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Borderline personality disorder (BPD) is a severe psychiatric condition that affects up to 2.7% of the population and is highly linked to functional impairment and suicide. Despite its severity, there is a lack of knowledge about its pathophysiology. Studies show genetic influence and childhood violence as factors that may contribute to the development of BPD; however, the involvement of neuroinflammation in BPD remains poorly investigated. This article aimed to explore the pathophysiology of BPD according to the levels of brain-derived neurotrophic factor (BDNF), inflammatory cytokines, and oxidative stress substances that exacerbate neuronal damage. Few articles have been published on this theme. They show that patients with BPD have a lower level of BDNF and a higher level of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in peripheral blood, associated with increased plasma levels of oxidative stress markers, such as malondialdehyde and 8-hydroxy-2-deoxyguanosine. Therefore, more research on the topic is needed, mainly with a pre-clinical and clinical focus.
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Human brain cholesterol acts as structural components of cellular membrane, synapse and dendrite formation.Researchers have found a possible association between low serum cholesterol levels and mood disorders though the literature from India in this regard is limited. To estimate serum levels of total cholesterol in patients with major depressive disorder. 75 patients of MDD were compared with equal number of age and sex matched controls. 5 ml of fasting sample of blood was obtained in a plain vacutainer to analyse total cholesterol level by Cholesterol oxidase-peroxidase method. Statistical analysis: The obtained results were tabulated and analyzed by multiple logistic regression analysis, independent t-test, Chi-square test and area under the curve. The mean level of cholesterol in cases (158.85±61.22 mg/dL) which was significantly lower compared to the controls (182.71±40.98 mg/dL) with P <0.01. The symptoms of MDD negatively correlated with lower serum cholesterol level with odds ratio of 0.99. There was statistically significant lower level of cholesterol in the MDD group below 140 mg/dL compared to the control group with P <0.001. As the measurement of total serum cholesterol is simple and cost effective, it can be used as an important biochemical marker for MDD.
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Objective: To determine the anti-neuroinflammatory activity of Moringa oleifera leaf extract (MLE) under lipopolysaccharide stimulation of mouse murine microglia BV2 cells in vitro. Methods: The cytotoxicity effect of MLE was investigated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide assay. The inflammatory response of BV-2 cells were induced with lipopolysaccharide. The generation of nitric oxide levels was determined by using Griess assay and the level of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) was evaluated by ELISA kit. The expression of iNOS, COX-2 as well as IκB-α was carried out by immunoblot analysis. Results: MLE reduced the nitric oxide production in concentration-dependent manner, and maintained the viability of BV-2 microglial cells which indicated absence of toxicity. In addition, MLE repressed the activation of nuclear factor kappa B by arresting the deterioration of IκB-α, consequently resulted in suppression of cytokines expression such as COX-2 and iNOS. Conclusions: MLE inhibitory activities are associated with the inhibition of nuclear factor kappa B transcriptional activity in BV2 microglial cells. Thus MLE may offer a substantial treatment for neuroinflammatory diseases.
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Ginger, one of worldwide consumed dietary spice, is not only famous as food supplements, but also believed to exert a variety of remarkable pharmacological activity as herbal remedies. In this study, a ginger constituent, 12-dehydrogingerdione (DHGD) was proven that has comparable anti-inflammatory activity with positive control 6-shogaol in inhibiting LPS-induced interleukin (IL)-6, tumor necrosis factor (TNF)-α, prostaglandin (PG) E₂, nitric oxide (NO), inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, without interfering with COX-1 in cultured microglial cells. Subsequent mechanistic studies indicate that 12-DHGD may inhibit neuro-inflammation through suppressing the LPS-activated Akt/IKK/NF-κB pathway. Furthermore, 12-DHGD markedly promoted the activation of NF-E2-related factor (Nrf)-2 and heme oxygenase (HO)-1, and we demonstrated that the involvement of HO-1 on the production of pro-inflammatory mediators such as NO and TNF-α by using a HO-1 inhibitor, Zinc protoporphyrin (Znpp). These results indicate that 12-DHGD may protect against neuro-inflammation by inhibiting Akt/IKK/IκB/NF-κB pathway and promoting Nrf-2/HO-1 pathway.
