Convergent mechanisms of key antioxidants and minerals, based on evidence from cell and animal models, with biologically plausible relevance to humans.
| Mechanism | Curcumin | Quercetin | Resveratrol | Zinc | Magnesium | Selenium (via GPx4) |
|---|---|---|---|---|---|---|
| Nrf2 activation → ↑ antioxidant enzymes | √ Strong | √ Strong | √ Moderate-Strong | √ Moderate | No direct activation | Indirect; form-dependent Nrf2 activation |
| SIRT1/PGC-1α activation → mitochondrial biogenesis | √ Moderate | √ Moderate | √ Strong | Emerging evidence (not a direct activator) | - | - |
| Mitochondrial protection → ↓ ROS, stabilized ΔΨm | √ Strong | √ Strong | √ Strong | Indirect (via Zn homeostasis, MT, Cu/Zn-SOD) | Indirect (ATP synthesis, TCA enzymes) | Strong (GPx4 protection of mitochondrial membranes) |
| NLRP3 inflammasome inhibition | √ Strong | √ Strong | Moderate | Modulatory; context-dependent | Emerging evidence of inhibition | Indirect (not NLRP3-specific) |
| Prevention of ferroptosis (lipid-peroxide-driven cell death) | Context-dependent modulator | Context-dependent modulator | Context-dependent modulator | - | - | Central anti-ferroptotic role (GPx4) |
| Immune metabolic effects (OXPHOS vs. glycolysis)* | Mild-Moderate | Moderate (SIRT1/PGC-1α in macrophages) | √ Strong OXPHOS shift | Limited direct evidence | Supports ATP-dependent immunity | Indirect (via redox balance) |
| Role in mitochondrial energy metabolism | Moderate | Moderate | √ Strong | Indirect support via Zn-dependent enzymes | Essential for ATP synthase & TCA cycle | GPx4 maintains membrane integrity |
Multiple antioxidants share convergent mechanisms: 1) Nrf2 activation (curcumin, quercetin, resveratrol, zinc) inducing coordinated antioxidant enzyme expression; 2) SIRT1/PGC-1α axis activation (curcumin, quercetin, resveratrol) promoting mitochondrial biogenesis; 3) NLRP3 inflammasome inhibition (curcumin, quercetin, zinc) preventing DAMP-mediated inflammation; 4) Immune cell metabolic reprogramming (resveratrol, zinc, magnesium) away from glycolytic pro-inflammatory states. *OXPHO is the metabolic pathway that mitochondria use to generate the majority of cellular ATP (energy) by coupling oxygen consumption to phosphorylation of ADP. OXPHOS is the primary mechanism by which mitochondria generate ATP, producing approximately 26-28 ATP molecules per glucose molecule (compared to only 2 ATP from glycolysis. GPx: glutathione peroxidase; OXPHOS: oxidative phosphorylation; ROS: reactive oxygen species; ΔΨm: mitochondrial membrane potential.
The supplementary material for this article is available at: https://www.explorationpub.com/uploads/Article/file/1001420_sup_1.pdf.
MP: Conceptualization, Writing—original draft, Writing—review & editing, Validation, Visualization. MC: Conceptualization, Writing—original draft, Writing—review & editing, Validation, Visualization. ED: Conceptualization, Writing—original draft, Writing—review & editing, Validation, Visualization. AG: Writing—original draft, Writing—review & editing, Validation. ER: Writing—original draft, Writing—review & editing, Validation. GM: Writing—original draft, Writing—review & editing, Validation. GP: Writing—review & editing, Supervision, Validation, Visualization. DP: Conceptualization, Project administration, Methodology, Supervision, Writing—original draft, Writing—review & editing, Validation, Visualization. All authors read and approved the submitted version.
The authors declare that they have no conflicts of interest.
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