Paeonol derivative-6 attenuates inflammation by activating ZEB2 in acute liver injury

Paeonol is a natural phenolic compound and isolated as an active ingredient from Moutan Cortex. Paeonol derivative-6 (DPF-6) is a derivative of paeonol improved in water solubility and bioavailability. Previous studies have reported that paeonol possesses a variety of pharmacological activities, such as antioxidant and anti-inflammatory properties. Moreover, we have previously verified that DPF-6 has anti-inflammatory effects. However, the role and fundamental mechanism of DPF-6 in acute liver injury (ALI) was still unclear. In this study, we indicated that DPF-6 inhibited inflammation and the expression of TNF-α, IL-6 and IL-1β in liver tissues and LPS-mediated L-02 cells, concomitant with the upregulated expression of ZEB2. More importantly, it was demonstrated that overexpression of ZEB2 inhibited the expression level of TNF-α, IL-6 and IL-1β in LPS-mediated L-02 cells. In contrast, knockdown of ZEB2 increased the expression level of TNF-α, IL-6 and IL-1β in LPS-mediated L-02 cells. Further studies showed that ZEB2 inhibited the inflammation cytokine secretion via JNK signaling pathway in L-02 cells. Taken together, all the above results indicate that DPF-6 increased the expression of ZEB2, consequently inhibited inflammation cytokine secretion through JNK signaling pathway, which may be utilized as a potential anti-inflammation monomeric compound in the treatment of ALI.