Subject(s)
Dietary Supplements , Ginger , Heme Oxygenase (Decyclizing) , Interleukins , Microglia , Nitric Oxide , Nitric Oxide Synthase , Prostaglandin-Endoperoxide Synthases , Spices , Tumor Necrosis Factor-alpha , ZincABSTRACT
@#Dysfunctional learning and memorization ability as well as emotion exist in multiple central nervous diseases, which are disastrous to patients and their family. Reports indicate that neuro-inflammation is involved in various central nervous diseases; additionally, it participates in the regulation of learning and memorization ability as well as emotion. This article reviews data on several human diseases of animal model and clinical researches and discusses the relationship between neuro-inflammation and cognitive function. Some therapeutic researches targeting neuro-inflammation to improve neurological diseases are also summarized, with an attempt to provide inspiration and advice for the to development of drugs for diseases alike.
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Objective To investigate the protective effect of microRNA-181b (miR-181b) on aged rats with sepsis-induced hippocampus injury in vivo. Methods Seventy-five male healthy old Sprague-Dawley (SD) rats were randomly divided into five groups (n = 15) using a random number table: sham operation group (Sham group), sepsis group [cecal ligation and puncture (CLP) group], miR-181b Agomir+CLP group (Ag+CLP group), miR-181b Antagomir+CLP group (An+CLP group) and normal saline (NS) control group (NS+CLP group). Rats sepsis model was reproduced by CLP, and in Sham group, the cecum of rats was separated only after abdominal operation without ligation or perforation. The rats in Ag+CLP group were given miR-181b Agomir 10 μL via lateral ventricle at 24 hours before CLP, the rats in An+CLP group were given 10 μL miR-181b Antagomir, and those in NS+CLP group were given 10 μL NS. At 6, 12, 24 hours after CLP, 5 rats of each group were sacrificed randomly, and hippocampus were harvested. The expression of miR-181b in hippocampus was determined by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The expression of nuclear factor-κB p65 (NF-κB p65) was determined by Western Blot. The contents of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). Results Compared with Sham group, the expression of miR-181b in hippocampus of CLP group was significantly decreased at 6 hours after CLP (2-ΔΔCT: 0.70±0.12 vs. 0.98±0.06, P < 0.05), and the expressions of NF-κB p65, IL-1β and TNF-α were significantly increased [NF-κB p65/Histone H3:0.30±0.03 vs. 0.07±0.01, IL-1β (ng/L): 120.39±8.02 vs. 50.55±11.12, TNF-α (ng/L): 59.48±4.60 vs. 40.31±3.96, all P < 0.05], this trend was continued till 24 hours, and these results indicated that there was obvious inflammation in hippocampus of sepsis rats. There was no statistical difference in the expression of miR-181b, NF-κB p65, IL-1β or TNF-α in hippocampus between NS+CLP group and CLP group, which indicated that injection of NS into the rat lateral ventricle, had not aggravated the damage degree of hippocampus. Compared with CLP group, the expression of miR-181b in hippocampus of Ag+CLP group was significantly increased at 6 hours after CLP (2-ΔΔCT: 1.87±0.25 vs. 0.70±0.12, P < 0.05), and the expressions of NF-κB p65, IL-1β and TNF-α were significantly lowered [NF-κB p65/Histone H3:0.16±0.03 vs. 0.30±0.03, IL-1β (ng/L): 73.76±8.17 vs. 120.39±8.02, TNF-α (ng/L): 49.52±4.77 vs. 59.48±4.60, all P < 0.05]. There was no statistical difference in the expression of miR-181b in hippocampus between An+CLP group and CLP group (2-ΔΔCT: 0.80±0.08 vs. 0.70±0.12 at 6 hours, 0.48±0.03 vs. 0.46±0.05 at 12 hours, 0.61±0.09 vs. 0.63±0.07 at 24 hours, all P > 0.05), but the expressions of NF-κB p65, IL-1β and TNF-α in hippocampus at 6 hours after CLP of An+CLP group were significantly higher than those of CLP group [NF-κB p65/Histone H3: 0.44±0.02 vs. 0.30±0.03, IL-1β (ng/L): 134.21±5.78 vs. 120.39±8.02, TNF-α (ng/L): 67.62±5.86 vs. 59.48±4.60, all P < 0.05], this trend was continued till 24 hours after CLP. The above results showed that overexpression of miR-181b might attenuate the inflammation of hippocampus through down-regulation of NF-κB, IL-1β and TNF-α. Conclusions The expression of hippocampal miR-181b was significantly decreased in septic rats. Up-regulation of miR-181b could inhibit the activation of NF-κB signal pathway and the release of the inflammatory cytokine IL-1β and TNF-α stimulated by sepsis, and alleviate the inflammatory reaction and hippocampus injury in rat with sepsis.
