Naringenin protects keratinocytes from oxidative stress injury via inhibition of the NOD2-mediated NF-κB pathway in pemphigus vulgaris

Abstract Naringenin is known to have anti-oxidative activity; however, the effect of naringenin on the progression of pemphigus vulgaris (PV) still remains unclear. This study aims to analyze the effect of naringenin on HaCaT cell apoptosis and oxidative damage under the treatment of PV serum. The results showed that PV serum significantly induced cell apoptosis compared with the control group; whereas, comparing with PV group, naringenin inhibited cell apoptosis. Moreover, PV serum increased the expression of bax and caspase-3, and decreased the expression of bcl-2; but naringenin significantly suppressed the expression of bax and caspase-3, induced the expression of bcl-2. Naringenin inhibited PV serum-induced disruption of cell–cell contacts. Naringenin also down-regulated the expression of Dsg1, Dsg3 and E-cadherin compared with the PV group. Additionally, naringenin noticeably decreased the PV serum-induced ROS production and alleviated PV serum induced the drop of mitochondrial membrane potential. Furthermore, naringenin increased the activity of SOD, GSH-Px and TAC under the treatment of PV serum. Naringenin also decreased the expression of NOD2, RIPK2 and NF-κB p-p65, but this effect could be reversed by muramyl dipeptide (MDP). In conclusion, these results suggested that naringenin protected keratinocytes from apoptosis and oxidative stress injury through inhibition of the NOD2-mediated NF-κB pathway.