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Sample records for molecule curcumin analog

  1. Curcumin and curcumin-like molecules: from spice to drugs.

    PubMed

    Marchiani, A; Rozzo, C; Fadda, A; Delogu, G; Ruzza, P

    2014-01-01

    Curcumin is the major yellow pigment extracted from turmeric, a commonly used spice in Asian cuisine and extensively employed in ayurvedic herbal remedies. A number of studies have shown that curcumin can be a prevention and a chemotherapeutic agent for colon, skin, oral and intestinal cancers. Curcumin is also well known for its antiinflammatory and antioxidant properties, showing high reactivity towards peroxyl radicals, and thus acting as a free radical scavenger. Recently, experimental studies have demonstrated that curcumin might be used in the prevention and the cure of Alzheimer's disease. Indeed, curcumin injected peripherally in vivo into aged Tg mice crossed the blood-brain barrier and bound to amyloid plaques, reducing amyloid levels and plaque formation decisively. The present review will resume the most recent developments in the medicinal chemistry of curcumin and curcumin-like molecules.

  2. Perspectives on Chemopreventive and Therapeutic Potential of Curcumin Analogs in Medicinal Chemistry

    PubMed Central

    Padhye, S.; Chavan, D.; Pandey, S.; Deshpande, J.; Swamy, K.V.; Sarkar, F.H.

    2011-01-01

    Curcumin is a natural polyphenol derived from the plant Curcuma longa, commonly called turmeric. Extensive research over past 50 years has indicated that this polyphenol is highly pleiotropic molecule capable of preventing and treating various cancers. The anticancer potential of Curcumin is severely affected by its limited systemic and target tissue bioavailability and rapid metabolism. In the present review article, we provide a summarized account of different drug delivery systems employed for tackling the problem of curcumin's bioavailability such as liposomes, phospholipid complexes and nanoparticles. Concomitantly we have reviewed the large volume of literature reports describing structural modifications of Curcumin and the anticancer potential of its analogs. Some of the difluorocurcumin analogs allowing longer circulation times and preferential accumulation in the pancreas seem to offer promising leads for conducting first in-depth animal studies and subsequently clinical trials for the use of these analogs for prevention of tumor progression and/or treatments of human malignancies. PMID:20370702

  3. Eliminating the Heart from the Curcumin Molecule: Monocarbonyl Curcumin Mimics (MACs)

    PubMed Central

    Shetty, Dinesh; Kim, Yong Joon; Shim, Hyunsuk; Snyder, James P.

    2015-01-01

    Curcumin is a natural product with several thousand years of heritage. Its traditional Asian application to human ailments has been subjected in recent decades to worldwide pharmacological, biochemical and clinical investigations. Curcumin’s Achilles heel lies in its poor aqueous solubility and rapid degradation at pH ~ 7.4. Researchers have sought to unlock curcumin’s assets by chemical manipulation. One class of molecules under scrutiny are the monocarbonyl analogs of curcumin (MACs). A thousand plus such agents have been created and tested primarily against cancer and inflammation. The outcome is clear. In vitro, MACs furnish a 10–20 fold potency gain vs. curcumin for numerous cancer cell lines and cellular proteins. Similarly, MACs have successfully demonstrated better pharmacokinetic (PK) profiles in mice and greater tumor regression in cancer xenografts in vivo than curcumin. The compounds reveal limited toxicity as measured by murine weight gain and histopathological assessment. To our knowledge, MAC members have not yet been monitored in larger animals or humans. However, Phase 1 clinical trials are certainly on the horizon. The present review focuses on the large and evolving body of work in cancer and inflammation, but also covers MAC structural diversity and early discovery for treatment of bacteria, tuberculosis, Alzheimer’s disease and malaria. PMID:25547726

  4. Structure- and isoform-specific glucuronidation of six curcumin analogs.

    PubMed

    Lu, Danyi; Liu, Hui; Ye, Wencai; Wang, Ying; Wu, Baojian

    2017-04-01

    1. In the present study, we aimed to characterize the glucuronidation of six curcumin analogs (i.e. RAO-3, RAO-8, RAO-9, RAO-18, RAO-19, and RAO-23) derived from galangal using human liver microsomes (HLM) and twelve expressed UGT enzymes. 2. Formation of glucuronide was confirmed using high-resolution mass spectrometry. Single glucuronide metabolite was generated from each of six curcumin analogs. The fragmentation patterns were analyzed and were found to differ significantly between alcoholic and phenolic glucuronides. 3. All six curcumin analogs except one (RAO-23) underwent significant glucuronidation in HLM and expressed UGT enzymes. In general, the methoxy group (close to the phenolic hydroxyl group) enhanced the glucuronidation liability of the curcumin analogs. 4. UGT1A9 and UGT2B7 were primarily responsible for the glucuronidation of two alcoholic analogs (RAO-3 and RAO-18). By contrast, UGT1A9 and four UGT2Bs (UGT2B4, 2B7, 2B15 and 2B17) played important roles in conjugating three phenolic analogs (RAO-8, RAO-9, and RAO-19). Interestingly, the conjugated double bonds system (in the aliphatic chain) was crucial to the substrate selectivity of gastrointestinal UGTs (i.e. UGT1A7, 1A8 and 1A10). 5. In conclusion, glucuronidation of six curcumin analogs from galangal were structure- and isoform-specific. The knowledge should be useful in identifying a curcumin analog with improved metabolic property.

  5. Experimental evidence for curcumin and its analogs for management of diabetes mellitus and its associated complications.

    PubMed

    Rivera-Mancía, Susana; Lozada-García, María Concepción; Pedraza-Chaverri, José

    2015-06-05

    Diabetes mellitus is a serious world health problem and one of the most studied diseases; a major concern about its treatment is that β-cell mass and functionality is hard to restore. In addition, it is frequently associated with severe complications, such as diabetic nephropathy and cardiomyopathy. The anti-inflammatory, anti-oxidative and anti-apoptotic properties of curcumin have made it a promising molecule for the treatment of this pathology; however, its solubility and bioavailability problems are still the subject of multiple studies. To cope with those difficulties, several approaches have been evaluated, such as the development of pharmaceutical formulations and curcumin analogs. This review discusses some of the studied therapeutic targets for curcumin in diabetes as well as the structural characteristics and targets of its analogs. The shortening of the central seven-carbon chain of curcumin has given rise to compounds without glucose-lowering effects but potentially useful for the treatment of diabetes complications; whereas preserving this chain retains the glucose-lowering properties. Most of the analogs discussed here have been recently synthesized and tested in animal models of type 1 diabetes; more studies in models of type 2 diabetes are needed.

  6. Fluorescent difluoroboron-curcumin analogs: An investigation of the electronic structures and photophysical properties

    NASA Astrophysics Data System (ADS)

    Margar, Sachin N.; Rhyman, Lydia; Ramasami, Ponnadurai; Sekar, Nagaiyan

    2016-01-01

    A comprehensive approach based on the density functional theory method was used to elicit the molecular and photophysical properties of four difluoroboron analogs of curcumin. The ground state geometry optimization, vertical absorption and the first excited state optimization were carried out using the B3LYP/6-31G(d) method. The geometry of the molecules remains planar both in the ground and excited states. There is a good correlation between the observed absorption (maximum deviation of 8%) and emission wavelength (maximum deviation of 22%) with the computed values. Different polarizability parameters were computed and compared with urea. The values obtained for the difluoroboron dyes are larger than those of urea, suggesting considerable charge transfer characteristics of the first excited state. This is further supported by the significant difference in the dipole moment. The outcome of this work should be useful towards the industrial applications of these curcumin-based dyes.

  7. Effect of curcumin analogs onα-synuclein aggregation and cytotoxicity

    PubMed Central

    Jha, Narendra Nath; Ghosh, Dhiman; Das, Subhadeep; Anoop, Arunagiri; Jacob, Reeba S.; Singh, Pradeep K.; Ayyagari, Narasimham; Namboothiri, Irishi N. N.; Maji, Samir K.

    2016-01-01

    Alpha-synuclein (α-Syn) aggregation into oligomers and fibrils is associated with dopaminergic neuron loss occurring in Parkinson’s disease (PD) pathogenesis. Compounds that modulate α-Syn aggregation and interact with preformed fibrils/oligomers and convert them to less toxic species could have promising applications in the drug development efforts against PD. Curcumin is one of the Asian food ingredient which showed promising role as therapeutic agent against many neurological disorders including PD. However, the instability and low solubility makes it less attractive for the drug development. In this work, we selected various curcumin analogs and studied their toxicity, stability and efficacy to interact with different α-Syn species and modulation of their toxicity. We found a subset of curcumin analogs with higher stability and showed that curcumin and its various analogs interact with preformed fibrils and oligomers and accelerate α-Syn aggregation to produce morphologically different amyloid fibrils in vitro. Furthermore, these curcumin analogs showed differential binding with the preformed α-Syn aggregates. The present data suggest the potential role of curcumin analogs in modulating α-Syn aggregation. PMID:27338805

  8. Synthesis and Cytotoxic Evaluation of Monocarbonyl Analogs of Curcumin as Potential Anti‐Tumor Agents

    PubMed Central

    Pan, Zheer; Chen, Chengwei; Zhou, Yeli; Xu, Feng

    2016-01-01

    Abstract Preclinical Research A series of mono‐carbonyl curcumin analogs with different substituents at the 4/4’‐position of the phenyl group were synthesized and screened for in vitro cytotoxicity against a panel of human cancer cell lines using a methyl thiazolyl tetrazolium assay. Several of the curcumin analogs, especially B114, exhibited a wide‐spectrum of anti‐tumor properties in all tested cell lines, indicating their potential in as anti‐cancer lead compounds. Further toxicity testing in the NRK‐52E kidney cell line revealed that the analogs A111, A113, and B114 had comparable or higher safety than curcumin. These data suggested that the introduction of appropriate substituents in the 4/4’‐positions could be a promising approach for curcumin‐based drug design. Drug Dev Res 77 : 43–49, 2016. © 2016 Wiley Periodicals, Inc. PMID:26846154

  9. Perspectives on New Synthetic Curcumin Analogs and their Potential Anticancer Properties

    PubMed Central

    Vyas, Alok; Dandawate, Prasad; Padhye, Subhash; Ahmad, Aamir; Sarkar, Fazlul

    2013-01-01

    Curcumin is the active component of dried rhizome of Curcuma longa, a perennial herb belonging to ginger family, cultivated extensively in south and southeastern tropical Asia. It is widely consumed in the Indian subcontinent, south Asia and Japan in traditional food recipes. Extensive research over last few decades has shown that curcumin is a potent anti-inflammatory agent with powerful therapeutic potential against a variety of cancers. It suppresses proliferation and metastasis of human tumors through regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases and other enzymes. It induces apoptotic cell death and also inhibits proliferation of cancer cells by cell cycle arrest. Pharmacokinetic data has shown that curcumin undergoes rapid metabolism leading to glucuronidation and sulfation in the liver and excretion in the feces, which accounts for its poor systemic bioavailability. The compound has, therefore, been formulated and administered using different drug delivery systems such as liposomes, micelles, polysaccharides, phospholipid complexes and nanoparticles that can overcome the limitation of bioavailability to some extent. Attempts to avoid rapid metabolism of curcumin until now have been met with limited success. This has prompted researchers to look for new synthetic curcumin analogs in order to overcome the drawbacks of limited bioavailability and rapid metabolism, and gain efficacy with reduced toxicity. In this review we provide a summarized account of novel synthetic curcumin formulations and analogs, and the recent progress in the field of cancer prevention and treatment. PMID:23116312

  10. A chemical analog of curcumin as an improved inhibitor of amyloid Abeta oligomerization.

    PubMed

    Orlando, Robert A; Gonzales, Amanda M; Royer, Robert E; Deck, Lorraine M; Vander Jagt, David L

    2012-01-01

    Amyloid-like plaques are characteristic lesions defining the neuropathology of Alzheimer's disease (AD). The size and density of these plaques are closely associated with cognitive decline. To combat this disease, the few therapies that are available rely on drugs that increase neurotransmission; however, this approach has had limited success as it has simply slowed an imminent decline and failed to target the root cause of AD. Amyloid-like deposits result from aggregation of the Aβ peptide, and thus, reducing amyloid burden by preventing Aβ aggregation represents an attractive approach to improve the therapeutic arsenal for AD. Recent studies have shown that the natural product curcumin is capable of crossing the blood-brain barrier in the CNS in sufficient quantities so as to reduce amyloid plaque burden. Based upon this bioactivity, we hypothesized that curcumin presents molecular features that make it an excellent lead compound for the development of more effective inhibitors of Aβ aggregation. To explore this hypothesis, we screened a library of curcumin analogs and identified structural features that contribute to the anti-oligomerization activity of curcumin and its analogs. First, at least one enone group in the spacer between aryl rings is necessary for measureable anti-Aβ aggregation activity. Second, an unsaturated carbon spacer between aryl rings is essential for inhibitory activity, as none of the saturated carbon spacers showed any margin of improvement over that of native curcumin. Third, methoxyl and hydroxyl substitutions in the meta- and para-positions on the aryl rings appear necessary for some measure of improved inhibitory activity. The best lead inhibitors have either their meta- and para-substituted methoxyl and hydroxyl groups reversed from that of curcumin or methoxyl or hydroxyl groups placed in both positions. The simple substitution of the para-hydroxy group on curcumin with a methoxy substitution improved inhibitor function by 6

  11. Mosquitocidal Properties of Natural Product Compounds Isolated From Chinese Herbs and Synthetic Analogs of Curcumin

    PubMed Central

    ANSTROM, DAVID M.; ZHOU, XIA; KALK, CODY N.; SONG, BAOAN; LAN, QUE

    2012-01-01

    Because of resistance to current insecticides and to environmental, health, and regulatory concerns, naturally occurring compounds and their derivatives are of increasing interest for the development of new insecticidal compounds against vectors of disease-causing pathogens. Fifty-eight compounds, either extracted and purified from plants native to China or synthetic analogs of curcumin, were evaluated for both their larvicidal activity against Aedes aegypti (L.) and their ability to inhibit binding of cholesterol to Ae. aegypti sterol carrier protein-2 in vitro. Of the compounds tested, curcumin analogs seem especially promising in that of 24 compounds tested five were inhibitors of Ae. aegyptisterol carrier protein-2 with EC50 values ranging from 0.65 to 62.87 μM, and three curcumin analogs exhibited larvicidal activity against fourth instar Ae. aegypti larvae with LC50 values ranging from 17.29 to 27.90 μM. Adding to the attractiveness of synthetic curcumin analogs is the relative ease of synthesizing a large diversity of compounds; only a small fraction of such diversity has been sampled in this study. PMID:22493854

  12. Interaction of metallic clusters with biologically active curcumin molecules

    NASA Astrophysics Data System (ADS)

    Gupta, Sanjeev K.; He, Haiying; Liu, Chunhui; Dutta, Ranu; Pandey, Ravindra

    2015-09-01

    We have investigated the interaction of subnano metallic Gd and Au clusters with curcumin, an important biomolecule having pharmacological activity. Gd clusters show different site preference to curcumin and much stronger interaction strength, in support of the successful synthesis of highly stable curcumin-coated Gd nanoparticles as reported recently. It can be attributed to significant charge transfer from the Gd cluster to curcumin together with a relatively strong hybridization of the Gd df-orbitals with curcumin p-orbitals. These results suggest that Gd nanoparticles can effectively be used as delivery carriers for curcumin at the cellular level for therapy and medical imaging applications.

  13. Monocarbonyl analogs of curcumin inhibit growth of antibiotic sensitive and resistant strains of Mycobacterium tuberculosis

    PubMed Central

    Baldwin, Patrick R.; Reeves, Analise Z.; Powell, Kimberly R.; Napier, Ruth J.; Swimm, Alyson I.; Sun, Aiming; Giesler, Kyle; Bommarius, Bettina; Shinnick, Thomas M.; Snyder, James P.; Liotta, Dennis C.; Kalman, Daniel

    2016-01-01

    Tuberculosis (TB) is a major public health concern worldwide with over 2 billion people currently infected. The rise of strains of Mycobacterium tuberculosis (Mtb) that are resistant to some or all first and second line antibiotics, including multidrug-resistant (MDR), extensively drug resistant (XDR) and totally drug resistant (TDR) strains, is of particular concern and new anti-TB drugs are urgently needed. Curcumin, a natural product used in traditional medicine in India, exhibits anti-microbial activity that includes Mtb, however it is relatively unstable and suffers from poor bioavailability. To improve activity and bioavailability, mono-carbonyl analogs of curcumin were synthesized and screened for their capacity to inhibit the growth of Mtb and the related Mycobacterium marinum (Mm). Using disk diffusion and liquid culture assays, we found several analogs that inhibit in vitro growth of Mm and Mtb, including rifampicin-resistant strains. Structure activity analysis of the analogs indicated that Michael acceptor properties are critical for inhibitory activity. However, no synergistic effects were evident between the monocarbonyl analogs and rifampicin on inhibiting growth. Together, these data provide a structural basis for the development of analogs of curcumin with pronounced anti-mycobacterial activity and provide a roadmap to develop additional structural analogs that exhibit more favorable interactions with other anti-TB drugs. PMID:25618016

  14. Synthetic Curcumin Analogs as Inhibitors of β -Amyloid Peptide Aggregation: Potential Therapeutic and Diagnostic Agents for Alzheimer's Disease.

    PubMed

    Bukhari, Syed Nasir Abbas; Jantan, Ibrahim

    2015-01-01

    There is a crucial need to develop new effective drugs for Alzheimer's disease (AD) as the currently available AD treatments provide only momentary and incomplete symptomatic relief. Amongst natural products, curcumin, a major constituent of turmeric, has been intensively investigated for its neuroprotective effect against β-amyloid (Aβ)-induced toxicity in cultured neuronal cells. The ability of curcumin to attach to Aβ peptide and prevent its accumulation is attributed to its three structural characteristics such as the presence of two aromatic end groups and their co-planarity, the length and rigidity of the linker region and the substitution conformation of these aromatics. However, curcumin failed to reach adequate brain levels after oral absorption in AD clinical trials due to its low water solubility and poor oral bioavailability. A number of new curcumin analogs that mimic the active site of the compound along with analogs that mimic the curcumin anti-amyloid effect combined with anticholinesterase effect have been developed to enhance the bioavailability, pharmacokinetics, water solubility, stability at physiological conditions and delivery of curcumin. In this article, we have summarized all reported synthetic analogs of curcumin showing effects on β-amyloid and discussed their potential as therapeutic and diagnostic agents for AD.

  15. An overview of structure-activity relationship studies of curcumin analogs as antioxidant and anti-inflammatory agents.

    PubMed

    Arshad, Laiba; Haque, Md Areeful; Abbas Bukhari, Syed Nasir; Jantan, Ibrahim

    2017-04-10

    Curcumin, extracted mainly from Curcuma longa rhizomes, has been reported to possess potent anti-inflammatory and anti-oxidant activities. Although safe at higher doses and exhibiting multiple biological activities, curcumin still has the problem of poor bioavailability which has been an attractive area of research over the last few years. A number of efforts have been made by modifying structural features of curcumin. This review highlights the structurally modified and more stable newly synthesized curcumin analogs that have been screened against antioxidant and anti-inflammatory activities. Also the structure-activity relationship to gain insight into future guidelines for scheming new compounds has been discussed, and further these analogs being more stable may serve as promising agents for use in different pathological conditions.

  16. Effect of curcumin analog on gamma-radiation-induced cellular changes in primary culture of isolated rat hepatocytes in vitro.

    PubMed

    Srinivasan, M; Sudheer, A Ram; Rajasekaran, K N; Menon, Venugopal P

    2008-10-22

    The present study was aimed to evaluate the radioprotective effect of curcumin analog, on gamma-radiation-induced toxicity in primary cultures of isolated rat hepatocytes. Hepatocytes were isolated from the liver of rats by collagenase perfusion. The DNA damage was analysed by single cell gel electrophoresis (comet assay). An increase in the severity of DNA damage was observed with the increase in gamma-radiation dose at 1-4 Gy in cultured rat hepatocytes. The levels of lipid peroxidative indices like thiobarbituric acid reactive substances (TBARSs) were increased significantly, whereas the levels of reduced glutathione (GSH) and antioxidant enzymes were significantly decreased in gamma-irradiated groups. The maximum damage to hepatocytes was observed at 4Gy gamma-irradiation. Pretreatment with different concentrations of curcumin analog (1.38, 6.91 and 13.82 microM) shows a significant decrease in the levels of TBARS and DNA damage. Pretreatment with curcumin analog prevents the loss of enzymic and non-enzymic antioxidants like GSH upon gamma-irradiation. The maximum protection of hepatocytes was observed at 6.91 microM of curcumin analog pretreatment. Thus, our result shows that pretreatment with curcumin analog protects the hepatocytes against gamma-radiation-induced cellular damage.

  17. Curcumin

    PubMed Central

    Chaudhari, Soham P.; Tam, Alison Y.; Barr, Jason A.

    2015-01-01

    Background: Herbal medicines are used by thousands of patients all over the world. However, they can often cause adverse effects. Turmeric, made from the root of Curcuma, longa, is a yellow spice used throughout South Asia for its flavor as well as for its medicinal properties. Curcumin is the main ingredient in turmeric. It is known for downregulating the expression of various proinflammatory cytokines and has been studied for its antiinflammatory mechanism. However, it has also been reported to cause contact dermatitis. Kumkum, a turmeric-based powder applied by Hindu women on their foreheads, has also been found as an allergen. Objective: The authors have reviewed the anti-inflammatory properties of curcumin and reports of contact dermatitis to understand the possible harmful effects of this commonly used spice, while also examining its beneficial role in dermatologic conditions. They aim to increase awareness regarding this common herb and its prevalent use not only in South Asia, but also in North America. Methods: A thorough literature search of the PubMed database was conducted to identify studies that examined the antiinflammatory role of curcumin and its role in contact dermatitis. Results: Eleven studies demonstrate that although curcumin does have antiinflammatory properties, it is an allergen. Conclusion: Curcumin has many valuable properties that can be exploited to treat dermatologic conditions. However, patients and dermatologists must be keen of possible allergic reactions. Further studies are needed to completely understand this widely used herb and its efficacy in dermatology. PMID:26705440

  18. Potential applications of curcumin and its novel synthetic analogs and nanotechnology-based formulations in cancer prevention and therapy.

    PubMed

    Mimeault, Murielle; Batra, Surinder K

    2011-08-23

    Curcumin has attracted great attention in the therapeutic arsenal in clinical oncology due to its chemopreventive, antitumoral, radiosensibilizing and chemosensibilizing activities against various types of aggressive and recurrent cancers. These malignancies include leukemias, lymphomas, multiple myeloma, brain cancer, melanoma and skin, lung, prostate, breast, ovarian, liver, gastrointestinal, pancreatic and colorectal epithelial cancers. Curcumin mediates its anti-proliferative, anti-invasive and apoptotic effects on cancer cells, including cancer stem/progenitor cells and their progenies, through multiple molecular mechanisms. The oncogenic pathways inhibited by curcumin encompass the members of epidermal growth factor receptors (EGFR and erbB2), sonic hedgehog (SHH)/GLIs and Wnt/β-catenin and downstream signaling elements such as Akt, nuclear factor-kappa B (NF-κB) and signal transducers and activators of transcription (STATs). In counterbalance, the high metabolic instability and poor systemic bioavailability of curcumin limit its therapeutic efficacy in human. Of great therapeutic interest, the selective delivery of synthetic analogs or nanotechnology-based formulations of curcumin to tumors, alone or in combination with other anticancer drugs, may improve their chemopreventive and chemotherapeutic efficacies against cancer progression and relapse. Novel curcumin formulations may also be used to reverse drug resistance, eradicate the total cancer cell mass and improve the anticarcinogenic efficacy of the current anti-hormonal and chemotherapeutic treatments for patients with various aggressive and lethal cancers.

