Paeoniflorin mitigates insulin-like growth factor 1-induced lipogenesis and inflammation in human sebocytes by inhibiting the PI3K/Akt/FoxO1 and JAK2/STAT3 signaling pathways

Abstract Insulin-like growth factor-1 (IGF-1) is considered as a pathogenic factor contributing to sebaceous gland dysfunction, which leads to acne vulgaris. Paeoniflorin (Pae), a bioactive monomer derived from total glycosides of paeony, has shown potential in treating various diseases. However, its anti-acne effects on human sebocytes are not well understood. In this study, we investigated the effects of Pae on acne development induced by IGF-1 in SZ95 sebocytes. Following IGF-1 stimulation, SZ95 sebocytes were exposed to Pae and then determined for proliferation, cell cycle, apoptosis, lipogenesis and pro-inflammatory cytokine secretion. We also analyzed the expression of proteins involved in the PI3K/Akt/FoxO1 and JAK2/STAT3 pathways. In vitro experiments demonstrated that Pae significantly inhibited colony formation, induced G1/S cell cycle arrest, promoted apoptosis, inhibited lipogenesis and cytokine synthesis in IGF-1-treated SZ95 sebocytes. Furthermore, Pae suppressed the phosphorylation of Akt, FoxO1, JAK2, and STAT3. Importantly, the sebo-suppressive and anti-inflammatory effects of Pae were enhanced by blocking PI3K and JAK2. In summary, our findings suggest that Pae has potent anti-proliferative and pro-apoptotic effects in SZ95 sebocytes. Additionally, Pae effectively protects against IGF-1-induced lipogenesis and inflammation by targeting the PI3K/Akt/FoxO1 and JAK2/STAT3 signaling pathways. Graphical Abstract