| Rank | Pathway / Axis | Cancer / Tumor Context | Normal Tissue Context | TSF | Primary Effect | Notes / Interpretation |
|---|---|---|---|---|---|---|
| 1 | Nrf2 / ARE antioxidant response | Context-dependent modulation | Nrf2 ↑; antioxidant enzymes ↑ | R, G | Redox buffering | Polyphenol-driven antioxidant response is the dominant mechanistic theme in non-malignant systems. |
| 2 | ROS / oxidative stress modulation | ROS ↓ (generally); pro-oxidant effects not dominant | Oxidative stress ↓ | P, R | Antioxidant effect | Most studies describe antioxidant protection rather than tumor-selective ROS elevation. |
| 3 | NF-κB inflammatory signaling | NF-κB ↓ (reported in limited models) | Inflammation tone ↓ | R, G | Anti-inflammatory modulation | Observed in inflammatory and oxidative injury systems; tumor-specific evidence is limited. |
| 4 | Intrinsic apoptosis (mitochondrial; limited data) | Apoptosis ↑ (reported in some in-vitro studies) | ↔ | G | Conditional cytotoxicity | Cytotoxic effects generally mild and concentration-dependent; not comparable to strong pro-oxidants. |
| 5 | Cell-cycle arrest | Cell-cycle modulation ↑ (limited evidence) | ↔ | G | Cytostasis (weak) | Evidence exists but is inconsistent and often extract-dependent. |
| 6 | PI3K → AKT signaling | Limited data; possible ↓ (reported in some systems) | ↔ | R, G | Survival pathway modulation | Not a consistently demonstrated primary mechanism. |
| 7 | Angiogenesis signaling (VEGF) | Limited data; possible ↓ | ↔ | G | Potential anti-angiogenic effect | Evidence sparse compared to stronger polyphenols like gallic or caffeic acid. |
| 8 | Invasion / metastasis (MMPs) | Limited evidence | ↔ | G | Uncertain tumor relevance | Not well characterized mechanistically in oncology models. |
| 9 | Metabolic modulation | Indirect via anti-inflammatory and antioxidant tone | Metabolic support ↑ | R, G | Systemic metabolic effect | Better supported in cardiometabolic contexts than direct anticancer contexts. |
| 10 | Extract variability / compositional heterogeneity | Activity varies by cultivar, processing, solvent | — | — | Translation constraint | Whole fruit extracts differ significantly in phenolic profile and potency. |
Time-Scale Flag (TSF): P / R / G