Sakuranetin downregulates inducible nitric oxide synthase expression by affecting interleukin-1 receptor and CCAAT/enhancer-binding protein β

In this study, we extracted the bark ofPrunus jamasakura and purified it to isolate the pharmacologically active constituents by monitoring nitric oxide (NO) production in rat hepatocytes that were treated with the pro-inflammatory cytokine, interleukin (IL)-1 β. Sakuranetin and (−)-naringenin, which were present in an ethyl acetate-soluble fraction of the bark extract, significantly inhibited NO induction and inducible nitric oxide synthase (iNOS) expression. These two flavanones decreased the expression of type 1 IL-1 receptor gene and phosphorylatio n of Akt, also known as protein kinase B, which is regulated by phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). Furthermore, sakuranetin decreased the phosphorylation of the activator isoforms of CCAAT/enhancer-binding protein β (C/EBPβ), which synergistically activates the transcription of theiNOS gene with nuclear factor κB (NF-κB). Therefore, sakuranetin inhibited the co-activating activity of C/EBPβ with NF-κB, leading to the suppression ofiNOS gene expression in hepatocytes. Taken together, sakuranetin in Pruni Cortex downregulated theiNOS gene by inhibiting PI3K/Akt signal transduction and the phosphorylation of C/EBP β. These results imply that sakuranetin may be primarily responsible for the anti-inflammatory effects of Pruni Cortex in the liver.
Source: Journal of Natural Medicines - Category: Drugs & Pharmacology Source Type: research