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Objective: To determine the anti-neuroinflammatory activity of Moringa oleifera leaf extract (MLE) under lipopolysaccharide stimulation of mouse murine microglia BV2 cells in vitro. Methods: The cytotoxicity effect of MLE was investigated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5- diphenyl-tetrazolium bromide assay. The inflammatory response of BV-2 cells were induced with lipopolysaccharide. The generation of nitric oxide levels was determined by using Griess assay and the level of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) was evaluated by ELISA kit. The expression of iNOS, COX-2 as well as IκB-α was carried out by immunoblot analysis. Results: MLE reduced the nitric oxide production in concentration-dependent manner, and maintained the viability of BV-2 microglial cells which indicated absence of toxicity. In addition, MLE repressed the activation of nuclear factor kappa B by arresting the deterioration of IκB-α, consequently resulted in suppression of cytokines expression such as COX-2 and iNOS. Conclusions: MLE inhibitory activities are associated with the inhibition of nuclear factor kappa B transcriptional activity in BV2 microglial cells. Thus MLE may offer a substantial treatment for neuroinflammatory diseases.
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Ginsenoside Rg1 is a common component of a variety of stroke and diabetes medications, but its anti-stroke effect in diabetic patients is unclear. The aim of this research is to test the therapeutic effect of Rg1 on ischemic stroke in diabetic rats, and elucidate the effect of Rg1 on post-stroke neuro-inflammation. Rg1 significantly reduced the infarct area percent, increased the behavioral score, and reduced the brain water content in diabetic rats after stroke in the diabetic rats. Rg1 reduced the post-stroke inflammatory response and decreased the expression of high mobility group box1 (HMGB1) protein significantly. Elevated level of HMGB1 activity by supplementing exogenous HMGB1 protein abolished the anti-stroke effect of Rg1, which suggests that HMGB1 is involved into the anti-stroke effect of Rg1 in the diabetic rats.
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AIM To investigate the anti-neuroinflammation effects of 4-hydroxybenzyl aldehyde (4-HBAL) from Gastrodia elata Blume on acute cerebral ischemic injury in rats and its nechanism of action.METHODS The rat model of acute cerebral ischemic injury was induced by injecting arachidonic acid via intracarotid artery.Brain tissue samples were taken from the animals 3 h after the model of acute cerebral ischemic injury.Tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) were detected in brain tissue to evaluate the effects of 4-HBAL in vivo.Lipopolysaccharid (LPS)-induced activation of BV-2 microglia cells model was used to explore the anti-neuroinflammation mechanism of 4-HBAL.RESULTS The experimental results showed that 4-HBAL had a significant protective effect on acute cerebral ischemic injury.It could significandy decrease the contents of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β),and obviously inhibit the production of nitric oxide (NO),prostaglandin E2 (PGE2) and TNF-α in LPS-stimulated BV-2 cell,and increase the production of interleukin-10 (IL-10) and transforming growth factors-β (TGF-β) in BV-2 cell.CONCLUSION The mechanism of 4-HBAL may be related to the suppression of the excessive activation of microglia after cerebral ischemia and the promotion of the transformation of microglia into anti-inflammatory phenotype.
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3,4,5-Trihydroxycinnamic acid (THC) is a derivative of hydroxycinnamic acids, which have been reported to possess a variety of biological properties such as anti-inflammatory, anti-tumor, and neuroprotective activities. However, biological activity of THC has not been extensively examined. Recently, we reported that THC possesses anti-inflammatory activity in LPS-stimulated BV2 microglial cells. However, its precise mechanism by which THC exerts anti-inflammatory action has not been clearly identified. Therefore, the present study was carried out to understand the anti-inflammatory mechanism of THC in BV2 microglial cells. THC effectively suppressed the LPS-induced induction of pro-inflammatory mediators such as NO, TNF-alpha, and IL-1beta. THC also suppressed expression of MCP-1, which plays a key role in the migration of activated microglia. To understand the underlying mechanism by which THC exerts these anti-inflammatory properties, involvement of Nrf2, which is a cytoprotective transcription factor, was examined. THC resulted in increased phosphorylation of Nrf2 with consequent expression of HO-1 in a concentration-dependent manner. THC-induced phosphorylation of Nrf2 was blocked with SB203580, a p38 MAPK inhibitor, indicating that p38 MAPK is the responsible kinase for the phosphorylation of Nrf2. Taken together, the present study for the first time demonstrates that THC exerts anti-inflammatory properties through the activation of Nrf2 in BV2 microglial cells, suggesting that THC might be a valuable therapeutic adjuvant for the treatment of inflammation-related disorders in the CNS.