姜黄素对胰腺癌细胞株生长的抑制作用及可能机制

目的研究姜黄素对胰腺癌细胞增殖的体外抑制作用．探讨其抗癌作用的分子生物学机制。方法MTT法、Annexln V-FITC／PI双染法、细胞周期分析法、透射电镜等方法检测姜黄素对Pan02细胞生长和凋亡的影响．RT—PCR检测姜黄素对Pan02细胞Bax，Bcl-2，COX2，Bak．Survfvin mRNA的表达。结果(1)姜黄素抑制Pan02细胞生长呈量效关系；(2)姜黄素处理组细胞周期发生改变．G2／M期细胞比例增多、S期细胞比例减少；(3)姜黄素处理组细胞发生凋亡．表现为凋亡细胞比例增多，形态上出现明显细胞凋亡：(4)姜黄素处理组Pan02细胞Bcl-2和Bak mRNA表达水平显著下降．COX-2．Bax mRNA表达水平显著升高，Survivin mRNA的表达水平没有变化。结论姜黄素能够抑制Pan02细胞增殖，它可改变细胞周期、诱导细胞凋亡．Bcl-2家族而不是IAP家族(至少不是Survivin)参与了Pan02细胞的凋亡过程。     

姜黄素与LY294002联合应用对前列腺癌PC-3细胞体外生长的影响

【摘要】 目的〓探讨姜黄素与PI3K/Akt抑制剂LY294002联合应用对前列腺癌PC-3细胞体外生长的影响。方法〓根据给药不同将实验分为对照组、姜黄素组、LY294002组和姜黄素组+LY294002联合组,分别加入等量的培养基、25 μmoL/L姜黄素、25 μmoL/L的LY294002和两种混合液。采用MTS法检测各组细胞的增殖情况、流式细胞仪术检测各组细胞凋亡情况、q-PCR测定各组细胞中NF-κB、P53及caspase-9的表达情况。结果〓姜黄素组、LY组和联合组的细胞增值率均较对照组明显降低,且联合组明显低于两个单独用药组(P<0.05)。姜黄素与LY294002联合作用前列腺癌PC-3细胞后,细胞总凋亡率较姜黄素及LY294002单独使用后明显增加(P值均<0.05)。联合用药组的NF-κB表达量明显低于两单独用药组(P<0.05),而P53和caspase-9的表达量均明显高于两单独用药组(P<0.05)。结论〓姜黄素与LY294002联合使用较两种药物单独使用更能有效抑制前列腺癌PC-3细胞的体外生长,作用机制可能是通过抑制NF-κB的表达从而抑制细胞增殖,并增加P53和caspase-9的表达从而促进细胞凋亡来实现的。     

星点设计-效应面法优化姜黄素牛血清白蛋白纳米粒的制备工艺

摘 要 目的：星点设计 效应面法优化姜黄素牛血清白蛋白纳米粒(CUR BSA NPs)的制备工艺,考察其外观粒径分布及体外释放特性。 方法: 以牛血清白蛋白为载体材料,姜黄素作为模型药物,采用去溶剂法制备CUR BSA NPs,通过星点设计 效应面法优化其制备工艺,并对CUR BSA NPs的外观形态、粒径分布、包封率、载药量及体外释放进行研究。 结果: CUR BSA NPs制备的最佳工艺条件为牛血清白蛋白浓度10 mg·ml-1,乙醇体积7.79 ml,搅拌速度915 r·min-1。根据优化处方工艺制备的CUR BSA NPs外观呈圆形或类圆形,平均粒径（203.93±83.10） nm,Zeta电位-40～-50 mV;包封率为86.53%,载药量为3.89%。 结论: 最优工艺条件下制备的CUR BSA NPs包封率和载药量高,粒径分布较为均匀,体外释放试验表明与姜黄素原料药相比制备的CUR BSA NPs有良好的缓释特性。     

