METHODS: In vitro anti-inflammatory activity and hydrogen peroxide (H2O2) scavenging activity were performed according to the established procedure. Inflammation was induced using CARR in BALB/c mice at the foot paw and peritoneal cavity. Hourly measurement of paw swelling was performed. The level of nitric oxide (NO), myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and nuclear factor κB (NF-κB) was determined using enzyme-linked immunosorbent assay (ELISA). Peritoneal fluid was collected to investigate total count, differential count of leukocytes, and capillary permeability.
RESULTS: In vitro anti-inflammatory evaluations revealed the potential role of MAOI to inhibit heat-induced protein denaturation and human red cell membrane destabilization. H2O2 inhibition activity of MAOI also proved their powerful role as an H2O2 scavenger. Treatment with MAOI in CARR-induced mice significantly reduced paw edema, leukocyte extravasation, and total and differential leukocyte count. The result of ELISA showed MAOI effectively reduce the level of COX-2, PGE2 and NF-κB in inflamed tissue.
CONCLUSIONS: In short, this study demonstrates that inhibition of H2O2 by MAOI alleviates CARR-induced paw edema possibly by inhibiting the H2O2-mediated NF-κB-COX-2 pathway. The present investigation identifies MAOI might reprofile for the treatment of acute inflammation also, the MAO enzyme may use as a novel therapeutic target to design and develop new class of anti-inflammatory agents.
OBJECTIVE: We investigated the effects of high-protein Malaysian diets prepared with palm olein, coconut oil (CO), or virgin olive oil on plasma homocysteine and selected markers of inflammation and cardiovascular disease (CVD) in healthy adults.
DESIGN: A randomized-crossover intervention with 3 dietary sequences of 5 wk each was conducted in 45 healthy subjects. The 3 test fats, namely palmitic acid (16:0)-rich palm olein (PO), lauric and myristic acid (12:0 + 14:0)-rich CO, and oleic acid (18:1)-rich virgin olive oil (OO), were incorporated at two-thirds of 30% fat calories into high-protein Malaysian diets.
RESULTS: No significant differences were observed in the effects of the 3 diets on plasma total homocysteine (tHcy) and the inflammatory markers TNF-α, IL-1β, IL-6, and IL-8, high-sensitivity C-reactive protein, and interferon-γ. Diets prepared with PO and OO had comparable nonhypercholesterolemic effects; the postprandial total cholesterol for both diets and all fasting lipid indexes for the OO diet were significantly lower (P < 0.05) than for the CO diet. Unlike the PO and OO diets, the CO diet was shown to decrease postprandial lipoprotein(a).
CONCLUSION: Diets that were rich in saturated fatty acids prepared with either PO or CO, and an OO diet that was high in oleic acid, did not alter postprandial or fasting plasma concentrations of tHcy and selected inflammatory markers. This trial was registered at clinicaltrials.gov as NCT00941837.
METHOD: The maternal fasting level of adipocytokines of 53 subjects with GDM and 43 normal pregnant (NGDM) was measured using multiplex immunoassay at 24-28 weeks, before delivery, immediate postpartum, and 2-6 months postpuerperium.
RESULTS: Higher levels of AFABP were associated with a 3.7-fold higher risk of GDM. Low chemerin levels were associated with a 3.6-fold higher risk of GDM. Interleukin-10 (IL-10) was inversely associated with the risk of GDM. SPARC had no association with GDM. AFABP was directly correlated to interleukin-6 (r = 0.50), insulin resistance index (r = 0.26), and body mass index (r = 0.28) and inversely correlated to C-reactive protein (r = -0.27). Chemerin levels were directly and strongly correlated with IL-10 (r = 0.41) and interleukin-4 (r = 0.50) and inversely correlated to insulin resistance index (r = -0.23) in GDM but not NGDM. In the longitudinal assessment, there were no significant differences in AFABP and chemerin concentrations of both studied groups.
CONCLUSION: AFABP and chemerin were associated with a higher risk of GDM. These adipocytokines were related to insulin resistance, body mass index, and inflammation in pregnant women diagnosed with GDM.
METHODS: The attenuating effects of syringin on the productions of prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), and the expressions of signaling molecules of the signaling pathways were investigated by using ELISA, Western blot, and qRT-PCR.
RESULTS: Syringin downregulated the NF-κB, MAPKs, and PI3K-Akt signal networks by significantly reducing PGE2 production in the macrophages via suppression of COX-2 gene and protein expression levels. It also reduced TNF-α and IL-1β secretion and their mRNA expression, suppressed phosphorylation of NF-κB (p65), IKKα/β, and IκBα, and restored ability of IκBα to degrade. Syringin dose-dependently attenuated Akt, p38 MAPKs, JNK, and ERK phosphorylation. Also, the expression of corresponding upstream signaling molecules toll-like receptor 4 (TLR4) and myeloid differentiation primary response gene 88 (MyD88) were down-regulated in response to syringin treatment.
