Curcumin,an active component of turmeric (Curcuma longa), and its effects on health

Turmeric (Curcuma longa) is a type of herb belonging to ginger family, which is widely grown in southern and south western tropical Asia region. Turmeric, which has an importance place in the cuisines of Iran, Malesia, India, China, Polynesia, and Thailand, is often used as spice and has an effect on the nature, color, and taste of foods. Turmeric is also known to have been used for centuries in India and China for the medical treatments of illnesses such as dermatologic diseases, infection, stress, and depression. Turmeric's effects on health are generally centered upon an orange-yellow colored, lipophilic polyphenol substance called “curcumin,” which is acquired from the rhizomes of the herb. Curcumin is known recently to have antioxidant, anti-inflammatory, anticancer effects and, thanks to these effects, to have an important role in prevention and treatment of various illnesses ranging notably from cancer to autoimmune, neurological, cardiovascular diseases, and diabetic. Furthermore, it is aimed to increase the biological activity and physiological effects of the curcumin on the body by synthesizing curcumin analogues. This article reviews the history, chemical and physical features, analogues, metabolites, mechanisms of its physiological activities, and effects on health of curcumin.     

Bidirectional interactions between dietary curcumin and gut microbiota

Abstract

Curcumin is a polyphenolic compound with a long history of use as an herbal remedy, dietary spice, and food-coloring agent. Despite curcumin possesses a wide range of biological and pharmacological activities, it exhibits extremely poor bioavailability, which makes its pharmacology intriguing and also hinders its clinical application. In recent years, there is ample evidence supporting the associations between the alteration of gut microbiota and many diseases. Interestingly, after oral administration, curcumin shows its preferential distribution and accumulation in the intestine. In view of the above aspects, we reviewed the updated knowledge regarding the bidirectional interactions between curcumin and gut microbiota from two perspectives: (1) gut microbiota regulation by curcumin and (2) curcumin biotransformation by digestive microbiota. Besides the study deals with 3 potential pharmacological implications: (1) identification of metabolites being more active and bioavaliable than parent curcumin; (2) assessment of contribution of gut microbiota regulation of curcumin to its pharmacological effects and (3) development of gut microbiota regulation-based disease prevention/treatment strategy for curcumin in view of its clinical safety. This review is important to deepen our understanding of the mechanisms of action of curcumin and to provide future directions about how to use this natural compound to combat human diseases.     

Multi-targeted therapy by curcumin: how spicy is it?

Although traditional medicines have been used for thousands of years, for most such medicines neither the active component nor their molecular targets have been very well identified. Curcumin, a yellow component of turmeric or curry powder, however, is an exception. Although inhibitors of cyclooxygenase-2, HER2, tumor necrosis factor, EGFR, Bcr-abl, proteosome, and vascular endothelial cell growth factor have been approved for human use by the United States Food and Drug Administration (FDA), curcumin as a single agent can down-regulate all these targets. Curcumin can also activate apoptosis, down-regulate cell survival gene products, and up-regulate p53, p21, and p27. Although curcumin is poorly absorbed after ingestion, multiple studies have suggested that even low levels of physiologically achievable concentrations of curcumin may be sufficient for its chemopreventive and chemotherapeutic activity. Thus, curcumin regulates multiple targets (multitargeted therapy), which is needed for treatment of most diseases, and it is inexpensive and has been found to be safe in human clinical trials. The present article reviews the key molecular mechanisms of curcumin action and compares this to some of the single-targeted therapies currently available for human cancer.     

Immunomodulatory effects of curcumin in allergy

Recent years have witnessed a global increase in allergy and asthma, particularly in developed countries. Attempts to develop effective control measures for allergy and asthma resulted in the exploration of alternate medicines including herbal remedies traditionally used in old world countries. Turmeric is known for its multiple health restoring properties, and has been used in treating several diseases including several respiratory disorders. Turmeric is a common spice used in the culinary preparations in South and East Asian countries. The active component of turmeric is curcumin, a polyphenolic phytochemical, with anti-inflammatory, antiamyloid, antiseptic, antitumor, and antioxidative properties. Curcumin was reported to have antiallergic properties with inhibitory effect on histamine release from mast cells. The effectiveness of curcumin in allergy and asthma has been further investigated using a murine model of allergy. The results indicate a marked inhibition of allergic response in animals treated with curcumin suggesting a major role for curcumin in reducing the allergic response. The present review focuses on the results of research aimed to understand the immunomodulation induced by curcumin and its associated roles in the amelioration of allergy. These findings needed further evaluation, extrapolation, and confirmation before using curcumin for controlling allergy and asthma in humans.     

