Therapeutic mechanisms and associated molecular pathways in disease treatment
| Mechanism | Description | Molecular target/pathway | References |
|---|---|---|---|
| Nrf2 pathway activation | Upregulates antioxidant response elements (ARE) leading to increased expression of detoxifying enzymes | Nrf2/ARE pathway | [5] |
| Direct ROS neutralization | EGCG’s hydroxyl groups directly donate electrons to neutralize reactive oxygen species like superoxide and hydroxyl radicals | O2, OH, H2O2 | [47] |
| COX-2 suppression | Directly inhibits cyclooxygenase-2 enzyme activity and expression | COX-2 enzyme | [48] |
| iNOS downregulation | Reduces inducible nitric oxide synthase expression, decreasing nitric oxide production | Enzyme | [5] |
| Leukotriene reduction | Inhibits 5-lipoxygenase activity, decreasing pro-inflammatory leukotrienes | 5-LOX enzyme | [49] |
| AP-1 modulation | Suppresses activator protein 1 transcription factor activity | AP-1 complex | [50] |
| Adhesion molecule suppression | Decreases expression of VCAM-1, ICAM-1, reducing inflammatory cell recruitment | VCAM-1, ICAM-1 | [51] |
| Metal ion chelation | Forms complexes with transition metals (Fe2+, Cu2+) preventing their participation in Fenton reactions that generate free radicals | Fe2+, Cu2+ ions | [52] |
| SOD enhancement | Increases expression and activity of superoxide dismutase, improving cellular antioxidant defense | SOD1, SOD2 | [53] |
| Glutathione system support | Enhances glutathione synthesis and recycling, maintaining cellular redox balance | GSH/GSSG ratio | [54] |
| NF-κB inhibition | Suppresses nuclear factor kappa B activation, reducing pro-inflammatory gene expression | NF-κB signaling pathway | [55] |
| Pro-inflammatory cytokine reduction | Decreases production of TNF-α, IL-1β, and IL-6 through multiple pathways | TNF-α, IL-1β, IL-6 | [56] |
| Mitochondrial protection | Preserves mitochondrial function and reduces oxidative damage | Electron transport chain | [57] |
| MAPK pathway modulation | Inhibits stress-activated protein kinases involved in inflammatory signaling | p38 MAPK, JNK, ERK | [58] |
| Lipid peroxidation prevention | Protects cellular membranes from oxidative damage through radical scavenging | Membrane lipids | [59] |
| NADPH oxidase inhibition | Reduces cellular superoxide production by inhibiting NOX enzymes | NOX family enzymes | [60] |
| Myeloperoxidase suppression | Decreases production of hypochlorous acid and other oxidizing species | MPO enzyme | [61] |
| Prostaglandin synthesis inhibition | Reduces inflammatory mediator production through multiple mechanisms | PGE2, PGD2 | [62] |
| Heat shock response | Induces heat shock proteins that protect against oxidative stress | HSP70, HSP90 | [63] |
| STAT3 pathway inhibition | Reduces inflammatory signaling through STAT3 suppression | STAT3 pathway | [64] |
5-LOX: 5-lipoxygenase; AP-1: activator protein 1; COX-2: cyclooxygenase-2; EGCG: epigallocatechin gallate; ERK: extracellular signal-regulated kinase; GSH: glutathione; GSSG: glutathione disulfide; HSP: heat shock proteins; ICAM-1: intercellular adhesion molecule-1; IL-1β: interleukin-1β; iNOS: inducible nitric oxide synthase; JNK: c-Jun N-terminal kinase; MAPK: mitogen-activated protein kinase; MPO: myeloperoxidase; NADPH: nicotinamide adenine dinucleotide phosphate; NOX: NADPH oxidase; Nrf2: nuclear factor erythroid 2-related factor 2; PGD2: prostaglandin D2; PGE2: prostaglandin E2; ROS: reactive oxygen species; SOD: superoxide dismutase; STAT3: transducer and activator of transcription 3; TNF-α: tumor necrosis factor-alpha; VCAM-1: vascular cell adhesion molecule-1