  19. Potential applications of curcumin and its novel synthetic analogs and nanotechnology-based formulations in cancer prevention and therapy

    PubMed Central

    2011-01-01

    Curcumin has attracted great attention in the therapeutic arsenal in clinical oncology due to its chemopreventive, antitumoral, radiosensibilizing and chemosensibilizing activities against various types of aggressive and recurrent cancers. These malignancies include leukemias, lymphomas, multiple myeloma, brain cancer, melanoma and skin, lung, prostate, breast, ovarian, liver, gastrointestinal, pancreatic and colorectal epithelial cancers. Curcumin mediates its anti-proliferative, anti-invasive and apoptotic effects on cancer cells, including cancer stem/progenitor cells and their progenies, through multiple molecular mechanisms. The oncogenic pathways inhibited by curcumin encompass the members of epidermal growth factor receptors (EGFR and erbB2), sonic hedgehog (SHH)/GLIs and Wnt/β-catenin and downstream signaling elements such as Akt, nuclear factor-kappa B (NF-κB) and signal transducers and activators of transcription (STATs). In counterbalance, the high metabolic instability and poor systemic bioavailability of curcumin limit its therapeutic efficacy in human. Of great therapeutic interest, the selective delivery of synthetic analogs or nanotechnology-based formulations of curcumin to tumors, alone or in combination with other anticancer drugs, may improve their chemopreventive and chemotherapeutic efficacies against cancer progression and relapse. Novel curcumin formulations may also be used to reverse drug resistance, eradicate the total cancer cell mass and improve the anticarcinogenic efficacy of the current anti-hormonal and chemotherapeutic treatments for patients with various aggressive and lethal cancers. PMID:21859497

  20. Anti-Lung Cancer Activity of the Curcumin Analog JZ534 In Vitro

    PubMed Central

    Wu, Jianzhang; Cai, Zhijian; Wei, Xiaoyan; Chen, Minxiao; Ying, Shilong; Shi, Lingyi; Xu, Ren-Ai; He, Fan; Liang, Guang; Zhang, Xiuhua

    2015-01-01

    This study investigated the anticancer effect of the curcumin analog JZ534 on lung cancer cell lines H460, A549, H1975, and HCC827. The antiproliferation effect of JZ534 was measured through the methylthiazoletetrazolium assay, and cell colony formation was observed. Cell cycle and apoptosis were determined by flow cytometry, and the preliminary mechanism was studied by Western blot. Results showed that JZ534 significantly inhibited the vitality and colony formation of lung cancer cells. JZ534 induced the G2/M cell cycle arrest of the cancer cells and suppressed the expression of cycle-related proteins, including cyclin B1 and Cdc2. Meanwhile, JZ534 induced cell apoptosis and upregulated the expression of apoptosis-related proteins, including cleaved caspase-3, Bax, and p53. At the same dose, JZ534 showed better antitumor activity than curcumin. These results suggest that JZ534 exhibits excellent anti-lung cancer activity by inhibiting the growth and inducing the apoptosis of lung cancer cells. Therefore, JZ534 is a promising lead compound for cancer treatment. PMID:25977922

  1. Dietary Curcumin Supplementation Counteracts Reduction in Levels of Molecules Involved in Energy Homeostasis after Brain Trauma

    PubMed Central

    Sharma, S.; Zhuang, Y.; Ying, Z.; Wu, A.; Gomez-Pinilla, F.

    2009-01-01

    Traumatic brain injury (TBI) is followed by an energy crisis that compromises the capacity of the brain to cope with challenges, and often reduces cognitive ability. New research indicates that events that regulate energy homeostasis crucially impact synaptic function and this can compromise the capacity of the brain to respond to challenges during the acute and chronic phases of TBI. The goal of the present study is to determine the influence of the phenolic yellow curry pigment curcumin on molecular systems involved with the monitoring, balance, and transduction of cellular energy, in the hippocampus of animals exposed to mild fluid percussion injury (FPI). Young adult rats were exposed to a regular diet (RD) without or with 500 ppm curcumin (Cur) for four weeks, before an FPI was performed. The rats were assigned to four groups: RD/Sham, Cur/Sham, RD/FPI, and Cur/FPI. We found that FPI decreased the levels of AMP-activated protein kinase (AMPK), ubiquitous mitochondrial creatine kinase (uMtCK) and cytochrome c oxidase II (COX-II) in RD/FPI rats as compared to the RD/sham rats. The curcumin diet counteracted the effects of FPI and elevated the levels of AMPK, uMtCK, COX-II in Cur/FPI rats as compared to RD/sham rats. In addition, in the Cur/sham rats, AMPK and uMtCK increased compared to the RD/sham. Results show the potential of curcumin to regulate molecules involved in energy homeostasis following TBI. These studies may foster a new line of therapeutic treatments for TBI patients by endogenous upregulation of molecules important for functional recovery. PMID:19393301

  2. Tiny molecule, big power: Multi-target approach for curcumin in diabetic cardiomyopathy.

    PubMed

    Karuppagounder, Vengadeshprabhu; Arumugam, Somasundaram; Giridharan, Vijayasree V; Sreedhar, Remya; Bose, Rajendran J C; Vanama, Jyothi; Palaniyandi, Suresh S; Konishi, Tetsuya; Watanabe, Kenichi; Thandavarayan, Rajarajan A

    2017-02-01

    Diabetic cardiomyopathy (DCM) is described as impaired cardiac diastolic and systolic functions. Diabetes mellitus (DM), a related cardiovascular disease, has become one of the major causes of death in DM patients. Mortality in these diseases is 2 to 3 times higher than in non-DM patients with cardiovascular disease. The progression of DCM and the cellular and molecular perturbations associated with the pathogenesis are complex and multifactorial. Although considerable progress has been achieved, the molecular etiologies of DCM remain poorly understood. There is an expanding need for natural antidiabetic medicines that do not cause the side effects of modern drugs. Curcumin, a pleiotropic molecule, from Curcuma longa, is known to possess numerous impacts such as scavenging free radical, antioxidant, antitumor, and antiinflammatory activities. The reports from preclinical and clinical findings revealed that curcumin can reverse insulin resistance, hyperglycemia, obesity, and obesity-related metabolic diseases. The current review provides an updated overview of the possible molecular mechanism of DCM and multitarget approach of curcumin in alleviating DCM and diabetic complication. Additionally, we mentioned the approaches that are currently being implemented to improve the bioavailability of this promising natural product in diabetes therapeutics.

  3. The characterization of the sol-gel encapsulated curcumin as a possible sensor for small biologically important molecules.

    PubMed

    Iwunze, M O; McEwan, D

    2007-05-15

    Curcumin, a known phytochemical antioxidant was found to be useful as a potential sensor for some small biologically important molecules. Hydrogen peroxide, the sodium salt of nitrite (NO2-), hydroxide (OH-), bromide (Br-) and iodide (I-) were observed to quench the fluorescence of sol-gel encapsulated curcumin, which emits radiation at 530 nm when excited at 420 nm. The observed bimolecular quenching constant which is related to the Stern-Volmer quenching constant, KSV, for the species studied in this work was determined by a modified Stern-Volmer relation for molecular surface accessibility, was observed to be specific for each of these anions and correlates quite well with their half-wave potentials, E1/2. The extent of permeability of these molecules through the pores of the sol-gel matrix was determined and they, also, correlated with these molecules' charge densities and sizes. In all the species, the reaction was quite exergonic and the free energy change, DeltaGoET, obtained in each case, suggest an outer-sphere, long range electron transfer mechanism. These observations open up the possible use of curcumin as a sensor for probing and characterizing some relevant bio-molecules in biological systems.

  4. Inhibition of NF-κB translocation by curcumin analogs induces G0/G1 arrest and downregulates thymidylate synthase in colorectal cancer.

    PubMed

    Rajitha, Balney; Belalcazar, Astrid; Nagaraju, Ganji Purnachandra; Shaib, Walid L; Snyder, James P; Shoji, Mamoru; Pattnaik, Subasini; Alam, Afroz; El-Rayes, Bassel F

    2016-04-10

    Cell cycle progression and DNA synthesis are essential steps in cancer cell growth and resistance. Thymidylate synthase (TS) is a therapeutic target for 5FU. Curcumin is a potent inhibitor of NF-κB. EF31 and UBS109 are potent synthetic analogues of curcumin. We tested the hypothesis that inhibition of NF-κB translocation by curcumin and its analogs EF31 and UBS109 can inhibit cell cycle progression and downregulate TS levels in colorectal cancer (CRC) cell lines. Two CRC cell lines (HCT116 and HT-29) were either untreated (control) or treated with IC50 concentrations of curcumin, EF31 UBS109 led to G0/G1 cell cycle arrest. Treatment with curcumin, EF31 or UBS109 inhibited NF-κB, downregulated survival pathways and inhibited cell cycle progression. Arrest in the G0/G1 phase was associated with downregulation of the transcription factor E2F-1 and its target gene TS. NF-κB over-expression induced E2F-1 and TS protein and mRNA levels in both cell lines. EF31 and UBS109 treatment significantly decreased tumor growth in compared to untreated tumors. EF31 and UBS109 are promising agents for the prevention and treatment of CRC.

  5. Heterocyclic cyclohexanone monocarbonyl analogs of curcumin can inhibit the activity of ATP-binding cassette transporters in cancer multidrug resistance.

    PubMed

    Revalde, Jezrael L; Li, Yan; Hawkins, Bill C; Rosengren, Rhonda J; Paxton, James W

    2015-02-01

    Curcumin (CUR) is a phytochemical that inhibits the xenobiotic ABC efflux transporters implicated in cancer multidrug resistance (MDR), such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins 1 and 5 (MRP1 and MRP5). The use of CUR in the clinic however, is complicated by its instability and poor pharmacokinetic profile. Monocarbonyl analogs of CUR (MACs) are compounds without CUR's unstable β-diketone moiety and were reported to have improved stability and in vivo disposition. Whether the MACs can be used as MDR reversal agents is less clear, as the absence of a β-diketone may negatively impact transporter inhibition. In this study, we investigated 23 heterocyclic cyclohexanone MACs for inhibitory effects against P-gp, BCRP, MRP1 and MRP5. Using flow cytometry and resistance reversal assays, we found that many of these compounds inhibited the transport activity of the ABC transporters investigated, often with much greater potency than CUR. Overall the analogs were most effective at inhibiting BCRP and we identified three compounds, A12 (2,6-bis((E)-2,5-dimethoxy-benzylidene)cyclohexanone), A13 (2,6-bis((E)-4-hydroxyl-3-methoxybenzylidene)-cyclohexanone) and B11 (3,5-bis((E)-2-fluoro-4,5-dimethoxybenzylidene)-1-methylpiperidin-4-one), as the most promising BCRP inhibitors. These compounds inhibited BCRP activity in a non-cell line, non-substrate-specific manner. Their inhibition occurred by direct transporter interaction rather than modulating protein or cell surface expression. From these results, we concluded that MACs, such as the heterocyclic cyclohexanone analogs in this study, also have potential as MDR reversal agents and may be superior alternatives to the unstable parent compound, CUR.

  6. Curcumin analog DM-1 in monotherapy or combinatory treatment with dacarbazine as a strategy to inhibit in vivo melanoma progression.

    PubMed

    Faião-Flores, Fernanda; Quincoces Suarez, José Agustín; Fruet, Andréa Costa; Maria-Engler, Silvya Stuchi; Pardi, Paulo Celso; Maria, Durvanei Augusto

    2015-01-01

    Malignant melanoma is a highly aggressive form of skin cancer with a high mortality rate if not discovered in early stages. Although a limited number of treatment options for melanoma currently exist, patients with a more aggressive form of this cancer frequently decline treatment. DM-1 is a sodium phenolate and curcumin analog with proven anticancer, anti-proliferative and anti-metastatic properties. In this paper, the DM-1 compound showed in vivo antitumor activity alone or in combination with chemotherapeutic DTIC in B16F10 melanoma-bearing mice. Beneficial effects such as melanoma tumor burden reduction with pyknotic nuclei, decreased nuclei/cytoplasmic ratio and nuclear degradation occurred after DM-1 treatment. No toxicological changes were observed in the liver, kidneys, spleen and lungs after DM-1 monotherapy or DTIC combined therapy. DTIC+DM-1 treatment induced the recovery of anemia arising from melanoma and immunomodulation. Both DM-1 treatment alone and in combination with DTIC induced apoptosis with the cleavage of caspase-3, -8 and -9. Furthermore, melanoma tumors treated with DM-1 showed a preferential apoptotic intrinsic pathway by decreasing Bcl-2/Bax ratio. Considering the chemoresistance exhibited by melanoma towards conventional chemotherapy drugs, DM-1 compound in monotherapy or in combination therapy provides a promising improvement in melanoma treatment with a reduction of side effects.

  7. Curcumin analog 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one exhibits enhanced ability on Nrf2 activation and protection against acrolein-induced ARPE-19 cell toxicity

    SciTech Connect

    Li, Yuan; Zou, Xuan; Cao, Ke; Xu, Jie; Yue, Tingting; Dai, Fang; Zhou, Bo; Lu, Wuyuan; Feng, Zhihui; Liu, Jiankang

    2013-11-01

    Curcumin, a phytochemical agent in the spice turmeric, has received increasing attention for its anticancer, anti-inflammatory and antioxidant properties. However, application of curcumin has been limited due to its insolubility in water and poor bioavailability both clinically and experimentally. In addition, the protective effects and mechanisms of curcumin in eye diseases have been poorly studied. In the present study, we synthesized a curcumin analog, 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one (C3), which displayed improved protective effect against acrolein-induced toxicity in a human retinal pigment epithelial cell line (ARPE-19). At 5 μM, curcumin completely protected against acrolein-induced cell oxidative damage and preserved GSH levels and mitochondrial function. Surprisingly, C3 displayed a complete protective effect at 0.5 μM, which was much more efficient than curcumin. Both 0.5 μM C3 and 5 μM curcumin induced Nrf2 nuclear translocation and Nrf2 target genes transcription similarly. Experiments using Nrf2 siRNA showed that the protective effects of curcumin and C3 were eliminated by Nrf2 knockdown. Additionally, both curcumin and C3 activated the PI3/Akt pathway, however, Nrf2 activation was independent of this pathway, and therefore, we hypothesized that both curcumin and C3 activated phase II enzymes via directly disrupting the Nrf2/Keap1 complex and promoting Nrf2's nuclear translocation. Since acrolein challenge of ARPE-19 cells has been used as a model of smoking and age-related macular degeneration (AMD), we concluded that the curcumin analog, C3, may be a more promising drug candidate for its potential application for the prevention and treatment of eye diseases, such as AMD. - Highlights: • We examine toxicity effects of cigarette smoking component acrolein in retina cells. • We report a more efficient curcumin analog (C3) protecting cellular function. • Mitochondrial function and phase II enzyme activation are the major

  8. Prospective of curcumin, a pleiotropic signalling molecule from Curcuma longa in the treatment of Glioblastoma.

    PubMed

    Luthra, Pratibha Mehta; Lal, Neetika

    2016-02-15

    GBM (Glioblastoma) is the most malignant human brain tumor with median survival of one year. The treatment involves surgery, radiotherapy and adjuvant chemotherapy mostly with the alkylation agents such as temozolomide (TMZ). Dietary polyphenol curcumin, isolated from the rhizome of the Curcuma longa (turmeric), has emerged as remarkable anti-cancer agent in the treatment of various peripheral cancers such as blood, lymphomas, multiple myeloma, melanoma as well as skin, lung, prostate, breast, ovarian, bladder, liver, gastrointestinal tract, pancreatic and colorectal epithelial cancers with a pleiotropic mode of action and also showed promise in alleviation of GBM. In this review, the mechanism of anticancer effect of curcumin in GBM has been discussed extensively. The clinical safety and pharmacokinetics of curcumin has been scrutinized to combat the challenges for the treatment of GBM.

  9. Modulatory effects of curcumin on apoptosis and cytotoxicity-related molecules in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients.

    PubMed

    Mohammadi, Asadollah; Fazeli, Bahare; Taheri, Marzieh; Sahebkar, Amirhossein; Poursina, Zohreh; Vakili, Vida; Yazdi, Shadi Zamanian; Keramati, Zahra; Boostani, Reza; Hampson, Ian; Rafatpanah, Houshang

    2017-01-01

    Apoptosis is a universal cellular defense mechanism against viral infection. Curcumin, an anti-inflammatory phytochemical, induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. Here, we investigated the impact of supplementation with curcumin on the expression of a panel of apoptosis- and cytotoxicity-related genes in patients suffering from HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), a progressive demyelinating neuroinflammatory disease caused by HTLV-1 infection. Twenty-one HAM/TSP patients enrolled in this study. Curcumin nanomicelles (80mg/day, orally) were administered once a day for 12 weeks. The mRNA levels of total Fas (tFas), membrane-bound Fas (mFas), Fas-Ligand (FasL), TNF-related apoptosis-inducing ligand (TRAIL), perforin, granzyme A, granzyme B and granulysin were analyzed before and after treatment in peripheral blood lymphocytes. Protein levels of Fas, FasL, TRAIL and granulysin were also measured in serum using ELISA. Curcumin supplementation inhibited FasL mRNA production and up-regulated the expression of pro-apoptotic molecules granzyme A (at the mRNA level) and granulysin (at the protein level), suggesting degranulation of granulysin-bearing cells following curcumin supplementation. Conversely, Curcumin did not affect Fas, TRAIL, perforin, granzyme B at the mRNA level, and anti-apoptotic molecules sFas, sFasL and sTRAIL at the protein level. The present results suggest that curcumin supplementation increases cytotoxicity-related molecules granzyme A and granulysin in patients with HAM/TSP.

  10. A novel double carbonyl analog of curcumin induces the apoptosis of human lung cancer H460 cells via the activation of the endoplasmic reticulum stress signaling pathway.

    PubMed

    Ye, Hui; Wei, Xiaoyan; Wang, Zhankun; Zhang, Shanshan; Ren, Jiye; Yao, Song; Shi, Lingyi; Yang, Lizhu; Qiu, Peihong; Wu, Jianzhang; Liang, Guang

    2016-09-01

    Curcumin can inhibit the growth of a variety of cancer cells; however, its poor bioavailability and pharmacokinetic profiles, which are attributed to its instability under physiological conditions, have limited its application in anticancer therapy. In the present study, we screened a double carbonyl analog of curcumin (A17) and analyzed its effects and mechanism of inducing apoptosis in human lung cancer H460 cells. The results showed that A17 not only induced CHOP expression in human lung cancer H460 cells, but also induced the apoptosis of H460 cells in a dose-responsive manner, and this effect was related to corresponding activation of some important components in the endoplasmic reticulum (ER) stress-mediated apoptosis pathway. When CHOP was knocked down by specific siRNA, A17-induced cell apoptosis was attenuated, thereby further demonstrating that the apoptotic pathway is ER stress‑dependent. Our studies demonstrated that A17 has better stability and antitumor activity than curcumin in H460 cells via an ER stress-mediated mechanism. These results imply that A17 could be further explored as a potential anticancer agent for the treatment of human non-small cell lung cancer (NSCLC).

  11. Design, synthesis and molecular docking of α,β-unsaturated cyclohexanone analogous of curcumin as potent EGFR inhibitors with antiproliferative activity.

    PubMed

    Xu, Yun-Yun; Cao, Yi; Ma, Hailkuo; Li, Huan-Qiu; Ao, Gui-Zhen

    2013-01-15

    A type of novel α,β-unsaturated cyclohexanone analogous, which designed based on the curcumin core structure, have been discovered as potential EGFR inhibitors. These compounds exhibit potent antiproliferative activity in two human tumor cell lines (Hep G2 and B16-F10). Among them, compounds I(3) and I(12) displayed the most potent EGFR inhibitory activity (IC(50) = 0.43 μM and 1.54 μM, respectively). Molecular docking of I(12) into EGFR TK active site was also performed. This inhibitor nicely fitting the active site might well explain its excellent inhibitory activity.

  12. Synthesis and biological evaluation of a novel class of curcumin analogs as anti-inflammatory agents for prevention and treatment of sepsis in mouse model.

    PubMed

    Zhao, Chengguang; Zhang, Yali; Zou, Peng; Wang, Jian; He, Wenfei; Shi, Dengjian; Li, Huameng; Liang, Guang; Yang, Shulin

    2015-01-01

    A novel class of asymmetric mono-carbonyl analogs of curcumin (AMACs) were synthesized and screened for anti-inflammatory activity. These analogs are chemically stable as characterized by UV absorption spectra. In vitro, compounds 3f, 3m, 4b, and 4d markedly inhibited lipopolysaccharide (LPS)-induced expression of pro-inflammatory cytokines tumor necrosis factor-α and interleukin-6 in a dose-dependent manner, with IC50 values in low micromolar range. In vivo, compound 3f demonstrated potent preventive and therapeutic effects on LPS-induced sepsis in mouse model. Compound 3f downregulated the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 MAPK and suppressed IκBα degradation, which suggests that the possible anti-inflammatory mechanism of compound 3f may be through downregulating nuclear factor kappa binding (NF-κB) and ERK pathways. Also, we solved the crystal structure of compound 3e to confirm the asymmetrical structure. The quantitative structure-activity relationship analysis reveals that the electron-withdrawing substituents on aromatic ring of lead structures could improve activity. These active AMACs represent a new class of anti-inflammatory agents with improved stability, bioavailability, and potency compared to curcumin. Our results suggest that 3f may be further developed as a potential agent for prevention and treatment of sepsis or other inflammation-related diseases.

  13. Combined treatment of curcumin and small molecule inhibitors suppresses proliferation of A549 and H1299 human non-small-cell lung cancer cells.

    PubMed

    Lin, Hui-Ping; Kuo, Li-Kuo; Chuu, Chih-Pin

    2012-01-01

    Curcumin (diferuloylmethane) is a phenolic compound present in turmeric and is ingested daily in many parts of the world. Curcumin has been reported to cause inhibition on proliferation and induction of apoptosis in many human cancer cell lines, including non-small cell lung cancer cells (NSCLC). However, the clinical application of curcumin is restricted by its low bioavailability. In this report, it was observed that combined treatment of a low dosage of curcumin (5-10 µM) with a low concentration (0.1-2.5 µM) of small molecule inhibitors, including AG1478, AG1024, PD173074, LY294002 and caffeic acid phenethyl ester (CAPE) increased the growth inhibition in two human NSCLC cell lines: A549 and H1299 cells. The observation suggested that combined treatment of a low dosage of curcumin with inhibitors against epidermal growth factor receptor (EGFR), insulin-like growth factor 1 (IGF-1R), fibroblast growth factors receptor (FGFR), phosphatidylinositol 3-kinases (PI3K) or NF-κB signaling pathway may be a potential adjuvant therapy beneficial to NSCLC patients.

  14. Curcumin: getting back to the roots.

    PubMed

    Shishodia, Shishir; Sethi, Gautam; Aggarwal, Bharat B

    2005-11-01

    The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to "get back to our roots."

  15. Atomistic study of macroscopic analogs to short-chain molecules.

    PubMed

    Welch, Kyle J; Kilmer, Clayton S G; Corwin, Eric I

    2015-02-01

    We use a bath of chaotic surface waves in water to mechanically and macroscopically mimic the thermal behavior of a short articulated chain with only nearest-neighbor interactions. The chaotic waves provide isotropic and random agitation to which a temperature can be ascribed, allowing the chain to passively explore its degrees of freedom in analogy to thermal motion. We track the chain in real time and infer end-to-end potentials using Boltzmann statistics. We extrapolate our results, by using Monte Carlo simulations of self-avoiding polymers, to lengths not accessible in our system. In the long-chain limit we demonstrate universal scaling of the statistical parameters of all chains in agreement with well-known predictions for self-avoiding walks. However, we find that the behavior of chains below a characteristic length scale fundamentally differs. We find that short chains have much greater compressional stiffness than would be expected. However, chains rapidly soften as length increases to meet with expected scalings.

  16. Single-molecule comparison of DNA Pol I activity with native and analog nucleotides

    NASA Astrophysics Data System (ADS)

    Gul, Osman; Olsen, Tivoli; Choi, Yongki; Corso, Brad; Weiss, Gregory; Collins, Philip

    2014-03-01

    DNA polymerases are critical enzymes for DNA replication, and because of their complex catalytic cycle they are excellent targets for investigation by single-molecule experimental techniques. Recently, we studied the Klenow fragment (KF) of DNA polymerase I using a label-free, electronic technique involving single KF molecules attached to carbon nanotube transistors. The electronic technique allowed long-duration monitoring of a single KF molecule while processing thousands of template strands. Processivity of up to 42 nucleotide bases was directly observed, and statistical analysis of the recordings determined key kinetic parameters for the enzyme's open and closed conformations. Subsequently, we have used the same technique to compare the incorporation of canonical nucleotides like dATP to analogs like 1-thio-2'-dATP. The analog had almost no affect on duration of the closed conformation, during which the nucleotide is incorporated. On the other hand, the analog increased the rate-limiting duration of the open conformation by almost 40%. We propose that the thiolated analog interferes with KF's recognition and binding, two key steps that determine its ensemble turnover rate.

  17. Curcumin analog UBS109 prevents bone marrow osteoblastogenesis and osteoclastogenesis disordered by coculture with breast cancer MDA-MB-231 bone metastatic cells in vitro.

