Antiviral and Anti‐Inflammatory Treatment with Multifunctional Alveolar Macrophage‐Like Nanoparticles in a Surrogate Mouse Model of COVID‐19

Empagliflozin, an established treatment for type 2 diabetes (T2DM), has shown beneficial effects on liver steatosis and fibrosis in animals and in humans with T2DM, non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). However, little is known about the effects of empagliflozin on liver function in advanced NASH with liver fibrosis and without diabetes. This study aimed to assess the effects of empagliflozin on hepatic and metabolic outcomes in a diet-induced obese (DIO) and insulin-resistant but non-diabetic biopsy-confirmed mouse model of advanced NASH. Male C57BL/6JRj mice with a biopsy-confirmed steatosis and fibrosis on AMLN diet (high fat, fructose and cholesterol) for 36-weeks were randomized to receive for 12 weeks: (a) Empagliflozin (10 mg/kg/d p.o.), or (b) vehicle. Metabolic outcomes, liver pathology, markers of Kupffer and stellate cell activation and lipidomics were assessed at the treatment completion. Empagliflozin did not affect the body weight, body composition or insulin sensitivity (assessed by intraperitoneal insulin tolerance test), but significantly improved glucose homeostasis as assessed by oral glucose tolerance test in DIO-NASH mice. Empagliflozin improved modestly the NAFLD activity score compared with the vehicle, mainly by improving inflammation and without affecting steatosis, the fibrosis stage and markers of Kupffer and stellate cell activation. Empagliflozin reduced the hepatic concentrations of pro-inflammatory lactosylceramides and increased the concentrations of anti-inflammatory polyunsaturated triglycerides. Empagliflozin exerts beneficial metabolic and hepatic (mainly anti-inflammatory) effects in non-diabetic DIO-NASH mice and thus may be effective against NASH even in non-diabetic conditions.

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Soluble epoxide hydrolase inhibitor trifluoromethoxyphenyl‐3‐(1‐propionylpiperidin‐4‐yl)urea prevents hyperalgesia through regulating NLRC4 inflammasome‐related pro‐inflammatory and anti‐inflammatory signaling pathways in the lipopolysaccharide‐induced pain mouse model

Drug Development Research ◽

10.1002/ddr.21786 ◽

2021 ◽

Author(s):

Ali Cagli ◽

Sefika Pinar Senol ◽

Meryem Temiz‐Resitoglu ◽

Demet Sinem Guden ◽

Ayse Nihal Sari ◽

...

Keyword(s):

Mouse Model ◽

Signaling Pathways ◽

Epoxide Hydrolase ◽

Soluble Epoxide Hydrolase ◽

Inflammatory Signaling ◽

Soluble Epoxide Hydrolase Inhibitor ◽

Anti Inflammatory

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Short-Term High-Fat Diet Consumption Reduces Hypothalamic Expression of the Nicotinic Acetylcholine Receptor α7 Subunit (α7nAChR) and Affects the Anti-inflammatory Response in a Mouse Model of Sepsis

Frontiers in Immunology ◽

10.3389/fimmu.2019.00565 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 3

Author(s):

Anelise Cristina Parras Souza ◽

Camilla Mendes Souza ◽

Camila Libardi Amaral ◽

Simone Ferreira Lemes ◽

Leticia Foglia Santucci ◽

...

Keyword(s):

Inflammatory Response ◽

Mouse Model ◽

Acetylcholine Receptor ◽

Nicotinic Acetylcholine Receptor ◽

High Fat Diet ◽

High Fat ◽

Short Term ◽

Nicotinic Acetylcholine ◽

Anti Inflammatory ◽

Α7 Subunit

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TAK1/AP-1-Targeted Anti-Inflammatory Effects of Barringtonia augusta Methanol Extract

Molecules ◽

10.3390/molecules26103053 ◽

2021 ◽

Vol 26 (10) ◽

pp. 3053

Author(s):

Anh Thu Ha ◽

Mi-Yeon Kim ◽

Jae Youl Cho

Keyword(s):

