三七总皂苷通过抗炎和调血脂作用抑制大鼠动脉粥样硬化形成

目的:利用高脂饮食叠加炎症刺激诱发大鼠动脉粥样硬化(AS)模型,在转录水平及信号转导方面探讨三七皂苷(PNS)防治炎性因素诱发AS的分子机制。方法:实验分为对照组、模型组和治疗组3组,分别腹腔注射给予无菌医用液体石蜡、酵母多糖(Zym,20mg/kg,1次/3天)、Zym(20mg/kg,1次/3天) PNS(100mg/kg,1次/天)。所有大鼠均喂食含3%胆固醇的高脂饲料。9周后,取血测定血脂水平和血液粘度;应用定量PCR法测定腹主动脉组织中抑制性核转录因子(IκBα)mRNA、心房肽(ANF)mR- NA、基质金属蛋白酶7(MMP7)mRNA以及炎性因子和脂肪酸合成酶(FAS)mRNA的表达;用Western Blotting法检测IκBα的表达。结果:Zym刺激引起大鼠血清总胆固醇、甘油三酯、全血粘度与血浆比粘度均显著升高,IκBαmRNA及其蛋白表达均明显降低,ANF mRNA、MMP7 mRNA和FAS mRNA表达均明显升高。与模型组相比,PNS能明显升高血脂水平、全血及血浆粘度,促进IκBαmRNA与蛋白以及ANF mRNA表达,抑制MMP7 mRNA和FAS mRNA表达。结论:PNS对炎症免疫诱发的AS有显著防治作用,其作用机制与促进IκBα的表达从而抑制相关炎症因子的生成有关,PNS对FAS的表达调节可能是其降脂的主要机制之一。     

炎症促进大鼠动脉粥样硬化初期内皮功能病变机制研究

目的:观察炎症因素诱导大鼠动脉粥样硬化发病过程中对血管内皮细胞的影响。方法:实验分为单纯高脂对照组和炎症组,分别腹腔注射给予无菌医用液体石蜡和酵母多糖(Zym,20mg/kg,1次/3天)。所有大鼠均喂食含3%胆固醇的高脂饲料,共8周。透射电镜观察主动脉超微结构;应用定量PCR法测定腹主动脉组织中诱导型一氧化氮合酶(iNOS)mRNA、血管细胞粘附分子(VCAM)-1 mRNA、以及基质金属蛋白酶7(MMP7)mRNA的表达。结果:炎症组可见游走于内膜下层的平滑肌细胞和和吞噬脂质颗粒的单核细胞,单纯高脂对照组仅见内皮细胞损伤和退行性变,未见内膜下层形成泡沫细胞,AS样病变较炎症组轻。与对照组相比,炎症组动脉壁iNOS mRNA表达降低,VCAM-1 mRNA及MMP7 mRNA标大量显著升高。结论:炎症刺激能够损伤动脉血管内皮细胞,诱导炎症因子释放增加,促进动脉粥样硬化的发生。     

构建抑制NF-κB信号通路的药物筛选模型

NF—κB已被证明在肿瘤和炎症过程中起到至关重要的作用。因此,建立抑制NF-κB信号通路的药物筛选模型至关重要。利用荧光素酶报告基因技术与蛋白印迹技术分别探索TNFα处理浓度及时间对NF-κB报告基因表达和NF—κB抑制亚单位It〈Bα降解的影响,进而构建NF—κB信号通路抑制剂药物筛选模型。实验结果表明,0．01nmol／LTNFα作用24h即能刺激HEK293T细胞中NF—κB报告基因较高水平的表达,且其表达量与TNFα的剂量和处理时间呈正相关性;0．01nmol／LTNFα作用5min即能使Panc-28细胞中IκBα明显降解,20min～30min几乎降解完全,之后IκBα含量又开始增加。NF-κB阳性抑制剂藤黄酸验证表明NF-κB萤光素酶报告基因检测筛选体系和NF—κB抑制亚单位降解筛选体系两种体系稳定可行。结果证明,两种模型可以用于NF—κB信号通路抑制剂药物的筛选。     

