Glycyrrhizin alleviates BoAHV-1-induced lung injury in guinea pigs by inhibiting the NF-κB/NLRP3 Signaling pathway and activating the Nrf2/HO-1 Signaling pathway.
Varicellovirus bovinealpha 1 (BoAHV-1) is a significant pathogen responsible for respiratory disease in cattle, capable of inducing lung damage independently or co-infection with bacteria. The widespread spread of BoAHV-1 in cattle herds has caused substantial economic losses to the cattle industry. The pathogenic mechanisms of BoAHV-1 are often relevant to robust inflammatory responses, increased oxidative burden, and the initiation of apoptosis. Glycyrrhizin (GLY) is a small-molecule triterpenoid saponin compound obtained from the herb liquorice, which has a broad spectrum of pharmacological properties such as antiviral, anti-inflammatory, and antioxidant effects. Furthermore, GLY regulates lung physiology by modulating oxidative stress, inflammatory response, and cell apoptosis through interference with the NF-κB/NLRP3 and Nrf2/HO-1 Signaling pathways. However, the potential of GLY to mitigate lung injury induced by BoAHV-1 and its underlying mechanism remains unclear. Therefore, in this study, we investigated the protective effect of GLY against pulmonary injury induced by BoAHV-1 in a guinea pig model by reducing viral load and suppressing the inflammatory response, oxidative stress, and apoptosis. The results of this study demonstrated that GLY exerted a protective effect against BoAHV-1-induced lung injury in guinea pigs. Specifically, GLY reduced the levels of pro-inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and interleukin (IL)-8 in guinea pig tissues while suppressing the expression of Caspase-1. Additionally, GLY reduced BoAHV-1 load and the number of TUNEL-positive lung cells in guinea pig lungs while inhibiting Caspase 3 protein expression. Furthermore, GLY significantly enhanced lung antioxidant capacity by increasing superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activity while simultaneously reducing malondialdehyde (MDA) levels. Lung histological observation and score further validated the protective effect of GLY on BoAHV-1-induced lung injury. Furthermore, we observed that the expression of phosphorylated NF-κB p65 (p-NF-κB p65) and NLRP3 proteins in the lung tissue of BoAHV-1-infected guinea pigs decreased after GLY treatment while the expression of Nrf2 and HO-1 proteins increased. These results indicated that GLY inhibited the NF-κB/NLRP3 Signaling pathway and activated the Nrf2/HO-1 Signaling pathway during BoAHV-1 infection. Ultimately, our findings demonstrated that GLY alleviates BoAHV-1-induced inflammation response, oxidative stress, and cell apoptosis by inhibiting the NF-κB/NLRP3 Signaling pathway and activating the Nrf2/HO-1 Signaling pathway to protect guinea pigs from lung injury caused by BoAHV-1. Ultimately, our findings demonstrated that GLY alleviates BoAHV-1-induced inflammation response, oxidative stress, and cell apoptosis by inhibiting the NF-κB/NLRP3 Signaling pathway and activating the Nrf2/HO-1 Signaling pathway to protect guinea pigs from lung injury caused by BoAHV-1. Importantly, this study provides a compelling argument for the GLY in combating respiratory disease in cattle caused by BoAHV-1.
Guo B
，Wang H
，Zhang Y
，Wang C
，Zhang H
，Zhao Y
，Qin J
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Helenalin from Centipeda minima ameliorates acute hepatic injury by protecting mitochondria function, activating Nrf2 pathway and inhibiting NF-κB activation.
Acute liver injury is a life-threatening syndrome that often caused by hepatocyte damage and is characterized by inflammatory and oxidative responses. Helenalin isolated from Centipeda minima (HCM) has been found to have anti-inflammatory and anti-oxidative effects. Here, this study aimed to investigate the effects and underlying mechanisms of HCM on Lipopolysaccharide/D-Galactosamine (LPS/D-GalN)-induced acute liver injury. Mice were intragastrically administered with various dose of HCM for 10 days; 2 h after the final treatment, the mice were injected with 50 μg/kg LPS and 800 mg/kg D-GalN. The histopathological changes, hepatocyte apoptosis, serum cytokines, oxidative stress and inflammatory cytokines were assessed. The results showed that HCM significantly ameliorated the hepatic injury, as evidenced by the attenuation of histopathological changes and the decrease in serum aminotransferase and total bilirubin activities. HCM markedly decreased hepatocyte apoptosis by modulating the mitochondria-dependent pathway, including the increase in the Bcl-2/Bax ratio, the inhibition of caspase-3, -8 and -9, and the inhibition of cytochrome C release. Moreover, HCM strongly alleviated oxidative stress, lipid peroxidation and reactive oxygen species (ROS) generation by activating the Nrf2 signaling pathway. In addition, HCM significantly attenuated inflammatory cytokines including TNF-α, IL6 and IL-1β as well as NO production by inhibiting TLR4 signaling transduction and NF-κB activation. In conclusion, HCM protects hepatocytes from damage induced by LPS/D-GalN, which may contribute to its ability to alleviate hepatocyte apoptosis by protecting the mitochondrial function, inhibit oxidative stress by activating the Nrf2 pathway, and attenuate inflammation by inhibiting NF-κB activation. This study demonstrates that HCM may be developed as a potential agent for the treatment of acute liver failure.
Li Y
，Zeng Y
，Huang Q
，Wen S
，Wei Y
，Chen Y
，Zhang X
，Bai F
，Lu Z
，Wei J
，Lin X
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