姜黄素与消化系统肿瘤的研究进展

姜黄素是一种疏水多酚,从姜黄中提取的姜黄磺胺类草药。半个世纪以来大量的研究表明姜黄素在体外及体内显示了各种诸如抗炎、细胞活素的释放、抗氧化、免疫调节、促进凋亡以及抗血管生成的特性。姜黄素同样也被证明是耐药性和放疗不敏感性的调解者。同样,在各种临床试验研究中证明了姜黄素抗肿瘤的作用,本文就姜黄素在消化系统肿瘤中的抗肿瘤机制做一综述。     

姜黄素抗肿瘤作用及机制研究进展

姜黄素是从草本植物姜黄、莪术等根茎中提取的一种植物多酚,有着广泛的药理作用,具有抗心血管疾病、抗肿瘤、抗微生物、抗抑郁、抗炎、抗氧化等生物学功能。抗肿瘤是姜黄素主要生物活性之一,抗肿瘤机制主要有:抑制肿瘤细胞增殖,诱导肿瘤细胞凋亡,抗肿瘤侵袭及转移,逆转肿瘤细胞耐药性及增加对化疗的敏感性等。本文就其抗肿瘤机制的研究进行综述,为姜黄素的进一步开发利用提供基础。     

姜黄素诱导肿瘤细胞凋亡的研究进展

姜黄素是从姜科植物的根茎姜黄中提取的一种植物多酚,具有抗炎、抗氧化、抗凝、抗动脉粥样硬化、抗肿瘤等药理作用。本文综述了姜黄素诱导肿瘤细胞凋亡的分子生物学机制研究进展。     

姜黄素现代药理研究进展

姜黄素是从姜黄属的姜黄中提取的一种醇类物,是唯一一种具酚基和醌基的天然药物。姜黄素毒性低,耐受性好,具有抗氧化、抗炎、降血脂、抗肿瘤、抑制血管增生,保肝等药理作用,特别是抗肿瘤作用,因此日益受到广泛的关注。本文对其理化性质,药效及毒性研究作一综述。     

姜黄素对COPD抗炎抗氧化作用研究进展

慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是一种以进行性、不完全可逆性气流受限为主要特征的慢性炎症性肺部疾病。该病是有害气体或颗粒导致肺部异常炎症有关[1]。姜黄素是从姜科植物姜黄中提取的一种酚类化合物,有抗氧化、抗炎、抗肿瘤等作用,近年来研究表明姜黄素对香烟诱导COPD大鼠有抗炎抗氧化作用。     

姜黄素治疗代谢综合征的研究进展

姜黄素是从姜黄中提取的一种多酚类物质,近年来对姜黄素的研究日趋广泛,已明确具有抗肿瘤,抗炎,抗氧化、降糖、降脂等多种药理作用,在临床上广泛应用于治疗肿瘤、肥胖、糖尿病等多种疾病.代谢综合征是一组以代谢紊乱为特征的症候群,包括中心性肥胖、糖脂代谢异常、高血压、非酒精性脂肪肝等,这些病理状态长期发展,可进一步导致心、脑血管患病率明显升高,研究发现姜黄素能够改善代谢综合征.现就近年来有关姜黄素治疗代谢综合征的研究进展综述如下.     

姜黄素增溶方法的研究进展

姜黄素是姜黄属植物主要生物活性成分之一,常用作天然色素和食品、化妆品的添加剂,具有抗肿瘤、抗炎、防治心血管系统疾病等广泛的药理作用。而溶解度、生物利用度偏低在很大程度上限制了其临床推广应用,如何解决这些问题是近年来的研究热点。本文通过查阅国内外相关文献,对近年来姜黄素提取过程和制剂过程增溶技术的研究进展进行综述,为其进一步开发利用提供一定的参考依据。     

姜黄素衍生物及复合物抗肿瘤的研究

近年来,包括姜黄素、姜黄素衍生物及复合物在内的姜黄家族的抗肿瘤能力已被越来越多的学者所关注,成为现代抗肿瘤研究的热点。姜黄素的去甲氧基化、氨基化、烯酮类、萜烯类等官能团修饰能通过提高姜黄素的水溶性和稳定性,提高其生物利用度,改善药代动力学,增强其抗癌能力。氧钒(vanadyl,IV)复合物、烷氧基联苯/姜黄素偶联物、姜黄素与磺丁基醚-β环糊精包被而成的复合物也均对肿瘤细胞有不同的杀伤抑制作用。现对几年来国内外姜黄素衍生物及复合物抗肿瘤的研究进行总结,旨在为进一步认识姜黄素的抗肿瘤机制,并对姜黄素进行改造提供思路。     

