Bergenin attenuates TNF-α-induced oxidative stress and inflammation in HaCaT cells by activating Nrf2 pathway and inhibiting NF-KB pathway

Purpose: To investigate the effect of bergenin in TNF-alpha-induced human immortalized keratinocytes. Methods: Human immortal keratinocyte cells (HaCaT) were incubated with tumor necrosis factor-alpha (TNF-alpha), and then treated with increasing concentrations of bergenin. Cell viability was determined using Cell Counting Kit-8 (CCK8), while oxidative stress and inflammation were evaluated using enzyme linked immunosorbent assay (ELISA). Results: Incubation with increasing concentrations of bergenin showed no significant effect on cell viability of HaCaT (p < 0.05). Tumor necrosis factor-alpha significantly induced up-regulation of interleukin (IL)-6 and IL-8 in HaCaT (p < 0.001), while bergenin significantly reduced the levels of IL-6 and IL-8 (p < 0.001). Bergenin also attenuated TNF-alpha-induced decrease in superoxide dismutase (SOD), as well as increase in malondialdehyde (MDA) and inducible nitric oxide synthase (iNOS). Protein expression of IKB alpha in HaCaT was decreased, while p-p65 and p-IKB alpha were increased by treatment with TNF-alpha. However, bergenin increased IKB alpha but decreased p-p65 and p-IKB alpha in TNF-alpha-induced HaCaT. Moreover, bergenin reduced Kelch-like ECH-associated protein 1 (Keap1), while enhancing transcription factor NF-E2 p45-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in TNF-alpha-induced HaCaT. Conclusion: Bergenin exerts antioxidant and anti-inflammatory effects on TNF-alpha-induced HaCaT by activating Nrf2 pathway and inactivating NF-KB pathway. Therefore, bergenin is a potential agent for the treatment of psoriasis.