Esculentoside A exerts anti-inflammatory activity in microglial cells

Esculentoside A (EsA) is a saponin isolated from the roots of Phytolacca esculenta. This study was designed to evaluate the pharmacological effects of EsA on lipopolysaccharide (LPS)-stimulated BV2 microglia and primary microglia cells. Our results indicated that EsA pretreatment significantly decreased LPS-induced production of Nitric Oxide (NO) and Prostaglandin E2 (PGE2) and impeded LPS-mediated upregulation of pro-inflammatory mediators' expression such as nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-12 (IL-12) and tumor necrosis factor-a (TNF-α) in both BV2 microglia and primary microglia cells. Moreover, EsA markedly suppressed nuclear factor-κB p65 (NF-κB p65) translocation by blocking IκB-α phosphorylation and degradation in LPS-treated BV2 cells. EsA also decreased phosphorylation level of mitogen-activated protein kinases (MAPKs) and inhibited NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome mediated caspase-1 activation in LPS-stimulated BV2 cells. Additionally, EsA decreased β-amyloid_1–42 (Aβ_1–42)-induced production of TNF-α, IL-1β and IL-6 in primary microglia. Thus, EsA might be a promising therapeutic agent for alleviating neuroinflammatory diseases.     

DATS通过NF-κB抑制LPS诱导小鼠肺泡巨噬细胞促炎细胞因子表达

目的探讨二烯丙基三硫(DATS)抑制脂多糖(LPS)诱导小鼠肺泡巨噬细胞肿瘤坏死因子-α(TNF-α)及白介素-1β表达的信号转导机制。方法体外培养MH-S细胞,用DATS和(或)LPS进行干预。反转录PCR检测细胞中TNF-α、IL-1β mRNA表达,电泳迁移率改变分析(EMSA)检测细胞核因子-κB(NF-κB)活性,Western blot检测细胞磷酸化(p-IκB)及非磷酸化IκB的表达。结果LPS刺激MH-S细胞可导致TNF-α、IL-1β mRNA、p-IκB表达增加及NF-κB活性升高。用DATS(0.1、0.5、2.5、5.0mg.L-1)预处理细胞30min后再给予LPS刺激,可使TNF-α、IL-1β mRNA表达降低,并呈剂量依赖性;升高的NF-κB活性及p-IκB表达均显不同程度的抑制。单独DATS对TNF-α、IL-1β mRNA表达及NF-κB活性无影响。结论DATS可通过抑制IκB磷酸化及NF-κB活化,进而下调LPS诱导小鼠肺泡巨噬细胞TNF-α、IL-1β mRNA表达。     

Sertraline ameliorates inflammation in CUMS mice and inhibits TNF-α-induced inflammation in microglia cells

Evidence indicates that inflammation plays a crucial role in depression. Therefore, new antidepressants might be identified by screening drugs for their anti-inflammatory actions. Sertraline hydrochloride (SERT), a widely used antidepressant, has anti-inflammatory effects in clinical studies, but the mechanism involved is unclear. In this study, we used cell and molecular biology to determine the possible anti-inflammatory mechanism of SERT in vivo and in vitro. Experimental data from the in vivo study showed that mice exposed to chronic unpredictable mild stress (CUMS) had significantly higher levels of major inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β] and inducible nitric oxide synthase [iNOS]) in peripheral and central tissues compared with the control group. Treatment of CUMS mice with SERT significantly reduced the levels of these inflammatory cytokines and inhibited the phosphorylation of nuclear factor-κB (NF-κB) and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α). Moreover, SERT reduced serum levels of transaminase in CUMS mice. Our in vitro study revealed that SERT suppressed TNF-α-induced NF-κB activation in a dose-dependent manner. SERT also inhibited the TNF-α-induced nuclear translocation of NF-κB by inhibiting IκB-α phosphorylation. Furthermore, SERT inhibited TNF-α-induced inflammatory cytokines in BV2 microglia cells. SERT directly bound to TNF-α and TNF-α receptor 1 (TNFR1) to potently block TNF-α/TNFR1-triggered signaling. These results indicate that SERT might treat depression by inhibiting the activation of microglia via the NF-κB signaling pathway. This study provides a basis for the research and development of antidepressants that act to reduce inflammation and the expression of inflammatory mediators.     