    PubMed

    Yamaguchi, Masayoshi; Zhu, Shijun; Weitzmann, M Neale; Snyder, James P; Shoji, Mamoru

    2015-03-01

    UBS109 is a curcumin analog that possesses antitumor properties has been shown to stimulate osteoblastogenesis and suppress osteoclastogenesis in vitro. This study was undertaken to determine whether UBS109 might alleviate the inhibitory activity of breast cancer cells on osteoblastic mineralization and stimulatory effects on osteoclastogenesis. Mouse bone marrow cells were cocultured with breast cancer MDA-MB-231 bone metastatic cells in vitro. UBS109 stimulated osteoblastic mineralization and suppressed adipogenesis and osteoclastogenesis in bone marrow culture. Coculture with MDA-MB-231 cells suppressed osteoblastic mineralization and enhanced osteoclastogenesis in bone marrow culture. Effects that were reserved by UBS109 (50-200 nM). Mineralization in preosteoblastic MC3T3-E1 cells was suppressed by coculture with MDA-MB-231 cells, while MDA-MB-231 cells did not have effects on osteoclastogenesis of RAW267.4 cells in vitro. UBS109 (500 nM) revealed toxic effects on MDA-MB-231 bone metastatic cells. This study demonstrates that UBS109, which is an antitumor agent, reveals restorative effects on bone marrow cell differentiation disordered by coculture with breast cancer MDA-MB-231 bone metastatic cells in vitro. This in vitro model may be a useful tool to evaluate the mechanism of breast cancer cell bone metastasis.

  18. Mouse pharmacokinetics and metabolism of the curcumin analog, 4-Piperidione,3,5-bis[(2-fluorophenyl)methylene]-acetate(3E,5E) (EF-24; NSC 716993)

    PubMed Central

    Reid, Joel M.; Buhrow, Sarah A.; Gilbert, Judith A.; Jia, Lee; Shoji, Mamoru; Snyder, James P.; Ames, Matthew M.

    2015-01-01

    Purpose Curcumin, a keto-enol constituent of turmeric, has in vitro and in vivo antitumor activity. However, in vivo potency is low due to poor oral absorption. The mono-carbonyl analog, 3,5-bis[(2-fluorophenyl)methylene]-4-piperidinone acetate (EF-24, NSC 716993), exhibited broad spectrum activity in the NCI anti-cancer cell line screen and potent anti-angiogenesis activity in a HUVEC cell migration assay. The purpose of this study was to characterize the preclinical pharmacology of EF-24 in mice. Methods EF-24 plasma stability, protein binding, pharmacokinetics and metabolism were characterized utilizing an LC/MS/MS assay. Results An LC/MS/MS assay that incorporated protein precipitation with methanol, reverse-phase HPLC separation under gradient elution using an aqueous methanol mobile phase containing 0.1% formic acid and positive electrospray ionization detection of the m/z 312 > 149 transition for EF-24. The assay was linear over the range 7.8-1000 nM. Plasma protein binding was > 98% with preferential binding to albumin. EF-24 plasma disposition in mice after i.v. administration of a 10 mg/kg dose was best fit to a 3-compartment open model. The terminal elimination half-life and plasma clearance values were 73.6 min and 0.482 L/min/kg, respectively. EF-24 bioavailability was 60% and 35% after oral and i.p. administration, respectively. NADPH-dependent metabolism of EF-24 loss in liver microsomal preparations yielded several metabolites consistent with EF-24 hydroxylation and reduction. PMID:24760417

  19. Curcumin as a Modulator of P-Glycoprotein in Cancer: Challenges and Perspectives

    PubMed Central

    Lopes-Rodrigues, Vanessa; Sousa, Emília; Vasconcelos, M. Helena

    2016-01-01

    Multidrug resistance (MDR) presents a serious challenge to the efficiency of cancer treatment, and may be associated with the overexpression of drug efflux pumps. P-glycoprotein (P-gp) is a drug efflux pump often found overexpressed in cases of acquired MDR. Nevertheless, there are no P-gp inhibitors being used in the current clinical practice, due to toxicity problems, drug interactions, or pharmacokinetic issues. Therefore, it is important to identify novel inhibitors of P-gp activity or expression. Curcumin is a secondary metabolite isolated from the turmeric of Curcuma longa L. which has been associated with several biological activities, particularly P-gp modulatory activity (by inhibiting both P-gp function and expression). However, curcumin shows extensive metabolism and instability, which has justified the recent and intensive search for analogs of curcumin that maintain the P-gp modulatory activity but have enhanced stability. This review summarizes and compares the effects of curcumin and several curcumin analogs on P-glycoprotein function and expression, emphasizing the potential of these molecules for the possible development of safe and effective inhibitors of P-gp to overcome MDR in human cancer. PMID:27834897

  20. Synergistic effects of the purine analog sulfinosine and curcumin on the multidrug resistant human non-small cell lung carcinoma cell line (NCI-H460/R).

    PubMed

    Andjelkovic, Tijana; Pesic, Milica; Bankovic, Jasna; Tanic, Nikola; Markovic, Ivanka D; Ruzdijic, Sabera

    2008-07-01

    Multidrug resistance (MDR) is the main obstacle to a successful chemotherapy of lung cancer. We tested the potential of sulfinosine and curcumin, alone and in combination, for modulating MDR in the human resistant, non-small cell lung carcinoma cell line (NCI-H460/R). First, we determined the mutational status of the p53 gene in NCI-H460/R cells by PCR-SSCP and DNA sequencing and identified mutations which could at least partially contribute to the development of the MDR phenotype. The effects of sulfinosine and curcumin were studied, both separately and in combination, at the level of cytotoxicity, cell cycle distribution and gene expression. Sulfinosine displayed dose-dependent growth inhibition in both resistant and control sensitive cell lines, whereas curcumin considerably inhibited their growth only at relatively high doses. When sulfinosine was combined with a low dose of curcumin the drugs exerted a synergistic cytotoxic effect in NCI-H460/R cells. The expression of MDR-related genes mdr1, gst-pi and topo IIalpha, was altered by sulfinosine and curcumin. The most pronounced effect was observed when the agents were applied together. Sulfinosine and curcumin caused perturbations in cell cycle distribution in the NCI-H460/R cell line. The combination of the two drugs induced a more pronounced cell cycle arrest in S and G(2)/M in NCI-H460/R cells. Our results show that sulfinosine and curcumin overcome MDR in non-small cell lung carcinoma cell line (NSCLC), especially in combination despite the presence of a mutated p53 gene.

  1. Preparation and affinity identification of glutamic acid-urea small molecule analogs in prostate cancer

    PubMed Central

    Zhang, Zhiwei; Zhu, Zheng; Yang, Deyong; Fan, Weiwei; Wang, Jianbo; Li, Xiancheng; Chen, Xiaochi; Wang, Qifeng; Song, Xishuang

    2016-01-01

    In recent years, study concerning activity inhibitors of prostate-specific membrane antigen (PSMA) has been concentrated on the glutamic urea (Glu-urea-R) small molecule and its analogs. The present study aimed to synthesize 4 analogs of Glu-urea-R and identify the affinities of these compounds to PSMA. The compounds were synthesized from raw materials, and the experimental procedures of the present study were in accordance with standard techniques under anhydrous and anaerobic conditions. Glu-urea-Lysine (Glu-urea-Lys), Glu-urea-Ornithine (Glu-urea-Orn), Glu-urea-Glutamine (Glu-urea-Gln) and Glu-urea-Asparagine (Glu-urea-Asn) were successfully synthesized, and their structures were confirmed to be as desired using nuclear magnetic resonance spectroscopy and mass spectrometry. An affinity assay was performed to detect the affinity between the various compounds and PSMA expressed from the prostate cancer LNCap cell line. Glu-urea-Gln had the highest affinity to PSMA, followed by Glu-urea-Asn, Glu-urea-Orn and Glu-urea-Lys. In conclusion, the present study demonstrated that Glu-urea-R specifically binds PSMA expressed in the LNCap cell line and inhibits its activity. PMID:27446384

  2. Anticarcinogenic effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione a curcumin analog on DMH-induced colon cancer model.

    PubMed

    Devasena, T; Rajasekaran, K N; Gunasekaran, G; Viswanathan, P; Menon, Venugopal P

    2003-02-01

    1,2-Dimethylhydrazine (DMH) is a toxic environmental pollutant which was reported also to be a colon-specific carcinogen. This study was performed to study the effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione, a bisdemethoxycurcumin analog (BDMC-A) on DMH-induced colon carcinogenesis in male Wistar rats and effects were compared with that of the reference drug, curcumin. Rats were given a weekly subcutaneous injection of DMH (20mg/kg body weight) in the groin, for 15 weeks. After a total experimental period of 32 weeks (including 2 weeks of acclimatization) tumor incidence was 100% in DMH-treated rats. Tumor was identified histologically as adenocarcinoma. Dysplasia, papillary pattern, cellular pleomorphism and carcinomatous glands were also noticed in DMH-treated rats. However, there was no colonic tumor in DMH+BDMC-A- and DMH+curcumin-treated rats but, lymphocyte infiltrations were observed. The levels of total bile acids and cholesterol in 24h fecal samples were significantly lower in DMH administered rats when compared to control rats, while, the excretion of bile acids and cholesterol were significantly increased and was near normal levels in DMH+BDMC-A- and DMH+curcumin-treated rats. In DMH-induced tumor bearing rats the levels of colonic and intestinal cholesterol was significantly increased whereas, the levels of phospholipid was decreased with a concomitant increase in the activities of phospholipase A (PLA) and phospholipase C (PLC), compared to untreated control rats. Intragastric administration of BDMC-A and curcumin to DMH administered rats significantly lowered the cholesterol content and raised the phospholipid content and lowered the activities of PLA and PLC towards near normal values. Our study shows that the protective effect of BDMC-A during DMH-induced colon carcinogenesis may be due to its modulatory effects on (i). histological changes, (ii). bile acids, (iii). cholesterol, and (iv). phospholipid metabolism in the target organ

  3. Bringing Curcumin to the Clinic in Cancer Prevention: a Review of Strategies to Enhance Bioavailability and Efficacy.

    PubMed

    Mahran, Rama I; Hagras, Magda M; Sun, Duxin; Brenner, Dean E

    2017-01-01

    Curcumin is widely available, inexpensive spice that has been used in ancient folk medicine for millennia, especially in India. Curcumin has the pharmacological properties that slow or reverse cellular proliferation and enhance apoptosis and differentiation associated with a diverse array of molecular effects. Despite its effective anticarcinogenesis properties, curcumin's poor solubility, instability, and extensive metabolism result in poor oral bioavailability. Strategies to enhance curcumin delivery include encapsulating or incorporating curcumin in a nanoparticle or microparticle drug delivery system, synthesizing more stable curcumin analogs that resist metabolism while retaining curcumin's pharmacological properties, and adding another natural product that has bioenhancing properties to curcumin or combination of two of these strategies. This review comprehensively explores curcumin's chemistry and pharmacology followed by comparing and contrasting a vast number of strategies designed to enhance curcumin's bioavailability and its therapeutic effects. The review provides insights into which curcumin formulation strategies have the greatest promise to reach clinical application.

  4. The Curcumin Analog C-150, Influencing NF-κB, UPR and Akt/Notch Pathways Has Potent Anticancer Activity In Vitro and In Vivo

    PubMed Central

    Hackler, László; Ózsvári, Béla; Gyuris, Márió; Sipos, Péter; Fábián, Gabriella; Molnár, Eszter; Marton, Annamária; Faragó, Nóra; Mihály, József; Nagy, Lajos István; Szénási, Tibor; Diron, Andrea; Párducz, Árpád; Kanizsai, Iván; Puskás, László G.

    2016-01-01

    C-150 a Mannich-type curcumin derivative, exhibited pronounced cytotoxic effects against eight glioma cell lines at micromolar concentrations. Inhibition of cell proliferation by C-150 was mediated by affecting multiple targets as confirmed at transcription and protein level. C-150 effectively reduced the transcription activation of NFkB, inhibited PKC-alpha which are constitutively over-expressed in glioblastoma. The effects of C-150 on the Akt/ Notch signaling were also demonstrated in a Drosophila tumorigenesis model. C-150 reduced the number of tumors in Drosophila with similar efficacy to mitoxantrone. In an in vivo orthotopic glioma model, C-150 significantly increased the median survival of treated nude rats compared to control animals. The multi-target action of C-150, and its preliminary in vivo efficacy would render this curcumin analogue as a potent clinical candidate against glioblastoma. PMID:26943907

  5. Design, synthesis, and evaluation of curcumin derivatives as Nrf2 activators and cytoprotectors against oxidative death.

    PubMed

    Tu, Zhi-Shan; Wang, Qi; Sun, Dan-Dan; Dai, Fang; Zhou, Bo

    2017-04-05

    Activation of nuclear factor erythroid-2-related factor 2 (Nrf2) has been proven to be an effective means to prevent the development of cancer, and natural curcumin stands out as a potent Nrf2 activator and cancer chemopreventive agent. In this study, we synthesized a series of curcumin analogs by introducing the geminal dimethyl substituents on the active methylene group to find more potent Nrf2 activators and cytoprotectors against oxidative death. The geminally dimethylated and catechol-type curcumin analog (compound 3) was identified as a promising lead molecule in terms of its increased stability and cytoprotective activity against the tert-butyl hydroperoxide (t-BHP)-induced death of HepG2 cells. Mechanism studies indicate that its cytoprotective effects are mediated by activating the Nrf2 signaling pathway in the Michael acceptor- and catechol-dependent manners. Additionally, we verified by using copper and iron ion chelators that the two metal ion-mediated oxidations of compound 3 to its corresponding electrophilic o-quinone, contribute significantly to its Nrf2-dependent cytoprotection. This work provides an example of successfully designing natural curcumin-directed Nrf2 activators by a stability-increasing and proelectrophilic strategy.

  6. Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells

    PubMed Central

    Li, Lei; Xiang, Dongxi; Shigdar, Sarah; Yang, Wenrong; Li, Qiong; Lin, Jia; Liu, Kexin; Duan, Wei

    2014-01-01

    To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells. PMID:24591829

  7. Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells.

    PubMed

    Li, Lei; Xiang, Dongxi; Shigdar, Sarah; Yang, Wenrong; Li, Qiong; Lin, Jia; Liu, Kexin; Duan, Wei

    2014-01-01

    To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells.

  8. Curcumin and Health.

    PubMed

    Pulido-Moran, Mario; Moreno-Fernandez, Jorge; Ramirez-Tortosa, Cesar; Ramirez-Tortosa, Mcarmen

    2016-02-25

    Nowadays, there are some molecules that have shown over the years a high capacity to act against relevant pathologies such as cardiovascular disease, neurodegenerative disorders or cancer. This article provides a brief review about the origin, bioavailability and new research on curcumin and synthetized derivatives. It examines the beneficial effects on health, delving into aspects such as cancer, cardiovascular effects, metabolic syndrome, antioxidant capacity, anti-inflammatory properties, and neurological, liver and respiratory disorders. Thanks to all these activities, curcumin is positioned as an interesting nutraceutical. This is the reason why it has been subjected to several modifications in its structure and administration form that have permitted an increase in bioavailability and effectiveness against different diseases, decreasing the mortality and morbidity associated to these pathologies.

  9. Interaction of curcumin with 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine liposomes: Intercalation of rhamnolipids enhances membrane fluidity, permeability and stability of drug molecule.

    PubMed

    Moussa, Zeinab; Chebl, Mazhar; Patra, Digambara

    2017-01-01

    Stability of curcumin in neutral and alkaline buffer conditions has been a serious concern for its medicinal applications. We demonstrate that the stability of curucmin can be improved in 1,2-Dioctadecanoyl-sn-glycero-3-phosphocholine (DSPC) liposomes. Curcumin strongly partition into liquid crystalline phase compared to solid gel phase of DSPC liposomes. Variation of fluorescence intensity of curcumin associated with liposomes with temperature successfully determines phase transition temperature of DSPC liposomes. However, at higher molar ratio curcumin can influence phase transition temperature by intercalating into deep hydrophobic layer of liposomes and facilitating fusion of two membrane phases. Rhamnolipids (RLs) are recently being applied for various biomedical applications. Here, we have explored new insight on intercalation of rhamnolipids with DSPC liposomes. Intercalation of rhamnolipids exceptionally increases partition of curcumin into solid gel phase of DSPC liposomes, whereas this increase is moderate in liquid crystalline phase. Fluorescence quenching study establishes that permeability and fluidity of the DSPC liposomes are enhanced in the presence of RLs. Membrane permeability and fluidity can be improved further by increasing the percentage of RLs in DSPC liposomes. The phase transition temperature of DSPC liposomes decreases with increase in percentage of RLs in DSPC liposomes by encouraging fusion between solid gel and liquid crystalline phases. Intercalation of RLs is found to further boost stability of drug, curcumin, in DSPC liposomes. Thus, mixing RLs with DSPC liposomes could potentially serve as a good candidate for drug delivery application.

  10. Curcumin as "Curecumin": from kitchen to clinic.

    PubMed

    Goel, Ajay; Kunnumakkara, Ajaikumar B; Aggarwal, Bharat B

    2008-02-15

    Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be "Curecumin".

  11. Curcumin as a potential protective compound against cardiac diseases.

    PubMed

    Jiang, Shuai; Han, Jing; Li, Tian; Xin, Zhenlong; Ma, Zhiqiang; Di, Wencheng; Hu, Wei; Gong, Bing; Di, Shouyin; Wang, Dongjin; Yang, Yang

    2017-03-06

    Curcumin, which was first used 3000 years ago as an anti-inflammatory agent, is a well-known bioactive compound derived from the active ingredient of turmeric (Curcuma longa). Previous research has demonstrated that curcumin has immense therapeutic potential in a variety of diseases via anti-oxidative, anti-apoptotic, and anti-inflammatory pathways. Cardiac diseases are the leading cause of mortality worldwide and cause considerable harm to human beings. Numerous studies have suggested that curcumin exerts a protective role in the human body whereas its actions in cardiac diseases remain elusive and poorly understood. On the basis of the current evidence, we first give a brief introduction of cardiac diseases and curcumin, especially regarding the effects of curcumin in embryonic heart development. Secondly, we analyze the basic roles of curcumin in pathways that are dysregulated in cardiac diseases, including oxidative stress, apoptosis, and inflammation. Thirdly, actions of curcumin in different cardiac diseases will be discussed, as will relevant clinical trials. Eventually, we would like to discuss the existing controversial opinions and provide a detailed analysis followed by the remaining obstacles, advancement, and further prospects of the clinical application of curcumin. The information compiled here may serve as a comprehensive reference of the protective effects of curcumin in the heart, which is significant to the further research and design of curcumin analogs as therapeutic options for cardiac diseases.

  12. Molecular analogs of the hemihelix: A computational study of chain molecules containing left- and right-handed helices

    NASA Astrophysics Data System (ADS)

    Pichierri, Fabio

    2014-08-01

    Using density functional theory (DFT) we design two novel chain molecules containing a left-handed (thia)helicene unit connected to a right-handed (thia)helicene unit via a phosphoroussbnd phosphorous (Psbnd P) bond. These chains represent the molecular analogs of the novel hemihelix structure recently discovered by a group of Harvard University scientists. The HOMO and LUMO levels of the heterochiral chains, termed hemihelicenes, are localized on the left- and right-handed blocks, respectively. In contrast, the frontier orbitals of the chains containing homochiral (thia)helicenes connected by a Psbnd P bond are delocalized all over the chain.

  13. CARBON DIOXIDE INFLUENCE ON THE THERMAL FORMATION OF COMPLEX ORGANIC MOLECULES IN INTERSTELLAR ICE ANALOGS

    SciTech Connect

    Vinogradoff, V.; Fray, N.; Bouilloud, M.; Cottin, H.; Duvernay, F.; Chiavassa, T.

    2015-08-20

    Interstellar ices are submitted to energetic processes (thermal, UV, and cosmic-ray radiations) producing complex organic molecules. Laboratory experiments aim to reproduce the evolution of interstellar ices to better understand the chemical changes leading to the reaction, formation, and desorption of molecules. In this context, the thermal evolution of an interstellar ice analogue composed of water, carbon dioxide, ammonia, and formaldehyde is investigated. The ice evolution during the warming has been monitored by IR spectroscopy. The formation of hexamethylenetetramine (HMT) and polymethylenimine (PMI) are observed in the organic refractory residue left after ice sublimation. A better understanding of this result is realized with the study of another ice mixture containing methylenimine (a precursor of HMT) with carbon dioxide and ammonia. It appears that carbamic acid, a reaction product of carbon dioxide and ammonia, plays the role of catalyst, allowing the reactions toward HMT and PMI formation. This is the first time that such complex organic molecules (HMT, PMI) are produced from the warming (without VUV photolysis or irradiation with energetic particles) of abundant molecules observed in interstellar ices (H{sub 2}O, NH{sub 3}, CO{sub 2}, H{sub 2}CO). This result strengthens the importance of thermal reactions in the ices’ evolution. HMT and PMI, likely components of interstellar ices, should be searched for in the pristine objects of our solar system, such as comets and carbonaceous chondrites.

  14. Carbon Dioxide Influence on the Thermal Formation of Complex Organic Molecules in Interstellar Ice Analogs

    NASA Astrophysics Data System (ADS)

    Vinogradoff, V.; Duvernay, F.; Fray, N.; Bouilloud, M.; Chiavassa, T.; Cottin, H.

    2015-08-01

    Interstellar ices are submitted to energetic processes (thermal, UV, and cosmic-ray radiations) producing complex organic molecules. Laboratory experiments aim to reproduce the evolution of interstellar ices to better understand the chemical changes leading to the reaction, formation, and desorption of molecules. In this context, the thermal evolution of an interstellar ice analogue composed of water, carbon dioxide, ammonia, and formaldehyde is investigated. The ice evolution during the warming has been monitored by IR spectroscopy. The formation of hexamethylenetetramine (HMT) and polymethylenimine (PMI) are observed in the organic refractory residue left after ice sublimation. A better understanding of this result is realized with the study of another ice mixture containing methylenimine (a precursor of HMT) with carbon dioxide and ammonia. It appears that carbamic acid, a reaction product of carbon dioxide and ammonia, plays the role of catalyst, allowing the reactions toward HMT and PMI formation. This is the first time that such complex organic molecules (HMT, PMI) are produced from the warming (without VUV photolysis or irradiation with energetic particles) of abundant molecules observed in interstellar ices (H2O, NH3, CO2, H2CO). This result strengthens the importance of thermal reactions in the ices’ evolution. HMT and PMI, likely components of interstellar ices, should be searched for in the pristine objects of our solar system, such as comets and carbonaceous chondrites.

  15. Lack of nucleophilic addition in the isoxazole and pyrazole diketone modified analogs of curcumin; implications for their antitumor and chemosensitizing activities.

    PubMed

    Labbozzetta, Manuela; Baruchello, Riccardo; Marchetti, Paolo; Gueli, Maria C; Poma, Paola; Notarbartolo, Monica; Simoni, Daniele; D'Alessandro, Natale

    2009-09-14

    Curcumin (CUR) can be considered as a good lead compound for the design of new anticancer drugs. Further, structure-activity relationship studies may clarify the importance of the redox activities in the antitumor effects of the drug. We have elaborated the alpha,beta-unsaturated 1,3-diketone moiety of CUR into the isoxazole (ISO) and pyrazole (PYR) derivatives. These derivatives should be much less prone to nucleophilic addition than CUR and benzyl mercaptan addition analyses showed that indeed they do not form isolable conjugated products. When compared with CUR, ISO and PYR exhibited increased cell growth inhibitory and pro-apoptotic effects in liver cancer HA22T/VGH cells as well as in other tumor cell types; in contrast to CUR, the antitumor effects of ISO or PYR were not influenced by concomitant administration of N-acetylcysteine, as a source of -SH groups, or buthionine sulfoximine, as an inhibitor of glutathione synthesis. Further, treatment with CUR, but not with ISO or PYR, significantly decreased the content of reduced glutathione in the HA22T/VGH cells. Finally, ISO and PYR lacked the ability of the parent compound to sensitize the HA22T/VGH cells to cisplatin (CIS), an effect which appeared to occur through an interaction of CUR and CIS at the level of the -SH groups. Thus, the ability of interacting with cell thiols might not be requested for the more potent antitumor activities of new diketone modified CUR derivatives, which might rely on other mechanisms, though possibly devoid of chemosensitization capabilities.

