Hyaluronic acid combined with Centella asiatica extract improve skin barrier function and alleviate inflammatory damage via JAK/STAT3 signaling pathway

Abstract Objective Psoriasis, as a chronic inflammatory skin disease, has complex pathogenesis, stubborn condition and high recurrence rate. Centella asiatica (L.) Urban (CA) is one of the commonly used Chinese herbal medicines in dermatology, which has multiple pharmacological activities such as promoting wound healing, anti-cell proliferation and anti-inflammation. Hyaluronic acid (HA) has become an excellent moisturizing ingredient and is widely used in skin care products. This study aims to explore the effects and mechanism of HA combined with CA on skin inflammatory injury and provide experimental basis for the future application research of HA and CA in inflammatory skin diseases. Methods In this study, the skin barrier repair function and the mechanisms of HA combined with CA were evaluated. The expressions of inflammatory factors and barrier related factors were detected in LPS-induced HaCaT cells. The effects on the migration and angiogenesis ability were analyzed in VEGF- induced HUVECs. Results HA with different molecular weights increased the contents of GSH and SOD in LPS-induced HaCaT cells, eliminated free radicals, reduced the production of ROS, and inhibited cell oxidative stress. Among them, HA with molecular weight of 6100Da was the best, followed by 1220KDa HA. It was found that the molecular weight of 1220KDa HA effectively inhibited IFN-γ mRNA level, increase the content of AQP3 and FLG in cells. Mechanism research showed that HA inhibited inflammation was related to block the transduction of NF-κB and JAK/STAT3 pathways. Meanwhile, 1220KDa HA (2 mg/mL) combined with ethyl acetate of CA (CAE, 25 µg/mL) could effectively inhibit the expression of MMP-1 in LPS-induced HaCaT cells, increase the expression of skin barrier related proteins AQP3 and FLG, and reduce the secretion of IL-17. HA combined with CAE enhanced the inhibition of NF-κB and JAK/STAT3 pathways, improving the inhibitory effects of CAE on IFN-γ and IL-6. In addition, after the intervention of HA combined with CAE, the migration and the angiogenesis abilities of VEGF-induced HUVEC cells were decreased. Conclusion HA combined with CAE can reduce release of inflammatory factors and improve the function of skin barrier via the inhibition of NF-κB and JAK/STAT3 pathways, alleviating psoriasis like inflammatory damage.