Intervening Effects and Molecular Mechanism of Quercitrin on PCV2-Induced Histone Acetylation, Oxidative Stress and Inflammatory Response in 3D4/2 Cells

Abstract

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.

Loranthus tanakae Franch. & Sav. Suppresses Inflammatory Response in Cigarette Smoke Condensate Exposed Bronchial Epithelial Cells and Mice

“…We detected quercitrin, afzelin, rhamnetin 3-rhamnoside, and rhamnocitrin 3-rhamnoside in LTE via HPLC analysis. Quercitrin decreased oxidative stress and inflammation induced by various stimuli in cells by suppressing NF-κB activation and Nrf2 translocation into the nucleus [ 40 , 41 ]. Afzelin has exhibited anti-inflammatory and anti-oxidative properties in several studies [ 34 , 42 , 43 , 44 ], agreeing with our results…”

Loranthus tanakae Franch. and Sav. Attenuates Respiratory Inflammation Caused by Asian Sand Dust

“…Afzelin has antioxidative and anti-inflammatory properties and exerts suppressive effects against particulate matter-induced inflammatory skin diseases and ultraviolet radiation-induced damage [25,26]. Quercitrin has shown antioxidative and anti-inflammatory properties in various experiments, and is linked with the suppression of NF-κB and overexpression of HO-1 [27]. Rhamnocitrin 3-rhamnoside and rhamnetin 3-rhamnoside showed strong antioxidant properties in our previous study [10].…”

Integrated chromatographic approach for the discovery of gingerol antioxidants from Dracocephalum heterophyllum and their potential targets

“…This binding initiates the transcription of downstream antioxidant proteins such as HO-1, NQO1 and NOX2, which play a role in combating oxidative damage. [37][38][39] In this work, the downstream antioxidant proteins HO-1, NQO1 and NOX2 were used as receptors for molecular docking experiments and western blot experiments with isolated gingerol to predict possible target proteins that these compounds in exerting their antioxidant activities.…”