DATS通过p38MAPK通路抑制LPS诱导的小鼠MH-S细胞TNF-α及IL-1β表达

目的探讨p38MAPK在二烯丙基三硫(DATS)抑制脂多糖(LPS)诱导小鼠肺泡巨噬细胞促炎细胞因子表达中的作用。方法体外培养MH-S细胞,用DATS和(或)LPS进行干预,Western blot检测细胞p38及磷酸化p38(p-p38)的表达;用LPS和(或)SB203580孵育细胞,反转录PCR检测细胞中TNF-α、IL-1βmRNA表达,Western blot检测细胞磷酸化(p-IκB)及非磷酸化IκB的表达。结果 LPS刺激MH-S细胞可导致p-p38表达增加,呈时间依赖性;用DATS(0.1、0.5、2.5、5.0 mg.L-1)预处理细胞30 min后再给予LPS刺激,p-p38表达呈剂量依赖性下降;单独DATS对p-p38表达无明显影响。p38特异性抑制剂SB203580可剂量依赖性地抑制LPS诱导的p-IκB蛋白、TNF-α及IL-1βmR-NA表达。结论 DATS可通过抑制p38MAPK通路抑制IκB磷酸化及NF-κB活化,进而下调LPS诱导小鼠肺泡巨噬细胞TNF-α、IL-1βmRNA表达。     

Protective effect of taraxasterol on acute lung injury induced by lipopolysaccharide in mice

Taraxasterol, a pentacyclic-triterpene isolated from Taraxacum officinale, has been reported to have potent anti-inflammatory properties. However, the effect of taraxasterol on lipopolysaccharide (LPS)-induced mice acute lung injury has not been investigated. The aims of this study were to investigate whether taraxasterol could ameliorate the inflammation response in LPS-induced acute lung injury and to clarify the possible mechanism. Male BALB/c mice were pretreated with taraxasterol 1 h before intranasal instillation of LPS. 7 h after LPS administration, the myeloperoxidase (MPO) in lung tissues, lung wet/dry ratio and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were detected. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) in the BALF were measured by ELISA. The extent of phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 were determined by western blotting. The results showed that taraxasterol attenuated the infiltration of inflammatory cells, the activity of myeloperoxidase (MPO), lung wet/dry ratio, and the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in a dose-dependent manner. Additionally, western blotting results showed that taraxasterol inhibited the phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 caused by LPS. Our data suggest that anti-inflammatory effects of taraxasterol against the LPS-induced ALI may be due to its ability of inhibition of the NF-κB and MAPK signaling pathways.     

Antrodia camphorata suppresses lipopolysaccharide-induced nuclear factor-κB activation in transgenic mice evaluated by bioluminescence imaging

In an earlier study, we found that Antrodia camphorata inhibited the production of lipopolysaccharide (LPS)-induced cytokines, inducible nitric oxide synthase, and cyclooxygenase-2 by blocking nuclear factor-κB (NF-κB) activation in cultured RAW 264.7 macrophages. This study was aimed at evaluating the inhibitory effects of the fermented culture broth of A. camphorata in terms of LPS-induced NF-κB activation in transgenic mice by using a non-invasive, real-time NF-κB bioluminescence imaging technique. Transgenic mice carrying the luciferase gene under the control of NF-κB were given A. camphorata (570 mg/kg, p.o.) for three consecutive days and then injected with LPS (4 mg/kg, i.p.). In vivo imaging showed that treatment with LPS increased the luminescent signal, whereas A. camphorata suppressed the LPS-induced inflammatory response significantly. Ex vivo imaging showed that A. camphorata suppressed LPS-induced NF-κB activity in the small intestine, mesenteric lymph nodes, liver, spleen, and kidney. Immunohistochemical staining revealed that A. camphorata suppressed production of the LPS-induced tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and NF-κB p65 subunit in these organs. Furthermore, A. camphorata attenuated the productions of LPS-induced TNF-α and IL-1β in serum from transgenic mice. We report the first confirmation of the anti-inflammatory action in vivo of this potentially beneficial mushroom.     

