Population Genetic Structure and Chemotype Diversity of Fusarium graminearum Populations from Wheat in Canada and North Eastern United States

Fusarium head blight (FHB) is a major disease in wheat causing severe economic losses globally by reducing yield and contaminating grain with mycotoxins. In Canada, Fusarium graminearum is the principal etiological agent of FHB in wheat, producing mainly the trichothecene mycotoxin, deoxynivalenol (DON) and its acetyl derivatives (15-acetyl deoxynivalenol (15ADON) and 3-acetyl deoxynivalenol (3ADON)). Understanding the population biology of F. graminearum such as the genetic variability, as well as mycotoxin chemotype diversity among isolates is important in developing sustainable disease management tools. In this study, 570 F. graminearum isolates collected from commercial wheat crops in five geographic regions in three provinces in Canada in 2018 and 2019 were analyzed for population diversity and structure using 10 variable number of tandem repeats (VNTR) markers. A subset of isolates collected from the north-eastern United States was also included for comparative analysis. About 75% of the isolates collected in the Canadian provinces of Saskatchewan and Manitoba were 3ADON indicating a 6-fold increase in Saskatchewan and a 2.5-fold increase in Manitoba within the past 15 years. All isolates from Ontario and those collected from the United States were 15ADON and isolates had a similar population structure. There was high gene diversity (H = 0.803–0.893) in the F. graminearum populations in all regions. Gene flow was high between Saskatchewan and Manitoba (Nm = 4.971–21.750), indicating no genetic differentiation between these regions. In contrast, less gene flow was observed among the western provinces and Ontario (Nm = 3.829–9.756) and USA isolates ((Nm = 2.803–6.150). However, Bayesian clustering model analyses of trichothecene chemotype subpopulations divided the populations into two clusters, which was correlated with trichothecene types. Additionally, population cluster analysis revealed there was more admixture of isolates among isolates of the 3ADON chemotypes than among the 15ADON chemotype, an observation that could play a role in the increased virulence of F. graminearum. Understanding the population genetic structure and mycotoxin chemotype variations of the pathogen will assist in developing FHB resistant wheat cultivars and in mycotoxin risk assessment in Canada.     

Occurrence of Fusarium Mycotoxins and Their Modified Forms in Forage Maize Cultivars

Forage maize is often infected by mycotoxin-producing Fusarium fungi during plant growth, which represent a serious health risk to exposed animals. Deoxynivalenol (DON) and zearalenone (ZEN) are among the most important Fusarium mycotoxins, but little is known about the occurrence of their modified forms in forage maize. To assess the mycotoxin contamination in Northern Germany, 120 natural contaminated forage maize samples of four cultivars from several locations were analysed by liquid chromatography-high resolution mass spectrometry (LC-HRMS) for DON and ZEN and their modified forms deoxynivalenol-3-glucoside (DON3G), the sum of 3- and 15-acetyl-deoxynivalenol (3+15-AcDON), α- and β-zearalenol (α-ZEL, β-ZEL). DON and ZEN occurred with high incidences (100 and 96%) and a wide range of concentrations, reaching levels up to 10,972 and 3910 µg/kg, respectively. Almost half of the samples (46%) exceeded the guidance value in complementary and complete feeding stuffs for ZEN (500 µg/kg), and 9% for DON (5000 µg/kg). The DON related mycotoxins DON3G and 3+15-AcDON were also present in almost all samples (100 and 97%) with amounts of up to 3038 and 2237 µg/kg and a wide range of concentrations. For the ZEN metabolites α- and β-ZEL lower incidences were detected (59 and 32%) with concentrations of up to 423 and 203 µg/kg, respectively. Forage maize samples were contaminated with at least three co-occurring mycotoxins, whereby 95% of all samples contained four or more mycotoxins with DON, DON3G, 3+15-AcDON, and ZEN co-occurring in 93%, together with α-ZEL in 57% of all samples. Positive correlations were established between concentrations of the co-occurring mycotoxins, especially between DON and its modified forms. Averaged over all samples, ratios of DON3G/DON and 3+15-AcDON/DON were similar, 20.2 and 20.5 mol%; cultivar-specific mean ratios ranged from 14.6 to 24.3 mol% and 15.8 to 24.0 mol%, respectively. In total, 40.7 mol% of the measured DON concentration was present in the modified forms DON3G and 3+15-AcDON. The α-ZEL/ZEN ratio was 6.2 mol%, ranging from 5.2 to 8.6 mol% between cultivars. These results demonstrate that modified mycotoxins contribute substantially to the overall mycotoxin contamination in forage maize. To avoid a considerable underestimation, it is necessary to analyse modified mycotoxins in future mycotoxin monitoring programs together with their parent forms.     

