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Tuesday, June 11, 2019

Inflammopharmacology

The role of magnesium in different inflammatory diseases

Abstract

Magnesium deficiency (MgD) can cause inflammation in human body. The known mechanisms of inflammation caused by MgD include activation of phagocytic cells, opening of calcium channels, activation of the N-methyl-d-aspartate (NMDA) receptor, and activation of nuclear factor (NF)-κB. In addition, MgD causes systemic stress response through neuroendocrinological pathways. The inflammation caused by MgD can result in pro-atherogenic changes in the metabolism of lipoproteins, endothelial dysfunction, and high blood pressure. Studies suggest that magnesium may play an important role in the pathophysiology of some inflammatory diseases. Several clinical trials and laboratory studies have been done on the functional role of magnesium. In this study, we review some inflammatory diseases, in which the magnesium has a role in their pathophysiology. Among these diseases, diabetes, asthma, preeclampsia, atherosclerosis, heart damage, and rheumatoid arthritis have been highlighted.



Urotensin-#receptor antagonist SB-706375 protected isolated rat heart from ischaemia–reperfusion injury by attenuating myocardial necrosis via RhoA/ROCK/RIP3 signalling pathway

Abstract

SB-706375 is a selective receptor antagonist of human urotensin-II (hU-II), which can block the aorta contraction induced by hU-II in rats. The effect of SB-706375 on myocardial ischaemia–reperfusion (I/R) injury is unclear. The major objective of this study was to investigate whether SB-706375 has a protective effect on myocardial I/R injury in rats and explore its possible mechanisms. Isolated hearts of Adult Sprague–Dawley were perfused in a Langendorff apparatus, and haemodynamic parameters, lactate dehydrogenase (LDH), creatine phosphokinase-MB (CK-MB), cardiac troponin I (cTnI), RhoA, and the protein expressions of U-II receptor (UTR), receptor-interacting protein 3 (RIP3), Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) and Rho-associated coiled-coil-containing protein kinase 2 (ROCK2) were assessed. We found that SB-706375 (1 × 10−6 and 1 × 10−5 mol/L) significantly inhibited the changes of haemodynamic parameters and reduced LDH and CK-MB activities and also cTnI level in the coronary effluents in the heart subjected to myocardial I/R injury. Further experiments studies showed that SB-706375 obviously prevented myocardial I/R increased RhoA activity and UTR, RIP3, ROCK1, and ROCK2 protein expressions. ROCK inhibition abolished the improving effect of SB-706375 on myocardial I/R-induced haemodynamic change in the isolated perfused rat heart. These findings suggested that SB-706375 provides cardio-protection against I/R injury in isolated rats by blocking UTR-RhoA/ROCK-RIP3 pathway.



Ginsenoside compound-K inhibits the activity of B cells through inducing IgD-B cell receptor endocytosis in mice with collagen-induced arthritis

Abstract

Previously, ginsenoside metabolite compound K (C-K) was able to reduce B cell proliferation and serum anti-type II collagen (anti-CII) antibody to normal levels in mice with collagen-induced arthritis (CIA); however, the mechanism by which C-K restores B cell balance is unclear. In the present work, C-K treatment not only alleviated the polyarthritis index, swollen joint count, pathological scores of spleen and joints, spleen index, B cell proliferation and the level of serum antibodies (IgG1, IgG2a and anti-collagen II), but C-K treatment also restored B cell subsets including regulatory B cells, plasma cells, memory B cells, mature B cells, and follicular B cells in CIA mice. Interestingly, C-K did not change the expression level of immunoglobulin D-type B-cell receptor (IgD-BCR) but promoted IgD-BCR endocytosis. C-K treatment enhanced β-arrestin1 expression, facilitating the colocalization between IgD and β-arrestin1, as well as colocalization between IgD and adaptor protein 2 (AP2). Inhibition of the β-arrestin1-AP2 interaction with barbadin significantly reduced the ability of C-K to attenuate IgD-BCR plasma membrane localization. These results taken together depict that C-K ameliorates CIA in part by inhibiting B cell activation through the triggering of IgD-BCR internalization in a β-arrestin1-AP2 dependent manner.



Correction to: The kinin B 1 and B 2 receptors and TNFR1/p55 axis on neuropathic pain in the mouse brachial plexus

Unfortunately, the Fig. 7 was wrongly downloaded in the original publication.



Inhibition of adiposity and related metabolic disturbances by polyphenol-rich extract of Boswellia serrata gum through alteration of adipo/cytokine profiles

Abstract

Background

The role of proinflammatory cytokines in adiposity is well established. The anti-inflammatory and antihyperglycemia effects of Boswellia serrata (B. Serrata) gum have been demonstrated by many investigators. The present study aimed to investigate the anti-obesity potential of B. serrata extract.

