TABLE 3.
The clinical studies of natural compounds against OA development by mediating the NRF2/ARE signaling pathway.
| Compounds | Models/Doses | Biological actions | Conclusions | Ref |
|---|---|---|---|---|
| Genistein | IL-1β-treated human chondrocytes/10 μM | NRF2↑, HO-1↑, COX-2↓, iNOS↓, MMP-1↓, MMP-3↓, MMP-13↓, collagen II↑, aggrecan↑ | Inhibits inflammation and ECM degradation by activating the NRF2/ARE signaling | Liu et al. (2019) |
| Myricetin | IL-1β-treated human chondrocytes/5, 10, and 15 μM | NRF2↑, HO-1↑, p65↓, IL-6↓, TNFα↓, COX-2↓, PGE2↓, iNOS↓, NO↓, MMP-13↓, ADAMTS5↓, collagen II↑, aggrecan↑ | Inhibits inflammation and ECM degradation by activating the NRF2/ARE signaling | Pan et al. (2019) |
| Morin | IL-1β-treated human OA chondrocytes/2.5, 5, and 10 μM | PGE2↓, NO↓, p65↓, NRF2↑, HO-1↑, MMP-1↓, MMP-3↓, MMP-13↓ | Inhibits inflammation and ECM degradation by activating the NRF2/ARE signaling | Qu et al. (2018) |
| Wogonin | IL-1β-treated human OA chondrocytes/10, 25, and 50 μM | IL-6↓, TNFα↓, COX-2↓, PGE2↓, iNOS↓, NO↓, MMP-3↓, MMP-9↓, MMP-13↓, ADAMTS5↓, collagen II↑, ACAN↑, NRF2↑, HO-1↑, NQO-1↑, p-ERK1/2↑ | Inhibits inflammation and ECM degradation by activating the NRF2/ARE signaling | Khan et al. (2017) |
| Polydatin | IL-1β-treated human chondrocytes/25, 50, and 100 μg/mL | NRF2↑, HO-1↑, IL-6↓, TNFα↓, COX-2↓, PGE2↓, iNOS↓, NO↓, MMP-13↓ | Inhibits inflammation and ECM degradation by activating the NRF2/ARE signaling | Tang et al. (2018) |
| Curcumin | IL-1β-treated human chondrocytes/20 and 40 μM | IL-6↓, TNFα↓, COX-2↓, iNOS↓, MMP-1↓, MMP-3↓, MMP-9↓, MMP-13↓, ADAMTS4↓, ADAMTS5↓, COL2A1↑, ACAN↑, NRF2↑, HO-1↑, NQO-1↑, GCLC↑, SOD-2↑ | Inhibits inflammation and ECM degradation by activating the NRF2/ARE signaling | Jiang et al. (2020a) |
| Piceatannol | IL-1β-treated human chondrocytes/1, 5, and 10 μM | IL-6↓, TNFα↓, COX-2↓, PGE2↓, iNOS↓, NO↓, MMP-13↓, ADAMTS5↓, collagen II↑, aggrecan↑, p65↓, NRF2↑, HO-1 | Inhibits inflammation and ECM degradation by activating the NRF2/ARE signaling | Tang et al. (2017) |
| ICA | IL-1β-treated HC-A/10−9M | ROS↓, GPX↑, SOD↑, MMP-3↓, MMP-9↓, MMP-13↓, ADAMTS4↓, GAG↑, NRF2↑, NQO-1↑ | Inhibits oxidative stress and ECM degradation by activating the NRF2/ARE signaling | Zuo et al. (2019) |
| CA | TNFα-treated C28/I2 cells/5, 10, and 20 μM | IL-1β↓, IL-6↓, IL-12↓, COX-2↓, PGE2↓, iNOS↓, NO↓, MMP-3↓, MMP-9↓, MMP-13↓, ADAMTS5↓, collagen II↑, aggrecan↑, ROS↓, p-PI3K↓, p-AKT↓, p65↓ | Inhibits inflammation, oxidative stress, and ECM degradation by activating the NRF2/ARE signaling | Qu et al. (2022) |
| Hederagenin | IL-1β-treated C28/I2 cells/5, 10, and 20 μM | IL-6↓, TNFα↓, COX-2↓, PGE2↓, iNOS↓, NO↓, ROS↓, MMP-1↓, MMP-3↓, MMP-9↓, MMP-13↓, ADAMTS5↓, collagen II↑, aggrecan↑, Bax↓, Bcl-2↑, cleaved caspase-3↓, p-JAK2↓, p-STAT3↓, MAPK↓, NRF2↑ | Inhibits inflammation, oxidative stress, chondrocyte apoptosis, and ECM degradation by activating the NRF2/ARE signaling | Shen et al. (2022) |
| SFN | H2O2-treated human OA chondrocytes/7 μM | NRF2↑, NOX4↓, COL2↑, ACAN↑, SOX9↑, IL-6↓, TNFα↓, MMP-13↓, ADAMTS5↓ | Inhibits inflammation, oxidative stress, and ECM degradation by activating the NRF2/ARE signaling | Yang et al. (2020a) |