Characterization and Immunopotentiating Effects of the Glycoprotein Isolated from Dioscorea Batatas

We demonstrate that glycoprotein isolated from Dioscorea batatas (GDB) has immunostimulatory effects including macrophage activation. Analysis of infiltration of inflammatory cells into peritoneal cavity showed GDB treatment significantly increased the recruitment of macrophages, lymphocytes, neutrophils, and monocytes into the peritoneal cavity. Treatment of spleen cells isolated from C57BL/6 mice with GDB significantly increased the proliferation of B cells and T cells induced by LPS and ConA, respectively. Treatment with GDB significantly increased the cytolytic capacity of NK cells and macrophages against YAC-1 and B16 cells, respectively. In order to further confirm and investigate the mechanism of GDB on macrophage activation, we analyzed the effects of GDB on the cytokine expression including iNOS, IL-1β, and TNF-α in mouse macrophage cell line, RAW 264.7 cells. RT-PCR and ELISA showed that GDB increased the expression of IL-1β, and TNF-α, whereas iNOS was not induced by GDB. Collectively, this series of experiments indicates that GDB stimulates immune system including macrophage activation.     

ent-Kaurenoids from the roots of Cacalia pilgeriana

Two new ent-kaurenoids,19-acetoxyl-ent-3β,17-dihydroxykaur-15-ene (1), 19-acetoxyl-ent-3β-hydroxykaur-15-en-17-al (2), together with seven known ent-kaurenoids: ent-kaur-16-en-19-al (3), ent-kaur-16-en-19-oic acid (4), ent-kauran-16β,17-diol (5), ent-15β, 16β-epoxy-17-hydroxykauran-19-oic acid (6),19-acetyl-ent-3β-hydroxyl-kaur-16-ene (7), ent-3β,19-dihydroxykaur-16-ene (8), ent-17-hydroxykaur-15-ene (9), were isolated from Cacalia pilgeriana. Their structures were elucidated by spectroscopic methods including 2D NMR spectral analysis.     

Physicochemical,Pharmacokinetic and Cytotoxicity of the Compounds Isolated from an Endophyte Fusarium oxysporum: In Vitro and In Silico Approaches

The present study was intended to characterize the secondary metabolites of the endophyte Fusarium oxysporum isolated from the plant Aglaonema hookerianum Schott. And to investigate the cytotoxic and other pharmacological properties of the isolated compounds as part of the drug discovery and development process. Different chromatographic techniques were adopted to isolate the bioactive compounds that were identified by spectroscopic techniques. The cytotoxic properties of the compounds were assessed in the Vero cell line via the trypan blue method. Moreover, physicochemical, pharmacokinetic, bioactivity and toxicity profiles of the compounds were also investigated through in silico approaches. After careful spectral analysis, the isolated compounds were identified as 3β,5α-dihydroxy-ergosta-7,22-dien-6-one (1), 3β,5α,9α-trihydroxy-ergosta-7,22-dien-6-one (2), p-hydroxybenzaldehyde (3), 3-(R)-7-butyl-6,8-dihydroxy-3-pent-11-enylisochroman-1-one (4) and beauvericin (5). An in vitro study in the Vero cell line revealed that the presence of the compounds reduced the number of cells, as well as the percentage of viable cells, in most cases. An in silico cytotoxic analysis revealed that compounds 1, 2 and 5 might be explored as cytotoxic agents. Moreover, compounds 3 and 4 were found to be highly mutagenic. The present study suggested that further thorough investigations are necessary to use these molecules as leads for the cytotoxic drug development process.     