姜黄素的临床研究进展

姜黄素具有广泛的药理活性,其作为治疗多种疾病的潜力药物的研究正越来越多的引起关注。多个临床Ⅰ期试验已证实,姜黄素口服安全且耐受性好;药动学表明,姜黄素口服不易吸收,生物利用度低。研究显示,姜黄素治疗乳腺癌、结肠癌、肠易激综合征、风湿性关节炎及动脉粥样硬化等有疗效。现总结了姜黄素临床研究的报道,以冀为姜黄素的应用研究提供参考。     

Curcumin protects mouse neuroblastoma Neuro-2A cells against hydrogen-peroxide-induced oxidative stress

Curcumin has been traditionally used in China and India for food and medicinal purposes. It has been shown to possess potent antioxidative activity both in vitro and in vivo. In the present study, the neuroprotective effects and the potential mechanisms of curcumin against H₂O₂-induced oxidative stress in mouse neuroblastoma Neuro-2A cells were investigated. Treatment with curcumin at 20 and 25 μg/mL for 1 h prior to H₂O₂ exposure significantly attenuated cell viability loss, reduced apoptosis, suppressed the elevation of intracellular reactive oxygen species (ROS) and calcium levels, and stabilised mitochondrial membrane potential. Furthermore, curcumin could block H₂O₂-mediated degradation of the protein IκBα and subsequent activation of nuclear factor κB, thus inhibiting the expression of its target gene cyclooxygenase 2. These results indicate that curcumin has potential protective effects against H₂O₂-induced oxidative stress in neuron cells, which might make curcumin a suitable therapeutic agent for prevention and treatment of neurodegenerative diseases associated with oxidative stress.     

Beta casein-micelle as a nano vehicle for solubility enhancement of curcumin; food industry application

Curcumin is a potent anticancer and antioxidant natural polyphenol poorly soluble in aqueous solutions. Beta-casein (B-CN), an amphiphilic self-assembling protein that can form micellar nanostructures, could be used as a carrier system for hydrophobic therapeutic agents such as curcumin. In this study, camel B-CN was used for curcumin encapsulation. Critical micelle concentration of camel B-CN was determined at 25, 30 and 37 °C using pyrene fluorescence and the solubility of curcumin was evaluated according to the solvent-evaporation technique. Presence of camel B-CN increased the solubility of curcumin at least 2500 fold. Analysis of fluorescence emission of curcumin showed that hydrophobic interactions are predominant in its formulation with B-CN. Additionally, the cytotoxicity of curcumin to human leukemia cell line K-562 was enhanced in the presence of B-CN micelles giving inhibitory concentration (IC₅₀) values of 26.5 and 17.7 μmol/L for free and encapsulated curcumin, respectively. Antioxidant activity of curcumin encapsulated in B-CN was higher than that of both free B-CN and curcumin.     

Phenolics,inflammation and nutrigenomics

Nutrigenomics is the study of the effects of bioactive compounds from food on gene expression. In the last several years, an increasing body of scientific evidence has demonstrated that individual compounds, as well as complex mixtures of chemicals, derived from food alter the expression of genes in the human body. By turning on or off genes, bioactives in food alter the concentration of specific proteins directly or indirectly associated with human diseases. Several human diseases result in multiple inflammatory responses which are associated with many diseases including arthritis, cancer, cardiovascular disease, dermatitis, asthma, obesity, and others. Detailed mechanisms of action as to how food derived components play an active role in prevention of inflammation have been elucidated. Such biologically active compounds include theaflavins and catechins from tea, curcumin from turmeric, resveratrol from grapes, and lactones from chicory. While chronic diseases are very complex, an opportunity exists to regulate genes involved in inflammation by enriching our diet with the specific foods inherently rich in such compounds, enriched foods containing standardized extracts of well studied sources, or dietary supplements. Copyright © 2006 Society of Chemical Industry     