人参皂苷Rg1通过Wnt3a/β-catenin信号通路影响糖尿病大鼠肾损伤的机制研究

摘要 目的：研究人参皂苷Rg1通过Wnt3aβ-catenin信号通路影响糖尿病大鼠肾损伤的机制。方法：将60只SD大鼠随机分为对照组、模型组、厄贝沙坦组、人参皂苷Rg1组。模型组、厄贝沙坦组、人参皂苷Rg1组经腹腔注射链脲佐菌素建立糖尿病模型,给予对照组、模型组生理盐水灌胃,厄贝沙坦组接受厄贝沙坦干预,人参皂苷Rg1组接受人参皂苷Rg1干预,各组均连续干预8周。比较各组大鼠血糖血脂水平、Wnt3a/β-catenin表达、肾损伤及肾脏炎症指标。结果：与对照组相比,人参皂苷Rg1组、厄贝沙坦组、模型组空腹血糖、总胆固醇、甘油三酯水平依次升高（P<0.05）。与对照组相比,人参皂苷Rg1组、厄贝沙坦组、模型组Wnt3a、β-catenin表达水平依次升高（P<0.05）。与对照组相比,人参皂苷Rg1组、厄贝沙坦组、模型组血肌酐、尿素氮、24 h尿蛋白水平依次升高（P<0.05）。与对照组相比,人参皂苷Rg1组、厄贝沙坦组、模型组C反应蛋白、单核细胞趋化蛋白-1、肿瘤坏死因子-α水平依次升高（P<0.05）。结论：人参皂苷Rg1可有效调节糖尿病大鼠血糖血脂水平,抑制肾脏炎症反应,缓解肾损伤,调控Wnt3a/β-catenin信号通路可能是其发挥作用的重要机制。     

BET蛋白通过调控NF-κB通路参与炎症基因转录

目的:探讨特异性抑制溴结构域(bromodomain and extra-terminal,BET)蛋白对血管内皮细胞激活与早期动脉粥样硬化形成的作用及其分子机制。方法:1.原代分离培养脐静脉内皮细胞和小鼠心脏血管内皮细胞后用肿瘤坏死因α(TNFα)刺激模拟炎症过程,以小分子化合物JQ1特异性抑制BET蛋白,分组如下:(1)对照组;(2)TNFα(25 ng/m L)处理组;(3)TNFα+JQ1处理组。采用Realtime-PCR及流式细胞术检测各组细胞炎症因子m RNA及蛋白水平的表达,采用5XκB荧光素酶报告基因检测各组核转录因子kappa B(NF-κB)转录活性。2.LDL受体基因敲除(LDLR-/-)小鼠随机分为2组:JQ1组(n=8,JQ1腹腔注射,50 mg/kg,每天一次)和对照组(n=8,DMSO溶媒组),同时给予高胆固醇饮食8周,采用免疫组化方法检测主动脉弓部血管细胞黏附分子-1(VCAM-1)表达水平。结果:与对照组相比,TNFα组炎症因子m RNA、蛋白表达明显上调(P0.01),使用JQ1干预后,炎症因子E选择素(E-selectin)、P选择素(P-selectin)、VCAM-1及白细胞介素-8(IL-8)m RNA及蛋白表达均明显下调(P0.01)。LDLR-/-小鼠高脂饮食诱导8周后JQ1显著下调了主动脉弓部VCAM-1蛋白表达。5XκB荧光素酶报告基因结果显示,与TNFα(-)相比,TNFα(+)组荧光素酶报告基因活性增强,JQ1可以显著下调报告基因活性(P0.01)。结论:BET蛋白通过调控NF-κB信号通路参与了血管内皮炎症基因转录;抑制BET蛋白下调了NF-κB目的基因表达从而减轻了内皮激活及高脂诱导的早期动脉粥样硬化病理改变。     