  16. Using Electron Induced Dissociation (EID) on an LC Time-Scale to Characterize a Mixture of Analogous Small Organic Molecules

    NASA Astrophysics Data System (ADS)

    Prakash, Aruna S.; Smith, Michael J. P.; Kaabia, Zied; Hurst, Glenn; Yan, Ci; Sims, Martin; Bristow, Anthony W. T.; Stokes, Peter; Parker, David; Mosely, Jackie A.

    2012-05-01

    LC ESI FTICR MS of a sample of cediranib identified this pharmaceutical target molecule plus an additional 10 compounds of interest, all of which were less than 10% total ion current (TIC) peak intensity relative to cediranib. LC FTICR tandem mass spectrometry using electron induced dissociation (EID) has been achieved and has proven to be the best way to generate useful product ion information for all of these singly protonated molecules. Cediranib [M + H]+ fragmented by EID to give 29 product ions whereas QTOF-CID generated only one very intense product ion, and linear ion trap-CID, which generated 10 product ions, but all with poor S/N. Twenty-six of the EID product ions were unique to this fragmentation technique alone. By considering the complementary LC-EID and LC-CID data together, all 10 unknown compounds were structurally characterized and proven to be analogous to cediranib. Of particular importance, EID produced unique product ion information for one of the low level cediranib analogues that enabled full characterization of the molecule such that the presence of an extra propylpyrrolidine group was discovered and proven to be located on the pyrrolidine ring of cediranib, solving an analytical problem that could not be solved by collision induced dissociation (CID). Thus, it has been demonstrated that EID is in harmony with the chromatography duty-cycle and the dynamic concentration range of synthetic compounds containing trace impurities, providing crucial analytical information that cannot be obtained by more traditional methodologies.

  17. Curcumin and aging

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Curcumin has been used commonly as a spice, food additive, and an herbal medicine worldwide. Known as a bioactive polyphenolic, curcumin has a broad range of beneficial properties to human health. Recently, active research on curcumin with respect to aging and related traits in model organisms has d...

  18. Crystal structures of the thi-box riboswitch bound to thiamine pyrophosphate analogs reveal adaptive RNA-small molecule recognition.

    PubMed

    Edwards, Thomas E; Ferré-D'Amaré, Adrian R

    2006-09-01

    Riboswitches are noncoding mRNA elements that bind small-molecule metabolites with high affinity and specificity, and they regulate the expression of associated genes. The thi-box riboswitch can exhibit a 1000-fold higher affinity for thiamine pyrophosphate over closely related noncognate compounds such as thiamine monophosphate. To understand the chemical basis of thi-box pyrophosphate specificity, we have determined crystal structures of an E. coli thi-box bound to thiamine pyrophosphate, thiamine monophosphate, and the structural analogs benfotiamine and pyrithiamine. When bound to monophosphorylated compounds, the RNA elements that recognize the thiamine and phosphate moieties of the ligand move closer together. This allows the riboswitch to recognize the monophosphate in a manner similar to how it recognizes the beta-phosphate of thiamine pyrophosphate. In the pyrithiamine complex, the pyrophosphate binding site is largely unstructured. These results show how the riboswitch can bind to various metabolites, and why the thi-box preferentially binds thiamine pyrophosphate.

  19. Measurements of Polyatomic Molecule Formation on an Icy Grain Analog Using Fast Atoms

    NASA Technical Reports Server (NTRS)

    Chutjian, A.; Madsunkov, S.; Shortt, B. J.; MacAskill, J. A.; Darrach, M. R.

    2006-01-01

    Carbon dioxide has been produced from the impact of a monoenergetic O(P-3) beam upon a surface cooled to 4.8 K and covered with a CO ice. Using temperature-programmed desorption and mass spectrometer detection, we have detected increasing amounts of CO2 formation with O(P-3) energies of 2, 5, 10, and 14 eV. This is the first measurement of polyatomic molecule formation on a surface with superthermal atoms. The goal of this work is to detect other polyatomic species, such as CH3OH, which can be formed under conditions that simulate the grain temperature, surface coverage, and superthermal atoms present in shock-heated circumstellar and interstellar regions.

  20. Synthesis of Large Molecules in Cometary Ice Analogs: Physical Properties Related to Self-Assembly Processes

    NASA Technical Reports Server (NTRS)

    Dworkin, Jason P.; Sandford, Scott A.; Deamer, David W.; Gillette, J. Seb; Zare, Richard N.; Allamandola, Louis J. (Technical Monitor)

    1999-01-01

    The combination of realistic laboratory simulations and infrared observations have revolutionized our understanding of interstellar dust and ice-the main component of comets. Since comets and carbonaceous micrometeorites may have been important sources of volatiles and carbon compounds on the early Earth, their organic composition may be related to the origin of life. Ices on grains in molecular clouds contain a variety of simple molecules. The D/H ratios of the comets Hale-Bopp and Hyakutake are consistent with a primarily interstellar ice mixture. Within the cloud and especially in the presolar nebula through the early solar system, these icy grains would have been photoprocessed by the ultraviolet producing more complex species such as hexamethylenetetramine, polyoxymethylenes, and simple keones. We reported at the 1999 Bioastronomy meeting laboratory simulations studied to identify the types of molecules which could have been generated in pre-cometary ices. Experiments were conducted by forming a realistic interstellar mixed-molecular ice (H2O, CH3OH, NH3 and CO) at approximately 10 K under high vacuum irradiated with UV light from a hydrogen plasma lamp. The gas mixture was typically 100:50:1:1, however when different ratios were used material with similar characteristics was still produced. The residue that remained after warming to room temperature was analyzed by HPLC, and by several mass spectrometric methods. This material contains a rich mixture of complex compounds with mass spectral profiles resembling those found in IDPs and meteorites. Surface tension measurements show that an amphiphilic component is also present. These species do not appear in various controls or in unphotolyzed samples. Residues from the simulations were also dispersed in aqueous media for microscopy. The organic material forms 10-40 gm diameter droplets that fluoresce at 300-450 nm under UV excitation. These droplets have a morphology and internal structure which appear

  1. The effect of curcumin on the stability of Aβ dimers.

    PubMed

    Zhao, Li Na; Chiu, See-Wing; Benoit, Jérôme; Chew, Lock Yue; Mu, Yuguang

    2012-06-28

    Aβ oligomers are potential targets for the diagnosis and therapy of Alzheimer's disease (AD). On the other hand, the molecule curcumin has been shown to possess significant therapeutic potential in many areas. In this paper, we use all-atom explicit solvent molecular dynamics simulations to study the effect of curcumin on the stability of Aβ amyloid protein oligomers. We observed that curcumin decreases the β-sheet secondary structural content within the Aβ oligomers without reducing the contacts between the monomers. The breaking of the β-sheet is found to be preceded by a deformation of the β-sheet structure due to hydrophobic interaction from the nearby curcumin. Furthermore, the π-stacking interaction between curcumin (keto ring and enol ring) and the aromatic residues of Aβ, which exists throughout the simulations, has also contributed to the diminishing of the β-sheet structure. Our analysis of the underwrapped amide-carbonyl hydrogen bonds reveals several stable dehydrons of the oligomer, especially the dehydron pair 34L and 41I, which curcumin tends to hover over. We have examined the paths of curcumin on the Aβ proteins and determined the common routes where curcumin lingers as it traverses around the Aβ. In consequence, our study has provided a detailed interaction picture between curcumin and the Aβ oligomers.

  2. Curcumin: a natural substance with potential efficacy in Alzheimer's disease.

    PubMed

    Potter, Pamela E

    2013-01-01

    Curcumin is a component of turmeric, a spice used in many types of cooking. Epidemiological evidence suggesting that populations that eat food with a substantial amount of curcumin were at lower risk of Alzheimer's disease (AD) led to the idea that this compound might have a neuroprotective effect. Curcumin has substantial antioxidant and anti-inflammatory effects, and is being used as a potential preventative agent or treatment for many types of cancer. There is evidence to suggest that the addition of curcumin to cultured neuronal cells decreases brain inflammation and protects against β-amyloid-induced neurotoxicity. Curcumin also protects against toxicity when β-amyloid is administered to produce animal models of AD. Curcumin decreases β-amyloid formation from amyloid precursor protein, and also inhibits aggregation of β-amyloid into pleated sheets. Studies in transgenic mice with overproduction of β-amyloid demonstrate a neuroprotective effect of curcumin as well. Cognitive function was also improved in these animal models. Clinical trials of curcumin in AD have not been very promising. It is possible that this is due to poor oral bioavailability of curcumin in humans, and thus several approaches are being developed to improve delivery systems or to create analogs that will mimic the neuroprotective effects and easily reach the brain. The lack of efficacy of curcumin in humans with AD may also result from treating for too short a time or starting treatment too late in the course of the disease, where substantial neuronal death has already occurred and cannot be reversed. Curcumin may be beneficial in protecting against development or progression of AD if taken over the long term and started before symptoms of AD become apparent.

  3. Anticancer Activity of Curcumin and Its Analogues: Preclinical and Clinical Studies.

    PubMed

    Allegra, Alessandro; Innao, Vanessa; Russo, Sabina; Gerace, Demetrio; Alonci, Andrea; Musolino, Caterina

    2017-01-02

    Curcumin has been shown to have a wide variety of therapeutic effects, ranging from anti-inflammatory, chemopreventive, anti-proliferative, and anti-metastatic. This review provides an overview of the recent research conducted to overcome the problems with the bioavailability of curcumin, and of the preclinical and clinical studies that have reported success in combinatorial strategies coupling curcumin with other treatments. Research on the signaling pathways that curcumin treatment targets shows that it potently acts on major intracellular components involved in key processes such as genomic modulations, cell invasion and cell death pathways. Curcumin is a promising molecule for the prevention and treatment of cancer.

  4. Biocompatible Lipid Nanoparticles as Carriers To Improve Curcumin Efficacy in Ovarian Cancer Treatment.

    PubMed

    Bondì, Maria Luisa; Emma, Maria Rita; Botto, Chiara; Augello, Giuseppa; Azzolina, Antonina; Di Gaudio, Francesca; Craparo, Emanuela Fabiola; Cavallaro, Gennara; Bachvarov, Dimcho; Cervello, Melchiorre

    2017-02-22

    Curcumin is a natural molecule with proved anticancer efficacy on several human cancer cell lines. However, its clinical application has been limited due to its poor bioavailability. Nanocarrier-based drug delivery approaches could make curcumin dispersible in aqueous media, thus overtaking the limits of its low solubility. The aim of this study was to increase the bioavailability and the antitumoral activity of curcumin, by entrapping it into nanostructured lipid carriers (NLCs). For this purpose here we describe the preparation and characterization of three kinds of curcumin-loaded NLCs. The nanosystems allowed the achievement of a controlled release of curcumin, the amounts of curcumin released after 24 h from Compritol-Captex, Compritol-Miglyol, and Compritol NLCs being, respectively, equal to 33, 28, and 18% w/w on the total entrapped curcumin. Considering the slower curcumin release profile, Compritol NLCs were chosen to perform successive in vitro studies on ovarian cancer cell lines. The results show that curcumin-loaded NLCs maintain anticancer activity, and reduce cell colony survival more effectively than free curcumin. As an example, the ability of A2780S cells to form colonies was decreased after treatment with 5 μM free curcumin by 50% ± 6, whereas, at the same concentration, the delivery of curcumin with NLC significantly (p < 0.05) inhibited colony formation to approximately 88% ± 1, therefore potentiating the activity of curcumin to inhibit A2780S cell growth. The obtained results clearly suggest that the entrapment of curcumin into NLCs increases curcumin efficacy in vitro, indicating the potential use of NLCs as curcumin delivery systems.

  5. Strategies to enhance the bioavailability of curcumin: a potential antitumor drug

    NASA Astrophysics Data System (ADS)

    Kumar, Abhishek; Chittigori, Joshna; Li, Lian; Samuelson, Lynne; Sandman, Daniel; Kumar, Jayant

    2012-02-01

    Curcumin is a polyphenol which has elicited considerable interest for its antioxidant and anti tumor properties. Although curcumin may be used as potential therapeutic drug, it is very sparingly soluble in water which makes it less bioavailable under physiological conditions. We report two approaches to make curcumin more bioavailable. The first approach involves fabricating colloidal dispersions of curcumin in the range of tens of nanometers. The second approach involves functionalization of curcumin with polyethylene glycol (PEG) to render it water dispersible or soluble. Since curcumin is a fluorescent molecule as well as a potential drug, its interactions with cells have been investigated using one and two photon confocal fluorescence imaging. We have also observed strong interaction between curcumin and metal ions, which may have physiological implications.

  6. Curcumin is an inhibitor of p300 histone acetylatransferase.

    PubMed

    Marcu, Monica G; Jung, Yun-Jin; Lee, Sunmin; Chung, Eun-Joo; Lee, Min-Jung; Trepel, Jane; Neckers, Len

    2006-03-01

    Histone acetyltransferases (HATs), and p300/CBP in particular, have been implicated in cancer cell growth and survival, and as such, HATs represent novel, therapeutically relevant molecular targets for drug development. In this study, we demonstrate that the small molecule natural product curcumin, whose medicinal properties have long been recognized in India and Southeast Asia, is a selective HAT inhibitor. Furthermore the data indicate that alpha, beta unsaturated carbonyl groups in the curcumin side chain function as Michael reaction sites and that the Michael reaction acceptor functionality of curcumin is required for its HAT-inhibitory activity. In cells, curcumin promoted proteasome-dependent degradation of p300 and the closely related CBP protein without affecting the HATs PCAF or GCN5. In addition to inducing p300 degradation curcumin inhibited the acetyltransferase activity of purified p300 as assessed using either histone H3 or p53 as substrate. Radiolabeled curcumin formed a covalent association with p300, and tetrahydrocurcumin displayed no p300 inhibitory activity, consistent with a Michael reaction-dependent mechanism. Finally, curcumin was able to effectively block histone hyperacetylation in both PC3-M prostate cancer cells and peripheral blood lymphocytes induced by the histone deacetylase inhibitor MS-275. These data thus identify the medicinal natural product curcumin as a novel lead compound for development of possibly therapeutic, p300/CBP-specific HAT inhibitors.

  7. Novel delivery system for natural products: Nano-curcumin formulations

    PubMed Central

    Rahimi, Hamid Reza; Nedaeinia, Reza; Sepehri Shamloo, Alireza; Nikdoust, Shima; Kazemi Oskuee, Reza

    2016-01-01

    Objective: Curcumin is extracted from Curcuma longa and regulates the intracellular signal pathways which control the growth of cancerous cell, inflammation, invasion and apoptosis. Curcumin molecules have special intrinsic features that can target the intracellular enzymes, genome (DNA) and messengers (RNA). A wide range of studies have been conducted on the physicochemical traits and pharmacological effects of curcumin on different diseases like cardiovascular diseases, diabetes, cancer, rheumatoid arthritis, Alzheimer’s, inflammatory bowel disease (IBD), and even it has wound healing. Oral bioavailability of curcumin is rather poor, which would certainly put some boundaries in the employment of this drug. Materials and Methods: Bibliographical searches were performed using MEDLINE/ScienceDirect/OVID up to February 2015 using the following keywords (all fields): (“Curcumin” OR “Curcuma longa”) AND [(nanoparticles) OR (Nanomicelles) OR (micro emulsions) OR (liposome) OR (phospholipid). Results: Consequently, for any developments of curcumin in the future, analogues of curcumin that have better bioavailability or substitute formulations are needed crucially. Conclusion: These studies indicated that nanotechnology can formulate curcumin effectively, and this nano-formulated curcumin with a potent ability against various cancer cells, were represented to have better efficacy and bioavailability under in vivo conditions. PMID:27516979

  8. Nanotechnology-Applied Curcumin for Different Diseases Therapy

    PubMed Central

    Ghalandarlaki, Negar; Ashkani-Esfahani, Soheil

    2014-01-01

    Curcumin is a lipophilic molecule with an active ingredient in the herbal remedy and dietary spice turmeric. It is used by different folks for treatment of many diseases. Recent studies have discussed poor bioavailability of curcumin because of poor absorption, rapid metabolism, and rapid systemic elimination. Nanotechnology is an emerging field that is potentially changing the way we can treat diseases through drug delivery with curcumin. The recent investigations established several approaches to improve the bioavailability, to increase the plasma concentration, and to enhance the cellular permeability processes of curcumin. Several types of nanoparticles have been found to be suitable for the encapsulation or loading of curcumin to improve its therapeutic effects in different diseases. Nanoparticles such as liposomes, polymeric nanoparticles, micelles, nanogels, niosomes, cyclodextrins, dendrimers, silvers, and solid lipids are emerging as one of the useful alternatives that have been shown to deliver therapeutic concentrations of curcumin. This review shows that curcumin's therapeutic effects may increase to some extent in the presence of nanotechnology. The presented board of evidence focuses on the valuable special effects of curcumin on different diseases and candidates it for future clinical studies in the realm of these diseases. PMID:24995293

  9. Multitargeting by curcumin as revealed by molecular interaction studies.

    PubMed

    Gupta, Subash C; Prasad, Sahdeo; Kim, Ji Hye; Patchva, Sridevi; Webb, Lauren J; Priyadarsini, Indira K; Aggarwal, Bharat B

    2011-11-01

    Curcumin (diferuloylmethane), the active ingredient in turmeric (Curcuma longa), is a highly pleiotropic molecule with anti-inflammatory, anti-oxidant, chemopreventive, chemosensitization, and radiosensitization activities. The pleiotropic activities attributed to curcumin come from its complex molecular structure and chemistry, as well as its ability to influence multiple signaling molecules. Curcumin has been shown to bind by multiple forces directly to numerous signaling molecules, such as inflammatory molecules, cell survival proteins, protein kinases, protein reductases, histone acetyltransferase, histone deacetylase, glyoxalase I, xanthine oxidase, proteasome, HIV1 integrase, HIV1 protease, sarco (endo) plasmic reticulum Ca(2+) ATPase, DNA methyltransferases 1, FtsZ protofilaments, carrier proteins, and metal ions. Curcumin can also bind directly to DNA and RNA. Owing to its β-diketone moiety, curcumin undergoes keto-enol tautomerism that has been reported as a favorable state for direct binding. The functional groups on curcumin found suitable for interaction with other macromolecules include the α, β-unsaturated β-diketone moiety, carbonyl and enolic groups of the β-diketone moiety, methoxy and phenolic hydroxyl groups, and the phenyl rings. Various biophysical tools have been used to monitor direct interaction of curcumin with other proteins, including absorption, fluorescence, Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopy, surface plasmon resonance, competitive ligand binding, Forster type fluorescence resonance energy transfer (FRET), radiolabeling, site-directed mutagenesis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), immunoprecipitation, phage display biopanning, electron microscopy, 1-anilino-8-naphthalene-sulfonate (ANS) displacement, and co-localization. Molecular docking, the most commonly employed computational tool for calculating binding affinities and predicting

  10. Effects of curcumin on Helicobacter pylori infection

    PubMed Central

    Vetvickova, Jana; Fernandez-Botran, Rafael

    2016-01-01

    Background Curcumin is a well-established natural molecule with significant biological and pharmaceutical effects. Its effects on Helicobacter pylori (H. pylori) infection have been repeatedly confirmed both in animal and human models. This study directly compared five different samples to evaluate if the effects are general or if they differ among samples. Methods Using a mouse model, we studied the effects of curcumin on lipid peroxide (LPO) level, myeloperoxidase (MPO) and urease activity, number of colonized bacteria, levels of anti-H. pylori antibodies, biofilm formation, IFN-γ, IL-4, gastrin and somatostatin levels in serum, and minimum inhibitory concentration. In addition, we evaluated the effects on biofilm production and antibacterial antibody response. Results In all tests, one sample (Sabinsa) was consistently the most active. Conclusions All curcumin samples showed some anti-H. pylori effects, but only some of the tested samples had significant activity. PMID:28149841

  11. A magnetically drivable nanovehicle for curcumin with antioxidant capacity and MRI relaxation properties.

    PubMed

    Magro, Massimiliano; Campos, René; Baratella, Davide; Lima, Giuseppina; Holà, Katerina; Divoky, Clemens; Stollberger, Rudolf; Malina, Ondrej; Aparicio, Claudia; Zoppellaro, Giorgio; Zbořil, Radek; Vianello, Fabio

    2014-09-08

    Curcumin possesses wide-ranging anti-inflammatory and anti-cancer properties and its biological activity can be linked to its potent antioxidant capacity. Superparamagnetic maghemite (γ-Fe2 O3 ), called surface-active maghemite nanoparticles (SAMNs) were surface-modified with curcumin molecules, due to the presence of under-coordinated Fe(III) atoms on the nanoparticle surface. The so-obtained curcumin-modified SAMNs (SAMN@curcumin) had a mean size of 13±4 nm. SAMN@curcumin was characterized by transmission and scanning electron microscopy, UV/Vis, FTIR, and Mössbauer spectroscopy, X-ray powder diffraction, bulk susceptibility (SQUID), and relaxometry measurements (MRI imaging). The high negative contrast proclivity of SAMN@curcumin to act as potential contrast agent in MRI screenings was also tested. Moreover, the redox properties of bound curcumin were probed by electrochemistry. SAMN@curcumin was studied in the presence of different electroactive molecules, namely hydroquinone, NADH and ferrocyanide, to assess its redox behavior. Finally, SAMN@curcumin was electrochemically probed in the presence of hydrogen peroxide, demonstrating the stability and reactivity of bound curcumin.

  12. Immunomodulatory effects of curcumin treatment on murine schistosomiasis mansoni.

    PubMed

    Allam, Gamal

    2009-01-01

    Curcumin is a polyphenol derived from the dietary spice turmeric. It has been shown to regulate numerous transcription factors, cytokines, adhesion molecules, and enzymes that have been linked to inflammation. In addition to inhibiting the growth of a variety of pathogens, curcumin has been shown to have nematocidal activity. The present study was designed to evaluate the schistosomicidal activity of curcumin in vivo as well as immunomodulation of granulomatous inflammation and liver pathology in acute schistosomiasis mansoni. Mice were infected each with 80 Schistosoma (S.) mansoni cercariae and injected intraperitoneally with curcumin at a total dose of 400mg/kg body weight. Curcumin was effective in reducing worm and tissue-egg burdens, hepatic granuloma volume and liver collagen content by 44.4%, 30.9%, 79%, and 38.6%, respectively. Curcumin treatment restored hepatic enzymes activities to the normal levels and enhanced catalase activity in the liver tissue of infected mice. Moreover, hepato-spleenomegaly and eosinophilia induced by S. mansoni infection were largely improved with curcumin treatment. Infected mice treated with curcumin showed low serum level of both interleukin (IL)-12 and tumor necrosis factor alpha (TNF-alpha), but IL-10 level was not significantly altered. Specific IgG and IgG1 responses against both soluble worm antigen (SWAP) and soluble egg antigen (SEA) were augmented with curcumin treatment, but IgM and IgG2a responses were not significantly changed. In conclusion, curcumin treatment modulates cellular and humoral immune responses of infected mice and lead to a significant reduction of parasite burden and liver pathology in acute murine schistosomiasis mansoni.

