Polyphenols Targeting MAPK Mediated Oxidative Stress and Inflammation in Rheumatoid Arthritis
Abstract
:1. Introduction
- Regulation of cyclooxygenase-2 activity;
- Inhibition of eicosanoid-generating enzymes (phospholipase A2 and cyclooxygenase);
- Inhibition of NO release;
- Regulation of cytokines;
- Inhibition of NF-κB;
- Regulation of MAPK pathway [24].
2. Pathogenesis of Rheumatoid Arthritis
3. Polyphenols and Rheumatoid Arthritis
3.1. Phenolic Acids
3.2. Stilbenes
3.3. Flavonoids
3.4. Other Compounds
4. Plant Polyphenols Targeting Oxidative Stress and Inflammation
4.1. Polyphenol’s Antioxidant Characteristics
4.2. Polyphenols and Their Interactions with Free Radicals
4.3. Enzyme Inhibition Included in Oxidation
5. Anti-Inflammatory Polyphenols
5.1. Polyphenols Have Modulatory Effects on the Cells Involved in Inflammations
5.2. Mechanism of Anti-Inflammatory Effects of Polyphenols
- Cucurmin suppresses NF-κB, reduces IL-1β and stimulates IL-6 and vascular endothelial growth factor (VEGF) by rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS);
- Cucurmin stimulates IL-6 and VEGF by RA-FLS and induces the apoptosis of RA-FLS;
- RSV inhibits Th-17, B-cells and the MAPK signaling pathway and reduces IL-6 and IL-1;
- EGCG suppresses NF-κB and MAPK and inhibits osteoclast differentiation;
- Extra virgin olive oil polyphenol extract (oleocanthal, oleacein, ligstroside aglycone monoaldehyde) reduces TNF-α, IL-1β, IL-6 pro-inflammatory cytokines, COX-1 and NF-κB translocation [53];
- Quercetin alters phosphatidylinositol 3-kinase/protein kinase B signaling pathway and reduces IL-1 and IL-6 [103].
6. The Roles of Polyphenols in MAPK Pathway in Rheumatoid Arthritis
Epigallocatechin-3-Gallate, Magnolol, and Other Polyphenols’ Anti-Inflammatory Properties against RA, via MAPK Pathway
7. p53 Gene Mutation via Oxidizing Agents in RA
8. Future Directions and Conclusions
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Acknowledgments
Conflicts of Interest
Abbreviations
LOX | 12-15 lipoxygenases |
AMPK | Activated protein kinase |
AP1 | Activator protein 1 |
AP-1 | Activator protein-1 |
ACLT | Anterior cruciate ligament transection |
ACPA | Anti-citrullinated protein antibodies |
ACLT | Artesunate attenuates |
BCL-2/Bax | B-cell lymphoma protein 2-associated X |
BMMs | Bone marrow macrophages |
JNK | c-Jun N-terminal kinases |
CRP | C-reactive proteins |
CAT | Catalase |
CIA | Collagen induced arthritis |
COX | Cyclooxygenase |
DLN | Draining lymph node |
EA | Ellagic acid |
ESP-B4 | Eosinophil stimulation promoter -leukotriene B4 |
EGCG | Epigallocatechin-3-gallate |
ESR | Erythrocytes sedimentations rate |
EVOO | Extra virgin olive oil |
ERK | Extracellular signal-directed kinase |
FA | Ferulic acid |
FLSs | Fibroblast-like synoviocytes |
GSH | Glutathione |
GPx | Glutathione peroxidase |
GR | Glutathione reductase |
GRO | Growth-regulated oncogene |
HLA | Human leukocyte antigen |
H2O2 | Hydrogen peroxide |
HO2 | Hydroxyl radical |
HT/PCy | Hydroxytyrosol and procyanidins |
IgG1, IgG2a | Immunoglobulins G |
IFN | Interferon |
IL | Interleukin |
LPS | lipopolysaccharide |
MnSOD | Manganese-subordinates superoxide dismutase |
MAPKKs | MAP kinase kinases |
MMP | Matrix metalloproteinases |
MAPK | Mitogen-activating protein kinase |
MIA | Monosodium iodoacetate |
MPO | Myeloperoxidase |
NADPH | Nicotinamides adenine dinucleotide phosphates |
NO | Nitric oxide |
NO2 | Nitrogen dioxide |