淫羊藿总黄酮通过AMPK/SIRT1/NFκB信号通路减轻自然衰老大鼠睾丸组织炎症反应

探讨淫羊藿总黄酮(Total flavonoids of Epimedium,TFE)对自然衰老大鼠睾丸组织中AMPK/SIRT1/NFκB信号通路的影响及其抗炎作用。将40只18月龄雄性SD大鼠随机分为TFE低、中、高剂量组和自然衰老组,每组10只。另取10只2月龄雄性SD大鼠作为青年对照组。TFE低、中、高剂量组分别以10、20、40 mg/kg剂量灌胃给药,青年对照组和自然衰老组大鼠均灌胃给予质量分数为1%羧甲基纤维素钠溶液,持续给药4个月。HE染色观察大鼠睾丸组织形态,Western blot法检测各组大鼠睾丸组织中AMPK、p-AMPK、SIRT1、acetylNFκBp65、IL-1β、TNFα蛋白表达水平。结果显示,与自然衰老组相比,TFE低、中、高剂量组大鼠睾丸组织形态结构均有明显改善,TFE可促进大鼠睾丸组织内p-AMPK和SIRT1蛋白表达,显著降低acetyl-NFκBp65及其下游炎症因子IL-1β、TNFα蛋白表达水平。实验结果表明,TFE可减轻自然衰老大鼠睾丸组织炎症反应,其机制可能与调控AMPK/SIRT1/NFκB信号通路有关。     

甘草酸对糖尿病大鼠心肌细胞凋亡和炎症反应的影响

目的:探讨甘草酸对糖尿病大鼠心肌细胞凋亡和炎症反应的影响。方法:雄性Wistar大鼠30只,随机分为3组:对照(Control)组、糖尿病(DM)组和甘草酸(Gly)组。以高脂高糖饮食及腹腔注射链尿佐菌素30 mg/kg建立糖尿病模型。模型建立后10周,Gly组每日予甘草酸200 mg/kg灌胃,DM和Control组用等量生理盐水灌胃。结果:与Control组比较,DM组大鼠体重下降,血糖、甘油三酯、总胆固醇及血浆心肌酶水平升高,心肌细胞凋亡增加,心肌Bax、IL-1β、TNF-α、p-NF-κB、HMGB1增高而Bcl-2下降(P0.05);与DM组比较,Gly组大鼠体重增加,血糖、甘油三酯和总胆固醇及血浆心肌酶水平下降,心肌细胞凋亡减少,心肌Bax、IL-1β、TNF-α、p-NF-κB、HMGB1下降而Bcl-2升高(P0.05)。结论:甘草酸治疗可减轻糖尿病大鼠心肌细胞凋亡及炎症反应。     

神经鞘磷脂合成酶2基因的缺失有抗动脉粥样硬化及抗炎作用

本文以神经鞘磷脂合成酶2基因敲除(sphingomyelin synthase 2 knockout,SMS2-/-)小鼠为研究对象,旨在探讨神经鞘磷脂(sphingomyelin,SM)代谢与动脉粥样硬化(atherosclerosis,AS)发生之间的关系。雄性3月龄SMS2-/-小鼠为实验组,同性别同月龄C57BL/6J(wild-type,WT)小鼠为对照组。用高脂高胆固醇饮食喂养两组小鼠,并给予胆盐以促进AS斑块的形成。喂养3个月后解剖观察小鼠主动脉弓,剖开胸腹主动脉进行油红染色以观察AS斑块发生情况;同时收集小鼠腹腔巨噬细胞,用脂多糖刺激后,提取核蛋白用Western blot方法检测核因子κB(nuclear factor-κB,NFκB)p65含量;高脂饮食喂养前后,小鼠断尾取血,酶法测定血清SM水平,用血脂检测试剂盒检测血脂水平。结果显示,高脂饮食喂养3个月后,SMS2-/-小鼠的主动脉弓和胸腹主动脉很少形成AS斑块,而WT小鼠则产生了较多AS斑块;高脂饮食喂养前后,SMS2-/-小鼠血清SM水平均明显低于WT小鼠(P0.05),而血脂水平并无显著性差异(P0.05);高脂饮食喂养后,SMS2-/-小鼠腹腔巨噬细胞经过脂多糖刺激产生的NFκBp65含量明显低于WT小鼠。以上结果提示,SMS2基因的缺失有抗AS及抗炎作用,因而可能成为临床治疗的新策略。     

