Potential molecular targets of natural product-derived compounds for psoriasis treatment. TNF-α, IL-17A, IL-22, IL-1α, Oncostatin-M, and IFN-γ promote the activation of STAT3, STAT1, TAK1/NF-kB, JNK, AKT, and p38 signaling systems, as well as ROS production. These signaling pathways and ROS production lead to inflammatory responses by increasing the expression or protein levels of NLRP3, caspase-3, caspase-1, and others in keratinocytes. They also contribute to abnormal keratinocyte proliferation by increasing the levels of SKP2, CEBPD, cyclin A, and cyclin D1. Piperine, shikonin, and genistein inhibit STAT3, while glycyrrhizin inhibits STAT3 activity through SIRT1 activation. Kaempferol and cudraxanthone D (Cud D) also inhibit STAT1 activity. Luteolin, genistein, Cud D, and liquirtin inhibit NF-kB transactivity, whereas indirubin inhibits NF-kB signaling by inhibiting TAK1 activity. 3H-1,2-dithiole-3-thione (D3T) and nitidine inhibit the JNK signaling pathway, a member of the MAPK signaling system, and indirubin and paeoniflorin inhibit p38, another signaling pathway. Leucosceptoside A (Leu A) inhibits the PI3K/AKT signaling pathway, while Leu A and kaempferol inhibit ROS overproduction. Furthermore, p53 is known to inhibit excessive keratinocyte proliferation, and nitidine activates the p53 pathway. Sharp arrow (→) indicates activation, and blunt arrow (⊣) indicates inhibition
