), a high glycemic diet (HGD, 34% sucrose), or a HGD with 0.2% curcumin (HGD + Curc) for 12 weeks. Global transcriptomic profiles, including protein coding and non-coding genes, of laser-captured endothelial microvessels of the hippocampus were analyzed via microarrays. Bioinformatic tools were utilized to uncover networks and functional pathways of differentially expressed genes modulated by curcumin as well as interactivity between transcription factors and major curcumin metabolites via in silico docking analysis. Results The HGD + Curc treatment influenced the differential expression of 1887 genes compared to HGD alone, which included messenger RNAs, microRNAs, long noncoding RNAs, and small nucleolar RNAs. Of these modulated genes, 307 overlapped and were negatively correlated with the fold change expression of the HGD versus LGD comparison. These protein coding and non-coding gene targets regulated by HGD+Curc were involved in pathways related to neurodegeneration, oxidative phosphorylation, blood-brain barrier permeability, cell signaling, and cellular metabolism. Discussion/conclusion The results from this study show that curcumin induces complex nutrigenomic modifications that could elucidate its neuroprotective effect against hippocampal microvascular dysfunction induced by a high glycemic diet.

  PublisherOA PDFDOI

• supplemental table s6

  Figshare · 2026-04-28

  articleOpen access1st authorCorresponding

  list of differentially expressed genes

  PublisherDOI

• Lipid-Lowering and Hepatoprotective Effects of Basil-Enriched Soybean Oil (BEO) in High-Fat-Diet-Fed Mice

  Metabolites · 2026-02-05

  articleOpen access

  Background: This study investigated the hypolipidemic and hepatoprotective effects of refined soybean oil supplemented with an Ocimum basilicum L. extract, characterized by HPLC and found to be rich in caftaric, caffeic, chicoric, and rosmarinic acids. Methods: After a 12-week model of diet-induced hyperlipidemia, we examined the plasma levels of TC, TG, Glucose, HDL-C, and LDL-C and the LDL-C/HDL-C ratio using enzymatic kits. The Plasma Hepatic and Biliary Marker Analysis was analysed following standardized hospital protocols with quality-controlled instrumentation. Results: The supplementation with Basil-Enriched Oil (BEO) resulted in a notable redistribution of lipids, significantly reducing the plasma total cholesterol (−75%), triglycerides (−96%), and glucose (−22%), while enhancing their hepatic sequestration. This was accompanied by a marked improvement in the LDL-C/HDL-C ratio and a reduction in hepatic oxidative stress (measured by MDA). Importantly, BEO preserved liver structure and prevented steatosis, despite inducing an increase in adaptive hepatomegaly. Conclusions: The results reveal a dual mechanism whereby the antioxidant properties of BEO collaborate with reprogrammed lipid metabolism, promoting safe hepatic storage rather than harmful circulating levels. These findings strongly advocate for the extract’s potential as a nutraceutical for addressing hyperlipidemia and related metabolic disorders by targeting both oxidative stress and lipid imbalance. Further research is required to confirm these effects in clinical settings and to confirm its long-term efficacy.

  PublisherOA PDFDOI

• supplemental table s6

  Figshare · 2026-04-28

  articleOpen access1st authorCorresponding

  list of differentially expressed genes

  PublisherDOI

• Citrus flavonoid supplement enhances glycemic and metabolic control in prediabetic patients on metformin: a randomized controlled trial

  Frontiers in Nutrition · 2025-08-19 · 5 citations

  articleOpen accessSenior author

  Background and objective Combining natural compounds with conventional drugs is an emerging strategy to improve the management of type 2 diabetes and its precursor, prediabetes. While metformin effectively lowers blood glucose and improves insulin sensitivity, it may cause side effects or lose efficacy over time. Natural agents, particularly polyphenols, are being explored as adjunct therapies to enhance glycemic control, mitigate adverse effects, and slow disease progression. This study evaluated the efficacy of a citrus bioflavonoid-based nutraceutical as an adjunct to metformin therapy in prediabetic individuals, with a focus on metabolic, inflammatory, oxidative, hormonal, and nutritional-clinical outcomes. Methods In this 12-week randomized, double-blind, placebo-controlled trial, participants received either metformin plus the citrus flavonoid supplement (250 mg/day) or metformin plus placebo. Results At the end of the intervention, the nutraceutical group demonstrated improved postprandial glucose metabolism, including a 5% reduction in 2-h OGTT glucose and preservation of active GLP-1 levels. In contrast, the placebo group exhibited a decline in GLP-1 and increased insulin resistance. Supplementation also resulted in a 12% reduction in TNF- α , a 7.5% increase in plasma antioxidant capacity (FRAP), and modest but significant decreases in body weight, fat mass, and BMI (all p ≤ 0.05). Additionally, systolic blood pressure was reduced by 4%, potentially associated with improved antioxidant status and higher dietary potassium intake. Conclusion These findings suggest that citrus flavonoids may serve as a safe and effective nutritional adjunct to metformin in the early management of prediabetes. Benefits include improved postprandial glycemia, maintenance of GLP-1 levels, reduced inflammation and oxidative stress, and modest improvements in body composition and blood pressure. Further long-term studies are warranted to confirm these outcomes and elucidate underlying mechanisms. Clinical trial registration https://clinicaltrials.gov/ , identifier NCT06005142.

