Table 5.

Pomegranate application in cartilage tissue engineering.

First Author	References	Experimental Model	Study Type	Findings
Ahmed	[109]	OA chondrocytes or cartilage explants were pre-treated with pomegranate fruit extract (PFE), co-treated with IL-1β. The amounts of PG were measured with a colorimetric assay. The expression of MMPs, pIkBα, and MAPKs was determined by WB and NF-kB by electrophoretic mobility shift assay (EMSA).	in vitro/cartilage explants, chondrocytes	PFE inhibited the IL-1β-induced PG breakdown, MMPs expression on protein and mRNA level, p38-MAPK, phosphorylation of inhibitor of kappa B alpha (IkBα), and NF-kB binding to DNA in OA cartilage explants.
Haseeb	[111]	The potential of PFE to suppress IL-1β-stimulated expression of IL-6, reactive oxygen species (ROS), and NF-κB by analyzing the activation of the kinases upstream of IκBα in PCH by WB.	in vitro/human chondrocytes	PFE inhibited the mRNA and protein expression of IL-6, ROS, and IL-1β-mediated phosphorylation IKKβ, degradation of IκBα, and activation and nuclear translocation of NF-κB/p65 in human chondrocytes. PFE exerted chondroprotective effects by suppressing the NF-kB pathway.
Akhtar	[113]	OA was surgically induced in the tibiofemoral joints of rabbits. In one group, animals were fed PFE in water for 8 wks postsurgery. In the second group, animals were fed PFE for 2 wks before surgery and for 8 wks postsurgery.	in vitro/in vivo rabbit chondrocytes	PFE-fed rabbits had lower levels of IL-6, MMP-13, and PGE2 in synovial fluid/plasma and showed higher expression of AGC and COL2A1 mRNA. PFE treatment significantly reduced IL-1β-induced MAPK and NF-κB inhibitors, and PGE2 production, which highlighted the chondroprotective effect of PFE in the treatment of OA.
Monsefi	[115]	Pregnant BALB/c mice were given PFE to investigate the effect on chondrogenesis. Their embryos were stained with alizarin red S and alcian blue. Bone Ca content in pregnant mice was also measured.	in vitro/in vivo mouse chondrocytes, MSCs	PFE was able to enhance bone/ cartilage formation. MSCs from fetal limb buds were cultured, exposed to PFE, the number of viable cells was greater than in control cultures. The number of cartilage nodules and their diameters were greater in PFE-treated cultures.
Ghoochani	[116]	Patients with knee OA and control drank 200 mL PFE/daily for 6 weeks, and the effect of this intervention on clinical signs was evaluated.	in vivo/OA patients	Significant increases in physical function of decrease in breakdown of cartilage enzymes and increase of anti-oxidant status in patients with knee OA were observed in PFE group.