Table 3. Characteristics of animal studies about the effect of pomegranate on osteoarthritis .
| Author (date) | Population | Intervention | Dose | Route | Duration | Histologic Findings | Laboratory Findings | Reference |
| Yang et al (2021) | TNF-α and IL-1β-induced OA mice (n = 18) |
Punicalin | 100 mg/kg BW | Intragastric | 28 Days | (1) Significant improvement in disorder of chondrocyte differentiation in the growth plate zone compared with arthritic control group (2) Significant promotion of the formation of calcified cartilage zone compared with arthritic control group (3) Prevention from cell escape in the superficial zone of tibia compared with arthritic control group |
(1) Inhibition of FOXO3 phosphorylation and cytoplasmic transfer compared with arthritic control group (2) Elevation in FOXO3 compared with arthritic control group (3) Promotion of anabolism via up-regulation of Sox-9 and COL2A1 compared with arthritic control group (4) Inhibition of catabolism via down-regulation of COL10A1, MMP-9, MMP-13, Runx2, IHH, PTHLH compared with arthritic control group |
47 |
| Shivnath et al (2020) | Collagenase-induced OA rats (n = 25) |
Punica granatum L. peel extract | 250 and 500 mg/kg BW | Orally | 30 Days | (1) Significant reduction in severity of the macroscopic lesion, histopathological score of cartilage including reduced severity in disorganization of chondrocytes and reduced surface cartilage erosion with retention of both proteoglycan and collagen content compared with arthritic control group (2) Significant inhibition of degradation of collagen compared with arthritic control group (3) Significant retention of proteoglycan content compared with arthritic control group |
(1) Significant dose-dependent inhibition of DPPH activity compared with arthritic control group (2) Significant reduction in serum alkaline phosphatase level, MMP-3 and COX-2 genes expression compared with arthritic control group (3) Significant increase in COL-2 gene expression compared with arthritic control group |
23 |
| Kong et al (2020) | DMM-induced OA mice (n = 60) |
Punicalagin | 20 mg/kg BW | Oral gavage | 56 Days | (1) Significant amelioration of thickening and hypercellularity of synovium compared with arthritic control group (2) Significant reduction in synovitis score compared with arthritic control group |
Significant decrease in intensity of cleaved caspase-3 and proportion of cellular apoptosis compared with arthritic control group | 24 |
| Lin et al (2020) | Surgical DMM-induced OA mice (n = 45) |
Ellagic acid | 40 mg/kg BW every 2 days | Intragastric | 56 Days | (1) Significant decrease in cartilage surface destruction, proteoglycan loss, and scores of OARSI compared with arthritic control group (2) Significant alleviation in synovitis compared with arthritic control group |
- | 25 |
| Elder et al (2020) | MIA-induced OA rats (n = 9) |
Punicalagin | 9.2 mM twice a week | Knee injection | 35 Days | Significant decrease in knee swelling and cartilage matrix loss compared with arthritic control group | - | 26 |
| Fu et al (2019) | Surgical DMM-induced OA mice (n = 60) |
Urolithin A | 20 mg/kg | Intragastric | 56 Days | (1) Significantly smoother surface of cartilage compared with arthritic control group (2) Significantly lower OARSI scores compared with arthritic control group (3) Significant decrease in calcification of cartilage surface and lower narrow of joint space compared with arthritic control group |
(1) Amelioration of p-PI3K and p-AKT expression compared with arthritic control group (2) Significant decrease in nuclear p65 expression compared with arthritic control group |
27 |
| Lee et al (2018) | Type II collagenase-induced OA rats (n = 5) |
POMx (70% acetone extract of pomegranate peels) | 15 and 150 mg/kg BW | Orally | 28 days | (1) Significant alleviation of OA progress during the initiation of knee cartilage degradation at high dose (150 mg/kg BW) compared with arthritic control group (2) Significant alleviation of OA symptoms and recovering the weight-bearing ratio at high dose (150 mg/kg BW) compared with arthritic control group |
- | 28 |
| Lee et al (2018) | Type II collagenase-induced OA rats (n = 5) |
Punicalagin | 0.25 and 0.5 mg/kg BW | Orally | 28 days | (1) Significant improvement of changes in weight-bearing ratio at high dose (0.5 mg/kg BW) compared with arthritic control group (2) Significant alleviation of cartilage breakdown at high dose (0.5 mg/kg BW) compared with arthritic control group |
- | 28 |
| Choi et al (2018) | Surgically-induced OA rats (n = 90) |
