Okra (Abelmoschus esculentus Linn) inhibits lipopolysaccharide-induced inflammatory mediators in BV2 microglial cells

Purpose: To investigate the inhibitory effects of okra (Abelmoschus esculentus Linn.) extract on the production of reactive oxygen species (ROS) and pro-inflammatory cytokines in lipopolysaccharide (LPS)-stimulated BV2 microglia.Methods: Okra was extracted with ethanol by Soxhlet extraction. Non-cytotoxic doses of okra at concentrations of 50, 100 and 200 μg/mL were used in this study. BV2 cells were cultured and treated with LPS in the presence or absence of okra at the concentrations indicated above. ROS, nitric oxide (NO), tumor necrotic factor alpha (TNF-α), interleukin 1 beta (IL-1β), phosphorylation levels of nuclear factor-kappa B (NF-kB) p65 and Akt were determined.Results: Treatment of BV2 cells with okra concentrations of 50, 100 and 200μg/mL significantly suppressed LPS-induced NO as well as ROS compared to untreated cells. There was also a significant decrease in the production of TNF-α and IL-1β in okra-treated BV2 microglia cells. The level of LPSinduced NF-kB p65 phosphorylation was significantly decreased by okra treatment. In addition, okra inhibited LPS-induced Akt phosphorylation, which is an upstream molecule of NF-kB.Conclusion: Okra exerts anti-oxidative and anti-inflammatory effects in LPS-stimulated BV2 microglial cells by suppressing Akt-mediated NF-κB pathway. This suggests that okra might be a valuable agent for the treatment of anti-neuroinflammatory diseases mediated by microglial cells.Keywords: Abelmoschus esculentus Linn, Inflammatory cytokines, Lipopolysaccharide, Neuroinflammation, Microglia, Reactive oxygen specie

AN OBSERVATIONAL STUDY OF THE EFFECT OF HEMOGLOBINOPATHY, ALPHA THALASSEMIA AND HEMOGLOBIN E ON P. VIVAX PARASITEMIA

Background: The protective effect of α-thalassemia, a common hematological disorder in Southeast Asia, against Plasmodium falciparum malaria has been well established. However, there are much less well understood the effect of α-thalassemia against P.vivax. Here, we aimed to investigate the proportion of α-thalassemia including the effect of α-thalassemia and HbE on the parasitemia of P.vivax in Southeast Asian malaria patients in Thailand. Methods: A total of 210 malaria patients, admitted to the Hospital for Tropical Diseases, Thailand during 2011-2012, consist of 159 Myanmeses, 13 Karens, 26 Thais, 3 Mons, 3 Laotians, and 6 Cambodians were recruited. Plasmodium spp. and parasite densities were determined. Group of deletion mutation (--SEA, -α3.7, -α4.2deletion) and substitution mutation (HbCS and HbE) were genotyped using multiplex gap-PCR and PCR-RFLP, respectively. Results: In our malaria patients, 17/210 homozygous and 74/210 heterozygous -α3.7 deletion were found. Only 3/210 heterozygous -α4.2 deletion and 2/210 heterozygous--SEA deletion were detected. HbE is frequently found with 6/210 homozygote and 35/210 heterozygote. The most common thalassemia allele frequencies in Myanmar population were -α3.7 deletion (0.282), followed by HbE (0.101), HbCS (0.016), -α4.2 deletion (0.009), and --SEA deletion (0.003). Only density of P.vivax in α-thalassemia trait patients (-α3.7/-α3.7, --SEA/αα, -α3.7/-α4.2) but not in silent α-thalassemia (-α3.7/αα, -α4.2/αα, ααCS/αα) were significantly higher compared with non α-thalassemia patients (p=0.027). Density of P.falciparum significantly increased in heterozygous HbE patients (p=0.046). Conclusions: Alpha-thalassemia trait is associated with high level of P.vivax parasitemia in malaria patients in Southeast Asia

Chronic Apocynin Treatment Attenuates Beta Amyloid Plaque Size and Microglial Number in hAPP(751)SL Mice

Background: NADPH oxidase is implicated in neurotoxic microglial activation and the progressive nature of Alzheimer’s Disease (AD). Here, we test the ability of two NADPH oxidase inhibitors, apocynin and dextromethorphan (DM), to reduce learning deficits and neuropathology in transgenic mice overexpressing human amyloid precursor protein with the Swedish and London mutations (hAPP(751)SL). Methods: Four month old hAPP(751)SL mice were treated daily with saline, 15 mg/kg DM, 7.5 mg/kg DM, or 10 mg/kg apocynin by gavage for four months. Results: Only hAPP(751)SL mice treated with apocynin showed reduced plaque size and a reduction in the number of cortical microglia, when compared to the saline treated group. Analysis of whole brain homogenates from all treatments tested (saline, DM, and apocynin) demonstrated low levels of TNFa, protein nitration, lipid peroxidation, and NADPH oxidase activation, indicating a low level of neuroinflammation and oxidative stress in hAPP(751)SL mice at 8 months of age that was not significantly affected by any drug treatment. Despite in vitro analyses demonstrating that apocynin and DM ameliorate Ab-induced extracellular superoxide production and neurotoxicity, both DM and apocynin failed to significantly affect learning and memory tasks or synaptic density in hAPP(751)SL mice. To discern how apocynin was affecting plaque levels (plaque load) and microglial number in vivo, in vitro analysis of microglia was performed, revealing no apocynin effects on beta-amyloid (Ab) phagocytosis, microglial proliferation, or microglial survival. Conclusions: Together, this study suggests that while hAPP(751)SL mice show increases in microglial number and plaque load, they fail to exhibit elevated markers of neuroinflammation consistent with AD at 8 months of age, which may be a limitation of this animal model. Despite absence of clear neuroinflammation, apocynin was still able to reduce both plaque size and microglial number, suggesting that apocynin may have additional therapeutic effects independent of anti-inflammatory characteristics

