ABSTRACT
The aim of this study is to investigate the protective effect of N-[2-(4-hydroxyphenyl)ethyl]-2-(2, 5-dimethoxyphenyl)-3-(3-methoxy-4-hydroxyphenyl)acrylamide (FLZ), a novel synthetic squamosamide cyclic derivative, against Parkinson's disease (PD) model mice induced by the inflammatory bacterial endotoxin, lipopolysaccharides (LPS) and the neurotoxin 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). C57/BL mice were ip injected LPS (5 mg x kg(-1)) once. One week following the LPS injection, mice received a subcutaneous injection of MPTP (25 mg x kg(-1)) once daily for 2 days. Eight weeks later, FLZ (25, 50 and 75 mg x kg(-1)) was orally administered to mice once daily for 60 days. The motor ability of the mice was evaluated by rod climbing test and footprint test. The dopamine (DA) levels in mouse striatum were determined by high performance liquid chromatography system. The tyrosine hydroxylase (TH)-positive cells were showed by immunohistochemical analysis. FLZ treatment significantly improved motor dysfunction of mice challenged by LPS plus MPTP. The increase of TH-positive cell numbers and elevation of DA levels may be contributed to the beneficial effects of FLZ on motor behavior. This study showed FLZ has significant therapeutic effect on LPS plus MPTP induced chronic PD model, which indicates its potential as a new candidate drug to treat PD.
Subject(s)
Animals , Male , Mice , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , 3,4-Dihydroxyphenylacetic Acid , Metabolism , Acrylamides , Pharmacology , Caffeic Acids , Pharmacology , Corpus Striatum , Metabolism , Dopamine , Metabolism , Homovanillic Acid , Metabolism , Lipopolysaccharides , Mice, Inbred C57BL , Motor Activity , Neurons , Metabolism , Parkinson Disease, Secondary , Metabolism , Pathology , Random Allocation , Tyrosine 3-Monooxygenase , MetabolismABSTRACT
<p><b>AIM</b>To study the protective action of ulinastatin against lipopolysaccharide (LPS)-induced acute lung injury in mice and the mechanism of its action.</p><p><b>METHODS</b>Mice were intraperitoneally injected with ulinastatin (50 and 100 ku x kg(-1)) or saline at a period of 12 h, separately, 30 min after the last injection of ulinastatin, except normal control, all mice of other groups were injected a dose of LPS 15 mg x kg(-1) via tail vein. The levels of TNFalpha in serum and lung were measured by ELISA. The expression of TNFalpha mRNA and iNOS mRNA in lung was assayed by RT-PCR. The expression of c-Fos and c-Jun protein in lung was measured by Western blotting method. And the NO2- / NO3- level in serum and MDA in lung were measured with kits.</p><p><b>RESULTS</b>The levels of NO2- / NO3- and TNFalpha in serum, MDA and TNFa in lung all increased after iv injection of LPS. The expressions of TNFa mRNA, iNOS mRNA, c-Fos and c-Jun in lung of LPS-injected mice were enhanced. Pretreatment with ulinastatin 100 ku x kg(-1) decreased the levels of NO2- / NO3- in serum and lung, reduced the index of lung, and inhibited the expressions of iNOS mRNA and c-Jun in lung induced by LPS in mice, while ulinastatin showed no effect on TNFa level in serum and lung.</p><p><b>CONCLUSION</b>Ulinastatin protected mice from acute lung injury induced by lipopolysaccharides via inhibiting the activation of c-Jun and iNOS mRNA expression.</p>
Subject(s)
Animals , Male , Mice , Blotting, Western , Glycoproteins , Pharmacology , Injections, Intraperitoneal , Lipopolysaccharides , Lung , Metabolism , Pathology , Mice, Inbred ICR , Nitric Oxide Synthase Type II , Genetics , Protective Agents , Pharmacology , Proto-Oncogene Proteins c-fos , Proto-Oncogene Proteins c-jun , RNA, Messenger , Genetics , Respiratory Distress Syndrome , Metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Necrosis Factor-alpha , Blood , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To design and synthesize a series of squamosamide cyclic analogues and to test their antioxidation activity.</p><p><b>METHODS</b>Eleven 3-substituted indole-2-one derivatives were designed and synthesized through 9 steps with p-hydroxyphenylacetic acid as the starting material and their structures were confirmed by nuclear magnetic resonance and mass spectrometry.</p><p><b>RESULTS</b>Eleven compounds showed antioxidation activity and the activities of compounds 9 and 13 matches the positive control FLZ-52.</p><p><b>CONCLUSION</b>Cyclic reconstruction with FLZ-52 as the lead compound have some antioxidation activity.</p>