Identification of enhanced cytokine generation following sepsis. Dream of magic bullet for mortality prediction and therapeutic evaluation

BACKGROUND AND THE PURPOSE OF THE STUDY: sepsis is one of the most widespread and lethal disease in Intensive Care Units (ICU). Based on pathophisyology of sepsis, it seems that routine laboratory tests combined with analysis of pro-inflammatory cytokines plasma levels, help clinicians to have more information about disease progress and its correct management. METHODS: This was a prospective observational study to determine the predictive role of Tumor Necrosis Factor alpha (TNF-α), Interleukin (IL)-1β and IL-6 as three main pro-inflammatory cytokines and Acute Physiology and Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assessment (SOFA) as two scoring systems in mortality of critically ill patients with severe sepsis. Fifty and five patients with criteria of severe sepsis were included in this study. An exclusion criterion was post Cardiopulmonary Resuscitation (CPR) status. Cytokines (TNF-α, IL-1β and IL-6) were assayed in the first, third and seventh days in blood of patients. RESULTS AND MAJOR CONCLUSION: Among three measured cytokines, sequential levels of TNF-α and IL-6 showed significant differences between survivors and nonsurvivors. IL-6 had a good correlation with outcome and scoring systems during the period of this study. The areas under the receiver operating characteristic (AUROC) curve indicated that APACHE II (0.858, 0.848, 0.861) and IL-6 (0.797, 0.799, 0.899) had discriminative power in prediction of mortality during sequental measured days. Multiple logestic regression analysis identified that evaluation of APACHE II and TNF-α in the first day and APACHE II and IL-6 in the third and seventh days of severe septic patients are independent outcome predictors. Results of this study suggest that IL-6 and APACHE II are useful cytokine and scoring systems respectively in prediction of mortality and clinical evaluation of severe septic patients.     

17β-Estradiol inhibition of PPARγ-induced adipogenesis and adipocyte-specific gene expression

Aim:

To investigate the molecular interaction of peroxisome proliferator-activated receptor γ (PPARγ) with 17β-estradiol (E) in the regulation of adipogenesis.

Methods:

Female ovariectomized (OVX) mice and differentiated 3T3-L1 adipocytes were treated with combinations of the PPARγ agonist troglitazone or E, and the variables and determinants of adipogenesis were measured using in vivo and in vitro approaches.

Results:

Troglitazone (250 mg·kg⁻¹·d⁻¹ for 13 weeks) decreased the size of adipocytes without the change in white adipose tissue (WAT) mass and increased the expression of adipocyte-specific genes, such as PPARγ, adipocyte fatty acid binding protein, and lipoprotein lipase, compared with OVX control mice. E (0.05 mg/pellet, sc implanted) significantly reduced WAT mass, adipocyte size, and adipose marker gene expression. When mice were concomitantly treated with troglitazone and E, E blunted the effects of troglitazone on WAT mass, adipocyte size, and adipose PPARγ target gene expression. Consistent with the in vivo data, E (10 μmol/L) treatment inhibited lipid accumulation and the expression of adipocyte-specific genes caused by troglitazone (10 μmol/L) in 3T3-L1 cells. E (10 μmol/L) also decreased troglitazone-induced PPARγ reporter activity through both estrogen receptor (ER) α and ERβ. Mechanistic studies indicated that E (0.1 μmol/L) decreased the DNA binding of PPARγ induced by troglitazone (1 μmol/L) and inhibited the recruitment of the PPARγ coactivator CREB-binding protein.

Conclusion:

These results suggest that in vivo and in vitro treatment of E interferes with the actions of PPARγ on adipogenesis by down-regulating adipogenesis-related genes, which are mediated through the inhibition of PPARγ coactivator recruitment. In addition, it is likely that the activities of PPARγ activators may be enhanced in estrogen-deficient states.     

Inhibition of COX-2 expression by endocannabinoid 2-arachidonoylglycerol is mediated via PPAR-γ

BACKGROUND AND PURPOSE

Endocannabinoids have both anti-inflammatory and neuroprotective properties against harmful stimuli. We previously demonstrated that the endocannabinoid 2-arachidonoylglycerol (2-AG) protects hippocampal neurons by limiting the inflammatory response via a CB₁ receptor-dependent MAPK/NF-κB signalling pathway. The purpose of the present study was to determine whether PPARγ, an important nuclear receptor, mediates 2-AG-induced inhibition of NF-κB phosphorylation and COX-2 expression, and COX-2-enhanced miniature spontaneous excitatory postsynaptic currents (mEPSCs).

