Abstract: Objective: To investigate the chemical composition and anti-inflammatory mechanism of Coregonus peled oil (CPO). Methods: CPO was extracted by ultrasonic homogenization and its major chemical components were detected. In addition, its fatty acid (FA) composition was analyzed by gas chromatography-mass spectrometry (GC-MS). Macrophage RAW264.7 cells were cultured as an inflammation model and stimulated with lipopolysaccharides (LPS). Cytotoxicity was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The accumulation of succinate was detected by liquid chromatography tandem mass spectrometry (LC-MS/MS). The concentration of nitric oxide (NO) and the activity of inducible nitric oxide synthase (iNOS) in the supernatant were measured by commercial kits. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the supernatant. The expression levels of CD68, CD86, Arg1, CD206, YM1 and HIF-1α were detected by quantitative real-time polymerase chain reaction (qPCR), and their protein expression levels were determined by Western blotting. Results: The major chemical constituents of CPO were palmitoleic acid, oleic acid, eicosapntemacnioc acid (EPA), and docosahexaenoic acid (DHA). CPO significantly inhibited the production of NO, iNOS, IL-6, TNF-α, and IL-1β as well as their gene expression levels. CPO blocked NF-κB activation by inhibiting the degradation of inhibitor α of NF-κB (IκBα) and decreasing p65 nuclear translocation in LPS-induced RAW264.7 cells. In addition, CPO promoted macrophage polarization from M1 to M2 types by inhibiting the phosphorylation of signal transducer and activator of transcription 1 (STAT1). The content of succinate and the expression levels of hypoxia-inducible factor-1α (HIF-1α) gene and protein indicated that CPO could inhibit the production of IL-1β by inhibiting the accumulation of succinate. Conclusion: The anti-inflammatory mechanism of CPO may be due to the inhibition of the NF-κB, STAT1, and succinate/HIF-1α signaling pathways.

Key words: Coregonus peled; fish oil; inflammation; polarization; succinate/hypoxia-inducible factor-1α