A protective study of curcumin associated with Cr6+ induced oxidative stress,genetic damage,transcription of genes related to apoptosis and histopathology of fish,Channa punctatus (Bloch, 1793)

Ameliorative potential of curcumin against Cr⁶⁺-induced eco-toxicological manifestations was assessed in liver of exposed Channa punctatus (Actinopterygii) in six groups for 45 d; Group I as control. Group II with 3 mg/L of curcumin; group III with 7.89 mg/L of Cr⁶⁺. Groups IV, V and VI were simultaneously co-exposed with 7.89 mg/L of Cr⁶⁺ and three different curcumin concentrations, 1, 2, and 3 mg/L, respectively. In group III, SOD-CAT, GR significantly (p < 0.05) increased; decreased GSH level; elevated MN and AC frequencies; and a significant (p < 0.05) up-regulation of cat (2.72-fold), p53 (1.73-fold), bax (1.33-fold) and apaf-1 (2.13-fold) together with a significant (p < 0.05) down-regulation of bcl-2 (0.51-fold). Co-exposure significantly (p < 0.05) brought down activities of SOD-CAT, GR, raised GSH, decreased micronuclei and apoptotic frequencies along with recovery of histopathological anomalies in liver. This study establishes the protective role of curcumin against Cr⁶⁺-induced hepatotoxicity in fish.     

Curcumin attenuates adhesion molecules and matrix metalloproteinase expression in hypercholesterolemic rabbits

Curcumin, the yellow substance found in turmeric, possesses antioxidant, anti-inflammation, anticancer, and lipid-lowering properties. Because we hypothesized that curcumin could ameliorate the development of atherosclerosis, the present study focused on the effects and potential mechanisms of curcumin consumption on high-cholesterol diet–induced atherosclerosis in rabbits. During our study, New Zealand white rabbits were fed 1 of 3 experimental diets: a normal diet, a normal diet enriched with 1% cholesterol (HCD), or an HCD supplemented with 0.2% curcumin. At the end of 8 weeks, blood samples were collected to determine the levels of serum lipids, cytokines, and soluble adhesion molecule levels. Gene expression of adhesion molecules and matrix metalloproteinases (MMPs) in aortas were measured by quantitative real-time polymerase chain reaction and Western blot. Compared with the HCD group, rabbits fed an HCD supplemented with 0.2% curcumin had significantly less aortic lesion areas and neointima thickening. Curcumin reduced the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and oxidized low-density lipoprotein cholesterol in serum by 30.7%, 41.3%, 30.4%, and 66.9% (all P < .05), respectively, but did not affect high-density lipoprotein cholesterol levels. In addition, curcumin attenuated HCD-induced CD36 expression, circulating inflammatory cytokines, and soluble adhesive molecule levels. Curcumin reduced the mRNA and protein expression of intracellular adhesion molecule-1, vascular cell adhesion molecule-1, P-selectin, and monocyte chemotactic protein-1, and it inhibited HCD-induced up-regulation of MMP-1, MMP-2, and MMP-9. Our results demonstrate that curcumin exerts an antiatherosclerotic effect, which is mediated by multiple mechanisms that include lowering serum lipids and oxidized low-density lipoprotein, thus modulating the proinflammatory cytokine levels and altering adhesion molecules and MMP gene expression.     