Curcumin against advanced glycation end products (AGEs) and AGEs-induced detrimental agents

Objectives: This study was aimed to review and collate effects of curcumin on generation of advanced glycation end products (AGEs) and AGEs induced detrimental agents.Methods: Pubmed, Googlescholar, ScienceDirect, and Scopus databases were searched. Searching was not limited to specific publication period. Only English language original articles (in vitro, experimental and human) which had examined the effect of curcumin on AGEs formation and AGEs induced apoptosis, oxidative stress or inflammatory responses were included. To review effect of curcumin on AGEs formation, search terms were as following: ‘‘curcumin” (title) and AGEs or pentosidine or methylglyoxal or carboxymethyllysine or glucosylation (title/abstract). Totally 104 articles were searched which 19 were selected for review. To review effect of curcumin on AGEs induced harmful agents, key words were as following: “curcumin” (title) and AGEs (title/abstract) and apoptosis or oxidative stress or DNA damage or cell injury or inflammatory or cell death or cell proliferation (title/abstract). Totally 126 articles were searched which 18 were found appropriate for review.Results: Regarding curcumin and AGEs formation, ten eligible articles (1 human trial, 5 animal models and 4 in vitro) and with regarding curcumin and AGEs-induced complications, 17 articles (5 on apoptosis, 9 on oxidative stress, and 3 on inflammatory responses) were selected. Except one, all studies indicated that curcumin is able to prevent AGEs formation and AGEs-induced disturbances with different potential mechanisms.Conclusion: Curcumin can inhibit AGEs formation and AGEs-induced disturbances. More RCT researches are suggested to evaluate beneficial effect of curcumin regarding AGEs in different age-related chronic diseases, with specific attention to AGEs memberships.     

叶酸和辛烯基琥珀酸酐双修饰菊粉胶束对姜黄素的荷载特性

叶酸修饰两亲性多糖是一种有效的疏水活性物质载体，能增加疏水活性物质的结肠靶向转运。以叶酸和辛烯基琥珀酸酐双修饰菊粉（folic acid octenylsuccinate inulin，FA-OS-菊粉）自聚集形成荷载姜黄素的胶束为研究对象，以胶束颗粒粒径、多分散性指数和姜黄素保留率为指标，探究了该胶束的热处理稳定性、冻融稳定性、贮藏稳定性及体外模拟胃肠液消化稳定性和释放特性。结果：荷载姜黄素FA-OS-菊粉胶束在热处理和贮藏过程中姜黄素保留率较高，但粒径和多分散性指数变化显著；消化结束时，FA-OS-菊粉胶束在模拟胃液中的姜黄素释放率小于2%，在模拟肠液中的姜黄素释放率小于10%，具有较好的控释效果。结论：荷载姜黄素FA-OS-菊粉胶束具有潜在的结肠靶向效果。     

Recent advances in emulsion-based delivery approaches for curcumin: From encapsulation to bioaccessibility

BackgroundCurcumin has been widely acknowledged for its health-promoting effects. However, its application is often limited by its poor water solubility and biochemical/structural degradation during physiological transit that restricts its bioavailability. Emulsion based approaches have attracted the most research attention to encapsulate curcumin and improve its stability, bioaccessibility and bioavailability.Scope and approachThis review summarizes the recent advances in application of different oil-in-water emulsion-based approaches, such as, conventional emulsions (surfactants-, protein- and protein-polysaccharide-stabilized emulsions), nanoemulsions, and Pickering emulsions that have been specifically used to deliver curcumin. Particular emphasis is given to factors affecting curcumin solubility, change in crystalline structure of curcumin upon dispersion and encapsulation efficiency. Changes in the droplet size and emulsion stability during in vitro oral-to-gastrointestinal digestion are discussed, with clear focus on the bioaccessibility of the encapsulated curcumin.Key findings and conclusionsKey factors that influence curcumin delivery include emulsion droplet size, oil composition, volume fraction, dispersion conditions of curcumin in the oil phase and the type of interfacial materials. Nanoemulsions have been the preferred choice for delivery of curcumin up to now. Although scarce in literature, emulsions stabilized by edible Pickering particles as shown by recent evidence are effective in protecting curcumin in an in vitro gastrointestinal setting due to their high coalescence stability. Further studies with emulsions stabilized by food-grade particles and accurate tracking of the physiological fate (in vitro to human trials) of different emulsion-based delivery vehicles are essential for rational designing of curcumin-rich functional foods with high bioaccessibility.     

