ABSTRACT
Acute kidney injury (AKI) is associated with a strong inflammatory response, and inhibiting the response effectively prevents or ameliorates AKI. A series of novel arylpropionic esters were designed, synthesized and evaluated their biological activity in LPS-stimulated RAW264.7 cells. Novel arylpropionic esters bearing multi-functional groups showed significant anti-inflammatory activity, in which, compound 13b exhibited the most potent activity through dose-dependent inhibiting the production of nitric oxide (NO, IC50 = 3.52 µM), TNF-α and IL-6 (84.1% and 33.6%, respectively), as well as suppressing the expression of iNOS, COX-2 and TLR4 proteins. In C57BL/6 mice with cisplatin-induced AKI, compound 13b improved kidney function, inhibited inflammatory development, and reduced pathological damage of kidney tissues. In brief, this arylpropionic ester scaffold may be developed as anti-inflammatory agents.
Subject(s)
Acute Kidney Injury/drug therapy , Anti-Inflammatory Agents/chemical synthesis , Esters/chemistry , Propionates/chemical synthesis , Animals , Anti-Inflammatory Agents/pharmacology , Cisplatin/metabolism , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Cytokines/metabolism , Drug Evaluation, Preclinical , Gene Expression Regulation/drug effects , Humans , Interleukin-6/metabolism , Male , Mice , Mice, Inbred C57BL , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Propionates/pharmacology , Quinolines/chemistry , RAW 264.7 Cells , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Two new dihydrostilbenoid glycosides, named 5-(2-phenylethyl)-3-hydroxyphenol-1-O-beta-D-glucopyranoside (1) and 6-(2-phenylethyl)-2,4-dihydroxy benzoic acid-2-O-beta-D-glucopyranoside (2), together with two known compounds, were isolated from the leaves of Litsea coreana Levl.. Their structures were established on the basis of NMR spectroscopic, MS and chemical data. Biological tests revealed that 1-3 exhibited moderate anti-inflammatory activity through an inhibitory effect on TNF-alpha, IL-1 production from RAW264.7 cell line activated with lipopolysaccharides (LPS).
Subject(s)
Anti-Inflammatory Agents/isolation & purification , Glucosides/isolation & purification , Litsea/chemistry , Stilbenes/isolation & purification , Animals , Anti-Inflammatory Agents/chemistry , Cells, Cultured , Glucosides/chemistry , Magnetic Resonance Spectroscopy , Mice , Plant Leaves/chemistry , Stilbenes/chemistryABSTRACT
OBJECTIVES: Nonalcoholic steatohepatitis (NASH), a metabolic disorder of the liver, may gradually evolve into fibrosis or cirrhosis. Recent studies have suggested that geniposide can effectively inhibit experimental liver fibrosis. Therefore, the aim of this study was to determine whether geniposide can influence the early phase of fibrogenesis in an animal model of NASH. METHODS: Male Sprague-Dawley rats were given a high fat diet alone or the same diet combined with geniposide at doses of 25, 50 or 100 mg/kg for six weeks. Ten rats received corresponding solvent as a normal control. KEY FINDINGS: Treatment with geniposide could improve liver histology through reducing the elevated liver index (liver weight/body weight), serum alanine aminotransferase and aspartate aminotransferase. Total cholesterol, triglycerides and free fatty acids in serum and liver decreased in geniposide-treated rats. Furthermore, geniposide increased serum insulin levels but reduced serum tumour necrosis factor-α level in high-fat diet rats. In addition, geniposide suppressed expression of CYP2E1 and increased peroxisome proliferator-activated receptor-α (PPARα) expression. These benefits may be associated with increased superoxide dismutase and decreased malondialdehyde in liver. CONCLUSIONS: Geniposide exerts protective effects against hepatic steatosis in rats fed with a high fat diet; the underlying mechanism may be associated with its antioxidant actions or regulation of adipocytokine release and expression of PPARα.