Table 2.
Summary of studies on the effects of green tea and epigallocatechin gallate (EGCG) on joint health.
| First Author, Year of Study, Citation | Experimental Design and Treatments | Effects of Green Tea or EGCG |
|---|---|---|
| Cellular Studies | ||
| Adcocks, 2002, [58] |
Model: Bovine cartilage explants cotreated with TNF-α (3 nM) Treatments: EGCG (0.2, 2, 20, or 200 µM) for 5 days Model: Human cartilage from an OA knee joint cotreated with IL-1β (3 nM), TNF-α (6 nM) Treatment: EGCG (20 µM) for 9 days |
Compared to the control group, the EGCG groups showed: ↓ Proteoglycan and type II collagen degradation |
| Ahmed, 2002, [68] |
Model: Human primary chondrocytes cotreated with IL-1β (5 ng/mL) Treatments: Control, EGCG (20, 50, 100, or 200 μM) for 24 h |
Compared to the control group, the EGCG groups showed: ↓ iNOS expression and NO production ↓ COX-2 expression and PGE2 production ↓ LDH release |
| Ahmed, 2004, [59] |
Model: Human primary chondrocytes or human cartilage explants cotreated with IL-1β (50 or 10 ng/mL) Treatments: EGCG (20, 50, 100, or 200 μM) for 24 or 72 h |
Compared to the control group, the EGCG groups showed: ↓ mRNA and protein expression of MMP-1 and MMP-13 in chondrocytes ↓ GAG release from human cartilage explants ↓ Transcription activity of NF-κB and AP-1 |
| Akhtar, 2011, [65] |
Model: Human primary chondrocytes with IL-1β (5 ng/mL) after EGCG Treatments: Control, EGCG (10–100 μM) for 24 h |
Compared to the IL-1β group, the IL-1β + EGCG groups showed: ↓ ENA-78, GM-CSF, GRO, GRO-α, IL-6, IL-8, MCP1, MCP-3, MIP-1β, GCP-2, MIP-3α, IP-10, NAP-2, LIF via ↓ activation of NF-κB and JNK-MAPK |
| Andriamanalijaona, 2005, [63] |
Model: Bovine primary articular chondrocytes Treatments: Pretreated with EGCG (20 or 50 µM) for 24 h and then cotreated with by IL-1β (10 ng/mL) for 24 h |
Compared to the control group, the EGCG groups showed: ↑ Type II collagen and aggrecan core protein expression ↑ mRNA expression of TGF-β1, TGF-β2, TGF-βR1, and TGF-βII ↓ mRNA levels of MMP-1, MMP-3, MMP-13, aggrecanase-1, aggrecanase-2, iNOS, COX-1, COX-2 (anti-inflammatory effect) ↓ MAPK (Erk1/Erk2, p38 kinase), NF-κB, and AP-1 activity |
| Bae, 2010a, [72] |
Model: Primary human articular cartilage with or without OA treated with EGCG. Then, cartilage is implanted to cartilage defects in rabbits Treatments: Control (no EGCG) and EGCG (1 mM) at 4 °C for 1–4 weeks |
Compared to the control group, the EGCG group showed: Preserving and repairing articular cartilage by reversibly regulating cell cycle at G0/G1 phase and NF-κB expression |
| Bae, 2010b, [60] |
Model: Human articular cartilage Treatments: Control (no RGCG), cotreated EGCG (1 mM), and pretreated EGCG for 2 weeks |
Compared to the control group, the EGCG group showed: ↑ GAG content and total collagen ↓ Denaturation of extracellular matrix |
| Elder, 2017, [76] |
Model: Porcine osteochondral xenograft Treatments: Control (no EGCG), EGCG at 0.04%, 0.2%, and 1% w/v |
Compared to the control group, the EGCG group showed: ↑ Compressive resistance of decellularized porcine cartilage ↑ Fixation on the decellularized porcine cartilage coefficient of friction against glass ↑ Strength of cartilage–bone interference in shear ↑ Mechanical properties |
| Heinecke, 2010, [66] |
Model: Equine primary articular cartilage Treatments: Pretreated with EGCG (4, 40, or 400 ng/mL) for 24 h and then cotreated with IL-1β (10 ng/mL) and TNF-α (1 ng/mL) for 24 h |
Compared to the control group, the EGCG groups showed: ↓ COX-2 expression and PGE2 production ↓ NF-κB translocation to the nucleus |
| Huang, 2010, [64] |
Model: Human primary osteoarthritic synovial adherent cells Treatments: Pretreated with EGCG (10, 20, or 50 μM) for 12 h and then cotreated with IL-1β for 12 h |
