As a kind of potent stimulus, lipopolysaccharide (LPS) has the ability to cause cell damage by activating toll-like receptor(TLR)4, then nuclear factor kappa B (NF-κB) translocates into the nucleus and changes the expression of related inflammatory genes. Baicalin is extracted from Radix Scutellariae, which possesses anti-inflammation, antioxidant and antibacterial properties. However, the effects of it on LPS-induced liver inflammation have not been fully elucidated. This study aims to investigate the anti-inflammatory effects of Baicalin on the LPS-induced liver inflammation and its underlying molecular mechanisms in chicken. The results of histopathological changes, serum biochemical analysis, NO levels and myeloperoxidase activity showed that Baicalin pretreatment ameliorated LPS-induced liver inflammation. ELISA and qPCR assays showed that Baicalin dose-dependently suppressed the production of IL-1β, IL-6 and TNF-α. Furthermore, the mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were significantly decreased by Baicalin. TLR4 is an important sensor in LPS infection. Molecular studies showed that the expression of TLR4 was inhibited by Baicalin pretreatment. In addition, Baicalin pertreatment inhibited NF-kB signaling pathway activation. All results demonstrated the protective effects of Baicalin pretreatmen against LPS-induced liver inflammation in chicken via negative regulation of inflammatory mediators through the down-regulation of TLR4 expression and the inhibition of NF-kB activation.

Nephrotoxicity of colistin is the major factor limiting its clinical application. However, the exact mechanism of colistin-induced nephrotoxicity is still elusive. N⁶-Methyladenosine (m⁶A) modification has been implicated in many biological processes, however, its role in colistin-induced nephrotoxicity needs to be elucidated. Mouse renal tubular epithelial cells (mRTECs) were treated with 200 μM colistin with or without METTL3 overexpression. Cells injury, m⁶A assay, oxidative stress and apoptosis were examined. Levels of m⁶A are decreased after colistin treatment in mRTECs. METTL3 is the major factor involved in abnormal m⁶A modification. METTL3 overexpression plays a protective role against colistin-induced oxidative stress and apoptosis. Moreover, METTL3 interacts with the microprocessor protein DGCR8 and positively modulates miR-873-5p mature process in an m⁶A-dependent manner. Further experiments show that miR-873-5p could regulate Keap1-Nrf2 pathway against colistin-induced oxidative stress and apoptosis. These studies revealed an important role of METTL3/m⁶A in colistin-induced nephrotoxicity and provide a new insight on m⁶A modification in drug induced toxicity.

Hypericum perforatum L., also known as Saint John’s Wort, has been well studied for its chemical composition and pharmacological activity. In this study, the antiviral activities of H. perforatum on infectious bronchitis virus (IBV) were evaluated in vitro and in vivo for the first time. The results of in vitro experiments confirmed that the antiviral component of H. perforatum was ethyl acetate extraction section (HPE), and results showed that treatment with HPE significantly reduced the relative messenger ribonucleic acid (mRNA) expression and virus titer of IBV, and reduced positive green immunofluorescence signal of IBV in chicken embryo kidney (CEK) cells. HPE treatment at doses of 480–120 mg/kg for 5 days, reduced IBV induced injury in the trachea and kidney, moreover, reduced the mRNA expression level of IBV in the trachea and kidney in vivo. The mRNA expression levels of IL-6, tumor necrosis factor alpha (TNF-α), and nuclear factor kappa beta (NF-κB) significantly decreased, but melanoma differentiation-associated protein 5 (MDA5), mitochondrial antiviral signaling gene, interferon alpha (IFN-α), and interferon beta (IFN-β) mRNA levels significantly increased in vitro and in vivo. Our findings demonstrated that HPE had significant anti-IBV effects in vitro and in vivo, respectively. In addition, it is possible owing to up-regulate mRNA expression of type I interferon through the MDA5 signaling pathway and down-regulate mRNA expression of IL-6 and TNF-α via the NF-κB signaling pathway. Moreover, the mainly active compositions of HPE analyzed by high-performance liquid chromatography/electrospray ionization–mass spectroscopy (ESI-MS) are hyperoside, quercitrin, quercetin, pseudohypericin, and hypericin, and a combination of these compounds could mediate the antiviral activities. This might accelerate our understanding of the antiviral effect of H. perforatum and provide new insights into the development of effective therapeutic strategies.

This study set out to assess the mitigative effects of curcumin on AFB1-induced necroptosis and inflammation in chicken liver. Ninety-six one-day-old AA broiler chickens were separated into four groups, including control group, AFB1 (1 mg/kg) group, curcumin (300 mg/kg) + AFB1 (1 mg/kg) group and curcumin (300 mg/kg) group. After 28 days treatment, livers were collected for different experimental analyses. The morphological observation results showed obvious necrotic characteristics, including cell swelling, rupture of cell and mitochondrial membranes and inflammation in chicken livers. AFB1 exposure increased oxidative stress index (ROS and MDA) and decreased the antioxidant activity markers (SOD, CAT and GSH) and ATPase activities in chickens' liver. ELISA results showed that AFB1 exposure significantly induced the cytokines (TNF-α, iNOS, IL-6 and IL-1β) release from the liver tissues. While, western blot and qRT-PCR results showed that the protein and mRNA expressions of inflammatory (TLR4/myd88/NF-κB) and necroptosis (RIPK1/RIPK3/MLKL) genes were up-regulated by AFB1 exposure. We suspect that signal crosstalk between TLR4 and TNF-α triggers inflammation and RIPK1/RIPK3 mediating necroptosis in AFB1-induced chicken liver injury. Curcumin can regulate the TLR4/RIPK signaling pathway, reduced oxidative stress biomarkers and inflammatory cytokines levels and attenuated the expression of necroptosis and inflammation genes altered by AFB1 to reduce necroptosis of chicken liver tissue. In conclusion, curcumin can protect against AFB1-induced necroptosis and inflammation by TLR4/RIPK pathway in chicken liver.