姜黄根茎中姜黄素类成分含量的产地差异及其与环境因子的CCA分析

采用HPLC法对产自四川崇州和犍为、广东四会、广西玉林和博白及金秀、云南马关的姜黄(Curcuma longaL.)根茎中姜黄素类成分含量进行测定,并利用典范对应分析方法(CCA)研究了不同产地姜黄根茎中姜黄素类成分含量与地理-气候因子及根际土壤养分因子间的相关性。结果表明:不同产地根际土壤中有机质、全N、全P和全K含量分别为14.03～32.79、0.39～0.92、0.56～1.55和2.29～9.23 g.kg-1,根际土壤养分含量差异较明显;姜黄多生长在中性偏酸、水肥性能良好的土壤中。姜黄根茎中姜黄素、去甲氧基姜黄素和双去甲氧基姜黄素含量及姜黄素类成分总含量的平均值分别为1.53%、0.42%、0.67%和2.61%;不同产地姜黄根茎中姜黄素类成分含量有显著差异,且同一产地采自不同采样点及不同采样时间的样品姜黄素类成分的含量也有一定差异。姜黄素类成分总含量以广西博白产姜黄根茎最高(4.29%)、广东四会产姜黄根茎最低(1.73%)。CCA分析结果表明:在经度、纬度、海拔、年均气温、极端最高温、极端最低温、年降水量、日照时数和无霜期等地理-气候因子中,年均气温和极端最低温与姜黄素类成分含量极显著正相关;而在pH值及有机质、全N、全P、全K含量等根际土壤养分因子中,有机质含量与姜黄素类成分含量极显著正相关。分析结果显示:影响姜黄根茎中姜黄素类成分含量的主要环境因子是年均气温、极端最低温和根际土壤的有机质含量。     

姜黄素类似物抑制肿瘤细胞增殖的细胞学机制研究进展

姜黄素是一种具有多种生物学效应的天然多酚类物质,但其较低的稳定性和生物利用率等因素限制了其实际临床应用,具有同样类似活性的姜黄素类似物或衍生物目前越来越受到关注。已发现多种化学合成姜黄素类似物小分子能在体外和体内抑制肿瘤细胞增殖,具有潜在的抗肿瘤活性。自噬和凋亡是细胞两种面对外界刺激采取的主动自主行为,近来发现大部分姜黄素类似物小分子能通过诱导自噬或(和)凋亡通路途径引起细胞死亡,该文结合笔者课题组前期研究结果就姜黄素类似物诱导的细胞学机制进行综述,以期为未来有关姜黄素类似物的抗肿瘤药理作用研究提供参考。     

Curcumin in plasma and urine: quantitation by high-performance liquid chromatography

Curcumin, a derivative of the plant Curcuma longa, is used extensively in the food industry. It is a major component of curry powder, and research has shown that curcumin may prevent cancer and other chronic diseases. We have developed a robust automated analytical method for the determination of curcumin in plasma and urine. The method involves extracting the curcumin from 0.2 ml sample volume with ethyl acetate/methanol organic solvents, and use of an internal standard, beta-17-estradiol acetate. Analysis utilizes a reversed-phase C(18) column and UV detection at 262 nm. Performance characteristics have been assessed. The assay is linear from 0.2 to 7.0 microgram/ml. The coefficient of variation for intra- and inter-day assays is <7.5%. The average recovery of curcumin from plasma and urine is greater than 96%. The data presented in this report demonstrate that the method provides rapid, sensitive, precise and accurate measurements of curcumin concentrations in plasma and urine.     

Oral curcumin supplementation improves fine motor function in the middle-aged rhesus monkey

Aged individuals experience decreased fine motor function of the hand and digits, which could result, in part, from the chronic, systemic state of inflammation that occurs with aging. Recent research for treating age-related inflammation has focused on the effects of nutraceuticals that have anti-inflammatory properties. One particular dietary polyphenol, curcumin, the principal curcuminoid of the spice turmeric, has been shown to have significant anti-inflammatory effects and there is mounting evidence that curcumin may serve to reduce systemic inflammation. Therefore, it could be useful for alleviating age-related impairments in fine motor function. To test this hypothesis we assessed the efficacy of a dietary intervention with a commercially available optimized curcumin to ameliorate or delay the effects of aging on fine motor function of the hand of rhesus monkeys. We administered oral daily doses of curcumin or a control vehicle to 11 monkeys over a 14- to 18-month period in which they completed two rounds of fine motor function testing. The monkeys receiving curcumin were significantly faster at retrieving a food reward by round 2 of testing than monkeys receiving a control vehicle. Further, the monkeys receiving curcumin demonstrated a greater degree of improvement in performance on our fine motor task by round 2 of testing than monkeys receiving a control vehicle. These findings reveal that fine motor function of the hand and digits is improved in middle-aged monkeys receiving chronic daily administration of curcumin.     