  PublisherOA PDFDOI

• Plant Polyphenols as Heart’s Best Friends: From Health Properties, to Cellular Effects, to Molecular Mechanisms of Action

  International Journal of Molecular Sciences · 2025-01-22 · 19 citations

  reviewOpen accessSenior author

  Polyphenols are micronutrients found in fruits, vegetables, tea, coffee, cocoa, medicinal herbs, fish, crustaceans, and algae. They can also be synthesized using recombinant microorganisms. Interest in plant-derived natural compounds has grown due to their potential therapeutic effects with minimal side effects. This is particularly important as the aging population faces increasing rates of chronic diseases such as cancer, diabetes, arthritis, cardiovascular, and neurological disorders. Studies have highlighted polyphenols' capacity to reduce risk factors linked to the onset of chronic illnesses. This narrative review discusses polyphenol families and their metabolism, and the cardioprotective effects of polyphenols evidenced from in vitro studies, as well as from in vivo studies, on different animal models of cardiac disease. This study also explores the molecular mechanisms underlying these benefits. Current research suggests that polyphenols may protect against ischemia, hypertension, cardiac hypertrophy, heart failure, and myocardial injury through complex mechanisms, including epigenetic and genomic modulation. However, further studies under nutritionally and physiologically relevant conditions, using untargeted multigenomic approaches, are needed to more comprehensively elucidate these mechanisms and firmly prove the cardioprotective effects of polyphenols.

  PublisherOA PDFDOI

• Argan Fruit Polyphenols Regulate Lipid Homeostasis, Prevent Liver Fat Accumulation, and Improve Antioxidant Defense in High-Calorie Diet Fed Mice: In Vivo Study and In Silico Prediction of Possible Underlying Mechanisms

  Metabolites · 2025-03-28 · 1 citations

  articleOpen access

  Background/Objectives: Argania spinosa L. Skeels is a Moroccan endemic plant widely used by the local population as folk medicine. This study aimed to investigate the effects of Argan fruit pulp on lipid metabolism disorders and liver steatosis in hypercaloric diet-fed mice. Methods: Animals were treated with the Argan fruit pulp extract and its fractions for 12 weeks at 100 and 200 mg Kg−1 BW daily. The analysis was conducted on lipid levels in plasma, liver, feces, and bile as well as on glycemia. The liver glutathione, malondialdehyde, and antioxidant enzyme activities were assessed. The hepatic steatosis was evaluated by measuring transaminases and alkaline phosphatase activities and examining histological sections. The polyphenol profiles were determined using HPLC-DAD. Possible underlying mechanisms in the hypolipidemic and hepatoprotective activities were predicted by molecular docking. Results: The crude extract and its aqueous fraction (rich in protocatechuic and gallic acids) significantly restored plasma lipids and glucose levels. Indeed, total cholesterol level (TCHO) was decreased in the liver but increased in bile and feces. The treatment also reduced body weight and liver and adipose tissue mass and prevented liver steatosis. The ethyl acetate fraction exhibited no effect on lipid metabolism but significantly prevented liver oxidative stress. The crude extract and its fractions appear to be nontoxic (LD50 > 5000 mg Kg−1) in mice. The phenolic acids demonstrated strong binding affinity to key targets involved in regulating lipid homeostasis, including ABCA-1, LXR, CYP7A1, HMH-CoA reductase, and PCSK-9. However, the identified flavonoids exhibited high affinities to targets involved in oxidative stress defense (SOD, CAT, and CYP2E1). Conclusions: The Argan fruit pulp, particularly its polyphenols, could be a promising natural approach for preventing cardio-metabolic diseases by improving lipid metabolism and reducing liver oxidative stress.

  PublisherOA PDFDOI

• Cell- and sex-specificity in the transcriptomic response of the hippocampal neurovascular unit to obesity

  Communications Biology · 2025-11-27 · 2 citations

  articleOpen access

  Obesity is a risk factor for vascular dementia and exhibits sex differences in comorbidities and prevalence. However, its cell-specific effects on the neurovascular unit (NVU) remain unknown. Here we show, using the ob/ob mouse model and single nuclei RNA sequencing, how obesity modulates the hippocampal NVU transcriptome in females. Obesity alters endothelial-specific differentially expressed genes (DEGs) involved in angiogenesis and blood brain barrier permeability. DEGs in common between endothelial cells and other NVU cells are associated with neurotransmission and autophagy. Some gene expression changes from each NVU cell type correlate with behavioral changes. Sex-based analyses comparing to our previously reported male data indicate that the NVU transcriptomic response to obesity is modified by sex in a cell-type specific manner. Endothelial and microglial cells exhibit greater sex-specificity than astrocytes and neurons. The findings from our work may help inform both sex-independent and sex-specific approaches to prevention and treatment for obesity-related dementia.

  PublisherOA PDFDOI

• Author response for "Brazilian Passion Fruit Modulates Vascular Inflammation and Gene Networks of Cholesterol Metabolism in Overweight Individuals"

  2025-10-23

  peer-review
  PublisherDOI

Frequent coauthors

• Christine Morand

  Centre de Recherche en Nutrition Humaine d'Auvergne

  2714 shared

• Ana Rodriguez‐Mateos

  King's College London

  2265 shared

• Aedín Cassidy

  2221 shared

• Inês Figueira

  Universidade Nova de Lisboa

  2213 shared

• Letizia Bresciani

  University of Parma

  2212 shared

• Patricia I. Oteiza

  University of California, Davis

  2211 shared

• Zhao Lu

  Instituto de Ciencia y Tecnología de Alimentos y Nutrición

  2209 shared

• Gow‐Chin Yen

  National Chung Hsing University

  2209 shared

Labs

• Wolfpack Brewing LabPI

Education

• Ph.D., Food Science

  University of California, Davis

  2002

• M.S., Food Science

  University of California, Davis

  1998

• B.S., Food Technology

  University of Belgrade

  1996