Solanum lycopersicum (tomato) ethanol extract elicits anti-inflammatory effects via the nuclear factor kappa B pathway and rescues mice from septic shock

Solanum lycopersicum, commonly known as tomato, is widely used in raw, cooked, or liquid forms because it contains nutritional compounds that are beneficial for human health, including carotenoids, lycopene, ascorbic acid, vitamins, and minerals. The tomato is perhaps the most widely studied fruit, especially with respect to its cardioprotective effects. In this study, we aimed to identify the anti-inflammatory mechanisms by which the tomato elicits its anti-inflammatory properties. We treated murine macrophage RAW 264.7 cells with a tomato ethanol extract and performed various biochemical assays including nitric oxide inhibition, cell viability, RNA extraction, expression of pro-inflammatory mediators and cytokines, and immunoblotting, as well we assessed cell survival rates. Our results have shown for the first time that a tomato ethanol extract treatment can suppress nitric oxide production in a dose-dependent manner without cytotoxicity. Moreover, it inhibits the expression of pro-inflammatory mediators and cytokines and elicits its anti-inflammatory effects via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. In addition, administration of tomato syrup potently rescued mice from septic shock induced by lipopolysaccharide injection. Collectively, our results elucidate details regarding the anti-inflammatory mechanisms of tomato.

Intestinal anti-inflammatory activity of Sasa quelpaertensis leaf extract by suppressing lipopolysaccharide-stimulated inflammatory mediators in intestinal epithelial Caco-2 cells co-cultured with RAW 264.7 macrophage cells

BACKGROUND/OBJECTIVES: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Previously, Sasa quelpaertensis leaves have been shown to mediate anti-inflammation and anti-cancer effects, although it remains unclear whether Sasa leaves are able to attenuate inflammation-related intestinal diseases. Therefore, the aim of this study was to investigate the anti-inflammatory effects of Sasa quelpaertensis leaf extract (SQE) using an in vitro co-culture model of the intestinal epithelial environment. MATERIALS/METHODS: An in vitro co-culture system was established that consisted of intestinal epithelial Caco-2 cells and RAW 264.7 macrophages. Treatment with lipopolysaccharide (LPS) was used to induce inflammation. RESULTS: Treatment with SQE significantly suppressed the secretion of LPS-induced nitric oxide (NO), prostaglandin E2 (PGE2), IL-6, and IL-1beta in co-cultured RAW 264.7 macrophages. In addition, expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumor necrosis factor (TNF)-alpha were down-regulated in response to inhibition of IkappaBalpha phosphorylation by SQE. Compared with two bioactive compounds that have previously been identified in SQE, tricin and P-coumaric acid, SQE exhibited the most effective anti-inflammatory properties. CONCLUSIONS: SQE exhibited intestinal anti-inflammatory activity by inhibiting various inflammatory mediators mediated through nuclear transcription factor kappa-B (NF-kB) activation. Thus, SQE has the potential to ameliorate inflammation-related diseases, including IBD, by limiting excessive production of pro-inflammatory mediators.

Peroxisome Proliferator-activated Receptor-gamma Agonist Inhibits Pro-inflammatory Gene Expressions and Cellular Proliferation of Fibroblast Like Synoviocytes from Patients with Rheumatoid Arthritis by Down-regulation of NF-kappaB / 대한류마티스학회지

OBJECTIVE: This study investigated the effect of rosiglitazone, a synthetic peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, on pro-inflammatory gene expressions and cellular proliferation of fibroblast like synoviocyte (FLS) from patients with rheumatoid arthritis (RA), and to determine whether these actions are mediated by nuclear factor-kappaB (NF-B) down-regulation. METHODS: Synovial tissues from patients with RA were obtained during total knee replacement surgery, and FLS were isolated. RA FLS were subsequently treated with 10 micrometer, 50 micrometer and 150 micrometer rosiglitazone with or without TNF-alpha (10 ng/mL) stimulation. FLS proliferation in response to rosiglitazone treatment was measured by MTT assay, and mRNA expressions of IL-1beta, IL-6, CCL-2, CCL-7, COX-2 and MMP-9 were determined by real-time quantitative RT-PCR. The effects of rosiglitazone on NF-kappaB activation were evaluated using electrophoretic mobility shift assay (EMSA). RESULTS: Rosiglitazone treatment without TNF-alpha induced a dose-dependent reduction in mRNA expressions of IL-1beta, IL-6, CCL-2, CCL-7, COX-2 and MMP-9 from RA FLS. When TNF-alpha were treated with rosiglitazone, mRNA expressions of COX-2, MMP-9 were reduced dose-dependently. But mRNA expressions of IL-1beta, IL-6, CCL-2, CCL-7 were increased in 10 micrometer rosiglitazone with TNF-alpha and then decreased as the concentration of rosiglitazone increased. Rosiglitazone treatment also suppressed FLS proliferation in a dose-dependent manner, and EMSA showed decreased NF-kappaB expression with rosiglitazone treatment. CONCLUSION: Rosiglitazone suppressed cellular proliferation and mRNA expressions of pro-inflammatory mediators by down-regulating the NF-kappaB signaling pathway in RA FLS. The outcomes suggest that activation of PPAR-gamma can be a novel therapeutic approach in RA.

The effect of high concentration of glucose on the production of proinflammatory cytokines and nitric oxide induced by lipopolysaccharides from periodontopathic bacteria / 대한치주과학회지

PURPOSE: Diabetes mellitus is a clinically and genetically heterogeneous group of metabolic disorders manifested by abnormally high levels of glucose in the blood. Mounting evidence demonstrates that diabetes is a risk factor for gingivitis and periodontitis. The circulating mononuclear phagocytes in diabetic patients with hyperglycemia are chronically exposed to high level of serum glucose. Thus, this study attempted to determine the effect of pre-exposure of monocytes and macrophages to high concentration of glucose on lipopolysaccharide (LPS)-induced production of pro-inflammatory mediators. MATERIAL AND METHODS: For this purpose, cells were cultured in medium containing normal (5 mM) or high glucose (25 mM) for 4-5 weeks before treatment for 24 h with LPS. LPS was highly purified from Porphyromonas gingivalis or Prevotella intermedia by phenol extraction. RESULT: Results showed that prolonged pre-exposure of cells to high glucose markedly increased LPS-stimulated NO secretion when compared to normal glucose. In addition to NO, high glucose also augmented LPS-stimulated IL-6, IL-8, and TNF-alpha secretion after cells were exposed to high glucose for 4 weeks. CONCLUSION: The present study demonstrates that pre-exposure of mononuclear phagocytes with high glucose augments LPS-stimulated production of pro-inflammatory mediators. These findings may explain why periodontal tissue destruction in diabetic patients is more severe than that in non-diabetic individuals.