Alcoholic liver damage (ALD) is a toxic liver damage caused by excessive drinking. Oxidative stress is one of the most crucial pathogenic factors leading to ALD. Magnolol is one of the main active constituents of traditional Chinese medicine Magnolia officinalis, which has been reported to possess many pharmacological effects including anti-inflammatory, anti-oxidant, and anti-tumor. However, the effects of magnolol on ALD remain unclear. In this study, we firstly evaluated the protective effects of magnolol on ALD, and then tried to clarify the mechanism underlying the pharmacological activities. AST, ALT, GSH-Px, and SOD were detected by respective kits. Histopathological changes of liver tissue were analyzed by H&E staining. The activities of PI3K, Nrf2, and NLRP3 signaling pathways activation were detected by western blotting analysis. It was showed that alcohol-induced ALT and AST levels were significantly reduced by magnolol, but the antioxidant enzymes of GSH-Px and SOD levels were significantly increased. Magnolol attenuated alcohol-induced pathologic damage such as decreasing hepatic cord swelling, hepatocyte necrosis, and inflammatory cell infiltration. Furthermore, it was found that magnolol inhibited oxidative stress through up-regulating the activities of HO-1, Nrf2, and PPARγ and the phosphorylation of PI3K and AKT. And magnolol also decreased inflammatory response by inhibiting the activation of NLRP3inflammasome, caspase-1, and caspase-3 signaling pathway. Above results showed that magnolol could prevent alcoholic liver damage, and the underlying mechanism was through activating PI3K/Nrf2/PPARγ signaling pathways as well as inhibiting NLRP3 inflammasome, which also suggested magnolol might be used as a potential drug for ALD.

Aflatoxin B1 (AFB1) is a secondary metabolite produced by Aspergillus flavus and parasitic aspergillus, mainly existing in cereals, peanuts, corn, and other crops, which seriously endanger poultry, human health, and environment. Morin, a flavonoid compound extracted from moraceae plants, possess antioxidant, antibacterial, and anti-inflammatory effects. However, whether morin has a protective effect on AFB1-induced liver and kidney damage in chicks has not been specifically reported. In this study, we mainly confirmed the protective effect of morin on AFB1-induced liver and kidney damage in chicks and clarified its mechanism. It was found that morin can significantly reduce the liver biochemical indicators of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and kidney indicators of creatinine (CRE) and urea nitrogen (BUN) levels. Meanwhile, histopathological examination showed that morin effectively relieved AFB1-caused liver damage, including hepatocyte disruption, swelling, and inflammatory cell infiltration, and effectively relieved kidney damage, including renal cell necrosis, exfoliation, and vacuolization. Further investigation of its mechanism demonstrated that morin significantly inhibited AFB1-induced heterophil extracellular traps (HETs) release, and decreased the level of malondialdehyde (MDA) but increased the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in vivo. Moreover, quantitative real-time PCR (qRT-PCR) analysis showed that morin also significantly decreased AFB1-induced mRNA expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), caspase-1, caspase-3, and caspase-11. In conclusion, all results confirmed that morin could protect AFB1-caused liver and kidney damage by inhibiting HETs release, regulating oxidative stress, and inhibiting inflammatory response, suggesting that morin can be utilized as a potential drug for prevention and treatment of aflatoxicosis in poultry breeding industry.

SARS-CoV-2, the causative agent of the COVID-19 pandemic, undergoes continuous evolution, highlighting an urgent need for development of novel antiviral therapies. Here we show a quantitative mass spectrometry-based succinylproteomics analysis of SARS-CoV-2 infection in Caco-2 cells, revealing dramatic reshape of succinylation on host and viral proteins. SARS-CoV-2 infection promotes succinylation of several key enzymes in the TCA, leading to inhibition of cellular metabolic pathways. We demonstrated that host protein succinylation is regulated by viral nonstructural protein (NSP14) through interaction with sirtuin 5 (SIRT5); overexpressed SIRT5 can effectively inhibit virus replication. We found succinylation inhibitors possess significant antiviral effects. We also found that SARS-CoV-2 nucleocapsid and membrane proteins underwent succinylation modification, which was conserved in SARS-CoV-2 and its variants. Collectively, our results uncover a regulatory mechanism of host protein posttranslational modification and cellular pathways mediated by SARS-CoV-2, which may become antiviral drug targets against COVID-19.