Long non-coding RNA THRIL promotes LPS-induced inflammatory injury by down-regulating microRNA-125b in ATDC5 cells

BackgroundOsteoarthritis is an age-related disorder of bone-joint that causes pain and disability in middle and older people. This study aimed to investigate the potential effects of long non-coding RNA (lncRNA) THRIL on lipopolysaccharide (LPS)-induced osteoarthritis cell injury model (ATDC5 cell inflammatory injury), as well as the possible internal molecular mechanisms.MethodsCell viability and apoptosis were assessed using CCK-8 assay and Guava Nexin assay, respectively. Cell transfection was conducted to change the expression of THRIL and microRNA-125b (miR-125b) in ATDC5 cells. qRT-PCR was performed to detect the expression of THRIL, miR-125b and pro-inflammatory cytokines IL-6, TNF-α and monocyte chemotactic protein 1 (MCP-1) in ATDC5 cells. ELISA was used to measure the concentrations of IL-6, TNF-α and MCP-1 in culture supernatant of ATDC5 cells. Finally, the protein expression of key factors involved in cell apoptosis, inflammatory response, JAK1/STAT3 and NF-κB pathways were evaluated using western blotting.ResultsLPS significantly induced ATDC5 cell inflammatory injury and up-regulated the expression of THRIL. Overexpression of THRIL aggravated the LPS-induced ATDC5 cell inflammatory injury. Suppression of THRIL had opposite effects. Moreover, THRIL negatively regulated the expression of miR-125b in ATDC5 cells. miR-125b participated in the effects of THRIL overexpression on LPS-induced ATDC5 cell inflammatory injury. Furthermore, overexpression of THRIL enhanced the LPS-induced JAK1/STAT3 and NF-κB pathways activation by down-regulating miR-125b.ConclusionTHRIL exerted pro-inflammatory roles in LPS-induced osteoarthritis cell injury model. Overexpression of THRIL promoted LPS-induced ATDC5 cell inflammatory injury by down-regulating miR-125b and then activating JAK1/STAT3 and NF-κB pathways.     

Exopolysaccharide of Laetiporus sulphureus var. miniatus downregulates LPS-induced production of NO, PGE2, and TNF-α in BV2 microglia cells via suppression of the NF-κB pathway

Our previous study showed that the exopolysaccharide (EPS) of Laetiporus sulphureus var. miniatus was well characterized and prevented cell damage in streptozotocin-induced apoptosis. However, little is known about the molecular mechanisms underlying its anti-inflammatory effects. Therefore, we attempted in this study to determine whether EPS induces a significant inhibition of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated murine BV2 microglia cells. Our results showed that EPS significantly inhibited LPS-induced pro-inflammatory mediators, such as nitric oxide (NO), prostaglandin E₂ (PGE₂), and tumor necrosis factor-α (TNF-α), without any significant cytotoxicity. EPS also downregulated mRNA and protein expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α in LPS-induced BV2 microglia cells. Our data also revealed that EPS treatment significantly reduced translocation of nuclear factor-κB (NF-κB) subunit p65 and its DNA-binding activity in LPS-stimulated BV2 microglia cells. Furthermore, we confirmed by using proteasome inhibitor N-acetyl-l-cysteine (NAC), that the inhibition of NF-κB activity influenced the expression of pro-inflammatory genes in LPS-induced BV2 microglia cells. As expected, NAC suppressed the expression of iNOS, COX-2, and TNF-α by blocking proteasome-mediated degradation. Taken together, our data indicate that EPS inhibits the expression of pro-inflammatory mediators by suppressing NF-κB activity.     

丙泊酚对BV-2小胶质细胞活化的影响

目的探讨丙泊酚对脂多糖(LPS)诱导的BV-2小胶质细胞活化的影响及其可能机制。方法体外培养小鼠BV-2小胶质细胞,随机分为LPS 1μg/ml组(A组)、丙泊酚30μM组(B组)、LPS 1μg/ml+丙泊酚30μM组(C组)和空白对照组(D组)。采用RT-PCR检测各组细胞中IL-1β和TNF-αmRNA表达量,Western blot检测总糖原合成酶激酶-3β(GSK-3β)和磷酸化GSK-3β(p-GSK-3β)的蛋白表达水平。结果 A、C组IL-1β、TNF-α及p-GSK-3表达量均较D组明显增加(P<0.05或P<0.01)。与A组相比,C组IL-1β和TNF-αmRNA表达量降低,而p-GSK-3β蛋白表达量增加(P<0.05)。结论丙泊酚30μM能在体外减轻LPS诱导的BV-2小胶质细胞释放IL-1β和TNF-α的水平,此作用可能与抑制GSK-3β活性有关。     

Moclobemide exerts anti-inflammatory effect in lipopolysaccharide-activated primary mixed glial cell culture

