ABSTRACT
BACKGROUND: Endothelial dysfunction (ED) is a marker of vascular damage and a precursor of cardiovascular diseases such as hypertension, which involve inflammation and organ damage. Nitric oxide (NO), produced by eNOS, which is induced by pAKT, plays a crucial role in the function of a healthy endothelium. METHODS: A combination of subfractions SF1 and SF3 (C4) of the aqueous fraction from Cucumis sativus (Cs-Aq) was evaluated to control endothelial dysfunction in vivo and on HMEC-1 cells to assess the involvement of pAkt in vitro. C57BL/6J mice were injected daily with angiotensin II (Ang-II) for 10 weeks. Once hypertension was established, either Cs-AqC4 or losartan was orally administered along with Ang-II for a further 10 weeks. Blood pressure (BP) was measured at weeks 0, 5, 10, 15, and 20. In addition, serum creatinine, inflammatory status (in the kidney), tissue damage, and vascular remodeling (in the liver and aorta) were evaluated. Cs-AqC4 was also tested in vitro on HMEC-1 cells stimulated by Ang-II to assess the involvement of Akt phosphorylation. RESULTS: Cs-AqC4 decreased systolic and diastolic BP, reversed vascular remodeling, decreased IL-1ß and TGF-ß, increased IL-10, and decreased kidney and liver damage. In HMEC-1 cells, AKT phosphorylation and NO production were increased. CONCLUSIONS: Cs-AqC4 controlled inflammation and vascular remodeling, alleviating hypertension; it also improved tissue damage associated with ED, probably via Akt activation.
Subject(s)
Cucumis sativus , Hypertension , Peptide Hormones , Mice , Animals , Proto-Oncogene Proteins c-akt , Angiotensin II/pharmacology , Vascular Remodeling , Mice, Inbred C57BL , Hypertension/chemically induced , Hypertension/drug therapy , Blood Pressure , Inflammation , Plant Components, AerialABSTRACT
Obesity is caused by lipid accumulation in adipose tissues inducing adipocyte dysfunction, characterized by insulin resistance, increased lipolysis, oxidative stress, and inflammation, leading to increased levels of adipokines. Herein the capacity of the subfractions (SFs) SF1, SF2, and SF3 from the Cucumis sativus aqueous fraction and their combinations (M) to control adipocyte dysfunction in vitro, in 3T3-L1 adipocytes was studied. Adipocytes, previously treated with dexamethasone or IL-1 to induce dysfunction, were incubated with different concentrations of the subfractions for 24 h. 2-deoxyglucose consumption and glycerol release were evaluated, and a surface model was constructed to determine the most effective SF concentrations to improve both parameters. Effective SF combinations were assessed in their capacity to control metabolic, pro-oxidative, and pro-inflammatory conditions. SF1, SF2 (40 µg/ml each) and SF3 (20 µg/ml) improved 2-deoxyglucose consumption by 87%, 57%, and 87%, respectively. SF1 and SF2 (5 µg/ml each) and SF3 (40 µg/mL) increased glycerol secretion by 10.6%, 18.9%, and 11.8%, respectively. Among five combinations tested, only M4 (SF1 40 µg/ml:SF2 60 µg/ml:SF3 30 µg/ml) and M5 (SF1 40 µg/ml:SF2 60 µg/mL:SF3 10 µg/ml) controlled effectively the metabolic, pro-oxidative, and proinflammatory conditions studied. Glycine, asparagine, and arginine were the main components in these SFs.
Subject(s)
Adipocytes/drug effects , Cucumis sativus/metabolism , Plant Extracts/pharmacology , 3T3-L1 Cells , Adipocytes/metabolism , Adipokines/metabolism , Adipose Tissue/metabolism , Animals , Cell Differentiation/drug effects , Inflammation/metabolism , Insulin/metabolism , Insulin Resistance , Mice , Obesity/metabolism , Oxidative Stress/drug effectsABSTRACT
In Mexico Agave angustifolia has traditionally been used to treat inflammation. The aim of this study was to measure the anti-inflammatory effect of the extract of A. angustifolia, the isolation and identification of active compounds. From the acetone extract two active fractions were obtained, (AsF13 and AaF16). For the characterization of pharmacological activity, the acute inflammatory model of mouse ear edema induced with TPA was used. The tissue exposed to TPA and treatments were subjected to two analysis, cytokine quantification (IL-1ß, IL-6, IL-10 and TNF-α) and histopathological evaluation. The active fraction (AaF16) consisted principally of 3-O-[(6'-O-palmitoyl)-ß-D-glucopyranpsyl] sitosterol. In AaF13 fraction was identified ß-sitosteryl glucoside (2) and stigmasterol (3). The three treatments tested showed a concentration-dependent anti-inflammatory effect (AaAc Emax = 33.10%, EC50 = 0.126 mg/ear; AaF13 Emax = 54.22%, EC50 = 0.0524 mg/ear; AaF16 Emax = 61.01%, EC50 = 0.050 mg/ear). The application of TPA caused a significant increase on level of IL-1ß, IL-6 and TNFα compared with basal condition, which was countered by any of the experimental treatments. Moreover, the experimental treatments induced a significant increase in the levels of IL-4 and IL-10, compared to the level observed when stimulated with TPA. Therefore, the anti-inflammatory effect of Agave angustifolia, is associated with the presence of 3-O-[(6'-O-palmitoyl)-ß-D-glucopyranosyl] sitosterol.
