1-(3-4-dihydroxyphenyl)-3-(2-methoxyphenyl)prop-2-en-1-one and Inflammation

Chalcone, a natural product, has a wide range of biological activities. L2H17, a chalcone derivative, was synthesized and screened in our previous study and exhibited excellent anti-inflammatory property in vitro. This study investigated the therapeutic potential of L2H17 on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the role of heme oxygenase-1 (HO-1).. An ALI animal model was induced by LPS (10 mg/kg) intratracheal instillation. The effect of L2H17 on LPS-induced structural damage was determined using hematoxylin and eosin (HE) staining, and tissue edema extent was examined. Bronchoalveolar lavage fluid (BALF) was harvested to assess the levels of related cytokines by enzyme-linked immunosorbent assay (ELISA), and superoxide dismutase (SOD) activity was also assessed. HO-1 expression was determined using immunohistochemistry and western blotting. The effects of L2H17 on LPS stimulation in RAW 264.7 and the involvement of the HO-1 pathway were investigated.. L2H17 alleviated the histopathological manifestations and tissue edema. Moreover, L2H17 decreased the production of pro-inflammatory factors in BALF and increased SOD activity. In vitro, L2H17 significantly reduced pro-inflammatory cytokine production. Additionally, L2H17 improved the expression of HO-1 in LPS-treated lung tissue and RAW 264.7. We also found that the inhibitory effect of L2H17 on the inflammatory responses was attenuated by an inhibitor of HO-1 activity, Tin protoporphyrin IX (SnPP).. Our data confirmed that L2H17 can exert protective effect on ALI in vitro and in vivo by inhibiting inflammatory responses and modulating the HO-1 pathway.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Chalcone; Chalcones; Disease Models, Animal; Gene Expression Regulation; Heme Oxygenase-1; Humans; Inflammation; Lipopolysaccharides; Lung; Macrophages; Male; Membrane Proteins; Metalloporphyrins; Mice; Mice, Inbred C57BL; Protoporphyrins; RAW 264.7 Cells

The prevalence of obesity has increased dramatically worldwide leading to increases in obesity-related complications, such as obesity-related glomerulopathy (ORG). Obesity is a state of chronic, low-grade inflammation, and increased inflammation in the adipose and kidney tissues has been shown to promote the progression of renal damage in obesity. Current therapeutic options for ORG are fairly limited and, as a result, we are seeing increased rates of progression to end-stage renal disease. Chalcones are a class of naturally occurring compounds with various pharmacological properties. 1-(3,4-Dihydroxyphenyl)-3-(2-methoxyphenyl)prop-2-en-1-one (L2H17) is a chalcone that we have previously synthesized and found capable of inhibiting the lipopolysaccharide-induced inflammatory response in macrophages. In this study, we investigated L2H17's effect on obesity-induced renal injury using palmitic acid-induced mouse peritoneal macrophages and high fat diet-fed mice. Our results indicate that L2H17 protects against renal injury through the inhibition of the mitogen-activated protein kinase/nuclear factor κB pathways significantly by decreasing the expression of proinflammatory cytokines and cell adhesion molecules and improving kidney histology and pathology. These findings lead us to believe that L2H17, as an anti-inflammatory agent, can be a potential therapeutic option in treating ORG.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Chalcones; Cytokines; Diet, High-Fat; Dietary Fats; Inflammation; Intercellular Adhesion Molecule-1; Kidney; Kidney Tubules; Lipoproteins, HDL; Lipoproteins, LDL; Macrophages, Peritoneal; Male; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; NF-kappa B; Obesity; Palmitic Acid; Renal Insufficiency; Signal Transduction; Triglycerides; Vascular Cell Adhesion Molecule-1