  13. Curcumin rescues Caenorhabditis elegans from a Burkholderia pseudomallei infection

    PubMed Central

    Eng, Su-Anne; Nathan, Sheila

    2015-01-01

    The tropical pathogen Burkholderia pseudomallei requires long-term parenteral antimicrobial treatment to eradicate the pathogen from an infected patient. However, the development of antibiotic resistance is emerging as a threat to this form of treatment. To meet the need for alternative therapeutics, we proposed a screen of natural products for compounds that do not kill the pathogen, but in turn, abrogate bacterial virulence. We suggest that the use of molecules or compounds that are non-bactericidal (bacteriostatic) will reduce or abolish the development of resistance by the pathogen. In this study, we adopted the established Caenorhabditis elegans-B. pseudomallei infection model to screen a collection of natural products for any that are able to extend the survival of B. pseudomallei infected worms. Of the 42 natural products screened, only curcumin significantly improved worm survival following infection whilst not affecting bacterial growth. This suggested that curcumin promoted B. pseudomallei-infected worm survival independent of pathogen killing. To validate that the protective effect of curcumin was directed toward the pathogen, bacteria were treated with curcumin prior to infection. Worms fed with curcumin-treated bacteria survived with a significantly extended mean-time-to-death (p < 0.0001) compared to the untreated control. In in vitro assays, curcumin reduced the activity of known virulence factors (lipase and protease) and biofilm formation. To determine if other bacterial genes were also regulated in the presence of curcumin, a genome-wide transcriptome analysis was performed on curcumin-treated pathogen. A number of genes involved in iron acquisition and transport as well as genes encoding hypothetical proteins were induced in the presence of curcumin. Thus, we propose that curcumin may attenuate B. pseudomallei by modulating the expression of a number of bacterial proteins including lipase and protease as well as biofilm formation whilst

  14. Curcumin-functionalized silk biomaterials for anti-aging utility.

    PubMed

    Yang, Lei; Zheng, Zhaozhu; Qian, Cheng; Wu, Jianbing; Liu, Yawen; Guo, Shaozhe; Li, Gang; Liu, Meng; Wang, Xiaoqin; Kaplan, David L

    2017-02-02

    Curcumin is a natural antioxidant that is isolated from turmeric (Curcuma longa) and exhibits strong free radical scavenging activity, thus functional for anti-aging. However, poor stability and low solubility of curcumin in aqueous conditions limit its biomedical applications. Previous studies have shown that the anti-oxidation activity of curcumin embedded in silk fibroin films could be well preserved, resulting in the promoted adipogenesis from human mesenchymal stem cells (hMSCs) cultured on the surface of the films. In the present study, curcumin was encapsulated in both silk fibroin films (silk/cur films) and nanoparticles (silk/cur NPs), and their anti-aging effects were compared with free curcumin in solution, with an aim to elucidate the mechanism of anti-aging of silk-associated curcumin and to better serve biomedical applications in the future. The morphology and structure of silk/cur film and silk/cur NP were characterized using SEM, FTIR and DSC, indicating characteristic stable beta-sheet structure formation in the materials. Strong binding of curcumin molecules to the beta-sheet domains of silk fibroin resulted in the slow release of curcumin with well-preserved activity from the materials. For cell aging studies, rat bone marrow mesenchymal stem cells (rBMSCs) were cultured in the presence of free curcumin (FC), silk/cur film and silk/cur NP, and cell proliferation and markers of aging (P53, P16, HSP70 gene expression and β-Galactosidase activity) were examined. The results indicated that cell aging was retarded in all FC, silk/cur NP and silk/cur film samples, with the silk-associated curcumin superior to the FC.

  15. Curcumin in inflammatory diseases.

    PubMed

    Shehzad, Adeeb; Rehman, Gauhar; Lee, Young Sup

    2013-01-01

    Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future.

  16. Curcumin-mediated decrease in the expression of nucleolar organizer regions in cervical cancer (HeLa) cells.

    PubMed

    Lewinska, Anna; Adamczyk, Jagoda; Pajak, Justyna; Stoklosa, Sylwia; Kubis, Barbara; Pastuszek, Paulina; Slota, Ewa; Wnuk, Maciej

    2014-09-01

    Curcumin, the major yellow-orange pigment of turmeric derived from the rhizome of Curcuma longa, is a highly pleiotropic molecule with the potential to modulate inflammation, oxidative stress, cell survival, cell secretion, homeostasis and proliferation. Curcumin, at relatively high concentrations, was repeatedly reported to be a potent inducer of apoptosis in cancer cells and thus considered a promising anticancer agent. In the present paper, the effects of low concentrations of curcumin on human cervical cancer (HeLa) cells were studied. We found curcumin-mediated decrease in the cell number and viability, and increase in apoptotic events and superoxide level. In contrast to previously shown curcumin cytotoxicity toward different cervical cancer lines, we observed toxic effects when even as low as 1 μM concentration of curcumin was used. Curcumin was not genotoxic to HeLa cells. Because argyrophilic nucleolar protein (AgNOR protein) expression is elevated in malignant cells compared to normal cells reflecting the rapidity of cancer cell proliferation, we evaluated curcumin-associated changes in size (area) and number of silver deposits. We showed curcumin-induced decrease in AgNOR protein pools, which may be mediated by global DNA hypermethylation observed after low concentration curcumin treatment. In summary, we have shown for the first time that curcumin at low micromolar range may be effective against HeLa cells, which may have implications for curcumin-based treatment of cervical cancer in humans.

  17. Curcumin phytosomal softgel formulation: Development, optimization and physicochemical characterization.

    PubMed

    Allam, Ahmed N; Komeil, Ibrahim A; Abdallah, Ossama Y

    2015-09-01

    Curcumin, a naturally occurring lipophilic molecule can exert multiple and diverse bioactivities. However, its limited aqueous solubility and extensive presystemic metabolism restrict its bioavailability. Curcumin phytosomes were prepared by a simple solvent evaporation method where free flowing powder was obtained in addition to a newly developed semisolid formulation to increase curcumin content in softgels. Phytosomal powder was characterized in terms of drug content and zeta potential. Thirteen different softgel formulations were developed using oils such as Miglyol 812, castor oil and oleic acid, a hydrophilic vehicle such as PEG 400 and bioactive surfactants such as Cremophor EL and KLS P 124. Selected formulations were characterized in terms of curcumin in vitro dissolution. TEM analysis revealed good stability and a spherical, self-closed structure of curcumin phytosomes in complex formulations. Stability studies of chosen formulations prepared using the hydrophilic vehicle revealed a stable curcumin dissolution pattern. In contrast, a dramatic decrease in curcumin dissolution was observed in case of phytosomes formulated in oily vehicles.

  18. Curcumin ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in mice.

    PubMed

    Ueki, Masaaki; Ueno, Masaki; Morishita, Jun; Maekawa, Nobuhiro

    2013-05-01

    Inflammatory mechanisms may play an important role in the pathogenesis of cisplatin-induced nephrotoxicity. Curcumin is an orange-yellow polyphenol present in curry spice and has anti-inflammatory and antioxidant effects. The purpose of this study was to determine the protective effects of curcumin on cisplatin-induced nephrotoxicity. Mice were randomly divided into four groups: control, cisplatin, cisplatin + curcumin and curcumin. Mice were given cisplatin (20 mg/kg body weight, intraperitoneally) with or without curcumin treatment (100 mg/kg body weight, intraperitoneally, immediately after cisplatin injection). Serum and renal tumor necrosis factor (TNF)-alpha and renal monocyte chemoattractant protein (MCP)-1 concentrations, intercellular adhesion molecule-1 (ICAM-1) mRNA expression in kidney, renal function and histological changes were determined 72 h after cisplatin injection. Serum TNF-alpha concentration in the cisplatin + curcumin group significantly decreased compared with that in the cisplatin group. Renal TNF-alpha and MCP-1 concentrations and ICAM-1 mRNA expression in kidney in the cisplatin + curcumin group also significantly decreased compared with those in the cisplatin group. Consequently, cisplatin-induced renal dysfunction and renal tubular necrosis scores were attenuated by curcumin treatment. These results indicate that curcumin acts to reduce cisplatin-induced nephrotoxicity through its anti-inflammatory effects. Thus, curcumin may become a new therapeutic candidate for the treatment of cisplatin-induced nephrotoxicity.

  19. Length of hydrocarbon chain influences location of curcumin in liposomes: Curcumin as a molecular probe to study ethanol induced interdigitation of liposomes.

    PubMed

    El Khoury, Elsy; Patra, Digambara

    2016-05-01

    Using fluorescence quenching of curcumin in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes by brominated derivatives of fatty acids, the location of curcumin has been studied, which indicates length of hydrocarbon chain has an effect on the location of curcumin in liposomes. Change of fluorescence intensity of curcumin with temperature in the presence of liposomes helps to estimate the phase transition temperature of these liposomes, thus, influence of cholesterol on liposome properties has been studied using curcumin as a molecule probe. The cooperativity due to the interactions between the hydrocarbon chains during melting accelerates the phase transition of DPPC liposomes in the presence of high percentage of cholesterol whereas high percentage of cholesterol generates a rather rigid DMPC liposome over a wide range of temperatures. We used ethanol to induce interdigitation between the hydrophobic chains of the lipids and studied this effect using curcumin as fluorescence probe. As a result of interdigitation, curcumin fluorescence is quenched in liposomes. The compact arrangement of the acyl chains prevents curcumin from penetrating deep near the midplane. In the liquid crystalline phase ethanol introduces a kind of order to the more fluid liposome, and does not leave space for curcumin to be inserted away from water.

  20. Curcumin attenuates osteogenic differentiation and calcification of rat vascular smooth muscle cells.

    PubMed

    Hou, Menglin; Song, Yan; Li, Zhenlin; Luo, Chufan; Ou, Jing-Song; Yu, Huimin; Yan, Jianyun; Lu, Lihe

    2016-09-01

    Vascular calcification has been considered as a biological process resembling bone formation involving osteogenic differentiation. It is a major risk factor for cardiovascular morbidity and mortality. Previous studies have shown the protective effects of curcumin on cardiovascular diseases. However, whether curcumin has effects on osteogenic differentiation and calcification of vascular smooth muscle cells (VSMCs) has not been reported. In the present study, we used an in vitro model of VSMC calcification to investigate the role of curcumin in the progression of rat VSMC calcification. Curcumin treatment significantly reduced calcification of VSMCs in a dose-dependent manner, detected by alizarin red staining and calcium content assay. Similarly, ALP activity and expression of bone-related molecules including Runx2, BMP2, and Osterix were also decreased in VSMCs treated with curcumin. In addition, flow cytometry analysis and caspase-3 activity assay revealed that curcumin treatment significantly suppressed apoptosis of VSMCs, which plays an important role during vascular calcification. Furthermore, we found that pro-apoptotic molecules including p-JNK and Bax were up-regulated in VSMCs treated with calcifying medium, but they were reduced in VSMCs after curcumin treatment. However, curcumin treatment has no effect on expression of NF-κB p65. Taken together, these findings suggest that curcumin attenuates apoptosis and calcification of VSMCs, presumably via inhibition of JNK/Bax signaling pathway.

  1. Intracellular ROS Protection Efficiency and Free Radical-Scavenging Activity of Curcumin

    PubMed Central

    Barzegar, Abolfazl; Moosavi-Movahedi, Ali A.

    2011-01-01

    Curcumin has many pharmaceutical applications, many of which arise from its potent antioxidant properties. The present research examined the antioxidant activities of curcumin in polar solvents by a comparative study using ESR, reduction of ferric iron in aqueous medium and intracellular ROS/toxicity assays. ESR data indicated that the steric hindrance among adjacent big size groups within a galvinoxyl molecule limited the curcumin to scavenge galvinoxyl radicals effectively, while curcumin showed a powerful capacity for scavenging intracellular smaller oxidative molecules such as H2O2, HO•, ROO•. Cell viability and ROS assays demonstrated that curcumin was able to penetrate into the polar medium inside the cells and to protect them against the highly toxic and lethal effects of cumene hydroperoxide. Curcumin also showed good electron-transfer capability, with greater activity than trolox in aqueous solution. Curcumin can readily transfer electron or easily donate H-atom from two phenolic sites to scavenge free radicals. The excellent electron transfer capability of curcumin is because of its unique structure and different functional groups, including a β-diketone and several π electrons that have the capacity to conjugate between two phenyl rings. Therfore, since curcumin is inherently a lipophilic compound, because of its superb intracellular ROS scavenging activity, it can be used as an effective antioxidant for ROS protection within the polar cytoplasm. PMID:22016801

  2. Curcumin suppresses the proliferation of gastric cancer cells by downregulating H19

    PubMed Central

    Liu, Gao; Xiang, Tian; Wu, Quan-Feng; Wang, Wei-Xing

    2016-01-01

    Curcumin, a major phytochemical in turmeric, inhibits the proliferation of many types of solid cancer cells by enhancing p53 expression. However, the long non-coding RNA H19 directly inhibits p53 activation and thus promotes gastric cancer progression. The aim of this study was to assess the role of H19 in curcumin-induced proliferative inhibition of gastric cancer. The gastric cancer cell line SGC-7901 was treated with curcumin at different concentrations and time points. The effect of curcumin on proliferation was assessed using cell counting kit-8 assays and flow cytometry with Ki67 staining. In addition, H19 expression was quantified by reverse transcription-quantitative polymerase chain reaction, and apoptosis was evaluated by flow cytometric detection of Annexin V and propidium iodide double staining. The protein expression of p53, B-cell lymphoma (Bcl)-2, Bcl-2-associated X protein (Bax) and c-Myc in curcumin-treated cells was detected by western blotting. The present study demonstrated that curcumin inhibited the proliferation of SGC7901 cells and suppressed H19 expression in a concentration-dependent manner, while p53 expression was enhanced. Ectopic expression of H19 in SGC7901 cells reversed curcumin-induced proliferative inhibition and downregulated p53 expression. Furthermore, while curcumin induced cell apoptosis and enhanced the expression ratio of Bax/Bcl-2, which are downstream molecules of p53, ectopic expression of H19 inhibited curcumin-induced cell apoptosis. In addition, curcumin decreased the expression of the c-Myc oncogene, and exogenous c-Myc protein reversed the curcumin-induced downregulation of H19 expression. These results suggested that curcumin inhibits the proliferation of gastric cancer cells by downregulating the c-Myc/H19 pathway. Therefore, curcumin may be considered a novel therapeutic strategy to inhibit gastric cancer cell growth. PMID:28105222

  3. Synthesis and Evaluation of the Anti-Oxidant Capacity of Curcumin Glucuronides, the Major Curcumin Metabolites

    PubMed Central

    Choudhury, Ambar K.; Raja, Suganya; Mahapatra, Sanjata; Nagabhushanam, Kalyanam; Majeed, Muhammed

    2015-01-01

    Curcumin metabolites namely curcumin monoglucuronide and curcumin diglucuronide were synthesized using an alternative synthetic approach. The anti-oxidant potential of these curcumin glucuronides was compared with that of curcumin using DPPH scavenging method and Oxygen Radical Absorbance Capacity (ORAC) assay. The results show that curcumin monoglucuronide exhibits 10 fold less anti-oxidant activity (DPPH method) and the anti-oxidant capacity of curcumin diglucuronide is highly attenuated compared to the anti-oxidant activity of curcumin. PMID:26783957

  4. A "roller-wheel" Pt-containing small molecule that outperforms its polymer analogs in organic solar cells

    DOE PAGES

    He, Wenhan; Wu, Qin; Livshits, Maksim Y.; ...

    2016-05-23

    A novel Pt-bisacetylide small molecule (Pt-SM) featuring “roller-wheel” geometry was synthesized and characterized. When compared with conventional Pt-containing polymers and small molecules having “dumbbell” shaped structures, Pt-SM displays enhanced crystallinity and intermolecular π–π interactions, as well as favorable panchromatic absorption behaviors. Furthermore, organic solar cells (OSCs) employing Pt-SM achieve power conversion efficiencies (PCEs) up to 5.9%, the highest reported so far for Pt-containing polymers and small molecules.

  5. Curcumin Nanomedicine: A Road to Cancer Therapeutics

    PubMed Central

    Yallapu, Murali M.; Jaggi, Meena; Chauhan, Subhash C.

    2013-01-01

    Cancer is the second leading cause of death in the United States. Conventional therapies cause widespread systemic toxicity and lead to serious side effects which prohibit their long term use. Additionally, in many circumstances tumor resistance and recurrence is commonly observed. Therefore, there is an urgent need to identify suitable anticancer therapies that are highly precise with minimal side effects. Curcumin is a natural polyphenol molecule derived from the Curcuma longa plant which exhibits anticancer, chemo-preventive, chemo- and radio-sensitization properties. Curcumin’s widespread availability, safety, low cost and multiple cancer fighting functions justify its development as a drug for cancer treatment. However, various basic and clinical studies elucidate curcumin’s limited efficacy due to its low solubility, high rate of metabolism, poor bioavailability and pharmacokinetics. A growing list of nanomedicine(s) using first line therapeutic drugs have been approved or are under consideration by the Food and Drug Administration (FDA) to improve human health. These nanotechnology strategies may help to overcome challenges and ease the translation of curcumin from bench to clinical application. Prominent research is reviewed which shows that advanced drug delivery of curcumin (curcumin nanoformulations or curcumin nanomedicine) is able to leverage therapeutic benefits by improving bioavailability and pharmacokinetics which in turn improves binding, internalization and targeting of tumor(s). Outcomes using these novel drug delivery systems have been discussed in detail. This review also describes the tumor-specific drug delivery system(s) that can be highly effective in destroying tumors. Such new approaches are expected to lead to clinical trials and to improve cancer therapeutics. PMID:23116309

  6. Neuroprotective properties of curcumin in Alzheimer's disease--merits and limitations.

    PubMed

    Chin, Dawn; Huebbe, Patricia; Pallauf, Kathrin; Rimbach, Gerald

    2013-01-01

    As demographics in developed nations shift towards an aging population, neurodegenerative pathologies, especially dementias such as Alzheimer's disease, pose one of the largest challenges to the modern health care system. Since there is yet no cure for dementia, there is great pressure to discover potential therapeutics for these diseases. One popular candidate is curcumin or diferuloylmethane, a polyphenolic compound that is the main curcuminoid found in Curcuma longa (family Zingiberaceae). In recent years, curcumin has been reported to possess anti-amyloidogenic, antiinflammatory, anti-oxidative, and metal chelating properties that may result in potential neuroprotective effects. Particularly, the hydrophobicity of the curcumin molecule hints at the possibility of blood-brain barrier penetration and accumulation in the brain. However, curcumin exhibits extremely low bioavailability, mainly due to its poor aqueous solubility, poor stability in solution, and rapid intestinal first-pass and hepatic metabolism. Despite the many efforts that are currently being made to improve the bioavailability of curcumin, brain concentration of curcumin remains low. Furthermore, although many have reported that curcumin possesses a relatively low toxicity profile, curcumin applied at high doses, which is not uncommon practice in many in vivo and clinical studies, may present certain dangers that in our opinion have not been addressed sufficiently. Herein, the neuroprotective potential of curcumin, with emphasis on Alzheimer's disease, as well as its limitations will be discussed in detail.

  7. Immune response modulation by curcumin in a latex allergy model

    PubMed Central

    Kurup, Viswanath P; Barrios, Christy S; Raju, Raghavan; Johnson, Bryon D; Levy, Michael B; Fink, Jordan N

    2007-01-01

    Background There has been a worldwide increase in allergy and asthma over the last few decades, particularly in industrially developed nations. This resulted in a renewed interest to understand the pathogenesis of allergy in recent years. The progress made in the pathogenesis of allergic disease has led to the exploration of novel alternative therapies, which include herbal medicines as well. Curcumin, present in turmeric, a frequently used spice in Asia has been shown to have anti-allergic and inflammatory potential. Methods We used a murine model of latex allergy to investigate the role of curcumin as an immunomodulator. BALB/c mice were exposed to latex allergens and developed latex allergy with a Th2 type of immune response. These animals were treated with curcumin and the immunological and inflammatory responses were evaluated. Results Animals exposed to latex showed enhanced serum IgE, latex specific IgG1, IL-4, IL-5, IL-13, eosinophils and inflammation in the lungs. Intragastric treatment of latex-sensitized mice with curcumin demonstrated a diminished Th2 response with a concurrent reduction in lung inflammation. Eosinophilia in curcumin-treated mice was markedly reduced, co-stimulatory molecule expression (CD80, CD86, and OX40L) on antigen-presenting cells was decreased, and expression of MMP-9, OAT, and TSLP genes was also attenuated. Conclusion These results suggest that curcumin has potential therapeutic value for controlling allergic responses resulting from exposure to allergens. PMID:17254346

  8. Myelopotentiating effect of curcumin in tumor-bearing host: Role of bone marrow resident macrophages

    SciTech Connect

    Vishvakarma, Naveen Kumar; Kumar, Anjani; Kumar, Ajay; Kant, Shiva; Bharti, Alok Chandra; Singh, Sukh Mahendra

    2012-08-15

    The present investigation was undertaken to study if curcumin, which is recognized for its potential as an antineoplastic and immunopotentiating agent, can also influence the process of myelopoiesis in a tumor-bearing host. Administration of curcumin to tumor-bearing host augmented count of bone marrow cell (BMC) accompanied by an up-regulated BMC survival and a declined induction of apoptosis. Curcumin administration modulated expression of cell survival regulatory molecules: Bcl2, p53, caspase-activated DNase (CAD) and p53-upregulated modulator of apoptosis (PUMA) along with enhanced expression of genes of receptors for M-CSF and GM-CSF in BMC. The BMC harvested from curcumin-administered hosts showed an up-regulated colony forming ability with predominant differentiation into bone marrow-derived macrophages (BMDM), responsive for activation to tumoricidal state. The number of F4/80 positive bone marrow resident macrophages (BMM), showing an augmented expression of M-CSF, was also augmented in the bone marrow of curcumin-administered host. In vitro reconstitution experiments indicated that only BMM of curcumin-administered hosts, but not in vitro curcumin-exposed BMM, augmented BMC survival. It suggests that curcumin-dependent modulation of BMM is of indirect nature. Such prosurvival action of curcumin is associated with altered T{sub H1}/T{sub H2} cytokine balance in serum. Augmented level of serum-borne IFN-γ was found to mediate modulation of BMM to produce enhanced amount of monokines (IL-1, IL-6, TNF-α), which are suggested to augment the BMC survival. Taken together the present investigation indicates that curcumin can potentiate myelopoiesis in a tumor-bearing host, which may have implications in its therapeutic utility. Highlights: ► Curcumin augments myelopoiesis in tumor-bearing host. ► Bone marrow resident macrophages mediate curcumin-dependent augmented myelopoiesis. ► Serum borne cytokine are implicated in modulation of bone marrow resident

  9. Curcumin and autoimmune disease.

    PubMed

    Bright, John J

    2007-01-01

    The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.

  10. REVIEW: Curcumin and Alzheimer's disease.

    PubMed

    Hamaguchi, Tsuyoshi; Ono, Kenjiro; Yamada, Masahito

    2010-10-01

    Curcumin has a long history of use as a traditional remedy and food in Asia. Many studies have reported that curcumin has various beneficial properties, such as antioxidant, antiinflammatory, and antitumor. Because of the reported effects of curcumin on tumors, many clinical trials have been performed to elucidate curcumin's effects on cancers. Recent reports have suggested therapeutic potential of curcumin in the pathophysiology of Alzheimer's disease (AD). In in vitro studies, curcumin has been reported to inhibit amyloid-β-protein (Aβ) aggregation, and Aβ-induced inflammation, as well as the activities of β-secretase and acetylcholinesterase. In in vivo studies, oral administration of curcumin has resulted in the inhibition of Aβ deposition, Aβ oligomerization, and tau phosphorylation in the brains of AD animal models, and improvements in behavioral impairment in animal models. These findings suggest that curcumin might be one of the most promising compounds for the development of AD therapies. At present, four clinical trials concerning the effects of curcumin on AD has been conducted. Two of them that were performed in China and USA have been reported no significant differences in changes in cognitive function between placebo and curcumin groups, and no results have been reported from two other clinical studies. Additional trials are necessary to determine the clinical usefulness of curcumin in the prevention and treatment of AD.

  11. A comparative study of diastereomeric complexes formed by a prochiral substrate and three structurally analogous chiral molecules on Pt(111)

    NASA Astrophysics Data System (ADS)

    Lemay, Jean-Christian; Dong, Yi; Groves, Michael N.; Demers-Carpentier, Vincent; Goubert, Guillaume; Lafleur-Lambert, Raphaël; Boukouvalas, John; Hammer, Bjørk; McBreen, Peter H.

    2016-04-01

    A comparative study of chemisorbed bimolecular diastereomeric complexes formed by three structurally analogous chiral modifiers and a prochiral substrate on Pt(111) was performed using scanning tunneling microscopy (STM) and density functional theory (DFT) methods. The experiments determine, subject to a number of assumptions, the abundant binding configurations and whether the complexed substrate is organized into pro-S or pro-R states. The overall prochiral ratio (pr) estimated in this manner may be compared in each case to literature values for the enantiomeric ratio (er) observed in catalysis experiments. The experiments were performed using ketopantolactone as the substrate and (R)-1-(1-naphthyl)ethylamine, (R)-N-Methyl-1-(1-naphthyl)ethylamine and (R)-1-naphthyl-1,2-ethanediol as the structurally analogous chiral modifiers. The STM measurements were performed at room temperature to better mimic conditions under which the catalytic studies reported in the literature were performed. The results are discussed in terms of the stereochemical effects of subtle modifications of the structure of the chiral modifier.

