Ligustrazine alleviates psoriasis-like inflammation through inhibiting TRAF6/c-JUN/NFκB signaling pathway in keratinocyte

Abstract

Ligusticum chuanxiong Hort (Ligusticum; Apiaceae) (accepted name, Ligusticum striatum DC, on "The Plant List" for the latest version) is a Chinese herbal medicine (CHM) which mainly distributed in Sichuan Basin, China. Chuanxiong is the dried rhizome of Ligusticum chuanxiong Hort. Ligustrazine, also known as tetramethylpyrazine (TMP), is a main active fraction of chuanxiong. The aim of this study was to clarify the underlying mechanisms by which TMP protect against psoriasis-like inflammation in keratinocytes. Here, we demonstrated that TMP alleviated the severity and PASI scores of IMQ-induced psoriasis-like skin lesion in vivo. For the histopathology level, TMP inhibited the over-proliferation of keratinocytes in the epidermis and the substantial immune cells influx in dermis. For the mechanism of the ability of TMP on regulating inflammation, we confirmed that TMP regulate the TRAF6/c-JUN/NFκB signaling pathway through analyzing the proteomics profiling and verifying the expression of TRAF6, pho-c-Jun, pho-NFκB, so that the downstream psoriasis-relevant genes transcribed by c-JUN or NFκB were down-regulated. Furthermore, we predicted TRAF6 as the potential binding point of TMP. Accordingly, our study demonstrated that TMP regulated psoriasis-like inflammation through inhibiting TRAF6/c-JUN/NFκB signaling pathway in keratinocytes, which potentially provides evidence of the mechanism of TMP in the treatment and prevention of psoriasis.

Keywords: Anti-inflammation; Keratinocyte; Ligustrazine; Psoriasis; TRAF6.