Anticancer and carcinogenic properties of curcumin: considerations for its clinical development as a cancer chemopreventive and chemotherapeutic agent

A growing body of research suggests that curcumin, the major active constituent of the dietary spice turmeric, has potential for the prevention and therapy of cancer. Preclinical data have shown that curcumin can both inhibit the formation of tumors in animal models of carcinogenesis and act on a variety of molecular targets involved in cancer development. In vitro studies have demonstrated that curcumin is an efficient inducer of apoptosis and some degree of selectivity for cancer cells has been observed. Clinical trials have revealed that curcumin is well tolerated and may produce antitumor effects in people with precancerous lesions or who are at a high risk for developing cancer. This seems to indicate that curcumin is a pharmacologically safe agent that may be used in cancer chemoprevention and therapy. Both in vitro and in vivo studies have shown, however, that curcumin may produce toxic and carcinogenic effects under specific conditions. Curcumin may also alter the effectiveness of radiotherapy and chemotherapy. This review article analyzes the in vitro and in vivo cancer-related activities of curcumin and discusses that they are linked to its known antioxidant and pro-oxidant properties. Several considerations that may help develop curcumin as an anticancer agent are also discussed.     

Biological properties of curcumin-cellular and molecular mechanisms of action

Curcuminoids, a group of phenolic compounds isolated from the roots of Curcuma longa (Zingiberaceae), exhibit a variety of beneficial effects on health and on events that help in preventing certain diseases. A vast majority of these studies were carried out with curcumin (diferuloyl methane), which is a major curcuminoid. The most detailed studies using curcumin include anti-inflammatory, antioxidant, anticarcinogenic, antiviral, and antiinfectious activities. In addition, the wound healing and detoxifying properties of curcumin have also received considerable attention. As a result of extensive research on the therapeutic properties of curcumin, some understanding on the cellular, molecular, and biochemical mechanism of action of curcumin is emerging. These findings are summarized in this review.     

姜黄素对幽门螺杆菌及其诱导人胃GES-1细胞损伤的影响

对姜黄素抑制幽门螺杆菌（Helicobacter pylori,Hp）及其诱导人胃GES-1细胞损伤的影响进行研究。抑菌实验结果显示,姜黄素可明显抑制Hp生长,其最低抑制浓度为200 μmol/L。采用Berthelot显色法检测Hp脲酶活力的变化情况,发现姜黄素对其也有明显的抑制作用,半数抑制浓度为1.735 mmol/L。通过噻唑蓝实验分析姜黄素对人胃GES-1细胞和Hp感染人胃GES-1细胞的影响。结果显示,短时间内（12 h）较低浓度（68 μmol/L）姜黄素对人胃GES-1细胞增殖无明显影响,但姜黄素浓度的增加和作用时间的延长可使细胞存活率明显下降。经68 μmol/L姜黄素作用12 h后,损伤模型组细胞形态有一定程度的复原,细胞存活率略有升高,但不显著（P＞0.05）;高浓度（136、680 μmol/L）姜黄素会导致细胞存活率明显下降。因此,姜黄素对Hp生长和脲酶活力有明显的抑制作用,但不足以缓解Hp对人胃GES-1细胞的损伤作用。     

Characterisation and food application of curcumin bound to sodium caseinate–polysaccharide electrostatic complexes

Electrostatic complexes between sodium caseinate (NaCas) and high‐methoxyl pectin (HMP) or carboxymethyl cellulose (CMC) were used to stabilise curcumin in this study. Effect of pH on the characteristics of the complex was evaluated, finding pH 4 was optimum. Zeta potential of NaCas‐CMC (?33.59) was larger than that of NaCas‐HMP (?22.19) at pH 4, implying higher colloidal stability. The complexes protected curcumin from heat treatment, and antioxidant activity of curcumin bound to the complexes was similar to that of native curcumin. Incorporation of sucrose partially prevented freeze drying‐induced aggregation of the complex, especially for NaCas‐HMP. In a model beverage, curcumin bound to the complexes showed higher colour stability. In vitro bioaccessibility of curcumin bound to NaCas‐HMP (53.0%) and NaCas‐CMC (51.6%) was higher than the native curcumin (21.4%). This study suggests that curcumin bound to the complexes, especially NaCas‐HMP‐bound curcumin may be used as a potential food colourant where transparency is needed.     

