To explore the effect and mechanism of circular RNA RAS p21 protein activator 2 (circRASA2) mediated by nobiletin (NOB) on lipopolysaccharide (LPS)-induced hPDLCs in periodontal ligament cells.

hPDLCs cells were divided into control group, model group (hPDLCs cells were treated with 10 μg·mL^-1 LPS for 24 h), NOB-H group (Based on the model group, 20 μmol·L^-1 NOB was given for 24 h), NOB+oe-NC group (hPDLCs cells transfected with oe-NC were treated with 20 μmol·L^-1 NOB) and NOB+oe-circRASA2 group (hPDLCs cells transfected with oe-circRASA2 were treated with 20 μmol·L^-1 NOB). Quantitative real time polymerase chain reaction was used to detect the mRNA expression levels of circRASA2. The secretion levels of inflammation-related factors were detected by enzyme-linked immunosorbent assay. Western blot analysis of slit homolog 2 (Slit2)/mitogen-activated protein kinase (MAPK) signaling pathway related protein expression levels.

The relative expression levels of circRASA2 in control group, model group and NOB-H group were 1.00±0.15, 2.83±0.50 and 1.36±0.27, respectively. The levels of interleukin-1β in control group, model group, NOB-H group, NOB+oe-NC group and NOB+oe-circRASA2 group were (144.82±24.89), (367.54±65.73), (228.51±40.24), (219.78±36.94) and (324.25±61.57) mg·mL^-1, respectively; interleukin-18 levels were (167.50±27.33), (394.68±74.96), (212.47±39.51), (205.93±41.18) and (358.11±66.27) mg·mL^-1, respectively; the relative expression levels of Slit2 protein were 1.00±0.18, 2.35±0.41, 1.61±0.29, 1.57±0.27 and 2.14±0.38, respectively; the ratios of phospho-p38 mitogen-activated protein kinase/p38 mitogen-activated protein kinase protein were 1.00±0.16, 2.08±0.37, 1.39±0.25, 1.33±0.21 and 1.92±0.34, respectively. The above indexes in the model group were compared with the control group, the NOB-H group was compared with the model group, and the NOB+oe-circRASA2 group was compared with the NOB+oe-NC group, and the differences were statistically significant (all P<0.05).

NOB alleviates LPS-induced inflammation and inhibits pyroptosis in hPDLCs cells by inhibiting circRASA2 expression, possibly by inhibiting Slit2/MAPK signaling pathway.