人参皂苷Rg1对游离脂肪酸诱导非酒精性脂肪肝细胞炎症的改善作用及机制研究

该研究探讨人参皂苷Rg1对非酒精性脂肪性肝细胞炎症反应的作用及其分子机制。用1 mmol/L游离脂肪酸处理HepG2和L02细胞24 h,再用20μg/mL或40μg/mL人参皂苷Rg1处理6 h;设置对照组、模型组、低剂量Rg1组、高剂量Rg1组。全自动生化仪检测各组细胞上清谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)的含量;酶联免疫吸附法测定细胞上清IL-1β、IL-6、TNF-α。RT-qPCR及Western blot检测NF-κB通路相关基因及蛋白的改变。免疫荧光染色观察NF-κB核转移;Western blot检测各组胞质与胞核内的NF-κB P65蛋白的表达。与对照组相比,模型组培养上清炎症指标明显增加(P<0.05);Rg1能降低炎症指标的表达(P<0.05)。Rg1能减少游离脂肪酸诱导的NF-κB磷酸化及其下游IL-1β、IL-6、TNF-α的表达,减少NF-κB P65从胞质向胞核的转移(P<0.05)。Rg1可通过抑制NF-κB活化减少NASH细胞模型炎症反应,为非酒精性脂肪性肝炎的治疗提供了可能的靶点。     

Trans‐repression of NFκB pathway mediated by PPARγ improves vascular endothelium insulin resistance

Previous study has shown that thiazolidinediones (TZDs) improved endothelium insulin resistance (IR) induced by high glucose concentration (HG)/hyperglycaemia through a PPARγ‐dependent‐NFκB trans‐repression mechanism. However, it is unclear, whether changes in PPARγ expression affect the endothelium IR and what the underlying mechanism is. In the present study, we aimed to address this issue. HG‐treated human umbilical vascular endothelial cells (HUVEC) were transfected by either PPARγ‐overexpressing (Ad‐PPARγ) or PPARγ‐shRNA‐containing (Ad‐PPARγ‐shRNA) adenoviral vectors. Likewise, the rats fed by high‐fat diet (HFD) were infected by intravenous administration of Ad‐PPARγ or Ad‐PPARγ‐shRNA. The levels of nitric oxide (NO), endothelin‐1 (ET‐1) and cytokines (TNFα, IL‐6, sICAM‐1 and sVCAM‐1) and the expression levels of PPARγ, eNOS, AKT, p‐AKT, IKKα/β and p‐IKKα/β and IκBα were examined; and the interaction between PPARγ and NFκB‐P65 as well as vascular function were evaluated. Our present results showed that overexpression of PPARγ notably increased the levels of NO, eNOS, p‐AKT and IκBα as well as the interaction of PPARγ and NFκB‐P65, and decreased the levels of ET‐1, p‐IKKα/β, TNFα, IL‐6, sICAM‐1 and sVCAM‐1. In contrast, down‐expression of PPARγ displayed the opposite effects. The results demonstrate that the overexpression of PPARγ improves while the down‐expression worsens the endothelium IR via a PPARγ‐mediated NFκB trans‐repression dependent manner. The findings suggest PPARγ is a potential therapeutic target for diabetic vascular complications.     

