Nobiletin alleviates palmitic acid‑induced NLRP3 inflammasome activation in a sirtuin 1‑dependent manner in AML‑12 cells.
Mol Med Rep. 2018 Dec ;18(6):5815-5822. Epub 2018 Oct 31. PMID: 30387829
The NOD‑like receptor family pyrin domain containing 3 (NLRP3) inflammasome has been reported to contribute to palmitic acid (PA)‑induced lipotoxicity. Nobiletin (Nob) is a polymethoxylated flavonoid derived from citrus fruits that has been reported to exert antioxidant and antitumor effects. However,its protective and regulatory mechanisms in PA‑induced lipotoxicity remain unclear. Therefore, the aim of the present study was to investigate the protective effects of Nob in AML‑12 cells against lipotoxicity and examine the underlying mechanism. Western blotting, reverse transcription‑quantitative polymerase chain reaction and ELISA assays were performed to investigate the activation of the NLRP3 inflammasome. Sirtuin 1 (SIRT1) small interfering RNA was used to knockdown SIRT1 expression in AML‑12 cells. The results demonstrated that PA effectively activated NLRP3 inflammasome and increased the expression and secretion of interleukin (IL)‑1β and IL‑18. Notably, the PA‑induced inflammasome activation was reversed by Nob, as indicated by the decreased expression levels of NLRP3, Caspase‑1, IL‑1β and IL‑18. Furthermore, Nob treatment with or without PA enhanced the expression of SIRT1 in AML‑12 cells, while knockdown of SIRT1 with SIRT1‑small interfering RNA reversed the anti‑inflammatory effects of Nob. Overall, the results of the present study indicated that Nob alleviated PA‑induced lipotoxicity in AML‑12 cells via the suppression of NLRP3 inflammasome activation in a SIRT1‑dependent manner. These results provide a possible basis of the underlying mechanism and, in turn, the potential application of Nob in the treatment of non‑alcoholic fatty liver disease.