Porcine circovirus type 2 (PCV2) is the main pathogen causing porcine circovirus-associated diseases (PCVD/PCVADs), and infection of the host induces immunosuppression. Since quercitrin (QUE) has anti-inflammatory and antiviral activity, it is worth exploiting in animal diseases. In this study, the interventional effects and the molecular mechanism of QUE on PCV2-induced oxidative stress and inflammatory responses in 3D4/2 cells and the modulation of histone acetylation modifications were investigated. The ROS production was measured by DCFH-DA fluorescent probes. HAT and HDAC enzyme activity were determined by ELISA. Histone acetylation, oxidative stress and inflammation-related gene expression levels were measured by q-PCR. Histone H3 and H4 (AcH3 and AcH4) acetylation, oxidative stress and inflammation-related protein expression levels were measured by Western blot. The results showed that QUE treatment at different concentrations on PCV2-infected 3D4/2 cells was able to attenuate the production of ROS. Moreover, QUE treatment could also intervene in oxidative stress and decrease the enzyme activity of HAT and the mRNA expression level of HAT1, while it increased the enzyme activity of HDAC and HDAC1 mRNA expression levels and downregulated histone H3 and H4 (AcH3 and AcH4) acetylation modification levels. In addition, QUE treatment even downregulated the mRNA expression levels of IL-6, IL-8, IκB, AKT and p38, but upregulated the mRNA expression levels of IL-10, SOD, GPx1, p65, Keap1, Nrf2, HO-1 and NQO1. As to protein expression, QUE treatment downregulated the levels of iNOS, p-p65 and IL-8 as well as the phosphorylation expression of IκB and p38, while it upregulated the levels of HO-1 and NQO1. It was shown that QUE at 25, 50 or 100 μmol/L regulated p38MAPK and PI3K/AKT signaling pathways by downregulating cellular histone acetylation modification levels while inhibiting the NF-κB inflammatory signaling pathway and activating the Nrf2/HO-1 antioxidant signaling pathway, thus regulating the production of inflammatory and antioxidant factors and exerting both anti-inflammatory and antioxidant effects.

Arthrospira platensis polysaccharide component 1 (PAP-1), a purified polysaccharide monomer isolated from Arthrospira platensis, exhibits pronounced antioxidant activity. To investigate the in vivo and in vitro regulatory effects of PAP-1 on antioxidant enzyme activities and inflammatory mediators in mice and RAW264.7 cells, the mice were administered PAP-1 by gavage, and the cells were cultured with PAP-1. Subsequently, serum, lung, spleen, and thymus tissues from mice, as well as the cultured RAW264.7 cells, were collected for analysis using RNA sequencing, commercial assay kits, immunohistochemistry, RT-qPCR, and Western blotting. The results demonstrated that PAP-1 significantly reduced the levels of oxidative stress-related indicators (NO, iNOS, MDA, MPO, and XOD), while markedly enhancing the activities of antioxidant enzymes (SOD, CAT, and GSH-Px) (p < 0.05), a trend consistently observed in both in vivo and in vitro experiments. Furthermore, PAP-1 upregulated the expression of key antioxidant genes and proteins, including HO-1, NQO1, GCLM, p62, Prdx1, and SLC7A11. Collectively, these findings indicate that PAP-1 exerts regulatory antioxidant effects in mice and RAW264.7 cells by enhancing antioxidant enzyme activity and suppressing oxidative stress responses, underscoring its potential as a natural antioxidant agent.