β-淀粉样蛋白对BV2小胶质细胞促炎作用的研究

目的探讨β-淀粉样蛋白(β-amyloid,Aβ)促进BV2小胶质细胞产生炎性因子IL-1β和TNFα的作用机制。方法体外培养BV2小胶质细胞,应用Aβ1-42作用于BV2小胶质细胞,或用吡咯烷二硫代氨基甲酸盐(PDTC)预孵育再给予Aβ1-42刺激,实时荧光定量反转录聚合酶链反应法(RT–PCR)检测IL-1β和TNFαmRNA表达;免疫印迹法(Western blot)检测胞核中NF-κB p65及其抑制蛋白胞浆中IkBα的表达。结果 Aβ1-42作用于BV2小胶质细胞后,Westernblot显示胞浆内IkBα表达下降,胞核内NF-κB p65表达明显增加,RT-PCR测定IL-1β和TNFαmRNA的表达增加;给予NF-κB信号通路特异阻断剂PDTC后,胞浆IkBα的下降和胞核内NF-κB p65的增加均被抑制,同时IL-1β和TNFαmRNA的表达亦受到抑制,PDTC的抑制效果呈剂量依赖性。结论 Aβ可通过激活小胶质细胞NF-κB信号通路促进IL-1β和TNFα的表达。     

Dll4蛋白在高脂饮食喂养大鼠脂肪组织炎症中的作用

目的 探讨Delta-like ligand 4（Dll4）蛋白在高脂饮食喂养大鼠脂肪组织中的表达及其与脂肪组织炎症的关系.方法 将20只SPF级雄性Sprague-Dawley大鼠随机分为正常饮食组（SD,n=10）和高脂饮食组（HFD,n=10）喂养16w后,应用免疫组化及Western blot方法检测脂肪组织中Dll4及炎症通路NF-κB磷酸化、IL-6的表达.结果 免疫组化结果显示,HFD组Dll4表达量显著升高（P〈0.001）;Western blot结果与免疫组化结果相一致,Dll4蛋白表达量是SD组的1.34倍（P〈0.01）;磷酸化核转录因子NF-κB表达水平升高,HFD组为SD组的2.03倍（P〈0.01）;HFD组炎症细胞因子IL-6水平明显升高,为SD组的3.02倍（P〈0.01）.结论 高脂饮食可增加脂肪组织中Dll4蛋白表达,促进了脂肪组织中炎症的发生.     

Baicalin effects on rats with spinal cord injury by anti‐inflammatory and regulating the serum metabolic disorder

Baicalin had neuroprotective effects on inhibiting neuronal cell apoptosis induced by spinal cord ischemic injury. This study aimed to explore the protective effects of Baicalin on rats with spinal cord injury (SCI) and its mechanism of action. The recovery of spinal cord nerve function in rats was evaluated by the Basso, Beattie, and Bresnahan (BBB) score and the combine behavioral score (CBS). The expressions of cytokines tumor necrosis factor α (TNF‐α), interleukin‐1β (IL‐1β), and IL‐6 were detected by the enzyme‐linked immunosorbent assay method. Expressions of inflammation‐related proteins were detected by Western blot. Multivariate statistical analysis was performed for serum metabolites. The BBB and CBS score results showed that Baicalin had a certain improvement on rats with SCI. SCI symptoms were significantly improved in low‐dose and high‐dose groups. The levels of TNF‐α, IL‐1β, and IL‐6 in the SCI group were significantly increased. The expressions of NF‐κB p65, NF‐κB p50, p‐IκBα, and IKKα in the SCI group showed the opposite trend compared with the low‐dose and high‐dose groups. Compared with the sham group, glutamine, levels of 3‐OH‐butyrate, N‐acetylaspartate, and glutathione were significantly reduced, and the levels of glutamate and betaine were significantly increased in the SCI group. When Baicalin was administered, the contents of glutamine synthase (GS) and glutaminase (GLS) were significantly reduced, indicating that Baicalin had the effect of improving GS and GLS. Baicalin has protective effects on improving SCI and lower extremity motor function, has a significant anti‐inflammatory effect, and regulates the serum metabolic disorder caused by SCI in rats.     