  12. Dissolution enhancement of curcumin via curcumin-prebiotic inulin nanoparticles.

    PubMed

    Fares, Mohammad M; Salem, Mu'taz Sheikh

    2015-01-01

    Dissolution enhancement of curcumin via prebiotic inulin designed to orally deliver poorly water-soluble curcumin at duodenum low acidity (pH 5.5) was investigated. Different prebiotic inulin-curcumin nanoparticles were synthesized in ethanol-water binary system at different pre-adjusted pH values. Characterization via FTIR, XRD and TGA revealed the formation of curcumin-inulin conjugates, whereas surface morphology via SEM and TEM techniques implied the formation of nanoparticle beads and nanoclusters. Prebiotic inulin-curcumin nanoparticles prepared at pH 7.0 demonstrated a maximum curcumin dissolution enhancement of ≈90% with respect to 30% for curcumin alone at pH 5.5. Power law constant values were in accordance with dissolution enhancement investigations. All samples show Fickian diffusion mechanism. XRD investigations confirm that inulin maintain its crystalline structure in curcumin-inulin conjugate structure, which confirms that it can exert successfully its prebiotic role in the gastrointestinal (GI) tract. Therefore, the use of curcumin-inulin nanoparticles can perform dual-mission in the GI tract at the duodenum environment; release of 90% of curcumin followed by prebiotic activity of inulin, which will probably play a significant role in cancer therapeutics for the coming generations.

  13. Therapeutic roles of curcumin: lessons learned from clinical trials.

    PubMed

    Gupta, Subash C; Patchva, Sridevi; Aggarwal, Bharat B

    2013-01-01

    Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn's disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin's pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF-κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E(2), prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the

  14. Curcumin targeting the thioredoxin system elevates oxidative stress in HeLa cells

    SciTech Connect

    Cai, Wenqing; Zhang, Baoxin; Duan, Dongzhu; Wu, Jincai; Fang, Jianguo

    2012-08-01

    The thioredoxin system, composed of thioredoxin reductase (TrxR), thioredoxin (Trx), and NADPH, is ubiquitous in all cells and involved in many redox-dependent signaling pathways. Curcumin, a naturally occurring pigment that gives a specific yellow color in curry food, is consumed in normal diet up to 100 mg per day. This molecule has also been used in traditional medicine for the treatment of a variety of diseases. Curcumin has numerous biological functions, and many of these functions are related to induction of oxidative stress. However, how curcumin elicits oxidative stress in cells is unclear. Our previous work has demonstrated the way by which curcumin interacts with recombinant TrxR1 and alters the antioxidant enzyme into a reactive oxygen species (ROS) generator in vitro. Herein we reported that curcumin can target the cytosolic/nuclear thioredoxin system to eventually elevate oxidative stress in HeLa cells. Curcumin-modified TrxR1 dose-dependently and quantitatively transfers electrons from NADPH to oxygen with the production of ROS. Also, curcumin can drastically down-regulate Trx1 protein level as well as its enzyme activity in HeLa cells, which in turn remarkably decreases intracellular free thiols, shifting the intracellular redox balance to a more oxidative state, and subsequently induces DNA oxidative damage. Furthermore, curcumin-pretreated HeLa cells are more sensitive to oxidative stress. Knockdown of TrxR1 sensitizes HeLa cells to curcumin cytotoxicity, highlighting the physiological significance of targeting TrxR1 by curcumin. Taken together, our data disclose a previously unrecognized prooxidant mechanism of curcumin in cells, and provide a deep insight in understanding how curcumin works in vivo. -- Highlights: ► Curcumin induces oxidative stress by targeting the thioredoxin system. ► Curcumin-modified TrxR quantitatively oxidizes NADPH to generate ROS. ► Knockdown of TrxR1 augments curcumin's cytotoxicity in HeLa cells. ► Curcumin

  15. Curcumin as a therapeutic agent in dementia: a mini systematic review of human studies.

    PubMed

    Brondino, Natascia; Re, Simona; Boldrini, Annalisa; Cuccomarino, Antonella; Lanati, Niccolò; Barale, Francesco; Politi, Pierluigi

    2014-01-01

    Dementia is a leading health problem worldwide, with Alzheimer's disease (AD) representing up to 60% of all dementia cases. A growing interest has recently risen on the potential use of natural molecules in this condition. Curcumin is a polyphenolic compound traditionally used in Indian medicine. Several in vitro and in vivo studies have found a protective effect of curcumin in AD. In the present systematic review we aimed to evaluate the state-of-the-art of clinical trials of curcumin in AD. We retrieved three published studies, while there are several ongoing clinical trials. To date there is insufficient evidence to suggest the use of curcumin in dementia patients. Of note, short-term use of curcumin appears to be safe. Several reasons could be responsible for the discrepancy between in vitro and in vivo findings and human trials, such as low bioavailability and poor study design.

  16. Curcumin induces cell death of the main molecular myeloma subtypes, particularly the poor prognosis subgroups

    PubMed Central

    Gomez-Bougie, Patricia; Halliez, Maxime; Maïga, Sophie; Godon, Catherine; Kervoëlen, Charlotte; Pellat-Deceunynck, Catherine; Moreau, Philippe; Amiot, Martine

    2015-01-01

    Multiple myeloma (MM), a plasma cell malignancy, remains incurable despite the development of new therapies. Curcumin anti-tumor effects were previously characterized in multiple myeloma, however only few MM cell lines were included in these studies. Since myeloma is a heterogeneous disease it is important to address the impact of myeloma molecular heterogeneity in curcumin cell death induction. In the present study, a large panel of human myeloma cell lines (HMCLs) (n = 29), representing the main molecular MM subgroups, was screened for curcumin sensitivity. We observed that curcumin cell death induction was heterogeneous, of note 16 HMCLs were highly sensitive to curcumin (LD50 < 20.5 μM), 6 HMCLs exhibited intermediate LD50 values (20.5 μM ≤ LD50 < 32.2 μM) and only 7 HMCLs were weakly sensitive (35 < LD50 < 56 μM). Cell lines harboring the t(11;14) translocation were less sensitive (median LD50 32.9 μM) than non-t(11;14) (median LD50 17.9 μM), which included poor prognosis t(4;14) and t(14;16) cells. Interestingly, curcumin sensitivity was not dependent on TP53 status. For the first time we showed that primary myeloma cells were also sensitive, even those displaying del(17p), another poor prognosis factor. We also unravel the contribution of anti-apoptotic Bcl-2 family molecules in curcumin response. We found that down-regulation of Mcl-1, an essential MM survival factor, was associated with curcumin-induced cell death and its knockdown sensitized myeloma cells to curcumin, highlighting Mcl-1 as an important target for curcumin-induced apoptosis. Altogether, these results support clinical trials including curcumin in association with standard therapy. PMID:25517601

  17. Protective effects of a natural product, curcumin, against amyloid β induced mitochondrial and synaptic toxicities in Alzheimer's disease.

    PubMed

    Reddy, P Hemachandra; Manczak, Maria; Yin, Xiangling; Grady, Mary Catharine; Mitchell, Andrew; Kandimalla, Ramesh; Kuruva, Chandra Sekhar

    2016-12-01

    The purpose of our study was to investigate the protective effects of a natural product-'curcumin'- in Alzheimer's disease (AD)-like neurons. Although much research has been done in AD, very little has been reported on the effects of curcumin on mitochondrial biogenesis, dynamics, function and synaptic activities. Therefore, the present study investigated the protective effects against amyloid β (Aβ) induced mitochondrial and synaptic toxicities. Using human neuroblastoma (SHSY5Y) cells, curcumin and Aβ, we studied the protective effects of curcumin against Aβ. Further, we also studied preventive (curcumin+Aβ) and intervention (Aβ+curcumin) effects of curcumin against Aβ in SHSY5Y cells. Using real time RT-PCR, immunoblotting and immunofluorescence analysis, we measured mRNA and protein levels of mitochondrial dynamics, mitochondrial biogenesis and synaptic genes. We also assessed mitochondrial function by measuring hydrogen peroxide, lipid peroxidation, cytochrome oxidase activity and mitochondrial ATP. Cell viability was studied using the MTT assay. Aβ was found to impair mitochondrial dynamics, reduce mitochondrial biogenesis and decrease synaptic activity and mitochondrial function. In contrast, curcumin enhanced mitochondrial fusion activity and reduced fission machinery, and increased biogenesis and synaptic proteins. Mitochondrial function and cell viability were elevated in curcumin treated cells. Interestingly, curcumin pre- and post-treated cells incubated with Aβ showed reduced mitochondrial dysfunction, and maintained cell viability and mitochondrial dynamics, mitochondrial biogenesis and synaptic activity. Further, the protective effects of curcumin were stronger in pretreated SHSY5Y cells than in post-treated cells, indicating that curcumin works better in prevention than treatment in AD-like neurons. Our findings suggest that curcumin is a promising drug molecule to treat AD patients.

  18. Synchronous fluorescence spectroscopic study of solvatochromic curcumin dye

    NASA Astrophysics Data System (ADS)

    Patra, Digambara; Barakat, Christelle

    2011-09-01

    Curcumin, the main yellow bioactive component of turmeric, has recently acquired attention by chemists due its wide range of potential biological applications as an antioxidant, an anti-inflammatory, and an anti-carcinogenic agent. This molecule fluoresces weakly and poorly soluble in water. In this detailed study of curcumin in thirteen different solvents, both the absorption and fluorescence spectra of curcumin was found to be broad, however, a narrower and simple synchronous fluorescence spectrum of curcumin was obtained at Δ λ = 10-20 nm. Lippert-Mataga plot of curcumin in different solvents illustrated two sets of linearity which is consistent with the plot of Stokes' shift vs. the ET30. When Stokes's shift in wavenumber scale was replaced by synchronous fluorescence maximum in nanometer scale, the solvent polarity dependency measured by λSFSmax vs. Lippert-Mataga plot or ET30 values offered similar trends as measured via Stokes' shift for protic and aprotic solvents for curcumin. Better linear correlation of λSFSmax vs. π* scale of solvent polarity was found compared to λabsmax or λemmax or Stokes' shift measurements. In Stokes' shift measurement both absorption/excitation as well as emission (fluorescence) spectra are required to compute the Stokes' shift in wavenumber scale, but measurement could be done in a very fast and simple way by taking a single scan of SFS avoiding calculation and obtain information about polarity of the solvent. Curcumin decay properties in all the solvents could be fitted well to a double-exponential decay function.

  19. Thymine and other prebiotic molecules produced from the ultraviolet photo-irradiation of pyrimidine in simple astrophysical ice analogs.

    PubMed

    Materese, Christopher K; Nuevo, Michel; Bera, Partha P; Lee, Timothy J; Sandford, Scott A

    2013-10-01

    The informational subunits of RNA or DNA consist of substituted N-heterocyclic compounds that fall into two groups: those based on purine (C₅H₄N₄) (adenine and guanine) and those based on pyrimidine (C₄H₄N₂) (uracil, cytosine, and thymine). Although not yet detected in the interstellar medium, N-heterocycles, including the nucleobase uracil, have been reported in carbonaceous chondrites. Recent laboratory experiments and ab initio calculations have shown that the irradiation of pyrimidine in ices containing H₂O, NH₃, or both leads to the abiotic production of substituted pyrimidines, including the nucleobases uracil and cytosine. In this work, we studied the methylation and oxidation of pyrimidine in CH₃OH:pyrimidine, H₂O:CH₃OH:pyrimidine, CH₄:pyrimidine, and H₂O:CH₄:pyrimidine ices irradiated with UV photons under astrophysically relevant conditions. The nucleobase thymine was detected in the residues from some of the mixtures. Our results suggest that the abundance of abiotic thymine produced by ice photolysis and delivered to the early Earth may have been significantly lower than that of uracil. Insofar as the delivery of extraterrestrial molecules was important for early biological chemistry on early Earth, these results suggest that there was more uracil than thymine available for emergent life, a scenario consistent with the RNA world hypothesis.

  20. Understanding the conformational flexibility and electrostatic properties of curcumin in the active site of rhAChE via molecular docking, molecular dynamics, and charge density analysis.

    PubMed

    Saravanan, Kandasamy; Kalaiarasi, Chinnasamy; Kumaradhas, Poomani

    2017-01-04

    Acetylcholinesterase (AChE) is an important enzyme responsible for Alzheimer's disease, as per report, keto-enol form of curcumin inhibits this enzyme. The present study aims to understand the binding mechanism of keto-enol curcumin with the recombinant human Acetylcholinesterase (rhAChE) from its conformational flexibility, intermolecular interactions, charge density distribution, and the electrostatic properties at the active site of rhAChE. To accomplish this, a molecular docking analysis of curcumin with the rhAChE was performed, which gives the structure and conformation of curcumin in the active site of rhAChE. Further, the charge density distribution and the electrostatic properties of curcumin molecule (lifted from the active site of rhAChE) were determined from the high level density functional theory (DFT) calculations coupled with the charge density analysis. On the other hand, the curcumin molecule was optimized (gas phase) using DFT method and further, the structure and charge density analysis were also carried out. On comparing the conformation, charge density distribution and the electrostatic potential of the active site form of curcumin with the corresponding gas phase form reveals that the above said properties are significantly altered when curcumin is present in the active site of rhAChE. The conformational stability and the interaction of curcumin in the active site are also studied using molecular dynamics simulation, which shows a large variation in the conformational geometry of curcumin as well as the intermolecular interactions.

  1. Curcumin: therapeutical potential in ophthalmology.

    PubMed

    Pescosolido, Nicola; Giannotti, Rossella; Plateroti, Andrea Maria; Pascarella, Antonia; Nebbioso, Marcella

    2014-03-01

    Curcumin (diferuloylmethane) is the main curcuminoid of the popular Indian spice turmeric (Curcuma longa). In the last 50 years, in vitro and in vivo experiments supported the main role of polyphenols and curcumin for the prevention and treatment of many different inflammatory diseases and tumors.The anti-inflammatory, antioxidant, and antitumor properties of curcumin are due to different cellular mechanisms: this compound, in fact, produces different responses in different cell types. Unfortunately, because of its low solubility and oral bioavailability, the biomedical potential of curcumin is not easy to exploit; for this reason more attention has been given to nanoparticles and liposomes, which are able to improve curcumin's bioavailability. Pharmacologically, curcumin does not show any dose-limiting toxicity when it is administered at doses of up to 8 g/day for three months. It has been demonstrated that curcumin has beneficial effects on several ocular diseases, such as chronic anterior uveitis, diabetic retinopathy, glaucoma, age-related macular degeneration, and dry eye syndrome. The purpose of this review is to report what has so far been elucidated about curcumin properties and its potential use in ophthalmology.

  2. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research.

    PubMed

    Jurenka, Julie S

    2009-06-01

    Curcuma longa (turmeric) has a long history of use in Ayurvedic medicine as a treatment for inflammatory conditions. Turmeric constituents include the three curcuminoids: curcumin (diferuloylmethane; the primary constituent and the one responsible for its vibrant yellow color), demethoxycurcumin, and bisdemethoxycurcumin, as well as volatile oils (tumerone, atlantone, and zingiberone), sugars, proteins, and resins. While numerous pharmacological activities, including antioxidant and antimicrobial properties, have been attributed to curcumin, this article focuses on curcumin's anti-inflammatory properties and its use for inflammatory conditions. Curcumin's effect on cancer (from an anti-inflammatory perspective) will also be discussed; however, an exhaustive review of its many anticancer mechanisms is outside the scope of this article. Research has shown curcumin to be a highly pleiotropic molecule capable of interacting with numerous molecular targets involved in inflammation. Based on early cell culture and animal research, clinical trials indicate curcumin may have potential as a therapeutic agent in diseases such as inflammatory bowel disease, pancreatitis, arthritis, and chronic anterior uveitis, as well as certain types of cancer. Because of curcumin's rapid plasma clearance and conjugation, its therapeutic usefulness has been somewhat limited, leading researchers to investigate the benefits of complexing curcumin with other substances to increase systemic bioavailability. Numerous in-progress clinical trials should provide an even deeper understanding of the mechanisms and therapeutic potential of curcumin.

  3. Curcumin Conjugated with PLGA Potentiates Sustainability, Anti-Proliferative Activity and Apoptosis in Human Colon Carcinoma Cells

    PubMed Central

    Waghela, Bhargav N.; Sharma, Anupama; Dhumale, Suhashini; Pandey, Shashibahl M.; Pathak, Chandramani

    2015-01-01

    Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid) and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116). The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy. PMID:25692854

  4. Protective effects of a natural product, curcumin, against amyloid β induced mitochondrial and synaptic toxicities in Alzheimer's disease

    PubMed Central

    Reddy, P Hemachandra; Manczak, Maria; Yin, Xiangling; Grady, Mary Catharine; Mitchell, Andrew; Kandimalla, Ramesh; Kuruva, Chandra Sekhar

    2016-01-01

    The purpose of our study was to investigate the protective effects of a natural product—‘curcumin’— in Alzheimer's disease (AD)-like neurons. Although much research has been done in AD, very little has been reported on the effects of curcumin on mitochondrial biogenesis, dynamics, function and synaptic activities. Therefore, the present study investigated the protective effects against amyloid β (Aβ) induced mitochondrial and synaptic toxicities. Using human neuroblastoma (SHSY5Y) cells, curcumin and Aβ, we studied the protective effects of curcumin against Aβ. Further, we also studied preventive (curcumin+Aβ) and intervention (Aβ+curcumin) effects of curcumin against Aβ in SHSY5Y cells. Using real time RT-PCR, immunoblotting and immunofluorescence analysis, we measured mRNA and protein levels of mitochondrial dynamics, mitochondrial biogenesis and synaptic genes. We also assessed mitochondrial function by measuring hydrogen peroxide, lipid peroxidation, cytochrome oxidase activity and mitochondrial ATP. Cell viability was studied using the MTT assay. Aβ was found to impair mitochondrial dynamics, reduce mitochondrial biogenesis and decrease synaptic activity and mitochondrial function. In contrast, curcumin enhanced mitochondrial fusion activity and reduced fission machinery, and increased biogenesis and synaptic proteins. Mitochondrial function and cell viability were elevated in curcumin treated cells. Interestingly, curcumin pre- and post-treated cells incubated with Aβ showed reduced mitochondrial dysfunction, and maintained cell viability and mitochondrial dynamics, mitochondrial biogenesis and synaptic activity. Further, the protective effects of curcumin were stronger in pretreated SHSY5Y cells than in post-treated cells, indicating that curcumin works better in prevention than treatment in AD-like neurons. Our findings suggest that curcumin is a promising drug molecule to treat AD patients. PMID:27521081

  5. Discovery of Curcumin, a Component of the Golden Spice, and Its Miraculous Biological Activities

    PubMed Central

    Gupta, Subash C; Patchva, Sridevi; Koh, Wonil; Aggarwal, Bharat B

    2012-01-01

    SUMMARY 1. Curcumin is the active ingredient of the dietary spice turmeric and has been consumed for medicinal purposes for thousands of years. Modern science has shown that curcumin modulates various signaling molecules, including inflammatory molecules, transcription factors, enzymes, protein kinases, protein reductases, carrier proteins, cell survival proteins, drug resistance proteins, adhesion molecules, growth factors, receptors, cell-cycle regulatory proteins, chemokines, DNA, RNA, and metal ions. 2. Because of this polyphenol's potential to modulate multiple signaling molecules, it has been reported to possess pleiotropic activities. First shown to have anti-bacterial activity in 1949, curcumin has since been shown to have anti-inflammatory, anti-oxidant, pro-apoptotic, chemopreventive, chemotherapeutic, anti-proliferative, wound healing, anti-nociceptive, anti-parasitic, and anti-malarial properties as well. Animal studies have suggested that curcumin may be active against a wide range of human diseases, including diabetes, obesity, neurologic and psychiatric disorders, and cancer, as well as chronic illnesses affecting the eyes, lungs, liver, kidneys, and gastrointestinal and cardiovascular systems. 3. Although many clinical trials evaluating curcumin's safety and efficacy against human ailments have already been completed, others are still ongoing. Moreover, curcumin is used as a supplement in several countries, including India, Japan, the United States, Thailand, China, Korea, Turkey, South Africa, Nepal, and Pakistan. Although inexpensive, apparently well tolerated, and potentially active, curcumin has yet not been approved for treatment of any human disease. 4. In this article, we discuss the discovery and key biological activities of curcumin, with a particular emphasis on its activities at the molecular, cellular, animal, and human levels. PMID:22118895

  6. Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases

    PubMed Central

    Sarkar, Avijit; De, Ronita; Mukhopadhyay, Asish K

    2016-01-01

    Curcumin, a yellow pigment and principal polyphenolic Curcuminoid obtained from the turmeric rhizome Curcuma longa, is commonly used as a food-coloring agent. Studies suggest that curcumin has a wide range of beneficial properties e.g., anti-inflammatory, anti-oxidant, anti-cancer, anti-proliferative, anti-fungal and anti-microbial. These pleiotropic activities prompted several research groups to elucidate the role of curcumin in Helicobacter pylori (H. pylori) infection. This is the first review with this heading where we discussed regarding the role of curcumin as an anti-H. pylori agent along with its potential in other gastrointestinal diseases. Based on several in vitro, early cell culture, animal research and few pre-clinical trials, curcumin projected as a potential therapeutic candidate against H. pylori mediated gastric pathogenesis. This review sheds light on the anti-H. pylori effects of curcumin in different models with meticulous emphasis on its anti-oxidant, anti-inflammatory and anti-carcinogenic effects as well as some critical signaling and effecter molecules. Remarkably, non-toxic molecule curcumin fulfills the characteristics for an ideal chemopreventive agent against H. pylori mediated gastric carcinogenesis but the foremost challenge is to obtain the optimum therapeutic levels of curcumin, due to its low solubility and poor bioavailability. Further, we have discussed about the possibilities for improving its efficacy and bioavailability. Lastly, we concluded with the anticipation that in near future curcumin may be used to develop a therapeutic drug against H. pylori mediated gastric ailments through improved formulation or delivery systems, facilitating its enhanced absorption and cellular uptake. PMID:26973412

  7. Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases.

    PubMed

    Sarkar, Avijit; De, Ronita; Mukhopadhyay, Asish K

    2016-03-07

    Curcumin, a yellow pigment and principal polyphenolic Curcuminoid obtained from the turmeric rhizome Curcuma longa, is commonly used as a food-coloring agent. Studies suggest that curcumin has a wide range of beneficial properties e.g., anti-inflammatory, anti-oxidant, anti-cancer, anti-proliferative, anti-fungal and anti-microbial. These pleiotropic activities prompted several research groups to elucidate the role of curcumin in Helicobacter pylori (H. pylori) infection. This is the first review with this heading where we discussed regarding the role of curcumin as an anti-H. pylori agent along with its potential in other gastrointestinal diseases. Based on several in vitro, early cell culture, animal research and few pre-clinical trials, curcumin projected as a potential therapeutic candidate against H. pylori mediated gastric pathogenesis. This review sheds light on the anti-H. pylori effects of curcumin in different models with meticulous emphasis on its anti-oxidant, anti-inflammatory and anti-carcinogenic effects as well as some critical signaling and effecter molecules. Remarkably, non-toxic molecule curcumin fulfills the characteristics for an ideal chemopreventive agent against H. pylori mediated gastric carcinogenesis but the foremost challenge is to obtain the optimum therapeutic levels of curcumin, due to its low solubility and poor bioavailability. Further, we have discussed about the possibilities for improving its efficacy and bioavailability. Lastly, we concluded with the anticipation that in near future curcumin may be used to develop a therapeutic drug against H. pylori mediated gastric ailments through improved formulation or delivery systems, facilitating its enhanced absorption and cellular uptake.

  8. Characterization of Sizes of Aggregates of Insulin Analogs and the Conformations of the Constituent Protein Molecules: A Concomitant Dynamic Light Scattering and Raman Spectroscopy Study.

    PubMed

    Zhou, Chen; Qi, Wei; Lewis, E Neil; Carpenter, John F

    2016-02-01

    To generate aggregates, 3 insulin analogs, lispro, aspart, and glulisine, were incubated without phenolic preservatives for 30 days at 37 °C. As a function of incubation time, aggregation was quantified with size exclusion chromatography, and the sizes of aggregates and the conformations of the constituent molecules were characterized with concomitant dynamic light scattering and Raman spectroscopy. During incubation, lispro was progressively converted into soluble aggregates with hydrodynamic diameters of circa 15 nm, and 95% of the native protein had aggregated at day 30. Raman spectroscopy documented that aggregation resulted in conversion of a large fraction of native alpha helix into nonnative beta sheet structure and a distortion of disulfide bonds. In contrast, for aspart and glulisine only 20% of the native proteins aggregated after 30 days, and minimal structural perturbations were detected. In addition, consistent with the relative aggregation rates during isothermal incubation, Raman spectroscopy showed that during heating the onset temperature for secondary structural perturbations of lispro occurred 7 °C-10 °C lower than those for aspart or glulisine. Overall the results of this study demonstrated that-as in the case during formation of amyloid fibrils from insulin-formation of soluble aggregates of lispro resulted in a high level of conversion of alpha helix into beta sheet.