姜黄素对胶质瘤U87细胞增殖和迁移能力的影响

目的：探讨姜黄素对胶质瘤细胞系U87细胞增殖及迁移能力的影响。方法应用CCK-8比色法检测经正常培养液及含不同浓度（25、50、100μmol/L）姜黄素的培养液培养24、48、72 h后的U87细胞的存活率;应用细胞划痕实验检测100μmol/L姜黄素对U87细胞迁移能力的影响;将20只SD大鼠制备成胶质瘤模型,随机分成对照组及实验1、2、3组,每组5只,模型制备后第7天对照组给予生理盐水灌胃,实验1、2、3组分别给予姜黄素100、200、300 mg/kg灌胃,1/d,连续14 d,第15天用microPET-CT对载瘤大鼠肿瘤体积进行测定。结果 U87细胞存活率随着培养液中姜黄素浓度的升高和培养时间的延长而降低（ P〈0．05）;给予100μmol/L姜黄素的培养液培养24和48 h后U87细胞迁移度均低于空白对照组（P〈0．05）;实验2、3组肿瘤体积均小于实验1组和对照组（P〈0．05）。结论姜黄素可抑制胶质瘤U87细胞的增殖及迁移。     

The anti-tumor efficacy of curcumin when delivered by size/charge-changing multistage polymeric micelles based on amphiphilic poly(β-amino ester) derivates

Modifying positive surface charge and reducing bulk size of nanoparticles has been proven beneficial to cancer cellular delivery, but meanwhile results in fast clearance and unspecific distribution in body after intravenous injection. How to balance these problems is still a challenge to construct an ideal nano-scaled drug delivery system in cancer treatment. Herein, we developed a multistage drug delivery system to enhance anticancer efficacy of curcumin (CUR), which could intelligently alter its size and surface charge after long-circulation and extravasation from leaky blood vessels at tumor sites. This micellar system was constructed by amphiphilic and pH-sensitive methoxy poly(ethylene glycol)-poly(lactide)-poly(β-amino ester) (MPEG-PLA-PAE) copolymers. As compared with MPEG-PLA micelles, MPEG-PLA-PAE micelles displayed several advantageous characteristics for drug delivery and treatment. We found that CUR-loaded MPEG-PLA-PAE micelles remained stable in murine plasma at 37 °C even with high drug loading. More interestingly, when the media pH decreased from 7.4 to 5.5, the micelles shrank from 171.0 nm to 22.6 nm and their surface charge increased to 24.8 mV meanwhile, which resulted in the significantly improved cell uptake of CUR by human breast cancer MCF-7 cells. Using indocyanine green (ICG) as a fluorescence probe, it was observed that MPEG-PLA-PAE micelles experienced longer circulation than MPEG-PLA micelles followed by accumulation at tumors with stronger fluorescence intensity. Consequently, MPEG-PLA-PAE micelles achieved enhanced cancer growth inhibition of 65.6% in vivo. All these findings demonstrated the potential of size/charge–changing MPEG-PLA-PAE micelles as a promising drug delivery system for tumor-targeted therapy.     

Ehrlich ascites carcinoma as model for studying the cardiac protective effects of curcumin nanoparticles against cardiac damage in female mice

While clinical innovation has improved, cancer or malignant growth stays a genuine medical issue and has been perceived as a significant factor in mortality and morbidity. Current work aimed to define the cardiac defensive effects of curcumin nanoparticles (Cur Nps) against EAC induced cardiac toxicity, injury, and alterations in apoptosis, proliferation, and cytokines immunoreactivity. Forty female mice were aimlessly and equally divided into four groups [Gp1, Control; Gp2, Cur NPs; Gp3, Ehrlich ascites carcinoma (EAC); Gp4, Co‐treatment of EAC with Cur NPs (Cur NPs + EAC)]. Serum lactate dehydrogenase (LDH), phosphocreatine kinase (CPK), creatine kinase myoglobin (CK‐MB), alkaline phosphatase (ALP), glutamic oxaloacetic transaminase (GOT), cholesterol, triglycerides, potassium ions, cardiac injury, P53, vascular endothelial growth factor protein (VEGF), Bax, and tumor necrosis factor alpha (TNFα) expressions were significantly elevated while sodium ions levels were significantly depleted in EAC when compared to control. Co‐treatment of EAC with Cur NPs (Cur NPs + EAC) improved these parameters as compared with EAC group. So, our results indicate that; Cur NPs induced protection to the blood and heart tissue during Ehrlich ascites carcinoma.     

