ABSTRACT
To examine the function of SIRT1 in neuronal differentiation, we employed all-trans retinoic acid (ATRA)-induced differentiation of neuroblastoma cells. Nicotinamide inhibited neurite outgrowth and tyrosine hydroxylase (TH) expression. Inhibition of PARP or histone deacetylase did not inhibit TH expression, showing the effect to be SIRT1 specific. Expression of FOXO3a and its target proteins were increased during the differentiation and reduced by nicotinamide. FOXO3a deacetylation was increased by ATRA and blocked by nicotinamide. SIRT1 and FOXO3a siRNA inhibited ATRA-induced up-regulation of TH and differentiation. Taken together, these results indicate that SIRT1 is involved in ATRA-induced differentiation of neuroblastoma cells via FOXO3a.
Subject(s)
Cell Differentiation , Forkhead Transcription Factors/metabolism , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Neoplasm Proteins/metabolism , Neuroblastoma/metabolism , Sirtuins/metabolism , Tyrosine 3-Monooxygenase/biosynthesis , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Collagen Type XI/metabolism , Forkhead Box Protein O3 , Forkhead Transcription Factors/genetics , Histone Deacetylases/metabolism , Humans , Neoplasm Proteins/genetics , Neuroblastoma/pathology , Neurons/metabolism , Neurons/pathology , Niacinamide/pharmacology , Sirtuin 1 , Sirtuins/genetics , Tretinoin/pharmacology , Tyrosine 3-Monooxygenase/genetics , Vitamin B Complex/pharmacologyABSTRACT
The dried unripe fruit of Rubus coreanus, which is well-known in Korea and referred to as 'Bok-bun-ja', has been employed as a traditional medicine for centuries. This crude drug is utilized in Korea for the management of impotence, spermatorrhea, enuresis, asthma and allergic diseases. The principal objective of the present study was to conduct a comparison of the antiinflammatory effects of ethanol extracts of the unripe (URCE), half-ripened (HRCE) and ripe fruits (RCE) of Rubus coreanus. URCE and HRCE were found to reduce the production of nitric oxide (NO) and prostaglandin E2 (PGE2) as well as pro-inflammatory cytokines, in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. However, RCE exerted no inhibitory effects against the production of NO and IL-6. The results of the study show that the degree of fruit ripening of Rubus coreanus affects the production of inflammatory mediators such as NO, PGE2 and inflammatory cytokines.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Fruit/chemistry , Plant Extracts/pharmacology , Rosaceae/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Cell Line , Cell Survival/drug effects , Cyclooxygenase 2/metabolism , Dinoprostone/metabolism , Electrophoresis, Polyacrylamide Gel , Fruit/growth & development , Immunoblotting , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Nitrites/metabolism , Plant Extracts/chemistry , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Foods of plant origin, especially fruits and vegetables, draw increased attention because of their potential benefits to human health. The aim of the present study was to determine in vitro anti-inflammatory activity of four different extracts obtained from the fruits of Rubus coreanus (aqueous and ethanol extracts of unripe and ripe fruits). Among the four extracts, the ethanol extract of unripe fruits of R. coreanus (URCE) suppressed nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. We also demonstrated that URCE by itself is a potent inducer of heme oxygenase-1 (HO-1). Inhibition of HO-1 activity by tin protoporphyrin, a specific HO-1 inhibitor, suppressed the URCE-induced reductions in the production of NO and PGE(2) as well as the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2). Our data suggest that URCE exerts anti-inflammatory effects in macrophages via activation of the HO-1 pathway and helps to elucidate the mechanism underlying the potential therapeutic value of R. coreanus extracts.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Fruit/metabolism , Heme Oxygenase-1/drug effects , Immunologic Factors/immunology , Macrophage Activation/drug effects , Macrophages/immunology , Plant Extracts/administration & dosage , Rosacea/metabolism , Animals , Anti-Inflammatory Agents/chemistry , Cell Line , Dose-Response Relationship, Drug , Ethanol/chemistry , Fruit/chemistry , Macrophages/drug effects , Mice , Plant Extracts/chemistryABSTRACT
Licorice, the roots of Glycyrrhiza inflata, is used by practitioners of alternative medicine to treat individuals with gastric or duodenal ulcers, bronchitis, cough, arthritis, adrenal insufficiency, and allergies. We investigated the anti-inflammatory properties of 4 licorice extracts: extracts of roasted licorice obtained by ethanol (rLE) or water extraction (rLW) and extracts of raw licorice obtained by ethanol (LE) or water extraction (LW). rLE demonstrated strong anti-inflammatory activity through its ability to reduce nitric oxide and prostaglandin E(2) production in the LPS-stimulated mouse macrophage cell, RAW264.7. It also inhibited the production of pro-inflammatory cytokines and CD14 expression on the LPS-stimulated RAW264.7 cells. Further study indicated that LPS-induced degradation and phosphorylation of Ikappa-Balpha, along with DNA-binding of NF-kappaB, was significantly inhibited by rLE exposure in RAW264.7 cells. In the murine model, we found that in vivo exposure to rLE-induced an increase in the survival rate, reduced plasma levels of TNF-alpha and IL-6, and increased IL-10 production in LPS-treated mice. Collectively, these data suggest that the use of rLE may be a useful therapeutic approach to various inflammatory diseases.