EXPERIMENTAL APPROACH

By using a whole-cell patch clamp electrophysiological recording technique and immunoblot analysis, we determined mEPSCs, expression of COX-2 and PPARγ, and phosphorylation of NF-kB in mouse hippocampal neurons in culture.

KEY RESULTS

Exogenous and endogenous 2-AG-produced suppressions of NF-κB-p65 phosphorylation, COX-2 expression and excitatory synaptic transmission in response to pro-inflammatory interleukin-1β (IL-1β) and LPS were inhibited by GW9662, a selective PPARγ antagonist, in hippocampal neurons in culture. PPARγ agonists 15-deoxy-Δ^12,14-prostaglandin J₂ (15d-PGJ₂) and rosiglitazone mimicked the effects of 2-AG on NF-κB-p65 phosphorylation, COX-2 expression and mEPSCs, and these effects were eliminated by antagonism of PPARγ. Moreover, exogenous application of 2-AG or elevation of endogenous 2-AG by inhibiting its hydrolysis with URB602 or JZL184, selective inhibitors of monoacylglycerol lipase (MAGL), prevented the IL-1β- and LPS-induced reduction of PPARγ expression. The 2-AG restoration of the reduced PPARγ expression was blocked or attenuated by pharmacological or genetic inhibition of the CB₁ receptor.

CONCLUSIONS AND IMPLICATIONS

Our results suggest that CB₁ receptor-dependent PPARγ expression is an important and novel signalling pathway in endocannabinoid 2-AG-produced resolution of neuroinflammation in response to pro-inflammatory insults.

LINKED ARTICLES

This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-7     

γ-分泌酶抑制剂在肺纤维化上皮间质转化中的作用

目的 检测体外转化生长因子（TGF）-β1诱导肺纤维化上皮间质转化（EMT）的形成情况并检测Notch信号特异性抑制剂γ-分泌酶抑制剂（DAPT）对其影响及可能机制。方法 将A549细胞分成对照组（RPMI 1640完全培养基培养）、TGF-β1组（在含有10 μg/L TGF-β1的RPMI 1640培养基中培养）、TGF-β1+DAPT组（在含有10 μg/L TGF-β1和2 μmol DAPT的RPMI 1640培养基中培养）、DAPT组（在含有2 μmol DAPT的RPMI 1640培养基中培养）。通过倒置显微镜观察细胞形态,实时荧光定量逆转录聚合酶链反应检测肺泡上皮细胞特异性蛋白E-钙黏合素以及间质细胞特异性蛋白α-肌动蛋白（α-SMA）mRNA相对表达水平,Western blot检测E-钙黏合素以及α-SMA蛋白表达水平。结果 倒置显微镜检查示,对照组细胞呈多边形,铺路石样,细胞间连接紧密;TGF-β1组细胞呈梭行,纺锤状,细胞间连接减少;TGF-β1+DAPT组仅有少量细胞呈梭形,多数细胞形态与对照组相似;DAPT组细胞形态大致同对照组。与对照组相比,TGF-β1组α-SMA蛋白及mRNA表达增加,而E-钙黏合素蛋白及mRNA表达减弱（P<0.05）;与TGF-β1组比较,TGF-β1+DAPT组α-SMA蛋白及mRNA表达水平降低,而E-钙黏合素蛋白及mRNA表达水平增加（P<0.05）;DAPT组与对照组2指标的蛋白与mRNA相对表达水平差异无统计学意义（P>0.05）。结论 TGF-β1可诱导肺上皮间质转化,而Notch信号抑制剂DAPT能够阻断、部分或全部逆转这一过程。     

Blockade of adipocyte differentiation by cordycepin

BACKGROUND AND PURPOSE

Cordyceps militaris has the potential to suppress differentiation of pre-adipocytes. However, the active entities in the extract and the underlying mechanisms of its action are not known. Hence, we investigated whether and how cordycepin (3′-deoxyadenosine), a constituent of C. militaris, inhibits adipogenesis.

EXPERIMENTAL APPROACH

Differentiation of 3T3-L1 pre-adipocytes and pre-adipocytes in primary cultures was induced by Insulin, dexamethasone and IBMX, and these were used as in vitro models of adipogenesis. The effects of cordycepin on adipogenesis were examined with particular focus on the regulation of CCAAT/enhancer-binding protein β (C/EBPβ) and PPARγ.