Compared to the control group, the EGCG groups showed: ↓ COX-2 upregulation ↓ PGE2 and IL-8 production ↓ Phosphorylation of IKKβ |
| Huang, 2015, [74] |
Model: Primary rabbit articular chondrocytes Treatments: Control, EGCG (5–20 µM) for 2, 4, and 6 days |
Compared to the control group, the EGCG groups showed: ↑ Chondrocyte growth and synthesis of the cartilage extracellular matrix ↑ Expression of aggrecan, collagen II, and SOX9 genes ↓ Gene expression of collagen I ↓ Dedifferentiation of chondrocytes |
| Jin, 2020, [62] |
Model: Primary porcine 3D encapsulated articular chondrocytes stimulated with IL-1β (10 ng/mL) Treatments: Control (no HA), EGCG (50 µM) + 2%HA, EGCG + 5%HA |
Compared to the no HA group, the EGCG + 5%HA group showed: ↓ Expression of proinflammatory genes (COX2, TNF-α, MMP1, MMP13, ADMTS5) ↑ Chondrogenic regeneration via ↑ gene expression of COL2, SOX9, ACAN |
| Rasheed, 2009, [73] |
Model: Human primary chondrocytes stimulated with ACE for 8 h Treatments: Pretreated with EGCG (25, 75, or 150 µM) for 2 h |
Compared to the control group, the EGCG groups showed: ↓ Gene expression and production of TNF-α and MMP-13 via ↓ p38-MAPK and JNK activation ↓ IκBα protein degradation in the cytoplasm, followed via ↓ activation and translocation of NF-κB to the nucleus |
| Rasheed, 2016, [67] |
Model: Human primary chondrocytes with and without IL-1β (5 ng/mL) Transfected with miRNA inhibitors Treatments: Control, IL-1β, IL-1β + EGCG (20–50 μM) for 24 h |
Compared to the IL-1β group, the IL-1β + EGCG groups showed: ↓ COX-2 expression, PGE2 production via ↑ hsa-miRNA-199a-3p expression |
| Rasheed, 2018, [87] |
Model: Human primary chondrocytes with and without IL-1β (5 ng/mL) Treatments: Control, IL-1β, IL-1β + EGCG (20–50 μM) for 24 h |
Compared to the IL-1β group, the IL-1β + EGCG groups showed: ↑ Expression 19 miRNAs, ↓ 17 miRNAs, and no change in 1311 miRNAs ↓ ADAMTS5 expression ↑ hsa-miRNA-140-3p expression |
| Singh, 2002, [69] |
Model: Human primary chondrocytes cotreated with IL-1β (2 ng/mL) Treatments: Control, EGCG (1, 10, 50, or 100 μM) for 12 or 24 h |
Compared to the control group, the EGCG groups showed: ↓ iNOS expression and NO production ↓ IκBα protein degradation in the cytoplasm, followed by activation and translocation of NF-κB to the nucleus |
| Singh, 2003, [70] |
Model: Human primary chondrocytes cotreated with IL-1β (2 ng/mL) Treatments: Control, EGCG (100 µM) for 30 min |
Compared to the control group, the EGCG groups showed: ↓ Phosphorylation of JNK isoforms ↓ Accumulation of hosphor-c-Jun and DNA binding activity of AP-1 ↔ Activation of extracellular signal-regulated kinase p44/p42 (ERKp44/p42) or p38-MAPK |
| Zhang, 2019, [71] |
Model: LPS-stimulated ATDC5 cells to mimic an inflammatory response during OA Treatments: Control, pre-GTP (100 µg/mL) for 24 hour, LPS, and GTP + LPS |
Compared to the LPS group, the GTP + LPS group showed: ↓ Cell damage ↓ MAPK and NF-κB cascades via positively regulating miRNA-9 |
| Zheng, 2019, [75] |
Model: Human fibroblast-like synoviocyte-OA cells Treatments: EGCG (4 mg/mL), GA, EGCG + GA, EGCG + GA-NPs for 72 h |
Compared to the EGCG group, the EGCG + GA-NPs group showed: ↓ Arthritic activity |
| Animal Studies | ||
| Haqqi, 1999, [88] |
Model: A mouse model of collagen-induced arthritis Treatments: Control, GTP (0.2% in water) for 7 weeks |
Compared to the control group, the GTP group showed: ↓ Arthritic incidence ↓ Total IgG and type II collagen-specific IgG levels in serum and arthritic joints ↓ Expression of proinflammatory genes (COX2, TNF-α, IFN-γ) in arthritic joints ↓ Joint infiltration by TNF-α and IFN-γ-producing cells in arthritic joints ↑ Neutral endopeptidase activity in arthritic joints |