  9. PoSSuM v.2.0: data update and a new function for investigating ligand analogs and target proteins of small-molecule drugs

    PubMed Central

    Ito, Jun-ichi; Ikeda, Kazuyoshi; Yamada, Kazunori; Mizuguchi, Kenji; Tomii, Kentaro

    2015-01-01

    PoSSuM (http://possum.cbrc.jp/PoSSuM/) is a database for detecting similar small-molecule binding sites on proteins. Since its initial release in 2011, PoSSuM has grown to provide information related to 49 million pairs of similar binding sites discovered among 5.5 million known and putative binding sites. This enlargement of the database is expected to enhance opportunities for biological and pharmaceutical applications, such as predictions of new functions and drug discovery. In this release, we have provided a new service named PoSSuM drug search (PoSSuMds) at http://possum.cbrc.jp/PoSSuM/drug_search/, in which we selected 194 approved drug compounds retrieved from ChEMBL, and detected their known binding pockets and pockets that are similar to them. Users can access and download all of the search results via a new web interface, which is useful for finding ligand analogs as well as potential target proteins. Furthermore, PoSSuMds enables users to explore the binding pocket universe within PoSSuM. Additionally, we have improved the web interface with new functions, including sortable tables and a viewer for visualizing and downloading superimposed pockets. PMID:25404129

  10. Curcumin inhibits cancer progression through regulating expression of microRNAs.

    PubMed

    Zhou, Siying; Zhang, Sijie; Shen, Hongyu; Chen, Wei; Xu, Hanzi; Chen, Xiu; Sun, Dawei; Zhong, Shanliang; Zhao, Jianhua; Tang, Jinhai

    2017-02-01

    Curcumin, a major yellow pigment and spice in turmeric and curry, is a powerful anti-cancer agent. The anti-tumor activities of curcumin include inhibition of tumor proliferation, angiogenesis, invasion and metastasis, induction of tumor apoptosis, increase of chemotherapy sensitivity, and regulation of cell cycle and cancer stem cell, indicating that curcumin maybe a strong therapeutic potential through modulating various cancer progression. It has been reported that microRNAs as small noncoding RNA molecules are related to cancer progression, which can be regulated by curcumin. Dysregulated microRNAs play vital roles in tumor biology via regulating expressions of target genes and then influencing multiple cancer-related signaling pathways. In this review, we focused on the inhibition effect of curcumin on various cancer progression by regulating expression of multiple microRNAs. Curcumin-induced dysregulation of microRNAs may activate or inactivate a set of signaling pathways, such as Akt, Bcl-2, PTEN, p53, Notch, and Erbb signaling pathways. A better understanding of the relation between curcumin and microRNAs may provide a potential therapeutic target for various cancers.

  11. Effect of curcumin caged silver nanoparticle on collagen stabilization for biomedical applications.

    PubMed

    Srivatsan, Kunnavakkam Vinjimur; Duraipandy, N; Begum, Shajitha; Lakra, Rachita; Ramamurthy, Usha; Korrapati, Purna Sai; Kiran, Manikantan Syamala

    2015-04-01

    The current study aims at understanding the influence of curcumin caged silver nanoparticle (CCSNP) on stability of collagen. The results indicated that curcumin caged silver nanoparticles efficiently stabilize collagen, indicated by enhanced tensile strength, fibril formation and viscosity. The tensile strength of curcumin caged silver nanoparticle cross-linked collagen and elongation at break was also found to be higher than glutaraldehyde cross-linked collagen. The physicochemical characteristics of curcumin caged nanoparticle cross-linked collagen exhibited enhanced strength. The thermal properties were also good with both thermal degradation temperature and hydrothermal stability higher than native collagen. CD analysis showed no structural disparity in spite of superior physicochemical properties suggesting the significance of curcumin caged nanoparticle mediated cross-linking. The additional enhancement in the stabilization of collagen could be attributed to multiple sites for interaction with collagen molecule provided by curcumin caged silver nanoparticles. The results of cell proliferation and anti-microbial activity assays indicated that curcumin caged silver nanoparticles promoted cell proliferation and inhibited microbial growth making it an excellent biomaterial for wound dressing application. The study opens scope for nano-biotechnological strategies for the development of alternate non-toxic cross-linking agents facilitating multiple site interaction thereby improving therapeutic values to the collagen for biomedical application.

  12. Determining the effects of lipophilic drugs on membrane structure by solid-state NMR spectroscopy: the case of the antioxidant curcumin.

    PubMed

    Barry, Jeffrey; Fritz, Michelle; Brender, Jeffrey R; Smith, Pieter E S; Lee, Dong-Kuk; Ramamoorthy, Ayyalusamy

    2009-04-01

    Curcumin is the active ingredient of turmeric powder, a natural spice used for generations in traditional medicines. Curcumin's broad spectrum of antioxidant, anticarcinogenic, antimutagenic, and anti-inflammatory properties makes it particularly interesting for the development of pharmaceutical compounds. Because of curcumin's various effects on the function of numerous unrelated membrane proteins, it has been suggested that it affects the properties of the bilayer itself. However, a detailed atomic-level study of the interaction of curcumin with membranes has not been attempted. A combination of solid-state NMR and differential scanning calorimetry experiments shows curcumin has a strong effect on membrane structure at low concentrations. Curcumin inserts deep into the membrane in a transbilayer orientation, anchored by hydrogen bonding to the phosphate group of lipids in a manner analogous to cholesterol. Like cholesterol, curcumin induces segmental ordering in the membrane. Analysis of the concentration dependence of the order parameter profile derived from NMR results suggests curcumin forms higher order oligomeric structures in the membrane that span and likely thin the bilayer. Curcumin promotes the formation of the highly curved inverted hexagonal phase, which may influence exocytotic and membrane fusion processes within the cell. The experiments outlined here show promise for understanding the action of other drugs such as capsaicin in which drug-induced alterations of membrane structure have strong pharmacological effects.

  13. Suppression of Experimental Choroidal Neovascularization by Curcumin in Mice

    PubMed Central

    Xie, Ping; Zhang, WeiWei; Yuan, Songtao; Chen, Zhiqiang; Yang, Qin; Yuan, DongQing; Wang, Feng; Liu, QingHuai

    2012-01-01

    Purpose To investigate the effects of curcumin on the development of experimental choroidal neovascularization (CNV) with underlying cellular and molecular mechanisms. Methods C57BL/6N mice were pretreated with intraperitoneal injections of curcumin daily for 3 days prior to laser-induced CNV, and the drug treatments were continued until the end of the study. The CNV area was analyzed by fluorescein-labeled dextran angiography of retinal pigment epithelium (RPE)-choroid flat mounts on day 7 and 14, and CNV leakage was evaluated by fluorescein angiography (FA) on day 14 after laser photocoagulation. The infiltration of F4/80 positive macrophages and GR-1 positive granulocytes were evaluated by immunohistochemistry on RPE-choroid flat mounts on day 3. Their expression in RPE-choroid complex was quantified by real-time PCR (F4/80) and Western blotting (GR-1) on day 3. RPE-choroid levels of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 were examined by ELISA on day 3. Double immunostaining of F4/80 and VEGF was performed on cryo-sections of CNV lesions on day 3. The expression of nuclear factor (NF)-κB and hypoxia-inducible factor (HIF)−1α in the RPE-choroid was determined by Western blotting. Results Curcumin-treated mice had significantly less CNV area (P<0.05) and CNV leakage (P<0.001) than vehicle-treated mice. Curcumin treatment led to significant inhibition of F4/80 positive macrophages (P<0.05) and GR-1 positive granulocytes infiltration (P<0.05). VEGF mainly expressed in F4/80 positive macrophages in laser injury sites, which was suppressed by curcumin treatment (P<0.01). Curcumin inhibited the RPE-choroid levels of TNF-α (P<0.05), MCP-1 (P<0.05) and ICAM-1 (P<0.05), and suppressed the activation of NF-κB in nuclear extracts (P<0.05) and the activation of HIF−1α (P<0.05). Conclusion Curcumin treatment led to the suppression of CNV development

  14. Biological and Pharmacological Evaluation of Dimethoxycurcumin: A Metabolically Stable Curcumin Analogue with a Promising Therapeutic Potential.

    PubMed

    Teymouri, Manouchehr; Barati, Nastaran; Pirro, Matteo; Sahebkar, Amirhosein

    2016-12-20

    Dimethoxycurcumin (DiMC) is a synthetic analogue of curcumin with superior inter-related pro-oxidant and anti-cancer activity, and metabolic stability. Numerous studies have shown that DiMC reserves the biologically beneficial features, including anti-inflammatory, anti-carcinogenic and cytoprotective properties, almost to the same extent as curcumin exhibits. DiMC lacks the phenolic-OH groups as opposed to curcumin, dimethoxycurcumin, and bis-demethoxycurcumin that all vary in the number of methoxy groups per molecule, and has drawn the attentions of researchers who attempted to discover the structure-activity relationship (SAR) of curcumin. In this regard, tetrahydrocurcumin (THC), the reduced and biologically inert metabolite of curcumin, denotes the significance of the conjugated α,β diketone moiety for the curcumin activity. DiMC exerts unique molecular activities compared to curcumin, including induction of androgen receptor (AR) degradation and suppression of the transcription factor activator protein-1 (AP-1). The enhanced AR degradation on DiMC treatment suggests it as a novel anticancer agent against resistant tumors with androgenic etiology. Further, DiMC might be a potential treatment for acne vulgaris. DiMC induces epigenetic alteration more effectively than curcumin, although both showed no direct DNA hypomethylating activity. Given the metabolic stability, nanoparticulation of DiMC is more promising for in vivo effectiveness. However, studies in this regard are still in its infancy. In the current review, we portray the various molecular and biological functions of DiMC reported so far. Whenever possible, the efficiency is compared with curcumin and the reasons for DiMC being more metabolically stable are elaborated. We also provide future perspective investigations with respect to varying DiMC-nanoparticles. This article is protected by copyright. All rights reserved.

  15. Magnetic purification of curcumin from Curcuma longa rhizome by novel naked maghemite nanoparticles.

    PubMed

    Magro, Massimiliano; Campos, Rene; Baratella, Davide; Ferreira, Maria Izabela; Bonaiuto, Emanuela; Corraducci, Vittorino; Uliana, Maíra Rodrigues; Lima, Giuseppina Pace Pereira; Santagata, Silvia; Sambo, Paolo; Vianello, Fabio

    2015-01-28

    Naked maghemite nanoparticles, namely, surface active maghemite nanoparticles (SAMNs), characterized by a diameter of about 10 nm, possessing peculiar colloidal stability, surface chemistry, and superparamagnetism, present fundamental requisites for the development of effective magnetic purification processes for biomolecules in complex matrices. Polyphenolic molecules presenting functionalities with different proclivities toward iron chelation were studied as probes for testing SAMN suitability for magnetic purification. Thus, the binding efficiency and reversibility on SAMNs of phenolic compounds of interest in the pharmaceutical and food industries, namely, catechin, tyrosine, hydroxytyrosine, ferulic acid, coumaric acid, rosmarinic acid, naringenin, curcumin, and cyanidin-3-glucoside, were evaluated. Curcumin emerged as an elective compound, suitable for magnetic purification by SAMNs from complex matrices. A combination of curcumin, demethoxycurcumin, and bis-demethoxycurcumin was recovered by a single magnetic purification step from extracts of Curcuma longa rhizomes, with a purity >98% and a purification yield of 45%, curcumin being >80% of the total purified curcuminoids.

  16. Modulation of curcumin-induced Akt phosphorylation and apoptosis by PI3K inhibitor in MCF-7 cells

    SciTech Connect

    Kizhakkayil, Jaleel; Thayyullathil, Faisal; Chathoth, Shahanas; Hago, Abdulkader; Patel, Mahendra; Galadari, Sehamuddin

    2010-04-09

    Curcumin has been shown to induce apoptosis in various malignant cancer cell lines. One mechanism of curcumin-induced apoptosis is through the PI3K/Akt signaling pathway. Akt, also known as protein kinase B (PKB), is a member of the family of phosphatidylinositol 3-OH-kinase regulated Ser/Thr kinases. The active Akt regulates cell survival and proliferation; and inhibits apoptosis. In this study we found that curcumin induces apoptotic cell death in MCF-7 cells, as assessed by MTT assay, DNA ladder formation, PARP cleavage, p53 and Bax induction. At apoptotic inducing concentration, curcumin induces a dramatic Akt phosphorylation, accompanied by an increased phosphorylation of glycogen synthase kinase 3{beta} (GSK3{beta}), which has been considered to be a pro-growth signaling molecule. Combining curcumin with PI3K inhibitor, LY290042, synergizes the apoptotic effect of curcumin. The inhibitor LY290042 was capable of attenuating curcumin-induced Akt phosphorylation and activation of GSK3{beta}. All together, our data suggest that blocking the PI3K/Akt survival pathway sensitizes the curcumin-induced apoptosis in MCF-7 cells.

  17. Curcumin: a potential neuroprotective agent in Parkinson's disease.

    PubMed

    Mythri, R B; Bharath, M M Srinivas

    2012-01-01

    Parkinson's disease (PD) is an age-associated neurodegenerative disease clinically characterized as a movement disorder. The motor symptoms in PD arise due to selective degeneration of dopaminergic neurons in the substantia nigra of the ventral midbrain thereby depleting the dopamine levels in the striatum. Most of the current pharmacotherapeutic approaches in PD are aimed at replenishing the striatal dopamine. Although these drugs provide symptomatic relief during early PD, many patients develop motor complications with long-term treatment. Further, PD medications do not effectively tackle tremor, postural instability and cognitive deficits. Most importantly, most of these drugs do not exhibit neuroprotective effects in patients. Consequently, novel therapies involving natural antioxidants and plant products/molecules with neuroprotective properties are being exploited for adjunctive therapy. Curcumin is a polyphenol and an active component of turmeric (Curcuma longa), a dietary spice used in Indian cuisine and medicine. Curcumin exhibits antioxidant, anti-inflammatory and anti-cancer properties, crosses the blood-brain barrier and is neuroprotective in neurological disorders. Several studies in different experimental models of PD strongly support the clinical application of curcumin in PD. The current review explores the therapeutic potential of curcumin in PD.

  18. Activation of α-secretase by curcumin-aminoacid conjugates.

    PubMed

    Narasingappa, Ramesh B; Narasingapa, Ramesh B; Javagal, Manjunatha R; Jargaval, Manjunatha R; Pullabhatla, Srinivas; Htoo, Htut Htut; Rao, Jagannatha K S; Hernandez, Jean-François; Govitrapong, Piyarat; Vincent, Bruno

    2012-08-10

    The extracellular senile plaques observed in Alzheimer's disease (AD) patients are mainly composed of amyloid peptides produced from the β-amyloid precursor protein (βAPP) by β- and γ-secretases. A third non-amyloidogenic α-secretase activity performed by the disintegrins ADAM10 and ADAM17 occurs in the middle of the amyloid-β peptide Aβ and liberates the large sAPPα neuroprotective fragment. Since the activation of α-secretase recently emerged as a promising therapeutic approach to treat AD, the identification of natural compounds able to trigger this cleavage is highly required. Here we describe new curcumin-based modified compounds as α-secretase activators. We established that the aminoacid conjugates curcumin-isoleucine, curcumin-phenylalanine and curcumin-valine promote the constitutive α-secretase activity and increase ADAM10 immunoreactivity. Strickingly, experiments carried out under conditions mimicking the PKC/muscarinic receptor-regulated pathway display different patterns of activation by these compounds. Altogether, our data identified new lead natural compounds for the future development of powerful and stable α-secretase activators and established that some of these molecules are able to discriminate between the constitutive and regulated α-secretase pathways.

  19. Advances in clinical study of curcumin.

    PubMed

    Yang, Chunfen; Su, Xun; Liu, Anchang; Zhang, Lin; Yu, Aihua; Xi, Yanwei; Zhai, Guangxi

    2013-01-01

    Curcumin has been estimated as a potential agent for many diseases and attracted great attention owing to its various pharmacological activities, including anti-cancer, and anti-inflammatory. Now curcumin is being applied to a number of patients with breast cancer, rheumatoid arthritis, Alzheimer's disease, colorectal cancer, psoriatic, etc. Several clinical trials have stated that curcumin is safe enough and effective. The objective of this article was to summarize the clinical studies of curcumin, and give a reference for future studies.

  20. Novel Curcumin Diclofenac Conjugate Enhanced Curcumin Bioavailability and Efficacy in Streptococcal Cell Wall-induced Arthritis

    PubMed Central

    Jain, S. K.; Gill, M. S.; Pawar, H. S.; Suresh, Sarasija

    2014-01-01

    Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; stability of curcumin-diclofenac conjugate in gastrointestinal fluids and in vitro efficacy have been evaluated. In vivo bioavailability of curcumin-diclofenac conjugate and curcumin in Sprague-Dawley rats, and antiarthritic activity of curcumin-diclofenac conjugate, curcumin and diclofenac in modified streptococcal cell wall-induced arthritis model in Balb/c mice to mimic rheumatoid arthritis in humans have also been studied. In all of the above studies, curcumin-diclofenac conjugate exhibited enhanced stability as compared to curcumin; its activity was twice that of diclofenac in inhibiting thermal protein denaturation taken as a measure of in vitro antiinflammatory activity; it enhanced the bioavailability of curcumin by more than five folds, and significantly (P<0.01) alleviated the symptoms of arthritis in streptococcal cell wall-induced arthritis model as compared to both diclofenac and curcumin. PMID:25425755

  1. A combined molecular docking and charge density analysis is a new approach for medicinal research to understand drug-receptor interaction: curcumin-AChE model.

    PubMed

    Renuga Parameswari, A; Rajalakshmi, G; Kumaradhas, P

    2015-01-05

    In the present study, a molecular docking analysis has been performed on diketone form of curcumin molecule with acetylcholinesterase (AChE). The calculated lowest docked energy of curcumin molecule in the active site of AChE is -11.21 kcal/mol; this high negative value indicates that the molecule exhibits large binding affinity towards AChE. When the curcumin molecule present in the active site of AChE, subsequently, its conformation has altered significantly and the molecule adopts a U-shape geometry as it is linear in gas phase (before entering into the active site). This conformational transition facilitates curcumin to form strong interaction with Phe330 of acyl-binding pocket and the choline binding site with indole ring of Trp84 and Asp72. The gas phase and the active site analysis of curcumin allows to understand the conformational geometry, nature of molecular flexibility, charge density redistribution and the variation of electrostatic properties of curcumin in the active site. To obtain the gas phase structure, the curcumin molecule was optimized using Hartree-Fock and density functional methods (B3LYP) with the basis set 6-311G(∗∗). A charge density analysis on both gas phase as well as the molecule lifted from the active site was carried out using Bader's theory of atoms in molecules (AIM). The difference in molecular electrostatic potential between the two forms of curcumin displays the difference in charge distribution. The large dipole moment of curcumin (7.54 D) in the active site reflects the charge redistribution as it is much less in the gas phase (4.34 D).

  2. Discovery and evaluation of novel anti-inflammatory derivatives of natural bioactive curcumin

    PubMed Central

    Zhang, Yali; Jiang, Xin; Peng, Kesong; Chen, Chengwei; Fu, Lili; Wang, Zhe; Feng, Jianpeng; Liu, Zhiguo; Zhang, Huajie; Liang, Guang; Pan, Zheer

    2014-01-01

    Curcumin is a natural active product that has various pharmacological activities such as anti-inflammatory effects. Here, we report the synthesis and evaluation of 34 monocarbonyl curcumin analogs as novel anti-inflammatory agents. Among the analogs, the symmetrical heterocyclic type displayed the strongest inhibition of lipopolysaccharide (LPS)-stimulated expression of pro-inflammatory cytokines in macrophages. Analogs S1–S5 and AS29 reduced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production in a dose-dependent manner and also displayed excellent stability and low cytotoxicity in vitro. In addition, analog S1 dose-dependently inhibited LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation. Furthermore, analogs S1 and S4 displayed a significant protective effect on LPS-induced septic death in mouse models, with 40% and 50% survival rates, respectively. These data demonstrate that the heterocyclic monocarbonyl curcumin analogs have potential therapeutic effects in acute inflammatory diseases. PMID:25395833

  3. Stronger proteasomal inhibition and higher CHOP induction are responsible for more effective induction of paraptosis by dimethoxycurcumin than curcumin.

    PubMed

    Yoon, M J; Kang, Y J; Lee, J A; Kim, I Y; Kim, M A; Lee, Y S; Park, J H; Lee, B Y; Kim, I A; Kim, H S; Kim, S-A; Yoon, A-R; Yun, C-O; Kim, E-Y; Lee, K; Choi, K S

    2014-03-13

    Although curcumin suppresses the growth of a variety of cancer cells, its poor absorption and low systemic bioavailability have limited its translation into clinics as an anticancer agent. In this study, we show that dimethoxycurcumin (DMC), a methylated, more stable analog of curcumin, is significantly more potent than curcumin in inducing cell death and reducing the clonogenicity of malignant breast cancer cells. Furthermore, DMC reduces the tumor growth of xenografted MDA-MB 435S cells more strongly than curcumin. We found that DMC induces paraptosis accompanied by excessive dilation of mitochondria and the endoplasmic reticulum (ER); this is similar to curcumin, but a much lower concentration of DMC is required to induce this process. DMC inhibits the proteasomal activity more strongly than curcumin, possibly causing severe ER stress and contributing to the observed dilation. DMC treatment upregulates the protein levels of CCAAT-enhancer-binding protein homologous protein (CHOP) and Noxa, and the small interfering RNA-mediated suppression of CHOP, but not Noxa, markedly attenuates DMC-induced ER dilation and cell death. Interestingly, DMC does not affect the viability, proteasomal activity or CHOP protein levels of human mammary epithelial cells, suggesting that DMC effectively induces paraptosis selectively in breast cancer cells, while sparing normal cells. Taken together, these results suggest that DMC triggers a stronger proteasome inhibition and higher induction of CHOP compared with curcumin, giving it more potent anticancer effects on malignant breast cancer cells.

  4. Lunar Analog

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita L.

    2009-01-01

    In this viewgraph presentation, a ground-based lunar analog is developed for the return of manned space flight to the Moon. The contents include: 1) Digital Astronaut; 2) Bed Design; 3) Lunar Analog Feasibility Study; 4) Preliminary Data; 5) Pre-pilot Study; 6) Selection of Stockings; 7) Lunar Analog Pilot Study; 8) Bed Design for Lunar Analog Pilot.

  5. Core-shell biopolymer nanoparticle delivery systems: synthesis and characterization of curcumin fortified zein-pectin nanoparticles.

    PubMed

    Hu, Kun; Huang, Xiaoxia; Gao, Yongqing; Huang, Xulin; Xiao, Hang; McClements, David Julian

    2015-09-01

    Biopolymer core-shell nanoparticles were fabricated using a hydrophobic protein (zein) as the core and a hydrophilic polysaccharide (pectin) as the shell. Particles were prepared by coating cationic zein nanoparticles with anionic pectin molecules using electrostatic deposition (pH 4). The core-shell nanoparticles were fortified with curcumin (a hydrophobic bioactive molecule) at a high loading efficiency (>86%). The resulting nanoparticles were spherical, relatively small (diameter ≈ 250 nm), and had a narrow size distribution (polydispersity index ≈ 0.24). The encapsulated curcumin was in an amorphous (rather than crystalline form) as detected by differential scanning calorimetry (DSC). Fourier transform infrared (FTIR) and Raman spectra indicated that the encapsulated curcumin interacted with zein mainly through hydrophobic interactions. The nanoparticles were converted into a powdered form that had good water-dispersibility. These core-shell biopolymer nanoparticles could be useful for incorporating curcumin into functional foods and beverages, as well as dietary supplements and pharmaceutical products.

  6. Binding of curcumin to senile plaques and cerebral amyloid angiopathy in the aged brain of various animals and to neurofibrillary tangles in Alzheimer's brain.

