Peony Seed Oil Inhibited Neuroinflammation by <scp>PPAR</scp>/<scp>RXR</scp> Signaling Pathway in D‐Gal Induced Mice

Essential fatty acids could regulate inflammation, especially n-3 PUFA (n-3 polyunsaturated fatty acids), which are considered to have a protective effect to inhibit neuroinflammation. Peony seed oil is one of the most abundant n-3 PUFAs in oils. but the mechanism of peony seed oil affecting inflammation in mice brains is still lacking convincing evidence. Sixty male C57BL/6J mice were randomly allocated into four groups: D-gal (D-galactose) induced model group, FO (D-gal + fish oil), PSO (D-gal + peony seed oil). After 10 weeks, the fatty acid composition in liver and brain tissues and potentially related genes were examined. Docosahexaenoic acid (DHA) was significantly higher, while arachidonic acid (AA) was significantly lower in both in the PSO and FO groups than that in the model group in the brain and liver. In the PSO and FO groups, the relative mRNA levels of <i>Fads1/2</i>, <i>Elovl2</i>, and <i>Acaa1a</i> were significantly up-regulated, but <i>Acox1</i> and <i>Acox3</i> were significantly down-regulated compared to the model group. In the PSO and FO groups, the relative protein levels of PPARG, RXRA, and IL-10 were significantly up-regulated, and the expressions of AGERs, TNF-α, PLA2, and PGF2α were significantly down-regulated compared to the model group. The phosphorylation-tau of total tau protein ratio was significantly lower in the PSO and FO groups than in the model group. Peony seed oil, rich in n-3 PUFA, inhibited neuroinflammation and rescued the disruption of alternative splicing of the <i>Mapt</i> gene by activating the PPAR/RXR signaling pathway and promoting n-3/n-6 biosynthesis.