| Jin, 2020, [62] |
Model: A rat model of surgically induced OA Treatments: Control (no HA), EGCG + 5%HA for 3 weeks |
Compared to the no HA group, the EGCG + HA group showed: ↓ Cartilage loss (GAG, type II collagen) ↓ Expression of collagen I and X |
| Leong, 2014, [90] |
Model: A mouse post-traumatic OA model using the destabilization of the medial meniscus (DMM) Male C57BL/6 mice (5–6 months old) Treatments: Sham, sham + EGCG (25 mg/kg), DMN, DMN + EGCG (25 mg/kg) for 4 and 8 weeks |
Compared to the DMN group, the DMN + EGCG group showed: ↓ Progression in early and midstage OA as shown by decreased Safranin O staining and OARSI scores ↓ OA-associated pain symptoms as shown by higher locomotor behavior (distance traveled) ↓ Degradation of both type II collagen and aggrecan in the articular cartilage matrix ↓ Staining of MMP-13 and ADAMTS5 in the articular cartilage ↓ Gene expression of MMP-1, MMP-3, MMP-8, MMP-13, ADAMTS5, IL-1β, and TNF-α in the articular cartilage ↑ Gene expression of MMP-repressing transcriptional regulator CITED2 in the articular cartilage ↓ CCR2 and IL-1β and TNF-α in the DRG |
| Sobhi, 2007, [89] |
Model: A mouse model of intra-articular carrageenan-induced OA Rats (150–200 g) Treatments: Control, OA, OA + GTE (1.5% w/v) for 3 weeks |
Compared to the OA group, the OA + GTE group showed: ↓ Plasma lipid peroxides, NO, and total thiols ↓ Numbers of inflammatory cells infiltrating the synovial membrane at arthritic joint ↓ Erosive necrosis, chondrodysplasia, congestion, edema, mineralization, and multinucleated giant cells infiltration No cartilage and bone erosion |
| Human Studies | ||
| Hashempur, 2018, [92] |
Model: Randomized open-label active-controlled clinical trial Adults (n = 55) with knee OA Treatments: Control group (diclofenac at 100 mg/d) and intervention group (GTE at 1500 mg/d plus diclofenac) for 4 weeks |
Compared to the control group, the intervention group showed: ↓ VAS pain, total WOMAC, WOMAC-physical function scores ↔WOMAC-pain, WOMAC-stiffness |
| Takiguchi, 2019, [18] | Model: 5-year cohort study (n = 11,091) (age range 40–72 years) with no history of knee OA | In men only, but not in women, older age, higher BMI, higher METs score, less smoking, and lower green tea consumption were associated with incident knee OA |
ACAN, aggrecan; ACE, AGE, advanced glycation end products; AP-1, apolipoprotein-1; CCR2, C-C Motif Chemokine Receptor 2; CIA, collagen-induced arthritis; CITED2, Cbp/p300-interacting transactivator 2; COL2, collagen type II; COX, cyclooxygenase; DRG, dorsal root ganglion; EGCG, epigallocatechin gallate; ENA-78, epithelial neutrophil activating peptide-78; ERK, extracellular signal-regulated kinases; GA, glucosamine; GAG, glycosaminoglycan; GCP-2, granulocyte chemotactic protein-2; GM-CSF, granulocyte macrophage colony stimulating factor; GRO, growth-related oncogene; GTE, green tea extract; GTP, green tea polyphenols; HA, hyaluronic acid; IFN-γ, interferon-γ; iNOS, inducible nitric oxide synthase; IL, interleukin-β; IP-10, interferon-gamma-inducible protein-10; JNK, c-jun N-terminal kinase; LDH, lactate dehydrogenase; LIF, leukemia inhibitory factor; LPS, lipopolysaccharide; MAPK, mitogen-activating protein kinases; MMP, matrix metalloproteinases; NAP-2, nucleosome assembly protein-2; NF-κB, nuclear factor kappa-B; NO, nitric oxide; NP, nanoparticles; OA, osteoarthritis; OARSI, osteoarthritis research society international; PGE2, prostaglandin E2; SOX9, SRY-Box Transcription Factor 9; TGF-β, transforming growth factor-β; TGF-βRII, transforming growth factor-β receptor-II; TNF-α, tumor necrosis factor-α; VAS, visual analogue scale; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index. ↑, increase; ↓, decrease; ↔, no change.