2025/01/01 by Jin, Xu
Agricultural and Biological Sciences · Biochemistry, Genetics and Molecular Biology · Medicine · #AMP-Activated Protein Kinase (AMPK) #AMPK #Alternative and Complementary Medicine #Anti-Inflammatory Agents #Antioxidants #Autoimmune Diseases #Caffeic Acid Phenethyl Ester #Cardiology #Cardiovascular Diseases #Covid-19 #Cytokines #Dermatitis #Diabetes Mellitus #Dietetics and Clinical Nutrition #Digestive #Digestive System Diseases #Diseases #Endothelial Function #Epigenetics #Epithelial Barrier #FOS: Clinical medicine #Flavonoids #Folic Acid #Garlic #Garlic and Onion Studies #Gastroenterology #Genomics, phytochemicals, and oxidative stress #Glutathione #Helicobacter pylori Infection #Hepatology #Immune System Diseases #Immunomodulation #Inflammation #Interleukin-6 #Macrophage Polarization #Medical Nutrition #Medical Sciences #Medical Specialties #Medicine and Health Sciences #Metabolic Syndrome #Methylation #Mitochondria #Mitochondrial Function #Mitogen-Activated Protein Kinases (MAPKs #Mucosal Immunity #NF-κB #NLRP3 #Nervous System Diseases #Neurocognitive Disorders #Neurodegenerative Diseases #Neurology #Neurosciences #Nitric Oxide Synthase (eNOS) #Non-Alcoholic Fatty Liver Disease #Non-Alcoholic Fatty Liver Disease (NAFLD) #Nrf2 #Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) #Nutritional Pharmacology #Nutritional and Metabolic Diseases #Onion #Oral #Oxidative Stress #PGC-1α #Periodontitis #Polyphenols #Precision Nutrition #Preventive Medicine #Primary Care #Propolis #Pulmonology #Reactive Oxygen Species #Redox Homeostasis #Respiratory Tract Diseases #Respiratory Tract Infections #SIRT1 #Sirtuins and Resveratrol in Medicine #Systemic Homeostasis #T-Lymphocytes #TGF-β #Th17 Cells #Type II Diabetes Mellitus #Wound Healing #and Skin Physiology
paper · doi:10.17605/osf.io/7b9c5
openalex publication_date 2025/01/01 · openalex created_date 2025/11/08 · openalex updated_date 2026/07/01
Background and Rationale Chronic cardio-metabolic, infectious, and neuro-regenerative disorders share a unified biochemical foundation characterized by oxidative overload, NF-κB/NLRP3-driven inflammation, impaired methylation flux, and disrupted endothelial–mitochondrial coupling. Conventional pharmacotherapies often target isolated pathways yet fail to restore systemic biochemical coherence. This project applies a multi-axis nutritional pharmacology perspective to explore how coordinated micronutrient signaling can re-establish redox–inflammatory–methylation balance—thereby promoting homeostatic recovery across metabolic, infectious, cognitive, and epithelial systems. Objectives Mechanistic Mapping – Define the interconnected signaling axes (Nrf2–HO-1, NF-κB/NLRP3, AMPK–SIRT1–PGC-1α, BH₄–eNOS–NO, and TGF-β/VEGF) that mediate the redox–inflammatory–methylation network. Clinical Integration – Consolidate human evidence from nutritional interventions targeting these axes in conditions including Type II Diabetes Mellitus, Non-Alcoholic Fatty Liver Disease (NAFLD), Helicobacter pylori infection, Post-/Long COVID, cognitive decline, and mucosal or dermal barrier injury. Systems-Level Modeling – Develop a translational “Three-Axis, Six-Module Framework” linking molecular correction to multi-organ functional recovery. Methods Overview A literature synthesis (2015–2024) integrates molecular, pre-clinical, and human RCT data on polyphenolic (propolis, quercetin), organosulfur (garlic-derived), and methylation-supportive (folate, zinc) nutrients. Mechanistic and clinical correlations were mapped using a systems-biology approach emphasizing cross-axis coupling among antioxidant defense, inflammatory resolution, and one-carbon metabolism. Expected Outcomes and Scientific Significance Establish evidence that physiological-range, multi-nutrient interventions can modulate Nrf2–NF-κB–AMPK–eNOS signaling coherence without pharmacologic toxicity. Provide a mechanistic basis for precision-dose nutritional pharmacology in systemic diseases defined by redox-methylation imbalance. Offer a translational framework for future trials uniting cardiovascular, hepatic, infectious, and neuro-barrier recovery domains under a single biochemical model of homeostasis.