Curcumin ameliorates impaired insulin/IGF signalling and memory deficit in a streptozotocin-treated rat model

Increased serum insulin levels and reduced peripheral insulin activities seen in insulin resistance syndrome are associated with age-dependent cognitive impairment and Sporadic Alzheimer’s Disease (SAD), suggesting a disturbance in the insulin signalling system in the brain and possibly being one of the causes of dementia. Therefore, the streptozotocin (STZ)-induced animal may be an appropriate model for the investigation of SAD and related dementia. This study was designed to investigate the beneficial effect of Curcumin (CUR), a neuroprotective agent, on intracerebroventricular (ICV) STZ-induced cognitive impairment in rats. For this purpose, adult male Wistar rats were bilaterally ICV injected with STZ (3 mg/kg). An artificial cerebrospinal fluid (aCSF) was given to the control group (SHAM) instead of STZ on days 1 and 3. Learning and memory performance were assessed using the “passive avoidance task” and the “Morris water maze test”. After confirmation of acquisition impairment with these tests, the STZ group was divided into two subgroups: STZ + vehicle (Vh) and STZ + CUR. The rats in the SHAM and STZ + Vh groups were administered intraperitoneally with 0.5 ml Vh and the rats in the STZ + CUR group were treated intraperitoneally with CUR (300 mg kg⁻¹ day⁻¹ in Vh) for 10 days starting from the 25th day after STZ injection. The Morris water maze test was reapplied on the 35th day after STZ injection and all of the rats were sacrificed on day 36 for quantitation of IGF-1 and for histopathological evaluation. Rats in the STZ + CUR group were found to have a higher performance in cognitive tests than rats in the STZ + Vh group (P < 0.01). In parallel with the cognitive tests, IGF-1 levels were decreased in all of the STZ-injected groups (1.78 ± 0.34) compared to the SHAM group (3.46 ± 0.41). In contrast, CUR treatment significantly increased IGF-1 levels (P < 0.001). The degree of neuronal loss decreased after CUR treatment compared to the SHAM group (P < 0.02). These results clearly indicate that CUR treatment is effective in reducing the cognitive impairment caused by STZ in rats, and may be a potential therapeutic agent for altering neurodegeneration in SAD.     

Proteomic analysis identifies proteins associated with curcumin-enhancing efficacy of irinotecan-induced apoptosis of colorectal cancer LOVO cell

Objective: We wish to implement a proteomics-based approach to pick and identify the proteins associated with curcumin enhancing efficacy of irinotecan inducing apoptosis of colorectal cancer LOVO cells, and further explore their synergy mechanism by bioinformatics. Methods: A colorectal cancer cell line (LOVO cell) treated by curcumin combined with irinotecan in different ways respectively was used as our comparative model. Protein spots were analyzed through MALDI-TOF/TOF. The location and function of differential protein spots were analyzed through UniProt database. Protein-protein interactions were examined through String software. Results: A total of 54 protein spots differentially expressed with 1.5-fold difference were picked, 11 of which were repeated. They mainly were involved in intracellular calcium pathways, cellular respiratory chain pathway and intracellular redox reaction pathways of LOVO cell. According to the function of various protein points, combining with varying curves of protein points in each treatment groups, we selected five interesting protein spots, 4 of which exists Protein-protein interactions, and they were close to the formation and reduction of disulfides in intracellular endoplasmic reticulum (ER). Conclusion: We selected preliminary but comprehensive data about differential expression protein spots of LOVO cell. Among these, the five interesting differential expression protein spots identified in this study may provide new insight into LOVO cell therapeutic biomarkers. Curcumin may suppress GSTM5 expression to enhance the lethal effect of irinotecan on LOVO cells, and maybe their combination via the affection of PDI and PRDX4 to disturb the formation and reduction of disulfides results in inducing apoptosis of LOVO cell.