Anticancer Effect of Curcumin on Human B Cell non-Hodgkin＇s Lymphoma

Curcumin(diferuloylmethane)isayellowpig mentfromtherhizomesofturmeric(Curcumalon gaL.)andisamajorcomponentofvariousrecipesforcurry.Curcuminhasbeenreportedtohaveanumberofpharmacologicaleffectsincludinganti inflammatory,anti oxidant,antiviral,antibacterialandantitumoreffects,whichisattractingmoreandmoreattentionofinvestigators.Curcuminhasin hibitoryeffectsonmanytumorssuchasfoestom achcancer,esophagealcancer,coloncancer,livercancer,mammarytumor,bladdercancer,skincanceraswellasDMBA inducedleukem…     

姜黄素潜在毒性作用的研究进展

姜黄素是源自植物姜黄的酚类物质，被广泛用作天然色素、调味剂、香料及防腐剂。一直以来，人们更多地关注姜黄素具有的多种生物活性的研究、开发和利用。然而有关其潜在的毒性作用及其机制的研究也不容忽视，本文就此方面的研究进展给予浅评。     

姜黄色素对阿霉素肾病大鼠转录因子活性的影响

目的探讨肾病综合征(NS)大鼠肾皮质组织转录因子核因子-κB(NF-κB)、活化蛋白-1(AP-1)DNA结合活性变化及姜黄色素(CC)对其活性的影响。方法应用凝胶电泳迁移率法(EMSA)和同位素放射自显影等方法,检测阿霉素肾病大鼠模型形成过程的不同时间点NF-κB、AP-1 DNA结合活性、血液生化指标和尿蛋白量,并观察CC治疗后上述指标的变化。结果大鼠经尾静脉注射阿霉素后7 d,24 h尿蛋白排泄量开始升高,21 d出现大量蛋白尿、低蛋白血症、高血脂症。注射阿霉素后第7天肾皮质组织中NF-κB活性开始升高,第28天达高峰,明显高于正常对照组(P<0.01);AP-1活性于第14天明显升高,第28天达高峰,明显高于正常对照组(P<0.01),但CC对NF-κB活性及24 h尿蛋白排泄量无影响。结论阿霉素肾病大鼠肾皮质中NF-κB、AP-1 DNA结合活性异常升高;CC能够抑制AP-1活性,但不能抑制NF-κB活性及减少尿蛋白排泄量。     

姜黄素对大鼠癫痫持续状态后海马神经元丢失的影响

目的：探讨姜黄素对大鼠癫痫持续状态（SE）后海马神经元丢失的影响。方法：Sprague-Dawley（SD）大鼠90只随机均分为癫痫组、姜黄素治疗组和对照组。建立氯化锂-匹罗卡品大鼠SE模型。应用尼氏染色方法动态观察SE后海马CA1区和CA3区存活神经元数量的动态变化。结果：与对照组相比，SE组CA1及CA3区存活神经元数量于SE后2h无明显变化，4h明显减少（P〈0．01），24h和72h后神经元数量减少最为明显；姜黄素组SE后6，24，72hCA3及CA1区存活神经元与对照组相比也有明显减少（P〈0．01），但较SE组多（P〈0．01）。结论：姜黄素对SE后海马神经元具有保护作用。     

高效液相色谱法测定姜黄通脉胶囊中姜黄素的含量

目的建立高效液相色谱法测定姜黄通脉胶囊中姜黄素含量的方法。方法采用高效液相色谱法,使用Diamonsil-C18色谱柱,流动相为乙腈-水(用磷酸调节pH值为2.5)(48∶52),流速为1.0mL/min,检测波长为430nm。结果姜黄素在2.675～53.500μg/mL浓度范围内呈良好的线性关系(相关系数r=0.9999),平均回收率为99.78%,相对标准偏差为0.59%。结论本方法简便可靠、分离度较好、结果稳定,可用于姜黄通脉胶囊的质量控制。     

姜黄素对BGC-823及MCF-7细胞内钙离子信号波动的研究

研究姜黄素诱导肿瘤细胞凋亡的可能机制 ,利用 fluo-4/AM荧光钙离子探针测定 BGC-82 3细胞与MCF-7细胞经姜黄素处理后的钙波变化 ,以及 BGC-82 3细胞经姜黄素处理后细胞内钙分布的变化。结果表明姜黄素可引起细胞内钙库的动员和钙离子的释放。提示 :细胞内源性钙离子的释放可能是姜黄素诱导细胞凋亡的信号调控机制之一     

Biochemical mechanism of modulation of human P-glycoprotein (ABCB1) by curcumin I, II, and III purified from Turmeric powder

