Pseudorabies virus (PRV) can cause acute swine disease leading to economic losses worldwide and is a potential causative agent of viral encephalitis in humans. Although effective vaccines are available, an increasing number of variants have emerged in China, and identifying effective antiviral agents against PRV to prevent latent infection is essential. In this study, we assessed the antiviral activity of luteolin against PRV in vitro and in vivo. Luteolin was found to significantly inhibit PRV at a noncytotoxic concentration (70 μM), with an IC50 of 26.24 μM and a selectivity index of 5.64. Luteolin inhibited the virus at the replication stage and decreased the expression of viral mRNA and gB protein. Luteolin reduced the apoptosis of PRV-infected cells, improved the survival rate of mice after lethal challenge, reduced the viral loads in the liver, kidney, heart, lung, and brain, reduced brain lesions, and slowed inflammation and oxidation reactions. Our results showed that luteolin has promise as a new alternative antiviral drug for PRV infection.
Pseudorabies virus (PRV) is one of the most significant pathogens of swine. In recent years, the continual emergence of novel PRV variants has caused substantial economic losses in the global pig industry. PRV can infect humans leading to symptoms of acute encephalitis with implications for public health. Thus, new measures are urgently needed to prevent PRV infection. This study evaluated the anti-PRV capability of dandelion aqueous extract (DAE) in vitro and in vivo. DAE was found to inhibit the multiplication of the PRV TJ strain in PK15 cells in a concentration-dependent manner, with a 50% inhibitory concentration (IC50) of 0.2559 mg/mL and a selectivity index (SI) of 14.4. DAE inhibited the adsorption and replication stages of the PRV life cycle in vitro, and the expression of IE180, EP0, UL29, UL44, and UL52 was inhibited in the presence of DAE. In vivo experiment results of mice show that a 0.5 g/kg dose of DAE injected intraperitoneally protected 28.6% of the mice from the lethal challenge; decreased the viral load in the liver, lung, brain, heart, and kidney of PRV-infected mice; and attenuated brain damage caused by PRV infection. Furthermore, DAE could also ameliorate viral infection through regulation of the levels of cytokines (IFN-γ, TNF-α, and IL-4) in PRV-infected mouse serum. These results demonstrated that DAE exhibited potent inhibitory capability against PRV infection in vitro and in vivo; DAE is therefore expected to be a candidate TCM herb for use against PRV infection.
Pseudorabies virus (PRV) belongs to the family Herpesviridae. PRV has a wide host range and can cause cytopathic effects (CPEs) in PK-15 cells. Therefore, PRV was used as a model to study the antiviral activity of piceatannol. The results showed that piceatannol could restrain PRV multiplication in PK-15 cells in a dose-dependent manner. The 50% inhibitory concentration (IC50) was 0.0307 mg/mL, and the selectivity index (SI, CC50/IC50) was 3.68. Piceatannol could exert an anti-PRV effect by reducing the transcription level of viral genes, inhibiting PRV-induced apoptosis and elevating the levels of IL-4, TNF-α and IFN-γ in the serum of mice. Animal experiments showed that piceatannol could delay the onset of disease, reduce the viral load in the brain and kidney and reduce the pathological changes in the tissues and organs of the mice to improve the survival rate of the mice (14.3%). Therefore, the anti-PRV activity of piceatannol in vivo and in vitro was systematically evaluated in this study to provide scientific data for developing a new alternative measure for controlling PRV infection.
Luteolin from Patrinia villosa exhibits strong antiviral activity. Here, the conditions for extracting and enriching luteolin from P. villosa were optimized. Response surface methodology was used to determine the optimal extraction parameters in terms of reflux time, solvent ratio, extraction temperature, material-to-liquid ratio, and number of extractions. Thereafter, a macroporous resin method was used to enrich luteolin from P. villosa. Finally, the following optimal extraction and enrichment conditions were established: an extraction time of 43.00 min, a methanol/hydrochloric acid solvent ratio of 13:1, an extraction temperature of 77.60 °C, a material/liquid ratio of 1:22, and a total of two extractions. NKA-9 was determined to be the most appropriate resin for enrichment. The ideal adsorption conditions were as follows: a pH of 5.0, a temperature of 25 °C, an initial luteolin concentration of 19.58 µg/mL, a sample loading volume of 2.9 BV, and a sample loading rate of 2 BV/h. The ideal desorption conditions were as follows: distilled water, 30% ethanol and 80% ethanol elution, and 5 BV at a flow rate of 2 BV/h. After optimization, the enrichment recovery rate was 80.06% and the luteolin content increased 3.8-fold. Additionally, the enriched product exhibited a significant inhibitory effect on PRV (Porcine pseudorabies virus) in vitro and in vivo, providing data for developing and applying luteolin from P. villosa.
Piceatannol is a naturally occurring polyphenolic compound that is widely found in grapes, blueberries, mushrooms, passion fruit and other edible fruits and vegetables. It has a variety of biological activities and pharmacological effects, including anti-inflammatory, antioxidation, antiaging, antiviral, antitumor, anticancer, antiatherosclerosis, antiparasitic, immunoregulatory, and cardiovascular protection effects. The aim of this study was to investigate the antiherpesvirus effects of piceatannol. Pseudorabies virus (PRV) belongs to the family Herpesviridae. PRV has a wide host range and can cause cytopathic effects (CPEs) in PK-15 cells. Therefore, PRV was used as a model to study the antiherpesvirus effect of piceatannol. In this study, we evaluated the antiviral activity of piceatannol against PRV in vitro and in vivo. The results showed that piceatannol could reatrain PRV multiplication in PK-15 cells in a dose-dependent manner. The 50% inhibitory concentration (IC50) was 0.0307 mg/mL, the IC50 was 0.0307 mg/mL, and the selectivity index (SI, CC50/IC50) was 3.68. The addition of piceatannol at different stages of PRV infection inhibited the viral adsorption and intracellular replication phases of PRV. Piceatannol significantly reduced the expression levels of the IE180, EP0, UL29, UL44, US6 and UL27 genes of PRV within 48 h, significantly reduced the expression levels of the PRV gB and gD proteins, and reduced PRV-induced apoptosis. Molecular docking showed that piceatannol had good binding activity with the PRV gB and gD proteins. The results of animal experiments in vitro indicated that piceatannol could delay the onset of disease, improve the survival rate of the mice (14.3%), reduce the viral load in the brain and kidney of the mice, alleviate the pathological changes in the mouse tissues and organs, and increase the levels of TNF-α, IEN-γ and IL-4 in the serum of the mice. These data indicate that piceatannol has good anti-PRV activity in vitro and in vivo, indicating that it could be a novel antiherpesvirus infection agent in the future.
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