KEY RESULTS

Cordycepin suppressed the lipid accumulation and induction of adipogenic markers that occurred on differentiation of pre-adipocytes and also blocked the down-regulation of a pre-adipocyte marker. This anti-adipogenic effect was reversible and mediated by an adenosine transporter, but not A₁, A₂ or A₃ adenosine receptors. This effect of cordycepin was not reproduced by other adenosine-related substances, including ATP, ADP and adenosine. Early induction of the adipogenic C/EBPβ–PPARγ pathway was suppressed by cordycepin. Blockade of mTORC1 via inhibition of PKB (Akt) and activation of AMP kinase was identified as the crucial upstream event targeted by cordycepin. In addition to its negative effect on adipogenesis, cordycepin suppressed lipid accumulation in mature adipocytes.

CONCLUSIONS AND IMPLICATIONS

These results suggest that the anti-adipogenic effects of cordycepin occur through its intervention in the mTORC1-C/EBPβ–PPARγ pathway. Cordycepin, by blocking both adipogenesis and lipid accumulation, may have potential as a therapeutic agent for effective treatment of obesity and obesity-related disorders.     

Long-term baicalin administration ameliorates metabolic disorders and hepatic steatosis in rats given a high-fat diet

Aim:

Baicalin, one of the major flavonoids in Scutellaria baicalensis, possesses antioxidant and anti-inflammatory properties. However, the effects of baicalin on metabolic disorders and hepatic steatosis have not been investigated.

Methods:

Body weight was examined in high-fat diet (HFD)-fed rats with or without baicalin treatment. At the end of the experiment, serum biochemical parameters, liver histology and lipid profile were analyzed to assess whether the animals were suffering from metabolic disorders or hepatic steatosis. In the liver, the phosphorylation of AMP activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) and the gene expression of some enzymes involved in lipogenesis were examined. The effects of baicalin on the phosphorylation of AMPK and lipid accumulation induced by high glucose in human hepatoma HepG2 cells were also examined.

Results:

Baicalin (80 mg/kg) administered ip for 16 weeks suppressed body weight gain in HFD-fed rats. Weight reduction was accompanied by the reduction of visceral fat mass. Baicalin significantly decreased the elevated serum cholesterol, free fatty acid and insulin concentrations caused by the HFD. Baicalin also suppressed systemic inflammation by reducing the serum level of tumor necrosis factor α. Baicalin reduced hepatic lipid accumulation, enhanced the phosphorylation of AMPK and ACC and down-regulated genes involved in lipogenesis, including fatty acid synthase and its upstream regulator SREBP-1c. In HepG2 cells, baicalin (5 and 10 μmol/L) increased the phosphorylation of AMPK and decreased lipid accumulation following the addition of high glucose.

Conclusion:

Our study suggests that baicalin might have beneficial effects on the development of hepatic steatosis and obesity-related disorders by targeting the hepatic AMPK.     

Cilostazol Decreases Ethanol-Mediated TNFalpha Expression in RAW264.7 Murine Macrophage and in Liver from Binge Drinking Mice

Alcoholic hepatitis is a leading cause of liver failure in which the increased production of tumor necrosis factor α (TNFα) plays a critical role in progression of alcoholic liver disease. In the present study, we investigated the effects of cilostazol, a selective inhibitor of type III phosphodiesterase on ethanol-mediated TNFα production in vitro and in vivo, and the effect of cilostazol was compared with that of pentoxifylline, which is currently used in clinical trial. RAW264.7 murine macrophages were pretreated with ethanol in the presence or absence of cilostazol then, stimulated with lipopolysacchride (LPS). Cilostazol significantly suppressed the level of LPS-stimulated TNFα mRNA and protein with a similar degree to that by pentoxifylline. Cilostazol increased the basal AMP-activated protein kinase (AMPK) activity as well as normalized the decreased AMPK by LPS. AICAR, an AMPK activator and db-cAMP also significantly decreased TNFα production in RAW264.7 cells, but cilostazol did not affect the levels of intracellular cAMP and reactive oxygen species (ROS) production. The in vivo effect of cilostazol was examined using ethanol binge drinking (6 g/kg) mice model. TNFα mRNA and protein decreased in liver from ethanol gavaged mice compared to that from control mice. Pretreatment of mice with cilostazol or pentoxifylline further reduced the TNFα production in liver. These results demonstrated that cilostazol effectively decrease the ethanol-mediated TNFα production both in murine macrophage and in liver from binge drinking mice and AMPK may be responsible for the inhibition of TNFα production by cilostazol.     

