Abstract: Pomegranate has shown a favorable effect on gingivitis/periodontitis, but the mechanisms
involved are poorly understood. The aim of this study was to test the effect of pomegranate peel
extract (PoPEx) on gingiva-derived mesenchymal stromal cells (GMSCs) under physiological and
inflammatory conditions. GMSC lines from healthy (H) and periodontitis (P) gingiva (n = 3 of each)
were established. The lines were treated with two non-toxic concentrations of PoPEX (low—10;
high—40 g/mL), with or without additional lipopolysaccharide (LPS) stimulation. Twenty-four
genes in GMSCs involved in different functions were examined using real-time polymerase chain
reaction (RT-PCR). PoPEx (mostly at higher concentrations) inhibited the basal expression of IL-6,
MCP-1, GRO-a, RANTES, IP-10, HIF-1a, SDF-1, and HGF but increased the expression of IL-8, TLR3,
TGF-b, TGF-b/LAP ratio, IDO-1, and IGFB4 genes in H-GMSCs. PoPEx increased IL-6, RANTES,
MMP3, and BMP2 but inhibited TLR2 and GRO-a gene expression in P-GMSCs. LPS upregulated
genes for proinflammatory cytokines and chemokines, tissue regeneration/repair (MMP3, IGFBP4,
HGF), and immunomodulation (IP-10, RANTES, IDO-1, TLR3, COX-2), more strongly in P-GMSCs.
PoPEx also potentiated most genes’ expression in LPS-stimulated P-GMSCs, including upregulation
of osteoblastic genes (RUNX2, BMP2, COL1A1, and OPG), simultaneously inhibiting cell proliferation.
In conclusion, the modulatory effects of PoPEx on gene expression in GMSCs are complex and
dependent on applied concentrations, GMSC type, and LPS stimulation. Generally, the effect is more
pronounced in inflammation-simulating conditions.