P-glycoprotein (Pgp, ABCB1) is an ATP-dependent drug efflux pump linked to development of multidrug resistance (MDR) in cancer cells. Previously [Biochem Pharmacol 2002;64:573-82], we reported that a curcumin mixture could modulate both function and expression of Pgp. This study focuses on the effect of three major curcuminoids--curcumin I, II and III purified from a curcumin mixture--on modulation of Pgp function in a multidrug resistant human cervical carcinoma cell line (KB-V1). The similar IC(50) values for cytotoxicity of curcuminoids of KB-V1, and KB-3-1 (parental drug sensitive cell line) suggest that these curcuminoids may not be substrates for Pgp. Treating the cells with non-toxic doses of curcuminoids increased their sensitivity to vinblastine only in the Pgp expressing drug resistant cell line, KB-V1, and curcumin I retained the drug in KB-V1 cells more effectively than curcumin II and III, respectively. Effects of each curcuminoid on rhodamine123, calcein-AM, and bodipy-FL-vinblastine accumulation confirmed these findings. Curcumin I, II and III increased the accumulation of fluorescent substrates in a dose-dependent manner, and at 15 microM, curcumin I was the most effective. The inhibitory effect in a concentration-dependent manner of curcuminoids on verapamil-stimulated ATPase activity and photoaffinity labeling of Pgp with the [(125)I]-iodoarylazidoprazosin offered additional support; curcumin I was the most potent modulator. Taken together, these results indicate that curcumin I is the most effective MDR modulator among curcuminoids, and may be used in combination with conventional chemotherapeutic drugs to reverse MDR in cancer cells.     

Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration

Studies in vitro and in animal models of colorectal and hepatocellular cancers suggest that curcumin is an effective chemopreventive agent. In this pilot trial, we investigated whether oral administration of curcumin results in concentrations of the agent in normal and malignant human liver tissue, which are sufficient to elicit pharmacological activity. In total, 12 patients with hepatic metastases from colorectal cancer received 450-3600 mg of curcumin daily, for 1 week prior to surgery. Levels of curcumin and its metabolites were measured by HPLC in portal and peripheral blood, bile and liver tissue. Curcumin was poorly available, following oral administration, with low nanomolar levels of the parent compound and its glucuronide and sulphate conjugates found in the peripheral or portal circulation. While curcumin was not found in liver tissue, trace levels of products of its metabolic reduction were detected. In patients who had received curcumin, levels of malondialdehyde-DNA (M(1)G) adduct, which reflect oxidative DNA changes, were not decreased in post-treatment normal and malignant liver tissue when compared to pretreatment samples. The results suggest that doses of curcumin required to furnish hepatic levels sufficient to exert pharmacological activity are probably not feasible in humans.     

In vitro and in vivo anti-tumoral effect of curcumin against melanoma cells

Curcumin, the active ingredient from the spice turmeric (Curcuma longa Linn), is known to be an anti-oxidant and an anti-inflammatory agent. It has been demonstrated recently to possess anti-angiogenic effects and pro-apoptotic activities against Ehrlich ascites tumor cells. In the current study, curcumin was found to be cytotoxic in vitro for B16-R melanoma cells resistant to doxorubicin either cultivated as monolayers or grown in three-dimensional (3-D) cultures (spheroids). We have demonstrated that the cytotoxic effect observed in the 2 culture types can be related to the induction of programmed cell death. In our in vivo studies, we examined the effectiveness of a prophylactic immune preparation of soluble proteins from B16-R cells, or a treatment with curcumin as soon as tumoral appearance, alone or in combination, on the murine melanoma B16-R. The combination treatment resulted in substantial inhibition of growth of B16-R melanoma, whereas each treatment by itself showed little effect. Moreover, animals receiving the combination therapy exhibited an enhancement of their humoral anti-soluble B16-R protein immune response and a significant increase in their median survival time (> 82.8% vs. 48.6% and 45.7% respectively for the immunized group and the curcumin-treated group). Our study shows that curcumin may provide a valuable tool for the development of a therapeutic combination against the melanoma.     

Protective effects of curcumin and photo-irradiated curcumin on circulatory lipids and lipid peroxidation products in alcohol and polyunsaturated fatty acid-induced toxicity

Alcohol is a neurotoxin associated with significant morbidity and mortality. Ethanol is found to induce a dose dependent increase in lipid peroxidation (LPO). The elevation in lipid peroxidative products and the loss of antioxidant defense potential are enhanced when alcohol is taken along with polyunsaturated fatty acid (PUFA) or heated PUFA. The present study was undertaken to evaluate the effects of curcumin and photo-irradiated curcumin on alcohol and PUFA induced LPO and lipid pro fi les in plasma. The levels of vitamin C and E were decreased significantly in alcohol + raw as well as heated PUFA groups. The treatment with curcumin and photo-irradiated curcumin (IC) increased their levels significantly. The increase was more significant in the IC group than the curcumin group. The levels of cholesterol, phospholipids (PL), triglycerides (TG), free fatty acids (FFA), thiobarbituric acid reactive substances (TBARS) and hydroperoxides (HP) were increased significantly in alcohol + raw as well as heated PUFA groups and the treatment with curcumin and IC, brought back the levels. But the IC reduced the levels more significantly than curcumin. Thus, our results indicate that IC is a more potent antioxidant than curcumin.