Curcumin-glutathione interactions and the role of human glutathione S-transferase P1-1

Curcumin (diferuloylmethane), a yellow pigment of turmeric with antioxidant properties has been shown to be a cancer preventative in animal studies. It contains two electrophilic alpha, beta-unsaturated carbonyl groups, which can react with nucleophilic compounds such as glutathione (GSH), but formation of the GSH-curcumin conjugates has not previously been demonstrated. In the present studies, we investigated the reactions of curcumin with GSH and the effect of recombinant human glutathione S-transferase(GST)P1-1 on reaction kinetics. Glutathionylated products of curcumin identified by FAB-MS and MALDI-MS included mono- and di-glutathionyl-adducts of curcumin as well as cyclic rearrangement products of GSH adducts of feruloylmethylketone (FMK) and feruloylaldehyde (FAL). The presence of GSTP1-1 significantly accelerated the initial rate of GSH-mediated consumption of curcumin in 10 mM potassium phosphate, pH 7.0, and 1 mM GSH. GSTP1-1 kinetics determined using HPLC indicated substrate inhibition (apparent K(m) for curcumin of 25+/-11 microM, and apparent K(i) for curcumin of 8+/-3 microM). GSTP1-1 was also shown to catalyze the reverse reaction leading to the formation of curcumin from GSH adducts of FMK and FAL.     

Induction of stress response renders human tumor cell lines resistant to curcumin-mediated apoptosis: role of reactive oxygen intermediates

Curcumin, a well-known dietary pigment derived from Curcuma longa, has been shown to be a potent antiinflammatory, antioxidant, and anticarcinogenic compound. The present study was designed to investigate the cytotoxic potential of curcumin against a range of human tumor cell lines in an attempt to understand its mechanism of action, which may lead to its possible therapeutic applications. We have shown that different cancer cell lines differ in their sensitivity to curcumin. Cell lines established from malignancies like leukemia, breast, colon, hepatocellular, and ovarian carcinomas underwent apoptosis in the presence of curcumin, whereas cell lines from lung, kidney, prostate, cervix, CNS malignancies, and melanomas showed resistance to the cytotoxic effects of curcumin. Sensitivity of the cancer cell lines to curcumin correlated with the generation of superoxide radicals as determined by the reduction of ferricytochrome C. Curcumin-resistant tumor cell lines showed significantly higher production of Hsp70, thus mounting a stress response and protecting the cells from the apoptotic cell death. These observations yield clues toward understanding the regulation of the cell death machinery by the stress proteins. Interestingly, curcumin had no effect on nontransformed cell lines, which showed neither superoxide generation nor the induction of a stress response. These observations demonstrate that curcumin is an interesting molecule with varied actions, depending on the cell type.     

Curcumin as a wound healing agent

Turmeric (Curcuma longa) is a popular Indian spice that has been used for centuries in herbal medicines for the treatment of a variety of ailments such as rheumatism, diabetic ulcers, anorexia, cough and sinusitis. Curcumin (diferuloylmethane) is the main curcuminoid present in turmeric and responsible for its yellow color. Curcumin has been shown to possess significant anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-mutagenic, anti-coagulant and anti-infective effects. Curcumin has also been shown to have significant wound healing properties. It acts on various stages of the natural wound healing process to hasten healing. This review summarizes and discusses recently published papers on the effects of curcumin on skin wound healing. The highlighted studies in the review provide evidence of the ability of curcumin to reduce the body's natural response to cutaneous wounds such as inflammation and oxidation. The recent literature on the wound healing properties of curcumin also provides evidence for its ability to enhance granulation tissue formation, collagen deposition, tissue remodeling and wound contraction. It has become evident that optimizing the topical application of curcumin through altering its formulation is essential to ensure the maximum therapeutical effects of curcumin on skin wounds.     

Potential therapeutic effects of curcumin in gastric cancer

Despite recent advancements in understanding of the biology of gastric cancer, treatment of patients with advanced gastric cancer remains a major problem. Among different type of phytochemicals, curcumin, a welltable -known phytochemical, has been shown to be a promising cancer chemopreventive agent. Pharmacokinetics, safety, and efficacy of curcumin have been evaluated in several clinical trials against numerous diseases, and for the treatment of human cancer. In the present review, we have collected in vitro and in vivo investigations and studied the chemosensitizing and anticancer effects of curcumin against the gastric cancer cells. In summary, curcumin has been found to have efficient chemosensitizing effect and also inhibits viability, proliferation, and migration of gastric cancer cells mainly via cell cycle arrest and induction of apoptosis by both mitochondrial-dependent and -independent pathways.     