Pomegranate concentrated powder | 200 mg/kg BW | Orally | 58 Days | (1) Significant decrease in knee thickness, capsule-exposed knee thickness, maximum extension angle of the knee, OA-like X-ray signs, number of synovial membrane BrdU-immunoreactive cells, femoral and tibial articular cartilage Mankin scores, synovial membrane epithelial lining thickness, number of inflammatory cells that infiltrated the synovial membrane, number of PARP-immunolabeled cells in femoral and tibial articular cartilage and synovial membrane, COX-2- and TNF-α-immunoreactive cells of femoral and tibial articular cartilage and synovial membrane compared with arthritic control group (2) Significant increase in total knee joint, femoral and tibial articular surface BMDs, femoral and tibial articular cartilage focal compressive strength, number of femoral and tibial articular cartilage BrdU-immunoreactive cells, thicknesses of femoral and tibial articular cartilage compared with arthritic control group |
(1) Significant decrease in femoral and tibial articular cartilage with synovial membrane PGE2 levels, 5-LPO activity of femoral and tibial articular cartilage with synovial membrane, femoral and tibial articular cartilage with synovial membrane MMP-2 and MMP-9 activity, synovial membrane COL-2 mRNA expression compared with arthritic control group (2) Significant increase in femoral and tibial articular cartilage COL-2 mRNA expression, Sox-9 and Aggrecan mRNA expression in femoral and tibial articular cartilage with synovial membrane compared with arthritic control group |
29 |
| Choi et al (2017) | Surgically induced OA rats (n = 140) |
Pomegranate concentrated powder | 200 mg/kg BW | Orally by gastric gavage | 28 Days | (1) Significant decrease in knee thickness, capsule-exposed knee thickness, maximum extension angle of the knee, numbers of synovial membrane BrdU-immunopositive cells, femoral and tibial articular cartilage Mankin scores, synovial membrane lining epithelium thickness, number of inflammatory cells infiltrating the synovial membrane tissue, numbers of PARP, COX-2, and TNF-α-immunopositive cells in femoral and tibial articular cartilage with synovial membrane tissue compared with arthritic control group (2) Significant increase in numbers of femoral and tibial articular cartilage BrdU-immunoreactive cells, femoral and tibial articular cartilage thicknesses compared with arthritic control group |
(1) Significant decrease in PGE2 levels, 5-LPO, MMP-2, and MMP-9 activities in femoral and tibial articular cartilage with synovial membrane tissue, COL-2 mRNA expression in synovial membrane tissue compared with arthritic control group (2) Significant increase in COL-2 mRNA expression in femoral and tibial articular cartilage, Sox-9 and aggrecan mRNA expression levels in femoral and tibial articular cartilage with synovial membrane tissue compared with arthritic control group |
30 |
| Akhtar et al. (2017) | Surgically-induced OA rabbits (n = 27) |
Pomegranate fruit extract in water | 34 mg/kg BW | Orally | 56 days and 70 days | (1) Significant decrease in disease severity grades of macroscopic articular cartilage lesions in joint compartments, mean score for the loss of Safranin-Ostaining, structural changes, and cluster formation, total histological score and scores for histological parameters, number of cells with active caspase-3 and PARP p85 in cartilage and caspase-mediated apoptosis pathway contributing to cartilage pathology compared with arthritic control group (2) Non-significant trend toward higher chondrocyte density compared with arthritic control group |
(1) Significant decrease in MMP-3, MMP-9, and MMP-13 expression and PGE2 level in synovial fluid compared with arthritic control group (2) Significant inhibition of circulating plasma and synovial fluid MMP-13 and synovial fluid IL-6 levels compared with arthritic control group (3) Significant increase in Aggrecan and COL2A1 expression compared with arthritic control group (4) No significant change in synovial fluid IL-1β-levels compared with arthritic control group |
31 |
| Hadipour-Jahromy et al. (2010) | MIA-induced OA mice (n = 30) |
Pomegranate juice | 4, 10, and 20 mL/kg BW | Orally |
14 days |
(1) Significant prevention from chondrocyte damage compared with arthritic control group (2) Significant focal increase in number of cells with less damage to proteoglycan in the epiphyseal plate compared with arthritic control group |
- | 32 |
OA: osteoarthritis; FOXO3: Forkhead box O3; Sox-9: SRY-box 9; COL2A1: Collagen Type II Alpha 1 Chain; COL10A1: Collagen Type X Alpha 1 Chain; MMP: matrix metalloproteinase; RUNX-2: runt-related transcription factor-2; IHH: Indian Hedgehog Signaling Molecule; PTHLH: Parathyroid Hormone Like Hormone; DPPH: 1,1-diphenyl-2-picrylhydrazyl; COX-2: cyclooxygenase-2; COL-2: collagen type-II; DMM: destabilization of the medial meniscus; OARSI: Osteoarthritis Research Society International; MIA: monosodium iodoacetate; PGE2: prostaglandin E2; LPO: Lipoxygenase; BrdU: 5-Bromo-2’-Deoxyuridine; PARP: cleaved poly ADP-ribose polymerase; TNF: tumor necrosis factor; BMD: bone mineral density; IL: interleukin.