An increasing body of evidence indicates that glial activation and neuroinflammation play an important role in the pathogenesis of psychiatric and neurodegenerative diseases. Activated glial cells secrete various cytokines that influence neurotransmission, hypothalamus–pituitary–adrenal axis activity, neuronal plasticity and neurogenesis. It has been suggested that alterations in cytokine networks are involved in the mechanism of action of antidepressant drugs. Until now, only a few studies demonstrated that some tricyclic antidepressants and selective serotonin reuptake inhibitors reduced production of pro-inflammatory cytokines in brain glia cells. We have investigated for the first time whether the antidepressant, moclobemide (a reversible selective inhibitor of monoamine oxidase-A) has an influence on pro-inflammatory cytokines [interleukin (IL)-1β and tumor necrosis factor (TNF)-α] and anti-inflammatory cytokine (IL-10) in primary rat mixed glial cell cultures stimulated by lipopolysaccharide (LPS). Our results showed that moclobemide used in a wide range of concentrations diminished LPS-stimulated IL-1β and TNF-α mRNAs expression in cellular extracts and remarkably reduced the levels of both pro-inflammatory cytokines in culture medium. In opposite to this, the drug had no influence on IL-10 mRNA and slightly reduced IL-10 concentration. Moreover, moclobemide decreased LPS-stimulated translocation of NFκB p65 subunit into cellular nuclei. These results suggest that moclobemide exerts anti-inflammatory effect in the central nervous system because it affects the balance between pro- and anti-inflammatory cytokines (IL-1β, TNF-α/IL-10) in primary mixed glial cell cultures.     

The anti-inflammatory effect of TR6 on LPS-induced mastitis in mice

[TRIAP]-derived decoy peptides have anti-inflammatory properties. In this study, we synthesized a TRIAP-derived decoy peptide (TR6) containing, the N-terminal portion of the third helical region of the [TIRAP] TIR domain (sequence “N”-RQIKIWFQNRRMKWK and -KPGFLRDPWCKYQML-“C”). We evaluated the effects of TR6 on lipopolysaccharide-induced mastitis in mice. In vivo, the mastitis model was induced by LPS administration for 24 h, and TR6 treatment was initiated 1 h before or after induction of LPS. In vitro, primary mouse mammary epithelial cells and neutrophils were used to investigate the effects of TR6 on LPS-induced inflammatory responses. The results showed that TR6 significantly inhibited mammary gland hisopathologic changes, MPO activity, and LPS-induced production of TNF-α, IL-1β and IL-6. In vitro, TR6 significantly inhibited LPS-induced TNF-α and IL-6 production and phosphorylation of NF-κB and MAPKs. In conclusion, this study demonstrated that the anti-inflammatory effect of TR6 against LPS-induced mastitis may be due to its ability to inhibit TLR4-mediated NF-κB and MAPK signaling pathways. TR6 may be a promising therapeutic reagent for mastitis treatment.     

Effect of active ingredient of Stephaniajaponica(Thunb.) Mierson lipopolysaccharide-induced activation of microglia

OBJECTIVE Microglia were considered to be the main immune cells in the central nervous system, which could maintain the homeostasis of the brain.Under pathological conditions, microglia undergo significant changes in morphology and release a large number of pro-inflammatory mediators. Numerous studies have shown that neuroinflammatory responses mediated by microglial over-activation are involved in the pathogenesis of multiple neurodegenerative diseases. Therefore, finding a safe and effective drug that can inhibit microglialoveractivation becomes one of the significant strategies to prevent and treat neurodegenerative diseases. In our previous studies, we found that the dichloromethane(CH_2Cl_2) fraction of the 80% EtOH extraction of Stephaniajaponica, could inhibit nitric oxide(NO) release in microglial cel line induced by LPS. The compound QJT-14,obtained from the fraction, exhibited good activity. The purpose of this study is to explore the potential mechanism of QJT-14 suppressing microglia over-activation.METHODS Cell viability and NO production were detected by MTT and Griess assay, respectively. The mRNA expression of IL-1β, IL-6, TNF-α were measured by real-time PCR. The production of IL-6, TNF-α were tested by ELISA.The protein expression of NF-κB P65 were tested by Western blotting. NF-κB P65 nuclear translocation was detected by immunofluorescence assay. RESULTS JT-14 could significantly suppress NO production in LPSinduced microglia cell line, and did not affect the cell viability within the concentration range. QJT-14 attenuated pro-inflammatory factors expression at m RNA and protein levels in LPS-induced microglia. QJT-14 could significantly inhibit NF-κB P65 protein expression induced by LPS.CONCLUSION QJT-14 could inhibit microglia activation by inhibiting NF-κB pathway. Thesere sults indicated that QJT-14 has a potential therapeutic effect on neurodegenerative diseases.     

