ABSTRACT
OBJECTIVE: To investigate the effect of Young Yum pill (YYP) on inflammatory mediators in cultured RAW 264.7 cells and elucidate the nuclear factor-kappa B (NF-κB)-related mechanism behind the action. METHODS: YYP was extracted with 95% ethanol Lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages were used to evaluate the effect of YYP on inflammatory mediators. Production of nitric oxide (NO) and prostaglandin E2 (PGE2) were measured by Griess test and enzyme-linked immunosorbent assay, respectively. The levels of genes and proteins involved in the generation of inflammatory mediators were examined using real-time polymerase chain reaction and Western blotting, respectively. RESULTS: YYP dose-dependently suppressed LPS-induced production of NO, PGE2 and tumor necrosis factor-α (TNF-α), and elevation of mRNA and protein levels of inducible NO synthase and cyclooxygenase-2 in RAW 264.7 macrophages. These observations were associated with decreased NF-κB p65 phosphorylation and nuclear localization, enhanced Akt (protein kinase B) phosphorylation, as well as reduced inhibitor of κB (IκB) α degradation and IκB kinase α/ß phosphorylation. CONCLUSION: The present study demonstrated an inhibitory effect of YYP on the NF-κB-regulated inflammatory mediators NO, PGE2 and TNF-α in LPS-stimulated RAW 264.7 macrophages, providing a pharmacological basis for the use of YYP in treating inflammatory disorders.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Inflammation Mediators/metabolism , Lipopolysaccharides/pharmacology , Macrophages/cytology , Macrophages/drug effects , NF-kappa B/metabolism , Signal Transduction/drug effects , Animals , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Dinoprostone/biosynthesis , Dose-Response Relationship, Drug , Gene Expression Regulation, Enzymologic/drug effects , Macrophages/metabolism , Mice , Nitric Oxide/biosynthesis , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , RAW 264.7 Cells , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
DWP208 is a sodium succinate form of ZYM-201 which is a triterpenoid glycoside isolated from Sanguisorba officinalis, a medicinal plant prescribed for various diseases, such as duodenal ulcers and bleeding in East Asian counties. We demonstrated that this compound is able to normalize the altered lipid metabolism induced by hyperglycemia and a high fat diet. In this study, we determined whether hyperlipidemic conditions induced with chronically treated alcohol can also be restored by DWP208. Similar to our previous results, orally administered DWP208 (1 to 10 mg/kg) also ameliorated the hyperlipidemia that was induced by alcohol. This compound reversed the alcohol-induced hyperlipidemia including (i) up-regulated hyperlipidemic parameters such as low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), atherosclerotic index (AI), triglyceride, and total cholesterol, and (ii) down-regulated hyperlipidemic parameters such as absolute body weight, superoxide dismutase (SOD) activity, and high-density lipoprotein (HDL) in serum and liver. According to our data, the ameliorative activity of DWP208 is due to its indirect anti-oxidative activity as a result of which lipid peroxide and hydroxyl radical levels were reduced and the activity of SOD was enhanced. Therefore, our data strongly suggest that DWP208 can be used as a remedy against alcohol-induced hyperlipidemia.