Green tea extract treatment reduces NFκB activation in mice with diet-induced nonalcoholic steatohepatitis by lowering TNFR1 and TLR4 expression and ligand availability

NFκB-mediated inflammation contributes to liver injury during nonalcoholic steatohepatitis (NASH). We hypothesized that antiinflammatory activities of green tea extract (GTE) during NASH would lower tumor necrosis factor receptor-1 (TNFR1)- and Toll-like receptor-4 (TLR4)-mediated NFκB activation. Male C57BL6/J mice (6 weeks old) were fed a low-fat (LF) or high-fat (HF) diet for 12 weeks to induce NASH. They were then randomized to continue on these diets supplemented with 0 or 2% GTE (n=10/group) for an additional 8 weeks prior to evaluating NASH, NFκB inflammation and TNFR1 and TLR4 receptor complexes and their respective ligands, TNFα and endotoxin. HF feeding increased (P<.05) serum alanine aminotransferase (ALT) activity and histological evidence of NASH compared with LF controls. HF-mediated increases in NFκB p65 phosphorylation were also accompanied by increased serum TNFα and endotoxin concentrations, mRNA expression of hepatic TNFR1 and TLR4 and MyD88 protein levels. GTE in LF mice had no effect (P>.05) on liver histology or inflammatory responses. However, GTE in HF mice decreased biochemical and histological parameters of NASH and lowered hepatic p65 phosphorylation in association with decreased serum TNFα, mRNA expression of TNFR1 and TLR4 and MyD88 protein. GTE in HF-fed mice also lowered serum endotoxin and up-regulated mRNA expression of duodenal occludin and zonula occluden-1 and ileal occludin and claudin-1 that were otherwise lowered in expression by HF feeding. These data suggest that dietary GTE treatment reduces hepatic inflammation in NASH by decreasing proinflammatory signaling through TNFR1 and TLR4 that otherwise increases NFκB activation and liver injury.     

NF-κB介导非对称性二甲基精氨酸上调大鼠主动脉诱导型一氧化氮合酶的表达

目的探讨非对称性二甲基精氨酸(ADMA)上调大鼠主动脉诱导型一氧化氮合酶(iNOS)的表达是否是通过激活NF-κB实现的。方法 Wistar大鼠50只随机分为四组:①对照组(n=10):标准饲料喂养。②H组(n=12):高脂饲料喂养。③A+H组(n=14):予ADMA[0.2mg/kgd]灌胃,高脂饲料喂养。④P+A+H组(n=14):予吡咯烷二硫代氨基甲酸盐(pyrrolidine dithiocarbamate,PDTC)[40mg/kgd]腹腔注射、ADMA[0.2mg/kgd]灌胃、高脂饲料喂养。对照组、H组予等体积的生理盐水灌胃及腹腔注射、A+H组给予等体积的生理盐水腹腔注射。18周后麻醉大鼠、取主动脉。以实时荧光定量PCR和Westen blotting分别检测iNOS mRNA和蛋白表达,以电泳迁移率变动分析(EMSA)和增强化学发光法(ECL)检测NF-κB活性。结果①A+H组iNOS mRNA和蛋白表达量较对照组和H组增加(P<0.05),P+A+H组较A+H组iNOSmRNA和蛋白表达量降低(P<0.05)。②A+H组NF-κB活性较对照组和H组显著升高(P<0.05),P+A+H组NF-κB活性较A+H组明显降低(P<0.05)③相关分析:NF-κB活性与iNOS mRNA和蛋白表达量呈正相关(相关系数r分别为0.854、0.876,P<0.05)。结论 ADMA可能通过激活NF-κB途径上调iNOS表达,从而促进动脉粥样硬化的发生发展。     

TNFα increases hypothalamic PTP1B activity via the NFκB pathway in rat hypothalamic organotypic cultures