Sauchinone suppresses lipopolysaccharide-induced inflammatory responses through Akt signaling in BV2 cells

Activated microglial cells play an important role in inflammatory responses in the central nervous system (CNS) that are involved in neurodegenerative diseases. Sauchinone has been shown to modulate the expression of inflammatory factors through nuclear factor-kappa B (NF-κB) signaling pathway. Here, we examined the effect of sauchinone on the inflammatory responses of microglia cells induced by lipopolysaccharide (LPS) and explored the mechanism underlying action of sauchinone. BV2 cells treated with LPS showed an up-regulation of nitric oxide (NO) and prostaglandin (PGE(2)) release, whereas sauchinone suppressed this up-regulation. Sauchinone inhibited both mRNA and protein expression of COX-2, iNOS, TNF-α and IL-1β. In addition, sauchinone blocked the activation of NF-κB through its inhibition of I-κB phosphorylation. Interestingly, sauchinone had no effect on the LPS-induced phosphorylation of mitogen activated protein kinases (MAP kinases; ERK1/2, p38, JNK), but it did inhibit Akt phosphorylation. These results suggest that the inhibitory effect of sauchinone on the LPS-induced production of inflammatory mediator in BV2 cells is associated with the suppression of the NF-κB and Akt signaling pathways. Therefore, sauchinone may be a useful treatment for neurodegenerative disease by inhibiting inflammatory responses in activated microglia.     

Anti-inflammatory effect of Yam Glycoprotein on lipopolysaccharide-induced acute lung injury via the NLRP3 and NF-κB/TLR4 signaling pathway

Acute lung injury (ALI) is a common lung disease accompanied by acute and persistent pulmonary inflammatory response syndrome, which leads to alveolar epithelial cells and capillary endothelial cell damage. Yam glycoprotein, separated from traditional Chinese yam, has been shown to have anti-inflammatory and immunomodulatory effects. In this experiment, we mainly studied the therapeutic effect and mechanism of a glycoprotein on the lipopolysaccharide (LPS)-induced ALI mice. An oral glycoprotein method was used to treat the mouse ALI model induced by LPS injection in the peritoneal cavity. Afterward, we measured the wet/dry (W/D) ratio, the activity of myeloperoxidase (MPO), the oxidative index superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-PX) and the production of inflammatory cytokines interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) to evaluate the effect of yam glycoprotein on lung tissue changes. We examined the protein expression of TLR4, ASC, NF-κBp65, p-NF-κBp65, Caspase-1, IκB, NLRP3, p-IκB, and β-actin by western blot analysis. Immunohistochemical analyses of NLRP3 and p-p65 in lung tissue were carried out to assess the mechanism of glycoprotein action. This result suggests that glycoprotein markedly depressed LPS-induced lung W/D ratio, MPO activity, MDA content SOD and GSH-Px depletion, and the contents of inflammatory cytokines IL-1β, IL-6, and TNF-α. Moreover, glycoprotein blocked TLR4/NF-κBp65 signaling activation and NLRP3inflammasome expression in LPS-induced ALI mice. As this particular study shows, glycoprotein has a safeguarding effects on LPS-induced ALI mice, possibly via activating NLRP3inflammasome and TLR4/NF-κB signaling pathways.     

Genipin alleviates LPS-induced acute lung injury by inhibiting NF-κB and NLRP3 signaling pathways

Genipin has been reported to have anti-inflammatory effect. However, its role on lipopolysaccharide (LPS)-induced acute lung injury (ALI) has not been explored. This study aimed to evaluate the effect of genipin on murine model of acute lung injury induced by LPS. The mice were treated with genipin 1 h before LPS administration. 12 h later, the myeloperoxidase (MPO) in lung tissues and lung wet/dry ratio were detected. The levels of TNF-α, IL-1β and IL-6 in bronchoalveolar lavage fluid (BALF) were measured by ELISA. Apart from this, we use western blot to detect the protein expression in the NF-κB and NLRP3 signaling pathways. The results showed that the treatment of genipin markedly attenuated the lung wet/dry ratio and the MPO activity. Moreover, it also inhibited the levels of TNF-α, IL-1β, IL-6 in the BALF. In addition, genipin significantly inhibited LPS-induced NF-κB and NLRP3 activation. In conclusion, these results demonstrate that genipin protected against LPS-induced ALI through inhibiting NF-κB and NLRP3 signaling pathways.     

