Heat-clearing and blood-cooling decoction alleviates psoriasis by suppressing proliferation and inflammatory response of keratinocytes via EZH2/NF-κB

Psoriasis is a chronic recurrent dermatological disease that patients always suffer from different comorbidities. Chinese herbal medicine has been commonly used in the treatment of psoriasis for a long history. However, the mechanism operating between Qing-Ying Dizhuo Decoction (QYDD) (a heat-clearing and blood-cooling decoction) and psoriasis remains unclear. This paper aimed to study the role of QYDD in psoriasis and its underlying mechanism. HaCaT cells were induced by a mixture of IL-22, IL-17A, oncostatin M, TNF-α and IL-1α (M5) to construct the in vitro model of psoriasis. CCK-8 assay was utilized to assess the cell proliferation ability. The expressions of KRT1, KRT6, TNF-α, IL-1β, IL-6, IL-23, EZH2, IκBα, p65 and IKK were determined by qRT-PCR, western blot and ELISA. M5 induction increased levels of KRT6, IL-1β, IL-6, TNF-α and IL-23, enhanced the proliferation ability of HaCaT cells and decreased KRT1 expression, while QYDD treatment reversed these trends. Overexpression of EZH2 reversed the inhibitory effects of QYDD on cell inflammatory response and proliferation of M5-induced HaCaT cells. QYDD suppressed M5-activated NF-κB signaling pathway as evidenced by decreased levels of phosphorylated IKK and p65 and increased level of phosphorylated IκBα, while overexpression of EZH2 offset, in part, the regulation of the NF-κB pathway by QYDD. An NF-κB activator (betulinic acid) weakened the inhibitory effect of QYDD on the inflammatory response of HaCaT keratinocytes. QYDD appears to inactivate the NF-κB signaling pathway by inhibiting EZH2, thereby repressing the proliferation and suppressing inflammatory response of HaCaT cells and attenuating psoriasis.