In obesity, levels of tumor necrosis-factor α (TNFα) are well known to be elevated in adipose tissues or serum, and a high-fat diet (HFD) reportedly increases TNFα expression in the hypothalamus. The expression levels of hypothalamic protein tyrosine phosphatase 1B (PTP1B), a negative regulator of leptin and insulin signaling, are also elevated by HFD, and several lines of evidence support a relationship between TNFα and PTP1B. It remains unclear however how TNFα acts locally in the hypothalamus to regulate hypothalamic PTP1B expression and activity. In this study, we examined whether TNFα can regulate PTP1B expression and activity using rat hypothalamic organotypic cultures. Incubation of cultures with TNFα resulted in increases in mRNA expression, protein levels and activity of PTP1B in a dose- and time-dependent manner, respectively compared with controls. TNFα-induced PTP1B protein levels were not influenced by co-incubation with the sodium channel blocker tetrodotoxin, indicating that the action of TNFα is independent of action potentials. TNFα also increased phosphorylation of p65, a subunit of nuclear factor-κB (NFκB), in a dose- and time-dependent manner. While incubation with inhibitors of NFκB did not affect basal levels of either p65 phosphorylation or PTP1B expression, it markedly suppressed both TNFα-induced p65 phosphorylation and PTP1B expression to almost basal levels. These data suggest that TNFα acts on the hypothalamus to increase hypothalamic PTP1B expression and activity via the NFκB pathway, and that TNFα-mediated induction of NFκB in the hypothalamus may cause leptin and insulin resistance in the hypothalamus by increasing hypothalamic PTP1B activity.     

Dietary soy and tea mitigate chronic inflammation and prostate cancer via NFκB pathway in the Noble rat model

Chronic inflammation and nuclear factor-kappa B (NFκB) have been implicated in prostate cancer development; thus, dietary factors that inhibit NFκB may serve as effective chemo-preventative agents. Prostate cancer risk is significantly lower in Asian countries compared to the United States, which has prompted interest in the potential chemopreventative action of Asian dietary components such as soy and green tea. This study examined the effects of dietary soy and tea on NFκB activation and inflammation in vivo using a hormone-induced rat model for prostate cancer. Male Noble rats implanted with estradiol and testosterone were divided into 4 dietary groups: control, soy, tea, or soy+tea. NFκB activation and inflammatory cytokines were measured post implantation. The combination of soy and tea suppressed NFκB p50 binding activity and protein levels via induction of IκBα. Soy and tea also decreased prostate inflammatory infiltration, increased Bax/BcL2 ratio and decreased protein expression of tumor necrosis factor-alpha, interleukin (IL)-6 and IL-1β compared to control. Soy and tea attenuated prostate malignancy by decreasing prostate hyperplasia. These effects were not apparent in groups treated with soy or tea alone. The ongoing in vivo studies thus far suggest that combination of foods, such as soy and tea, may inhibit hormone-induced proinflammatory NFκB signals that contribute to prostate cancer development.     

Parthenolide attenuates LPS-induced fever, circulating cytokines and markers of brain inflammation in rats

Parthenolide, a sesquiterpene lactone, has been reported to exhibit a variety of anti-inflammatory and immunomodulatory effects. To test the effect of parthenolide on brain inflammatory responses, brain oxidative stress and fever, we treated rats with parthenolide (1 mg/kg), simultaneously or 1 h prior to a systemic (i.p.) challenge with a moderate dose (100 μg/kg) of lipopolysaccharide (LPS). The initial hypothermia was exaggerated; the second phase of the biphasic LPS-induced fever and circulating interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) were significantly attenuated only in parthenolide-pretreated animals. In the hypothalamus, markers of NFκB/NF-IL6 pathway activation (inhibitor κBα, NF-IL6 and the serin/threonin kinase-like protein mRNA expression) and markers of oxidative stress (including nuclear respiratory factor 1) and NFκB immunoreactivity were significantly reduced while NF-IL6 immunoreactivity and suppressor of cytokine signaling 3 mRNA expression remained unaltered, 8 h after LPS-stimulation with parthenolide-pretreatment. Importantly, this response was accompanied by decreased mRNA expression of the rate limiting enzyme in prostaglandin synthesis, cyclooxygenase 2 (COX2), known for its critical role in fever induction pathways. A direct action of parthenolide on brain cells was also confirmed in a primary neuro-glial cell culture of the vascular organ of the lamina terminalis a pivotal brain structure for fever manifestation with a leaky blood-brain barrier. In summary, pretreatment with parthenolide attenuates the febrile response during LPS-induced systemic inflammation by reducing circulating IL-6 and TNFα and decreasing hypothalamic NFκB/NF-IL6 activation, oxidative stress and expression of COX2. Thus parthenolide appears to have the potential to reduce brain inflammation.