Methods

The effects of B. serrata extract on lipase activity and acute food intake were investigated. The present study aimed to investigate the anti-obesity potential of B. serrata extract. The effects on lipase activity and acute food intake were investigated. Body weight changes, biochemical and histopathological markers were demonstrated in rats fed a high-fat diet.

Results

Boswellia serrata extract inhibited alterations in pancreatic lipase activity, but orlistat was more efficacious. B. serrata and ephidrene, but not orlistat, significantly suppressed cumulative food intake in mice. In obese rats, B. serrata or orlistat significantly decreased weight gain and weight of visceral white adipose tissue. B. serrata-treated animals exhibited a significant reduction in serum glucose, TC, TG, LDL-C, FFA, IL-1β, TNF-α, insulin and leptin levels of obese rat groups while HDL-C and adiponectin levels were significantly increased by orlistat or B. serrata extract. Histopathological examination of the liver revealed that B. serrata was more effective than orlistat in alleviating steatosis and adipocyte hypertrophy shown in obese control rats.

Conclusions

Boswellia serrata is as effective as orlistat in preventing obesity, hyperlipidemia, steatosis and insulin resistance. These actions may be mediated by suppression of food intake and decrease levels of TNF-α, IL-1β and leptin resistance along with increasing adiponectin.



Effect of Synadenium grantii and its isolated compound on dysmenorrhea behavior model in mice

Abstract

Objective

This study aimed to evaluate the effects of the methanol extract of Synadenium grantii Hook f. stems and its main isolated compound Query3,4,12,13-tetraacetylforbol-20-phenylacetate (1) on experimental dysmenorrhea in mice.

Methods

Female Swiss mice (n = 6–15) of 6–8 weeks old were used, selected according to the period of the estrous cycle. Animals in proestrus were treated intraperitoneally (i.p.) for 3 days with estradiol. They orally received, on the 4th day, S. grantii extract, the compound 1, ibuprofen or hyoscine butylbromide (Buscopan compound®). Then they were injected (i.p.) with oxytocin 1 h later and individually observed regarding the abdominal writhing for 45 min. The uterus was weighed, photographed and fixed in paraffin for histological analysis.

Key findings

The extract inhibited the abdominal writhing and similar results were obtained with compound 1 and the positive control drugs Ibuprofen and hyoscine butylbromide. Reduction of uterus volume and histological inflammatory parameters, such as oedema and leukocyte infiltrate, were observed in animals treated with the extract and compound 1.

Conclusions

Our data show promising activity of the extract against dysmenorrhea, indicating important anti-inflammatory activity. Compound 1 appears to be, at least in part, the main responsible for this promising biological effect.



Losartan suppresses the inflammatory response in collagen-induced arthritis by inhibiting the MAPK and NF-κB pathways in B and T cells

Abstract

The angiotensin II type 1 receptor (AT1R) antagonist losartan has been confirmed to have a moderate anti-inflammatory effect in vitro and in vivo. However, how it affects immune cells in Rheumatoid Arthritis (RA) is still unknown. We found that in human synovial tissues, AT1R is significantly expressed on T cells and B cells. Treatment with losartan (15 mg/kg) alone and in combination with a low dose of methotrexate (MTX 0.25 mg/kg/3 days) significantly suppressed the progression of CIA. Secondary paw swelling, joint destruction and the presence of pro-inflammatory cytokines (TNF-α and IFN-γ) in the serum were alleviated after treatment. The therapeutic effects of losartan were based on reduced T-cell and B-cell activation, specifically by decreased cell vitality and pro-inflammatory cytokine production. In addition, losartan combined with a low dose of MTX achieved a similar therapeutic effect, while protecting liver and kidney from MTX damage. Mechanistically, losartan inhibits the production of pro-inflammatory mediators, reduces the phosphorylation of p38, ERK, and p65, p50 nuclear transposition in T cells and B cells. Phosphorylation of JNK is not affected by losartan in the CIA rat model. losartan can be used as an effective RA treatment, which exhibits anti-arthritic effects potentially through down-regulating the phosphorylation of p38, ERK and signaling through NF-κB. While achieving similar anti-rheumatic effects, a combination therapy of losartan with a low dose of MTX, can protect from liver and renal damage caused by giving a high dose of MTX.



A randomised, double-blind, placebo-controlled trial of a multi-strain probiotic in patients with asymptomatic ulcerative colitis and Crohn's disease

Abstract

Background

There is considerable interest in the possible importance of the gut microflora in the pathophysiology of the inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn's disease (CD). Probiotics offer a potential adjuvant treatment in these patients by modifying the intestinal milieu, but reports of their efficacy are conflicting.