Modulation of Inflammatory Cytokines and Mitogen-activated Protein Kinases by Acetate in Primary Astrocytes

Acetate supplementation attenuates neuroglia activation in a rat model of neuroinflammation by a mechanism associated with an increase in brain acetyl-CoA, an alteration in histone acetylation, and reduction of interleukin (IL)-1β expression. We propose that reduced astroglial activation occurs by disrupting astrocyte-derived inflammatory signaling and cytokine release. Using primary astroglial cultures, we found that LPS (0–25 ng/ml, 4 h) increased tumor necrosis factor (TNF-α) and IL-1β in a concentration-dependent manner, which was reduced by treatment with sodium acetate (12 mM). LPS did not alter H3K9 acetylation or IL-6 levels, whereas acetate treatment increased H3K9 acetylation by 2-fold and decreased basal levels of IL-6 by 2-fold. Acetate treatment attenuated the LPS-induced increase in TNF-α mRNA, but did not reverse the mRNA levels of other pro-inflammatory cytokines. By contrast, LPS decreased TGF-β1 and IL-4 protein and TGF-β1 mRNA, all of which was reversed with acetate treatment. Further, we found that acetate treatment completely reversed LPS-induced phosphorylation of MAPK p38 and decreased basal levels of phosphorylated extracellular signal-regulated kinases1/2 (ERK1/2) by 2-fold. Acetate treatment also reversed LPS-elevated NF-κB p65, CCAAT/enhancer-binding protein beta protein levels, and reduced basal levels of phosphorylated NF-κB p65 at serine 536. These results suggest that acetate treatment has a net anti-inflammatory effect in LPS-stimulated astrocytes that is largely associated with a disruption in MAPK and NF-κB signaling.     

Schisandrin B inhibits LPS-induced inflammatory response in human umbilical vein endothelial cells by activating Nrf2

Schisandrin B (SchB), an active ingredient extracted from Schisandra chinensis (Turcz.) Baill, has been known to have anti-oxidant and anti-inflammatory activities. In this study, we investigated the anti-inflammatory effects and mechanism of SchB in LPS-stimulated human umbilical vein endothelial cells (HUVECs). The effects of SchB on VCAM-1, ICAM-1, NF-κB and Nrf2 expression were detected by western blot analysis. The effects of SchB on TNF-α and IL-8 production were detected by ELISA. The results showed that SchB strongly suppressed the production of TNF-α and IL-8 in HUVECs stimulated with LPS. SchB also inhibited LPS-induced VCAM-1 and ICAM-1 expression. Furthermore, SchB blocked the activation of NF-κB induced by LPS. In addition, SchB increased the expression of Nrf2 and HO-1 in a concentration-dependent manner. And the inhibition of TNF-α and IL-8 production by SchB was blocked by transfection with Nrf2 siRNA. Our findings showed that SchB inhibited LPS-induced inflammation in HUVECs by activating Nrf2 signaling pathway.     

2-Deoxy-d-glucose attenuates sevoflurane-induced neuroinflammation through nuclear factor-kappa B pathway in vitro

ObjectSevoflurane, one of the most commonly used anesthetics in clinic, induced neuroinflammation and caused cognitive impairment. 2-deoxy-d-glucose (2-DG) is a synthetic analogue of glucose and is clinically used in medical imaging safely.MethodsWe examined the effect of 2-DG on sevoflurane-induced neuroinflammation in the mouse primary microglia cells. Mouse microglia cells were treated with 4.1% sevoflurane for 6 h to examine the expression of interleukin (IL)-6 and tumor necrosis factor (TNF-α) and activation of nuclear factor-kappa B (NF-κB). Pyrrolidine dithiocarbamate (PDTC) or 2-DG was used 1 h before sevoflurane treatment.ResultsIn the present study, we found that sevoflurane increased level of IL-6 and TNF-α through activating NF-κB signaling, and that 2-DG reduced sevoflurane-induced increase in IL-6 and TNF-α and nuclear NF-κB in microglia cells.ConclusionOur data suggests that NF-κB signaling pathway could be a target for sevoflurane-induced neuroinflammation and 2-DG might be a potential therapy to prevent or treat sevoflurane-induced neuroinflammation.