Oligodendrocytes: biology and pathology

Oligodendrocytes are the myelinating cells of the central nervous system (CNS). They are the end product of a cell lineage which has to undergo a complex and precisely timed program of proliferation, migration, differentiation, and myelination to finally produce the insulating sheath of axons. Due to this complex differentiation program, and due to their unique metabolism/physiology, oligodendrocytes count among the most vulnerable cells of the CNS. In this review, we first describe the different steps eventually culminating in the formation of mature oligodendrocytes and myelin sheaths, as they were revealed by studies in rodents. We will then show differences and similarities of human oligodendrocyte development. Finally, we will lay out the different pathways leading to oligodendrocyte and myelin loss in human CNS diseases, and we will reveal the different principles leading to the restoration of myelin sheaths or to a failure to do so

Original article. Patterns of microglial innate immune responses elicited by amyloid β_1–42 and lipopolysaccharide: the similarities of the differences

Abstract Background: As part of their innate immune response to changes in the central nervous system environment, normally quiescent microglia become activated and increase expression of pattern recognition receptors, scavenger receptors, and production of inflammatory cytokines, proteinases, reactive oxygen species (ROS), and free radicals. These molecules have been implicated in the pathogenesis and progression of several neurodegenerative disorders including Alzheimer disease (AD). Objective: We compared patterns of microglial innate immune responses elicited by nonfibrillar amyloid β peptide (nfAβ1-42) to those elicited by lipopolysaccharide (LPS). Methods: Murine BV-2 microglial cells were exposed to either nfAβ1-42 or LPS for 12 h. Then, total RNA from each condition was isolated and expression levels of Toll-like receptor (TLR)-4, scavenger receptor class A (SRMARCO) and class B (SR-BI), CD36, and matrix metalloproteinase (MMP)-9 were determined by reverse transcription-quantitative real-time polymerase chain reaction. The amount of hydrogen peroxide (H2O2) and nitric oxide (NO) in the cell-free supernatant at 24 h were determined using 10-acetyl-3,7-dihydroxyphenoxazine (Amplex Red) and Griess reagent, respectively. Results: nfAβ1-42 and LPS significantly increased expression of TLR-4, SR-MARCO, CD36, and MMP-9 and production of H2O2 and NO in BV-2 microglial cells compared with that of unstimulated cells. However, expression of SR-BI was significantly induced only when the cells were exposed to nfAβ1-42. Conclusion: These findings indicate that pattern of microglial innate immune responses elicited by nfAβ1-42 overlap with that elicited by LPS and suggest a specific role of microglial SR-BI expression in AD pathogenesis.</jats:p

Additional file 1 of Haematological profile of malaria patients with G6PD and PKLR variants (erythrocytic enzymopathies): a cross-sectional study in Thailand

Additional file 1: Table S1. Mean and standard deviation (SD) for clinical parameters of malaria patients without thalassaemia and haemoglobinopathies (p-values were determined using the Student’s t-test.

Antioxidant and anti-inflammatory activities of Oroxylum indicum Kurz (L.) fruit extract in lipopolysaccharide-stimulated BV2 microglial cells

&#x0D; &#x0D; &#x0D; &#x0D; Purpose: To investigate the anti-inflammatory effects and antioxidant activity of Oroxylum indicum (L.) Kurz fruit extract in lipopolysaccharide (LPS)-stimulated BV2 microglia.&#x0D; Methods: BV2 cells were treated with LPS for 24 h in the presence or absence of O. indicum fruit extract. Then, nitric oxide (NO), reactive oxygen species (ROS) and interleukin 6 (IL-16) levels were measured using Griess reagent assay, CM-H2DCFDA and enzyme-linked immunosorbent (ELISA) assays, respectively. The in vitro antioxidant property of the extract was also investigated by 1,1- diphenyl-2-picrylhydrazyl (DPPH) and 2,2’-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) assays.&#x0D; Results: Levels of IL-6, NO, and ROS in LPS-treated BV2 cells were significantly higher than those in control (p &lt; 0.01). However, exposure of LPS-treated BV2 cells to O. indicum extract led to a marked decrease in the levels of these parameters, when compared to the untreated cells (p &lt; 0.01). Results from DPPH and ABTS assays showed that the O. indicum extract exhibited good antioxidant properties, with total flavonoid and total phenolic contents of 115.58 ± 1.09 and 131.04 ± 2.37 mg/g of dried extract, respectively.&#x0D; Conclusion: The results demonstrate that O. indicum fruit exerts anti-oxidant and anti-inflammatory effects in LPS-stimulated BV2 cells. Thus O. indicum fruit might be beneficial in the development of novel anti-oxidative and anti-neuroinflammatory herbal medicines. However, the mechanisms by which O. indium fruits reduces NO and IL-6 needs to be further investigated.&#x0D; &#x0D; &#x0D; &#x0D; </jats:p