Table 1.
Characteristics of the studies included with the nutrigenomic targets.
| Nutraceutical | OA Pathways Involved | Modulation Action | Main Findings | Journal | Authors | Year |
|---|---|---|---|---|---|---|
| Apigenin | ┤ HIF 2α | ↓ ADAMTS-4 ↓ COX-2 ↓ MMP |
Apigenin blocks osteoarthritis development as Hif-2α inhibitor. | Journal of Cellular and Molecular Medicine | Cho et al. [110] | 2019 |
| Berberine | → PI3K/AKT ┤ NF-κB |
↓ ADAMTS-4 ↓ COX-2 ↓ MMP |
Berberine activates PI3K/Akt and NF-κB pathways. | Phytomedicine | Wong et al. [111] | 2019 |
| Chondroitin Sulfate | ┤ NF-κB | ↓ ADAMTS-4 ↓ COX-2 ↓ MMP |
Separate administration of chondroitin sulfate raised expression of Comp and reduced TLRs, and NF-κB expressions in cartilage. | Probiotics and Antimicrobial Proteins | Korotkyi et al. [112] | 2021 |
| Curcumin | → ERK1/2 | ↓ Chondrocyte Apoptosis | Curcumin inhibits apoptosis of chondrocytes through activation ERK1/2 signaling pathways induced autophagy. | Nutrients | Li et al. [52] | 2017 |
| ┤NF-κB | ↓ ADAMTS-4 ↓ COX-2 ↓ MMP |
Curcumin reduces inflammation in knee osteoarthritis through blocking TLR4/MyD88/NF-κB signal pathway. | Drug Development Research | Zhang et al. [113] | 2018 | |
| → Nrf2/HO-1 | ↑ GPX1,3,4 ↑ SOD1 ↑ CAT ↑ GST |
Curcumin inhibits chondrocytes inflammation through the Nrf2/ARE signaling pathway, thereby exerting cartilage protective effects. | Cell Stress and Chaperones | Jiang et al. [114] | 2020 | |
| ┤ TLR4/NF-κB | ↓ ADAMTS-4 ↓ COX-2 ↓ MMP |
Curcumin improve neuroinflammatory process by reducing microglia/macrophage activation and neuronal apoptosis through a mechanism involving the TLR4/NF-κB signaling pathway in microglia/macrophages. | International Journal of Molecular Sciences | Panaro et al. [115] | 2020 | |
| ┤ NF-κB | ↓ ADAMTS-4 ↓ COX-2 ↓ MMP |
Curcumin reduces expression of NF-κB and ROCK1. | Journal of Cellular and Molecular Medicine | Qiu et al. [116] | 2020 | |
| Eupatilin | ┤ NF-κB ┤ JNK ┤ p38MAPK |
↓ ADAMTS-4 ↓ COX-2 ↓ MMP |
Eupatilin suppressed expression of MMPs, ADAMTSs in chondrocytes by reducing JNK phosphorylation and NF-κB and MAPK signaling. | Pharmaceuticals | Lee et al. [117] | 2021 |
| Genistein | → Nrf2/HO-1 | ↑ GPX1,3,4 ↑ SOD1 ↑ CAT ↑ GST |
Genistein downregulates MMPs, ADAMTSs via NF-κB signaling pathway by blocking IκB degradation and activating Keap1/Nrf2 pathway. | Nutrients | Liu et al. [118] | 2019 |
| ┤ NF-κB | ↓ ADAMTS-4 ↓ COX-2 ↓ MMP |
BioMed Research International | Yaun et al. [119] | 2019 | ||
| Molecular Medicine Report | Zou et al. [120] | 2020 | ||||
| Glucosamine | → mTOR | ↓ Chondrocyte Apoptosis | Glucosamine promotes osteoblast proliferation by modulating autophagy via the mTOR pathway. | Biomedicine & Pharmacotherapy | Lv et al. [121] | 2018 |
| → Wnt/β-catenin | ↓ Chondrocyte Apoptosis | GlcN increases β-catenin nuclear translocation, thus promoting chondrocyte proliferation. | International Journal of Molecular Medicine | Ma et al. [49] | 2018 | |
| Green tea polyphenol | ┤ NF-κB | ↓ ADAMTS-4 ↓ COX-2 ↓ MMP |
L-theanine inhibits upregulation of MMPs, as well as inhibiting NF-κB | Nutrients | Bai et al. [122] | 2020 |
| Green tea catechins increase NF-κB inhibitors expression | Antioxidants | Luk et al. [123] | 2020 | |||
| →PI3K/AKT | ↓ FOX-O1 | Epigallocatechin-3-gallate modulating AKT-FoxO1 via upregulating miR-486-5p. | Archives of Biochemistry and Biophysics | Chang et al. [124] | 2020 | |
| Jaceosidin | ┤ NF-κB | ↓ ADAMTS-4 ↓ COX-2 ↓ MMP |
Jaceosidin attenuates cartilage destruction by suppressing MMPs, ADAMTSs and the NFκB signaling pathway by blocking IκB degradation. | Journal of Cellular and Molecular Medicine | Lee et al. [117] | 2019 |