Bezafibrate enhances proliferation and differentiation of osteoblastic MC3T3-E1 cells via AMPK and eNOS activation

Aim:

To investigate the effects of bezafibrate on the proliferation and differentiation of osteoblastic MC3T3-E1 cells, and to determine the signaling pathway underlying the effects.

Methods:

MC3T3-E1 cells, a mouse osteoblastic cell line, were used. Cell viability and proliferation were examined using MTT assay and colorimetric BrdU incorporation assay, respectively. NO production was evaluated using the Griess reagent. The mRNA expression of ALP, collagen I, osteocalcin, BMP-2, and Runx-2 was measured using real-time PCR. Western blot analysis was used to detect the expression of AMPK and eNOS proteins.

Results:

Bezafibrate increased the viability and proliferation of MC3T3-E1 cells in a dose- and time-dependent manner. Bezafibrate (100 μmol/L) significantly enhanced osteoblastic mineralization and expression of the differentiation markers ALP, collagen I and osteocalcin. Bezafibrate (100 μmol/L) increased phosphorylation of AMPK and eNOS, which led to an increase of NO production by 4.08-fold, and upregulating BMP-2 and Runx-2 mRNA expression. These effects could be blocked by AMPK inhibitor compound C (5 μmol/L), or the PPARβ inhibitor GSK0660 (0.5 μmol/L), but not by the PPARα inhibitor MK886 (10 μmol/L). Furthermore, GSK0660, compound C, or N^G-nitro-L-arginine methyl ester hydrochloride (L-NAME, 1 mmol/L) could reverse the stimulatory effects of bezafibrate (100 μmol/L) on osteoblast proliferation and differentiation, whereas MK886 only inhibited bezafibrate-induced osteoblast proliferation.

Conclusion:

Bezafibrate stimulates proliferation and differentiation of MC3T3-E1 cells, mainly via a PPARβ-dependent mechanism. The drug might be beneficial for osteoporosis by promoting bone formation.     

Z-ligustilide attenuates lipopolysaccharide-induced proinflammatory response via inhibiting NF-KB pathway in primary rat microglia

Aim:

To investigate the anti-inflammatory effect of Z-ligustilide (LIG) on lipopolysaccharide (LPS)-activated primary rat microglia.

Methods:

Microglia were pretreated with LIG 1 h prior to stimulation with LPS (1 μg/mL). After 24 h, cell viability was tested with MTT, nitric oxide (NO) production was assayed with Griess reagent, and the content of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein (MCP-1) was measured with ELISA. Protein expression of the nuclear factor-κB (NF-κB) p65 subunit, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) was detected with immunocytochemistry 1 h or 24 h after LPS treatment.

Results:

LIG showed a concentration-dependent anti-inflammatory effect in LPS-activated microglia, without causing cytotoxicity. Pretreatment with LIG at 2.5, 5, 10, and 20 μmol/L decreased LPS-induced NO production to 75.9%, 54.4%, 43.1%, and 47.6% (P<0.05 or P< 0.01), TNF-α content to 86.2%, 68.3%, 40.1%, and 39.9% (P<0.01, with the exception of 86.2% for 2.5 μmol/L LIG), IL-1β content to 31.5%, 27.7%, 0.6%, and 0% (P<0.01), and MCP-1 content to 84.4%, 50.3%, 45.1%, and 42.2% (P<0.05 or P<0.01), respectively, compared with LPS treatment alone. LIG (10 μmol/L) significantly inhibited LPS-stimulated immunoreactivity of activated NF-κB, COX-2, and iNOS (P<0.01 vs LPS group).

Conclusion:

LIG exerted a potent anti-inflammatory effect on microglia through inhibition of NF-κB pathway. The data provide direct evidence of the neuroprotective effects of LIG and the potential application of LIG for the treatment of the neuroinflammatory diseases characterized by excessive microglial activation.