Chemical modification of curcumin: Solubility and antioxidant capacity

The aim of this study was to develop a chemical method for demythylation of curcumin. The methoxy groups reduced solubility and low bioavailability of curcumin. The treatment of curcumin with hydrogen bromide or choline chloride increased cucumin water solubility from 1 mg/mL to 30 or 25 mg/mL, respectively. ¹HNMR spectra showed that the chemical shift of O-methoxy groups at 3.9 ppm disappeared upon chemical treatment of curcumin, and indicated that these groups were removed especially after hydrogen bromide treatment. The antioxidant activity of treated curcumin and untreated curcumin was measured using different in vitro assays (i.e., 1,1-diphenyl-2-picrylhydrazyl and 2,2’-azino-bis (3-ethylbenzo-thiazoline-6-sulfonic acid) radical scavenging, and phosphomolybdenum complex formation). A remarkable increase in 1,1-diphenyl-2-picrylhydrazyl and 2,2’-azino-bis (3-ethylbenzo-thiazoline-6-sulfonic acid) radical scavenging was observed as curcumin-hydrogen bromide > curcumin-Choline chloride > curcumin. The formation of phosphomolybdenum complex was found to increase in the order of curcumin-choline cloride > curcumin-hydrogen bromide > curcumin with EC₅₀ 30, 41, and 114 µg/mL, respectively. In conclusion, hydrogen bromide-treated curcumin could be used as potential antioxidant in new functional foods.     

花青素与姜黄素在食品包装领域的应用

花青素和姜黄素对于活性包装至关重要,探讨其内在机理,可为花青素、姜黄素智能包装膜的相关研究提供理论参考。本文综述了花青素、姜黄素的结构和性质、提取方法、抗氧化活性、花青素和姜黄素在食品包装上的应用以及两种色素混合在食品包装上的应用。花青素和姜黄素由于其自身结构特点,在不同的pH下有不同的颜色,花青素作为颜色指示剂变色范围广,但性质不稳定,易受到外界因素影响。姜黄素稳定性高于花青素,但变色范围窄。此外,两者均具有很好的抗氧化活性,可作为颜色指示剂与抗氧化剂应用在食品包装中。花青素和姜黄素的变色特点、稳定性以及功能活性对食品新鲜度指示包装的性能具有显著的影响,将两种色素混合作为指示剂添加到食品包装中,有助于提高花青素的稳定性,从而获得更好的指示效果。     

Enhancement of Curcumin Solubility by Phase Change from Crystalline to Amorphous in Cur‐TPGS Nanosuspension

Nanosuspensions (NSs) were fabricated to enhance water solubility, dissolution rate, and oral adsorption of water insoluble curcumin using sonoprecipitation method. As a good stabilizer, d ‐α‐Tocopherol polyethylene glycol 1000 succinate (TPGS) was used to improve the stability of curcumin‐TPGS NSs (Cur‐TPGS NSs). Ultrasonic homogenization (UH) could effectively enhance the solubility of curcumin and to produce homogeneous NSs with small particle sizes. Water solubility of curcumin was significantly improved from 0.6 μg/mL in pure water to 260 μg/mL in the mixture of curcumin and TPGS (1:10) with UH treatment. The mean particle size of Cur‐TPGS NSs was decreased significantly after UH and maintained between 208 and 246 nm. Lyophilized powder of Cur‐TPGS NSs was dissolved about 91.08% whereas the pristine curcumin powder was dissolved only 6.5% at pH 7.4. This study showed a great potential of Cur‐TPGS NSs as a good nano‐formulation of curcumin with enhanced solubility and improved oral adsorption.