Aims

To assess the efficacy of a multi-strain probiotic (Symprove™, Symprove Ltd, Farnham, United Kingdom) in quality of life issues and intestinal inflammation in patients with asymptomatic UC and CD.

Methods

A single-centre, randomised, double-blind, placebo-controlled trial of adult patients with asymptomatic IBD. Patients received 4 weeks of treatment with the probiotic or placebo (1 ml/kg/day). The primary efficacy measure was the difference in change in the IBD Quality of Life Questionnaire results (QOL) between probiotic vs. placebo at week 4. Secondary outcome measures included analyses of the change in laboratory findings, including faecal calprotectin (FCAL).

Results

Over 500 patients were recruited to the study and 81 and 61 patients with UC and CD, respectively were randomised and completed the study. There were no significant differences in IBD-QOL scores between placebo and the probiotic groups. Similarly, there were no significant changes observed in the laboratory data. However, the differences in FCAL between patients with UC before and after probiotics versus placebo approached statistical significance with a p value of 0.076. Post-hoc analyses showed that the FCAL levels were significantly (p < 0.015) reduced in the UC patients receiving the probiotic as opposed to placebo. No significant changes were seen in CD. No serious adverse events were observed.

Conclusion

This multi-strain probiotic is associated with decreased intestinal inflammation in patients with UC, but not in CD and is well tolerated. Further research is required to see if the probiotic reduces the incidence of clinical relapses in asymptomatic IBD patients.



Anti-inflammatory effects of Chinese propolis in lipopolysaccharide-stimulated human umbilical vein endothelial cells by suppressing autophagy and MAPK/NF-κB signaling pathway

Abstract

This study aimed to investigate the possible benefits of Chinese poplar propolis (CP) in inhibiting inflammation using vascular endothelial cells (VECs) cultured in a nutrient-rich condition exposed to lipopolysaccharide (LPS). Cell proliferation was detected by sulforhodamine B assay and EdU kit. The production of reactive oxygen species (ROS) and level of mitochondrial membrane potential were determined with fluorescent probe DCHF and JC-1, respectively. Protein expression was examined by immunofluorescence staining and western blotting. The results showed that CP (6.25, 12.5, and 25 Î¼g/mL) significantly reduced LPS-induced cytotoxicity, and when challenged with CP substantially suppressed ROS overproduction and protected mitochondrial membrane potential. CP treatment significantly inhibited autophagy by inhibiting LC3B distribution and accumulation, and elevating the p62 level in an mTOR-independent manner but mainly by suppressing the translocation of p53 from the cytoplasm to the nucleus. Furthermore, CP treatment markedly reduced protein levels of TLR4 at 12 and 24 h and significantly suppressed nuclear translocation of NF-κB p65 from cytoplasm to nucleus. In addition, CP treatment significantly reduced the phosphorylation of JNK, ERK1/2, and p38 MAPK. Our findings demonstrated that CP protects VECs from LPS-induced oxidative stress and inflammation, which might be associated with depressing autophagy and MAPK/NF-κB signaling pathway. The results provided novel insights for the potential use of nutrient-rich propolis against inflammation.



25-hydroxycholesterol reduces inflammation, viral load and cell death in ZIKV-infected U-87 MG glial cell line

Abstract

Zika virus (ZIKV) infection is a global health issue due to its worldwide diffusion and to the related effects on neural progenitor cells with severe consequences on developing brain as well as on the central nervous system of adults. Previous studies showed that ZIKV infection induces an increment of IL1B expression in the central nervous system and also in the blood. IL-1β is a pro-inflammatory cytokine essential for cellular defence, tissue repair and neuroinflammation, a mechanism seen to be associated with several neuroinflammatory diseases. 25-hydroxycholesterol (25-HC) is a natural oxysterol, derived from hydroxylation of cholesterol, possessing important antiviral activity possibly correlated to its ability to alter host membrane structures. Furthermore, 25-HC is involved in the modulation of IL1B gene expression, being able to suppress IL-1β driven inflammation probably by blocking the activation of the SREB proteins. In our study, we analysed the antiviral action of 25-HC in ZIKV-infected U-87 MG cells, also evaluating its impact on inflammation and cell death. We demonstrated that 25-HC is able to reduce inflammation and cell death caused by ZIKV infection and also to diminish intracellular ZIKV load in U-87 MG glial cell line. Considering its antiviral activity and its ability to penetrate blood–brain barrier, 25-HC could be proposed, based on our results and literature findings, as a potential anti-ZIKV agent.



Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

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