NF-κB | Nuclear factor kappa light chain enhancer of activated B cells |
NFATC1 | Nuclear factor of activated T cells cytoplasmic-1 |
OA | Osteoarthritis |
OPG | Osteoprotegerin |
p38 | a mitogen-activating protein kinase |
PRRs | Pattern recognition receptor |
OONO | Peroxynitrite |
PIA | Pristane-induced arthritis |
PGE2 | Prostaglandins E2 |
PA | Punicalagin |
AA | Reactive amyloids |
RNS | Reactive Nitrogen Species |
ROS | Reactive oxygen species |
RANKL | Receptor activator of nuclear factors kappa-B-ligand |
RANTES | Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted |
RSV | Resveratrol |
RA | Rheumatoid arthritis |
RA-FLS | Rheumatoid arthritis fibroblast-like synoviocytes |
RF | Rheumatoid factor |
RASF | Rheumatoid pain aggravation synovial fibroblasts |
SSCP | Single-stranded conformation polymorphism |
SOD | Superoxide dismutase |
SJC-28 | Swollen 28-joint count |
SF | Synovial fibroblast |
TJC-28 | Tender 28-joint Count |
TR | Thioredoxin reductase |
TLR | Toll-like receptor |
TGF-β | transforming growth factor beta |
TwHF | Tripterygium wilfordii hook factor |
TNF-α | Tumor necrosis factor |
CII | Type II collagen |
UV | Ultraviolet |
UCOC | Uncarboxylated osteocalcin |
VEGF | Vascular endothelial growth factor |
XDH | Xanthine dehydrogenase |
XO | Xanthine oxidase |
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Polyphenols | Source | Experimental Setup | Actioning Mechanism | Ref. |
---|---|---|---|---|
Ferulic acid | apple, sugar beet, popcorn, grains, vegetables | Macrophage, monocytes, Rats | NFATc1, c-Fos, NF-κB, MMP | [32] |
N-feruloyl serotonin | safflower seed | AA | CRP, LOX, TNF-α, iNOS, IL-1β | [33] |
Resveratrol | red grapes, peanut, soy | CIA, FLS | COX-2, PGE2, NADPH oxidase, ROS, p38, MAPK, ERK1/2, NF-κB | [39] |
Epigallocatechin-3-gallate | green tea, strawberries, blackberries | CIA rat | IL-6, TNF-α, IFN-γ | [129,130] |
Gallic acid | cinnamon bark | AIA rat | TNF-α | [32,33,147] |
EVOO polyphenol extract | EVOO, fruit of olea, olives | CIA | TNF-α, IL-1β, IL-6, PEG2, p38, JNK, p65 | [55] |
Curcumin | turmeric rhizome | RA-FLS | IL-1β, IL-6, NF-κB, ERK1/2 | [70] |
p-Coumaric acid | gnetum | AIA | TNF-α, IgG | [34] |
Emodin | rhubarb, asian knotweed | Synovial membrane in human | MMP-1, MMP-9, NF-κB, MAPK | [57] |
Hesperidin | soybean, sweet orange, tangerine | Wistar rat | GSH, SOD, catalase | [47,48] |
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Behl, T.; Upadhyay, T.; Singh, S.; Chigurupati, S.; Alsubayiel, A.M.; Mani, V.; Vargas-De-La-Cruz, C.; Uivarosan, D.; Bustea, C.; Sava, C.; et al. Polyphenols Targeting MAPK Mediated Oxidative Stress and Inflammation in Rheumatoid Arthritis. Molecules 2021, 26, 6570. https://doi.org/10.3390/molecules26216570
Behl T, Upadhyay T, Singh S, Chigurupati S, Alsubayiel AM, Mani V, Vargas-De-La-Cruz C, Uivarosan D, Bustea C, Sava C, et al. Polyphenols Targeting MAPK Mediated Oxidative Stress and Inflammation in Rheumatoid Arthritis. Molecules. 2021; 26(21):6570. https://doi.org/10.3390/molecules26216570
Chicago/Turabian StyleBehl, Tapan, Tanuj Upadhyay, Sukhbir Singh, Sridevi Chigurupati, Amal M. Alsubayiel, Vasudevan Mani, Celia Vargas-De-La-Cruz, Diana Uivarosan, Cristiana Bustea, Cristian Sava, and et al. 2021. "Polyphenols Targeting MAPK Mediated Oxidative Stress and Inflammation in Rheumatoid Arthritis" Molecules 26, no. 21: 6570. https://doi.org/10.3390/molecules26216570