CONCLUSION: The suppressive effect of syringin on the inflammatory signaling molecules in MyD88-dependent pathways suggested it's potential as a drug candidate for development into an agent for treatment of various immune-mediated inflammatory disorders.
METHODS: Blood and pancreas were collected from adult male diabetic rats receiving 28days treatment with VVSAE orally. Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin and lipid profile levels and activity levels of anti-oxidative enzymes (superoxide dismutase-SOD, catalase-CAT and glutathione peroxidase-GPx) in the pancreas were determined by biochemical assays. Histopathological changes in the pancreas were examined under light microscopy and levels of insulin, glucose transporter (GLUT)-2, tumor necrosis factor (TNF)-α, Ikkβ and caspase-3 mRNA and protein were analyzed by real-time PCR (qPCR) and immunohistochemistry respectively. Radical scavenging activity of VVSAE was evaluated by in-vitro anti-oxidant assay while gas chromatography-mass spectrometry (GC-MS) was used to identify the major compounds in the extract.
RESULTS: GC-MS analyses indicated the presence of compounds that might exert anti-oxidative, anti-inflammatory and anti-apoptosis effects. Near normal FBG, HbAIc, lipid profile and serum insulin levels with lesser signs of pancreatic destruction were observed following administration of VVSAE to diabetic rats. Higher insulin, GLUT-2, SOD, CAT and GPx levels but lower TNF-α, Ikkβ and caspase-3 levels were also observed in the pancreas of VVSAE-treated diabetic rats (p<0.05 compared to non-treated diabetic rats). The extract possesses high in-vitro radical scavenging activities.
CONCLUSION: In conclusions, administration of VVSAE to diabetic rats could help to protect the pancreas against oxidative stress, inflammation and apoptosis-induced damage while preserving pancreatic function near normal in diabetes.
METHODS: Mice were dosed intraperitoneally with mefenamic acid either as a single dose (100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil) or as single daily doses for 14 days (50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day). Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN) and creatinine activities were measured.
RESULTS: Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine.
CONCLUSION: RESULTS from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.
Results: This review discusses the current status of mesenchymal stem cell (MSC) therapy for SCI, criteria to considering for the application of MSC therapy and novel biological therapies that can be applied together with MSCs to enhance its efficacy. Bone marrow-derived MSCs (BMSCs), umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (ADSCs) have been trialed for the treatment of SCI. Application of MSCs may minimize secondary injury to the spinal cord and protect the neural elements that survived the initial mechanical insult by suppressing the inflammation. Additionally, MSCs have been shown to differentiate into neuron-like cells and stimulate neural stem cell proliferation to rebuild the damaged nerve tissue.
Conclusion: These characteristics are crucial for the restoration of spinal cord function upon SCI as damaged cord has limited regenerative capacity and it is also something that cannot be achieved by pharmacological and physiotherapy interventions. New biological therapies including stem cell secretome therapy, immunotherapy and scaffolds can be combined with MSC therapy to enhance its therapeutic effects.
Main Body: Increasing evidence of the cardioprotective effects of both invasive and non-invasive vagal nerve stimulation (VNS) suggests that these may be feasible methods to treat myocardial ischemia/reperfusion injury via anti-inflammatory regulation. The mechanisms through which auricular VNS controls inflammation are yet to be explored. In this review, we discuss the potential of autonomic nervous system modulation, particularly via the parasympathetic branch, in ameliorating MI. Novel insights are provided about the activation of the cholinergic anti-inflammatory pathway on cardiac macrophages. Acetylcholine binding to the α7 nicotinic acetylcholine receptor (α7nAChR) expressed on macrophages polarizes the pro-inflammatory into anti-inflammatory subtypes. Activation of the α7nAChR stimulates the signal transducer and activator of transcription 3 (STAT3) signaling pathway. This inhibits the secretion of pro-inflammatory cytokines, limiting ischemic injury in the myocardium and initiating efficient reparative mechanisms. We highlight recent developments in the controversial auricular vagal neuro-circuitry and how they may relate to activation of the cholinergic anti-inflammatory pathway.
Conclusion: Emerging published data suggest that auricular VNS is an inexpensive healthcare modality, mediating the dynamic balance between pro- and anti-inflammatory responses in cardiac macrophages and ameliorating cardiac ischemia/reperfusion injury.