Influence of a combination of triptolide and ferulic acid on the activities of CYP450 enzymes and oxidative stress in HaCaT cells

Topical administration of triptolide (TP) is effective in the treatment of rheumatoid arthritis (RA), but it can also induce skin irritation. Previous studies have used data mining strategies to analyze the application of Tripterygium wilfordii in the treatment of RA and have shown that TP and ferulic acid (FA) can be used in combination due to their component compatibility. The aims of the present study were to investigate the mechanisms underlying the effects of TP treatment and to identify its effects on metabolism and oxidative damage in the skin. MTT assay results suggested that the HaCaT cell survival rate was significantly increased when the compatibility ratio of TP to FA was 1:100. Moreover, the combination of TP with FA (TP + FA) did not significantly affect the activities of the cytochrome P40 (CYP) enzymes CYP family 1 subfamily A member 2 (CYP1A2), CYP2E1 and CYP3A4, when used as a ‘cocktail’. It was found that TP + FA significantly decreased the production levels of reactive oxygen species (ROS), superoxide dismutase and malondialdehyde in HaCaT cells, while significantly increasing levels of glutathione and catalase. In addition, TP + FA significantly increased nuclear factor erythroid 2-related factor 2 protein expression, compared with TP alone. Thus, the present results indicated that the underlying mechanism of TP + FA efficacy may be related to decreased ROS production level in HaCaT cells, increased production levels of key antioxidant factors and increased antioxidant activity of the epidermis, all of which were correlated with a protective effect against oxidative damage.