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 p...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.展开更多
Background: Acne vulgaris is characterized by the enhancement of sebaceous lipogenesis and sebum secretion, and apart from retinoids and some natural products there are few effective antiacne agents that directly supp...Background: Acne vulgaris is characterized by the enhancement of sebaceous lipogenesis and sebum secretion, and apart from retinoids and some natural products there are few effective antiacne agents that directly suppress sebum production and accumulation in sebaceous glands. Objective: We examined the effects of β-cryptoxanthin (β-CRX), which is a carotenoid pigment most abundant in Citrus unshiu Marcovich (Satsuma mandarin orange) and plays a role as a vitamin A precursor on sebum production and accumulation in hamster sebaceous gland cells (sebocytes). Materials and methods: The regulation of sebum production was examined by the measurement of triacylglycerols (TGs), the major sebum component, and oil red O staining in insulindifferentiated hamster sebocytes. The expression of diacylglycerol acyltransferase-1 (DGAT-1), a rate-limiting enzyme of TG biosynthesis, and perilipin 1 (PLIN1), a lipid storage droplet protein, was analyzed using real-time PCR and Western blotting. Results: Hamster sebocytes constitutively produced TGs during cultivation and the production of TGs was enhanced by insulin treatment. Both constitutive and insulin-enhanced TG productions were dose- and time-dependently inhibited by β-CRX as well as 13-cis retinoic acid. In addition, the gene expression of DGAT-1 was suppressed by β-CRX in the sebocytes. Furthermore, the insulin-en- hanced sebum accumulation as lipid droplets was reduced in the β-CRX-treated cells. Moreover, β-CRX was found to suppress the gene expression and production of PLIN1 in insulin-differentiated hamster sebocytes. Conclusions: These results provide novel evidence that β-CRX is an effective candidate for acne therapy by its ability to exert dual inhibitory actions against DGAT-1-dependent TG production and PLIN1-mediated lipiddroplet formation in hamster sebocytes.展开更多
基金supported by the National Natural Science Foundation of China(Project No.81773345 and 82104856)Basic and Applied Basic Research Foundation of Guangdong Province(No.SL2023A04J01298).
文摘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.
文摘Background: Acne vulgaris is characterized by the enhancement of sebaceous lipogenesis and sebum secretion, and apart from retinoids and some natural products there are few effective antiacne agents that directly suppress sebum production and accumulation in sebaceous glands. Objective: We examined the effects of β-cryptoxanthin (β-CRX), which is a carotenoid pigment most abundant in Citrus unshiu Marcovich (Satsuma mandarin orange) and plays a role as a vitamin A precursor on sebum production and accumulation in hamster sebaceous gland cells (sebocytes). Materials and methods: The regulation of sebum production was examined by the measurement of triacylglycerols (TGs), the major sebum component, and oil red O staining in insulindifferentiated hamster sebocytes. The expression of diacylglycerol acyltransferase-1 (DGAT-1), a rate-limiting enzyme of TG biosynthesis, and perilipin 1 (PLIN1), a lipid storage droplet protein, was analyzed using real-time PCR and Western blotting. Results: Hamster sebocytes constitutively produced TGs during cultivation and the production of TGs was enhanced by insulin treatment. Both constitutive and insulin-enhanced TG productions were dose- and time-dependently inhibited by β-CRX as well as 13-cis retinoic acid. In addition, the gene expression of DGAT-1 was suppressed by β-CRX in the sebocytes. Furthermore, the insulin-en- hanced sebum accumulation as lipid droplets was reduced in the β-CRX-treated cells. Moreover, β-CRX was found to suppress the gene expression and production of PLIN1 in insulin-differentiated hamster sebocytes. Conclusions: These results provide novel evidence that β-CRX is an effective candidate for acne therapy by its ability to exert dual inhibitory actions against DGAT-1-dependent TG production and PLIN1-mediated lipiddroplet formation in hamster sebocytes.