| Omega-3 PUFA | ┤ p38MAPK | ↓ Chondrocyte Apoptosis | PUFA inactivates of p38MAPK | International Journal of Molecular Medicine | Wang et al. [58] | 2016 |
| → PI3K/AKT ┤ NF-κB |
↓ MMPs | PUFA metabolite suppresses MMP-13 secretion by activating PI3K/AKT pathway directly, while inhibiting NF-κB pathway. | Connective Tissue Research | Lu et al. [74] | 2020 | |
| OOP | ┤ NF-κB ┤ p38MAPK |
↓ ADAMTS-4 ↓ COX-2 ↓ MMP |
OOPs inhibited IL-1β-induced expression of inflammatory mediators through suppressing NF-κB and MAPK activation in chondrocytes. | Food & Function | Feng et al. [125] | 2017 |
| → Nrf2/HO-1 ┤ NF-κB |
↓ ADAMTS-4 ↓ COX-2 ↓ MMP |
OOPs can activate Nrf-2 signaling and the blockage of NF-κB nuclear translocation | Cells | Serrelli et al. [126] | 2020 | |
| ┤ NF-κB | ↓ ADAMTS-4 ↓ COX-2 ↓ MMP |
OOPs reduce the inflammatory and catabolic factors mediated by NF-κB (IL-1ß, IL-6, COX-2 and MMP-3 | Aging | Varela-Eirín et al. [127] | 2020 | |
| ┤ NF-κB | ↓ ADAMTS-4 ↓ COX-2 ↓ MMP |
Mechanistically, OOPs exhibited an anti-inflammatory effect by inactivating the PI3K/AKT/NF-κB pathway. | Journal of Cellular Physiology | Chen et al. [128] | 2021 | |
| Quercitin | ┤ NF-κB | ↓ ADAMTS-4 ↓ COX-2 ↓ MMP |
Quercetin inhibits IL-1b and TNF-a production via TLR-4/NF-κB pathway. | Journal of International Medical Research | Zhang et al. [129] | 2019 |
| Resveratrol | →Wnt/β-catenin | ↓ Chondrocyte Apoptosis | Rev increased osteoblastogenesis and bone formation through stimulation of Wnt signaling pathway. | Journal of Cell Physiology | Ashrafizadeh et al. [47] | 2020 |
| →Nrf2/HO-1 | ↑ GPX1,3,4 ↑ SOD1 ↑ CAT ↑ GST |
Res modulates the Nrf2 activation by inhibiting Keap1, Nrf2 gene expression, changing the upstream mediators of Nrf2, and potentiating the nuclear translocation of Nrf2. | Biomedicine & Pharmacotherapy | Farkhondeh et al. [130] | 2020 | |
| →PI3K/AKT | ↓ FOX-O1 | Resveratrol may exert anti-OA effect by enhancing the self-limiting mechanism of inflammation through TLR4/Akt/FoxO1 axis. | Drug Design, Development and Therapy | Xu et al. [131] | 2020 | |
| ┤ NF-κB | ↓ ADAMTS-4 ↓ COX-2 ↓ MMP |
Resveratrol alleviates the interleukin-1β-induced chondrocytes injury through the NF-κB signaling pathway. | Journal of Orthopaedic Surgery and Research | Yi et al. [132] | 2020 | |
| Sulforaphane | → Nrf2/HO-1 | ↑ GPX1,3,4 ↑ SOD1 ↑ CAT ↑ GST |
Sulforaphane ameliorates oxidative stress suppressing inflammatory cytokines and activating Keap1/Nrf2 pathway. | Free Radical Biology and Medicine | Yang et al. [133] | 2020 |
| Sulforaphane inhibits the production of inflammatory cytokines. | PLoS ONE | Moon et al. [134] | 2021 | |||
| ┤ JNK | ↓ ADAMTS-4 ↓ COX-2 ↓ MMP |
Sulforaphane inhibits osteoclastogenesis by suppressing autophagy modulating JNK pathway. | Molecules | Lou et al. [135] | 2021 | |
| Wogonin | ┤ NF-κB | ↓ ADAMTS-4 ↓ COX-2 ↓ MMP |
Wogonin downregulates NF-κB pathway and genes involved in inflammatory-response. | Nature: Scientific Report | Khan et al. [136] | 2017 |
Abbreviations: ADAMTS = A disintegrin and metalloproteinase with thrombospondin motifs; AKT = Tyrosine kinase A; CAT = Catalase; COX-2 = Cyclooxygenase-2; ERK = Extracellular signal-regulated kinases; FOX-O1 = Forkhead box protein O1; GPX = glutathione peroxidase; GST = Glutatione S-transferasi; HIF-2α = Hypoxia-inducible factor; HO-1 = Heme oxygenase 1; MAPK = Mitogen-activated protein kinases; MMP = Matrix metalloproteinase; mTOR = mammalian target of rapamycin; NF-κB = Nuclear factor kappa-light-chain-enhancer of activated B cells; Nrf2 = Nuclear factor-erythroid factor-2; OOP = Olive Oil Polyphenols; PI3K = Fosfoinositide 3-chinasi; PUFA = Polyunsaturated Fatty Acids; SOD = Superoxide dismutase; TLR4 = Toll-like receptor; Wnt = Wingless-related integration site.