Mouse Model ◽

Methanol Extract ◽

Folk Medicine ◽

Activator Protein 1 ◽

Western Blot Assay ◽

In Vivo Experiments ◽

Chemokine Ligand ◽

Anti Inflammatory ◽

Inflammatory Effect

Barringtonia augusta methanol extract (Ba-ME) is a folk medicine found in the wetlands of Thailand that acts through an anti-inflammatory mechanism that is not understood fully. Here, we examine how the methanol extract of Barringtonia augusta (B. augusta) can suppress the activator protein 1 (AP-1) signaling pathway and study the activities of Ba-ME in the lipopolysaccharide (LPS)-treated RAW264.7 macrophage cell line and an LPS-induced peritonitis mouse model. Non-toxic concentrations of Ba-ME downregulated the mRNA expression of cytokines, such as cyclooxygenase and chemokine ligand 12, in LPS-stimulated RAW264.7 cells. Transfection experiments with the AP-1-Luc construct, HEK293T cells, and luciferase assays were used to assess whether Ba-ME suppressed the AP-1 functional activation. A Western blot assay confirmed that C-Jun N-terminal kinase is a direct pharmacological target of Ba-ME action. The anti-inflammatory effect of Ba-ME, which functions by β-activated kinase 1 (TAK1) inhibition, was confirmed by using an overexpression strategy and a cellular thermal shift assay. In vivo experiments in a mouse model of LPS-induced peritonitis showed the anti-inflammatory effect of Ba-ME on LPS-stimulated macrophages and acute inflammatory mouse models. We conclude that Ba-ME is a promising anti-inflammatory drug targeting TAK1 in the AP-1 pathway.

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The formyl peptide receptor agonist Ac2-26 alleviates neuroinflammation in a mouse model of pneumococcal meningitis

Journal of Neuroinflammation ◽

10.1186/s12974-020-02006-w ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

Marvin Rüger ◽

Eugenia Kipp ◽

Nadine Schubert ◽

Nicole Schröder ◽

Thomas Pufe ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Bacterial Meningitis ◽

Mouse Model ◽

Post Infection ◽

Pneumococcal Meningitis ◽

Hippocampal Formation ◽

Formyl Peptide Receptor ◽

Formyl Peptide ◽

Anti Inflammatory ◽

Deficient Mice

Abstract Background Bacterial meningitis is still a cause of severe neurological disability. The brain is protected from penetrating pathogens by the blood-brain barrier and the innate immune system. The invading pathogens are recognized by pattern recognition receptors including the G-protein-coupled formyl peptide receptors (FPRs), which are expressed by immune cells of the central nervous system. FPRs show a broad spectrum of ligands, including pro- and anti-inflammatory ones. Here, we investigated the effects of the annexin A1 mimetic peptide Ac2-26 in a mouse model of pneumococcal meningitis. Methods Wildtype (WT) and Fpr1- and Fpr2-deficient mice were intrathecally infected with Streptococcus pneumoniae D39 (type 2). Subsequently, the different mice groups were treated by intraperitoneal injections of Ac2-26 (1 mg/kg body weight) 2, 8, and 24 h post-infection. The extent of inflammation was analyzed in various brain regions by means of immunohistochemistry and real-time reverse transcription polymerase chain reaction (RT-PCR) 30 h post-infection. Results Ac2-26-treated WT mice showed less severe neutrophil infiltration, paralleled by a reduced induction of pro-inflammatory glial cell responses in the hippocampal formation and cortex. While meningitis was ameliorated in Ac2-26-treated Fpr1-deficient mice, this protective effect was not observed in Fpr2-deficient mice. Irrespective of Ac2-26 treatment, inflammation was more severe in Fpr2-deficient compared to Fpr1-deficient mice. Conclusions In summary, this study demonstrates anti-inflammatory properties of Ac2-26 in a model of bacterial meningitis, which are mediated via FPR2, but not FPR1. Ac2-26 and other FPR2 modulators might be promising targets for the development of novel therapies for Streptococcus pneumoniae-induced meningitis.

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