Oral delivery of curcumin bound to chitosan nanoparticles cured Plasmodium yoelii infected mice

Curcumin has been shown to have anti malarial activity, but poor bioavailability and chemical instability has hindered its development as a drug. We have bound curcumin to chitosan nanoparticles to improve its bioavailability and chemical stability. We found that curcumin bound to chitosan nanoparticles did not degrade that rapidly in comparison to free curcumin when such particles were incubated in mouse plasma in vitro at room temperature. The uptake of bound curcumin from chitosan nanoparticles by mouse RBC was much better than from free curcumin. Oral delivery of curcumin bound chitosan nanoparticles to normal mice showed that they can cross the mucosal barrier intact and confocal microscopy detected the nanoparticles in the blood. Curcumin loaded chitosan nanoparticles when delivered orally improved the bioavailability of curcumin in the plasma and RBC. While mice infected with a lethal strain of Plasmodium yoelii (N-67) died between 8 and 9 days post infection, feeding of chitosan nanoparticles alone made them to survive for five more days. Feeding 1mg of native curcumin to infected mice per day for seven days resulted in survival of one third of mice but under the same condition when 1mg of curcumin bound to chitosan nanoparticles was fed all the mice survived. Like chloroquine, curcumin inhibited parasite lysate induced heme polymerization in vitro in a dose dependent manner and curcumin had a lower IC(50) value than chloroquine. We believe that binding of curcumin to chitosan nanoparticles increases its chemical stability and enhances its bioavailability when fed to mice. In vitro data suggest that it can inhibit hemozoin synthesis which is lethal for the parasite.     

Effect of glutathione depletion on caspase-3 independent apoptosis pathway induced by curcumin in Jurkat cells

Curcumin, a yellow pigment from Curcuma longa, exhibits anti-inflammatory, antitumor, and antioxidative properties. Although its precise mode of action has not been elucidated so far, numerous studies have shown that curcumin may induce apoptosis in normal and cancer cells. Previously, we showed that in Jurkat cells curcumin induced nontypical apoptosis-like pathway, which was independent of mitochondria and caspase-3. Now we show that the inhibition of caspase-3 by curcumin, which is accompanied by attenuation of internucleosomal DNA fragmentation, may be due to elevation of glutathione, which increased in curcumin-treated cells to 130% of control. We have demonstrated that glutathione depletion does not itself induce apoptosis in Jurkat cells; though, it can release cytochrome c from mitochondria and caspase-3 from inhibition by curcumin, as shown by Western blot. The level of Bcl-2 protein was not affected by glutathione depletion even upon curcumin treatment. Altogether, our results show that in Jurkat cells curcumin prevents glutathione decrease, thus protecting cells against caspase-3 activation and oligonucleosomal DNA fragmentation. On the other hand, it induces nonclassical apoptosis via a still-unrecognized mechanism, which leads to chromatin degradation and high-molecular-weight DNA fragmentation.     

Can curcumin provide an ideal contraceptive?

The population explosion, unintended pregnancies, sexually transmitted diseases, and cancer (cervical and breast) continue to cause major public health issues worldwide. Curcumin, diferuloyl methane, the yellow pigment component of the curry spice turmeric (Curcuma longa), has immense biological effects and has recently drawn considerable attention. Curcumin has antibacterial, antiviral, antiinflammatory, and anticancer properties. It has shown a lack of toxicity in animals and human clinical trials. Yet, its effect on reproduction has not been examined. The present study was conducted to examine if curcumin affects sperm function in vitro and fertility in vivo. Sperm (human and murine) were collected and incubated with curcumin to examine the effect on motility, capacitation/acrosome reaction, and in vitro fertilization. The effect on in vivo fertility using the mouse model was also examined. Incubation of sperm with curcumin caused a concentration-dependent decrease in sperm forward motility, capacitation/acrosome reaction, and murine fertilization in vitro. At higher concentrations, there was a complete block of sperm motility and function within 5-15 min. Administration of curcumin, especially intravaginally, caused a significant (P<0.001) reduction in fertility. The antifertility effect of curcumin was reversible. This is the first study to report the inhibitory effect of curcumin on sperm function, fertilization, and fertility. The findings suggest that curcumin may constitute a double-edged sword to block conception, infection, and cancer, thus providing an ideal contraceptive.