    PubMed

    Mutsuga, Mayu; Chambers, James Kenn; Uchida, Kazuyuki; Tei, Meina; Makibuchi, Takao; Mizorogi, Tatsuya; Takashima, Akihiko; Nakayama, Hiroyuki

    2012-01-01

    The binding of curcumin to senile plaques (SPs) and cerebral amyloid angiopathy (CAA) was examined in the aged brain of various animal species and a human patient with Alzheimer's disease (AD), together with its binding to neurofibrillary tangles (NFTs). Brain sections were immunostained with anti-amyloid β protein 1-42 (Aβ42) and anti-amyloid β protein 1-40 (Aβ40) antibodies. These sections were also stained with alkaline Congo red, periodic acid-methenamine silver (PAM), and curcumin (0.009% curcumin solution) with or without formic acid pretreatment. The sections from the AD brain were also immunostained for anti-paired helical filament-tau (PHF-tau), and were stained with Gallyas silver for NFTs. Some SPs in the AD, monkey, dog, bear, and amyloid precursor protein transgenic mouse (APP Tg-mouse) brains contained congophilic materials, and were intensely positive for curcumin. In addition, curcumin labeled some diffuse SPs negative for Congo red in the AD, monkey, bear, and APP Tg-mouse brains. In all animals, CAA was intensely positive for both Congo red and curcumin. The specific curcumin staining activity was lost by formic acid pretreatment. In the AD brain, NFTs positive for PHF-tau and Gallyas silver were moderately stained with curcumin. These findings indicate that curcumin specifically binds to the aggregated Aβ molecules in various animals, and further to phosphorylated tau protein, probably according to its conformational nature.

  7. A Curcumin Derivative That Inhibits Vinyl Carbamate-Induced Lung Carcinogenesis via Activation of the Nrf2 Protective Response

    PubMed Central

    Shen, Tao; Jiang, Tao; Long, Min; Chen, Jun; Ren, Dong-Mei; Wong, Pak Kin

    2015-01-01

    Abstract Aims: Lung cancer has a high worldwide morbidity and mortality. The employment of chemopreventive agents is effective to reduce lung cancer. Nuclear factor erythroid 2-related factor 2 (Nrf2) mitigates insults from both exogenous and endogenous sources and thus has been verified as a target for chemoprevention. Curcumin has long been recognized as a chemopreventive agent, but poor bioavailability and weak Nrf2 induction have prohibited clinical application. Thus, we have developed new curcumin derivatives and tested their Nrf2 induction. Results: Based on curcumin, we synthesized curcumin analogs with five carbon linkages and established a structure–activity relationship for Nrf2 induction. Among these derivatives, bis[2-hydroxybenzylidene]acetone (BHBA) was one of the most potent Nrf2 inducers with minimal toxicity and improved pharmacological properties and was thus selected for further investigation. BHBA activated the Nrf2 pathway in the canonical Keap1-Cys151-dependent manner. Furthermore, BHBA was able to protect human lung epithelial cells against sodium arsenite [As(III)]-induced cytotoxicity. More importantly, in an in vivo vinyl carbamate-induced lung cancer model in A/J mice, preadministration of BHBA significantly reduced lung adenocarcinoma, while curcumin failed to show any effects even at high doses. Innovation: The curcumin derivative, BHBA, is a potent inducer of Nrf2. It was demonstrated to protect against As(III) toxicity in lung epithelial cells in an Nrf2-dependent manner. Furthermore, compared with curcumin, BHBA displayed improved chemopreventive activities in a carcinogen-induced lung cancer model. Conclusion: Taken together, our results demonstrate that BHBA, a curcumin analog with improved Nrf2-activating and chemopreventive activities both in vitro and in vivo, could be developed into a chemoprotective pharmacological agent. Antioxid. Redox Signal. 23, 651–664. PMID:25891177

  8. Curcumin: the Indian solid gold.

    PubMed

    Aggarwal, Bharat B; Sundaram, Chitra; Malani, Nikita; Ichikawa, Haruyo

    2007-01-01

    Turmeric, derived from the plant Curcuma longa, is a gold-colored spice commonly used in the Indian subcontinent, not only for health care but also for the preservation of food and as a yellow dye for textiles. Curcumin, which gives the yellow color to turmeric, was first isolated almost two centuries ago, and its structure as diferuloylmethane was determined in 1910. Since the time of Ayurveda (1900 Bc) numerous therapeutic activities have been assigned to turmeric for a wide variety of diseases and conditions, including those of the skin, pulmonary, and gastrointestinal systems, aches, pains, wounds, sprains, and liver disorders. Extensive research within the last half century has proven that most of these activities, once associated with turmeric, are due to curcumin. Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, and anticancer activities and thus has a potential against various malignant diseases, diabetes, allergies, arthritis, Alzheimer's disease, and other chronic illnesses. These effects are mediated through the regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other enzymes. Curcumin exhibits activities similar to recently discovered tumor necrosis factor blockers (e.g., HUMIRA, REMICADE, and ENBREL), a vascular endothelial cell growth factor blocker (e.g., AVASTIN), human epidermal growth factor receptor blockers (e.g., ERBITUX, ERLOTINIB, and GEFTINIB), and a HER2 blocker (e.g., HERCEPTIN). Considering the recent scientific bandwagon that multitargeted therapy is better than monotargeted therapy for most diseases, curcumin can be considered an ideal "Spice for Life".

  9. Sustained release Curcumin loaded Solid Lipid Nanoparticles

    PubMed Central

    Jourghanian, Parisa; Ghaffari, Solmaz; Ardjmand, Mehdi; Haghighat, Setareh; Mohammadnejad, Mahdieh

    2016-01-01

    Purpose: curcumin is poorly water soluble drug with low bioavailability. Use of lipid systems in lipophilic substances increases solubility and bioavailability of poorly soluble drugs. The aim of this study was to prepare curcumin loaded Solid Lipid Nanoparticles (SLNs) with high loading efficiency, small particle size and prolonged release profile with enhanced antibacterial efficacy. Methods: to synthesize stable SLNs, freeze- Drying was done using mannitol as cryoprotectant. Cholesterol was used as carrier because of good tolerability and biocompatibility. SLNs were prepared using high pressure homogenization method. Results: optimized SLNs had 112 and 163 nm particle size before and after freeze drying, respectively. The prepared SLNs had 71% loading efficiency. 90% of loaded curcumin was released after 48 hours. Morphologic study for formulation was done by taking SEM pictures of curcumin SLNs. Results show the spherical shape of curcumin SLNs. DSC studies were performed to determine prolonged release mechanism. Antimicrobial studies were done to compare the antimicrobial efficacy of curcumin SLNs with free curcumin. DSC studies showed probability of formation of hydrogen bonds between cholesterol and curcumin which resulted in prolonged release of curcumin. Lipid structure of cholesterol could cause enhanced permeability in studied bacteria to increase antibacterial characteristics of curcumin. Conclusion: the designed curcumin SLNs could be candidate for formulation of different dosage forms or cosmeceutical products. PMID:27123413

  10. Curcumin ameliorates autoimmune diabetes. Evidence in accelerated murine models of type 1 diabetes

    PubMed Central

    Castro, C N; Barcala Tabarrozzi, A E; Winnewisser, J; Gimeno, M L; Antunica Noguerol, M; Liberman, A C; Paz, D A; Dewey, R A; Perone, M J

    2014-01-01

    Type 1 diabetes (T1DM) is a T cell-mediated autoimmune disease that selectively destroys pancreatic β cells. The only possible cure for T1DM is to control autoimmunity against β cell-specific antigens. We explored whether the natural compound curcumin, with anti-oxidant and anti-inflammatory activities, might down-regulate the T cell response that destroys pancreatic β cells to improve disease outcome in autoimmune diabetes. We employed two accelerated autoimmune diabetes models: (i) cyclophosphamide (CYP) administration to non-obese diabetic (NOD) mice and (ii) adoptive transfer of diabetogenic splenocytes into NODscid mice. Curcumin treatment led to significant delay of disease onset, and in some instances prevented autoimmune diabetes by inhibiting pancreatic leucocyte infiltration and preserving insulin-expressing cells. To investigate the mechanisms of protection we studied the effect of curcumin on key immune cell populations involved in the pathogenesis of the disease. Curcumin modulates the T lymphocyte response impairing proliferation and interferon (IFN)-γ production through modulation of T-box expressed in T cells (T-bet), a key transcription factor for proinflammatory T helper type 1 (Th1) lymphocyte differentiation, both at the transcriptional and translational levels. Also, curcumin reduces nuclear factor (NF)-κB activation in T cell receptor (TCR)-stimulated NOD lymphocytes. In addition, curcumin impairs the T cell stimulatory function of dendritic cells with reduced secretion of proinflammatory cytokines and nitric oxide (NO) and low surface expression of co-stimulatory molecules, leading to an overall diminished antigen-presenting cell activity. These in-vitro effects correlated with ex-vivo analysis of cells obtained from curcumin-treated mice during the course of autoimmune diabetes. These findings reveal an effective therapeutic effect of curcumin in autoimmune diabetes by its actions on key immune cells responsible for β cell death. PMID

  11. Fabrication and vibration characterization of curcumin extracted from turmeric (Curcuma longa) rhizomes of the northern Vietnam.

    PubMed

    Van Nong, Hoang; Hung, Le Xuan; Thang, Pham Nam; Chinh, Vu Duc; Vu, Le Van; Dung, Phan Tien; Van Trung, Tran; Nga, Pham Thu

    2016-01-01

    In this report, we present the research results on using the conventional method and microwave technology to extract curcuminoid from turmeric roots originated in different regions of Northern Vietnam. This method is simple, yet economical, non-toxic and still able to achieve high extraction performance to get curcuminoid from turmeric roots. The detailed results on the Raman vibration spectra combined with X-ray powder diffraction and high-performance liquid chromatography/mass spectrometry allowed the evaluation of each batch of curcumin crystalline powder sample received, under the conditions of applied fabrication technology. Also, the absorption and fluorescence spectroscopies of the samples are presented in the paper. The information to be presented in this paper: absorption and fluorescence spectroscopies of the samples; new experimental study results on applied technology to mass-produce curcumin from turmeric rhizomes; comparative study results between fabricated samples and marketing curcumin products-to state the complexity of co-existing crystalline phase in curcumin powder samples. We noticed that, it is possible to use the vibration line at ~959 cm(-1)-characteristic of the ν C=O vibration, and the ~1625 cm(-1) line-characteristic of the ν C=O and ν C=C vibration in curcumin molecules, for preliminary quality assessment of naturally originated curcumin crystalline powder samples. Data on these new optical spectra will contribute to the bringing of detailed information on natural curcumin in Vietnam, serving research purposes and applications of natural curcumin powder and nanocurcumin in Vietnam, as well as being initial materials for the pharmaceutical, cosmetics or functional food industries.

  12. 2,2'-Fluorine mono-carbonyl curcumin induce reactive oxygen species-Mediated apoptosis in Human lung cancer NCI-H460 cells.

    PubMed

    Liu, Guo-Yun; Zhai, Qiang; Chen, Jia-Zhuang; Zhang, Zhuo-Qing; Yang, Jie

    2016-09-05

    In this paper, we synthesized three fluorine-substituted mono-carbonyl curcumin analogs and evaluated their cytotoxicity against several cancer cells by the MTT assay. The results exhibited that all the three compounds were more active than the leading curcumin. Especially, 2,2'-F mono-carbonyl curcumin, 1a, surfaced as an important lead compound displaying almost 4-fold cytotoxicity relative to curcumin. More importantly, 1a was more stable in (RPMI)-1640 medium and more massive uptake than curcumin, which may be relationship to their cytotoxicity, apoptotic acitivity and reactive oxygen species generation. And then, the generation of reactive oxygen species can disrupt the intracellular redox balance, induce lipid peroxidation, cause the collapse of the mitochondrial membrane potential and ultimately lead to apoptosis. The results not only suggest that 2,2'-F mono-carbonyl curcumin (1a) may cause cancer cells apoptosis through reactive oxygen species-Mediated pathway, but also gives us an important information for design of mono-carbonyl curcumin analog.

  13. Photoprotective efficiency of PLGA-curcumin nanoparticles versus curcumin through the involvement of ERK/AKT pathway under ambient UV-R exposure in HaCaT cell line.

    PubMed

    Chopra, Deepti; Ray, Lipika; Dwivedi, Ashish; Tiwari, Shashi Kant; Singh, Jyoti; Singh, Krishna P; Kushwaha, Hari Narayan; Jahan, Sadaf; Pandey, Ankita; Gupta, Shailendra K; Chaturvedi, Rajnish Kumar; Pant, Aditya Bhushan; Ray, Ratan Singh; Gupta, Kailash Chand

    2016-04-01

    Curcumin (Cur) has been demonstrated to have wide pharmacological window including anti-oxidant and anti-inflammatory properties. However, phototoxicity under sunlight exposure and poor biological availability limits its applicability. We have synthesized biodegradable and non-toxic polymer-poly (lactic-co-glycolic) acid (PLGA) encapsulated formulation of curcumin (PLGA-Cur-NPs) of 150 nm size range. Photochemically free curcumin generates ROS, lipid peroxidation and induces significant UVA and UVB mediated impaired mitochondrial functions leading to apoptosis/necrosis and cell injury in two different origin cell lines viz., mouse fibroblasts-NIH-3T3 and human keratinocytes-HaCaT as compared to PLGA-Cur-NPs. Molecular docking studies suggested that intact curcumin from nanoparticles, bind with BAX in BIM SAHB site and attenuate it to undergo apoptosis while upregulating anti-apoptotic genes like BCL2. Real time studies and western blot analysis with specific phosphorylation inhibitor of ERK1 and AKT1/2/3 confirm the involvement of ERK/AKT signaling molecules to trigger the survival cascade in case of PLGA-Cur-NPs. Our finding demonstrates that low level sustained release of curcumin from PLGA-Cur-NPs could be a promising way to protect the adverse biological interactions of photo-degradation products of curcumin upon the exposure of UVA and UVB. Hence, the applicability of PLGA-Cur-NPs could be suggested as prolonged radical scavenging ingredient in curcumin containing products.

  14. Preparation of novel curcumin-imprinted polymers based on magnetic multi-walled carbon nanotubes for the rapid extraction of curcumin from ginger powder and kiwi fruit root.

    PubMed

    Zhang, Zhaohui; Chen, Xing; Rao, Wei; Long, Fang; Yan, Liang; Yin, Yuli

    2015-01-01

    A novel molecularly imprinted polymer based on magnetic phenyl-modified multi-walled carbon nanotubes was synthesized using curcumin as the template molecule, methacrylic acid as the functional monomer and ethylene glycol dimethacrylate as the cross-linker. The phenyl groups contained in the magnetic imprinted polymers acted as the assisting functional monomer. The magnetic imprinted polymers were characterized by scanning electron microscopy, Fourier-transform infrared spectroscopy and vibrating sample magnetometry. Adsorption studies demonstrated that the magnetic imprinted polymers possessed excellent selectivity toward curcumin with a maximum capacity of 16.80 mg/g. Combining magnetic extraction and high-performance liquid chromatography technology, the magnetic imprinted polymer based on magnetic phenyl-modified multi-walled carbon nanotubes was applied for the rapid separation and enrichment of curcumin from ginger powder and kiwi fruit root successfully.

  15. Green synthesis of curcumin conjugated nanosilver for the applications in nucleic acid sensing and anti-bacterial activity.

    PubMed

    El Khoury, Elsy; Abiad, Mohamad; Kassaify, Zeina G; Patra, Digambara

    2015-03-01

    Silver nanoparticles (Ag NPs) are often synthesized by chemical and physical methods. Natural and non-toxic molecules are recently being replaced for nanoparticles preparation. In this paper we have used curcumin, which interacts with Ag+ and subsequently synthesizes silver nanoparticles. Further continuation of the reaction often makes aggregation and forms dark brown/black silver oxide. Presence of glycerol in the reaction mixture gives mono-disperse curcumin conjugated Ag NPs, which can be made stable by capping with polyvinylpyrolidone (PVP). XRD data confirm that curcumin conjugated Ag NPs are crystalline in nature with a mean crystalline size of 13.27 nm. The Ag NPs are spherical and in the range of 10-50 nm though their hydrodynamic radius is found to be higher, ∼294 nm, due to polyvinylpyrolidone capping and aggregation of nanoparticles in solution. The production of curcumin conjugated Ag NPs follows first order kinetics and the effect of curcumin concentration during formation of Ag NPs indicates a linear enhancement in the production of Ag NPs with an increase in concentration of curcumin. These curcumin conjugated silver nanoparticles show anti-bacterial activity and can successfully determine nucleic acid (DNA and RNA) in the concentration range 100-1000 ng/mL with a linear regression coefficient >0.997 using Resonance Rayleigh Scattering spectra.

  16. Temperature-dependent spectroscopic evidences of curcumin in aqueous medium: a mechanistic study of its solubility and stability.

    PubMed

    Jagannathan, Ramya; Abraham, Priya Mary; Poddar, Pankaj

    2012-12-20

    In curcumin, keto-enol-enolate equilibrium of the heptadiene-dione moiety determines its physiochemical and antioxidant properties. However, its poor solubility in water at neutral pH and room temperature decreases its bioavailability. Potential therapeutic applications have triggered an interest in manipulating the solubility of curcumin in water as its stability and solubility in water remains poorly understood. Here, the mechanism behind its solubility at various temperatures and the influence of interplay of temperature, intramolecular H-bonding, and intermolecular forces is reported, which leads to aggregation-disaggregation at various temperatures. Remarkable change is observed in temperature-dependent electronic transition behavior of curcumin, however, the absorption spectra after cooling and heating cycles remain unchanged, hinting much better thermal stability of curcumin in water than previously thought. This study indicates that it is perhaps the breaking of intramolecular hydrogen bonding which leads to exposure of polar groups and hence responsible for the dissolution of curcumin at higher temperature. The formation of intermolecular aggregates might be responsible behind a better room temperature stability of the molecules after cooling its aqueous suspension from 90 to 25 °C. These curcumin solubility studies have great application in biological research with reference to bioavailability and to understand target oriented mode of action of curcumin.

  17. Stability of curcumin in different solvent and solution media: UV-visible and steady-state fluorescence spectral study.

    PubMed

    Mondal, Satyajit; Ghosh, Soumen; Moulik, Satya P

    2016-05-01

    In aqueous solution, curcumin is photodegradable (light sensitive), it is also self-degradable in the dark. In basic medium, the second process is enhanced. The dark process has been studied in water and also in a number of protic and aprotic solvents, and aqueous solutions of ionic liquids, pluronics, reverse micelles and salt. The kinetics of the process followed the first order rate law; a comparative as well as individual assessment of which has been made. The kinetics of curcumin self-degradation has been found to be fairly dependent on salt (NaCl) concentration. Curcumin molecules in solution may remain in the enol or keto-enol form. From the visible spectral analysis, an estimate of the proportions of these forms in aqueous ethanol medium has been made. The temperature effect on the visible and fluorescence spectra of curcumin has been also studied. The steady state fluorescence anisotropy of the photoactive curcumin has been evaluated in different solvent and solution media. The reversibility of the steady state fluorescence anisotropy of curcumin on heating and cooling conditions has been examined. The results herein presented are new and ought to be useful as the study of physicochemistry of curcumin has been gaining importance in the light of its biological importance.

  18. Molecular recognition of curcumin (Indian Ayurvedic medicine) by the supramolecular probe, p-t-butyl calix(8)arene

    NASA Astrophysics Data System (ADS)

    Meenakshi, C.; Jayabal, P.; Ramakrishnan, V.

    2014-06-01

    The thermodynamic property of the host-guest complexes formed between the curcumin, component of Indian Ayurvedic medicine turmeric, a drug molecule, with the supra molecule, p-t-butyl calix(8)arene was studied. p-t-Butyl calix(8)arene has been used as a host molecule and curcumin as a guest molecule. Optical absorption spectral studies were carried out to investigate the molecular recognition properties of p-t-butyl calix(8)arene with curcumin. The stochiometry of the host-guest complexes formed and the binding constant were determined. An interesting 1:1 and 4:1 stochiometric host-guest complexes were formed. Job's continuous method of variation and Benesi-Hildebrand expression were used for the determination of binding constant and the stochiometry of the host-guest complex formed.

  19. Molecular recognition of curcumin (Indian Ayurvedic medicine) by the supramolecular probe, p-t-butyl calix(8)arene.

    PubMed

    Meenakshi, C; Jayabal, P; Ramakrishnan, V

    2014-06-05

    The thermodynamic property of the host-guest complexes formed between the curcumin, component of Indian Ayurvedic medicine turmeric, a drug molecule, with the supra molecule, p-t-butyl calix(8)arene was studied. p-t-Butyl calix(8)arene has been used as a host molecule and curcumin as a guest molecule. Optical absorption spectral studies were carried out to investigate the molecular recognition properties of p-t-butyl calix(8)arene with curcumin. The stochiometry of the host-guest complexes formed and the binding constant were determined. An interesting 1:1 and 4:1 stochiometric host-guest complexes were formed. Job's continuous method of variation and Benesi-Hildebrand expression were used for the determination of binding constant and the stochiometry of the host-guest complex formed.

  20. In situ synthesis and surface functionalization of gold nanoparticles with curcumin and their antioxidant properties: an experimental and density functional theory investigation

    NASA Astrophysics Data System (ADS)

    Singh, Dheeraj K.; Jagannathan, Ramya; Khandelwal, Puneet; Abraham, Priya Mary; Poddar, Pankaj

    2013-02-01

    Curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is an active component of turmeric; it is responsible for its characteristic yellow color and therapeutic potential, but its poor bioavailability remains a major challenge. In order to improve the bioavailability of curcumin, various approaches have been used. One of the possible approaches to increase the bioavailability of curcumin is its conjugation on the surface of metal nanoparticles. Therefore, in the present study, we report the binding of curcumin on the surface of gold nanoparticles (AuNPs). The AuNPs were synthesized by the direct reduction of HAuCl4 using curcumin in the aqueous phase, without the use of any other reducing agents. We found that curcumin acts both as a reducing and capping agent, stabilizing the gold sol for many months. Moreover, these curcumin-capped AuNPs also show good antioxidant activity which was confirmed by the DPPH (2,2-diphenyl-l-picrylhydrazyl) radical test. Thus, the surface functionalization of AuNPs with curcumin may pave a new way of using the curcuminoids towards possible drug delivery and therapeutics. Apart from the experimental study, a detailed quantum chemical calculation using density functional theory (DFT) has been performed, in order to investigate the formation of a complex of curcumin with Au3+ ions in different possible conformational isomeric forms. Our theoretical calculations indicate the evidence of electron transfer from curcumin into the Au center and essentially indicate that as a consequence of complexation, Au3+ ions are reduced to Au0. Our theoretical results also propose that it is the breakage of intramolecular H-bonding that probably leads to the increased availability of curcumin in the presence of gold ions and water molecules.Curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is an active component of turmeric; it is responsible for its characteristic yellow color and therapeutic

  1. Modulation of the photophysical properties of curcumin in nonionic surfactant (Tween-20) forming micelles and niosomes: a comparative study of different microenvironments.

    PubMed

    Mandal, Sarthak; Banerjee, Chiranjib; Ghosh, Surajit; Kuchlyan, Jagannath; Sarkar, Nilmoni

    2013-06-13

    The modulation of the photophysical properties of curcumin inside two different types of microenvironments provided by nonionic surfactant forming micelles and vesicles (niosomes) has been investigated using steady state and time-resolved fluorescence spectroscopy. The formation of small unilamellar Tween-20/cholesterol niosomes with narrow size distribution has been successfully demonstrated by means of dynamic light scattering (DLS) and transmission electron microscopy (TEM) techniques. Our results indicate that niosomes are a better possible delivery system than the conventional surfactants forming normal micelles to suppress the level of degradation of curcumin. The enhanced fluorescence intensity along with the significant blue-shift in the emission maxima of curcumin upon encapsulation into the hydrophobic microenvironments of micelles and niosomes is a consequence of the reduced interaction of curcumin with the water molecules. We found that the more rigid and confined microenvironment of niosomes enhances the steady state fluorescence intensity along with the fluorescence lifetime of curcumin more than in micelles. The rigidity of the niosome membrane which arises basically due to the presence of cholesterol molecules increases the level of interaction between curcumin and the oxoethylene units of Tween-20 molecules. It is also possible for the hydroxyl groups of the cholesterol moieties to form intermolecular hydrogen bonds with curcumin to perturb nonradiative deactivation mechanism through excited state intramolecular hydrogen atom transfer (ESIHT).

  2. In situ synthesis and surface functionalization of gold nanoparticles with curcumin and their antioxidant properties: an experimental and density functional theory investigation.

    PubMed

    Singh, Dheeraj K; Jagannathan, Ramya; Khandelwal, Puneet; Abraham, Priya Mary; Poddar, Pankaj

    2013-03-07

    Curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is an active component of turmeric; it is responsible for its characteristic yellow color and therapeutic potential, but its poor bioavailability remains a major challenge. In order to improve the bioavailability of curcumin, various approaches have been used. One of the possible approaches to increase the bioavailability of curcumin is its conjugation on the surface of metal nanoparticles. Therefore, in the present study, we report the binding of curcumin on the surface of gold nanoparticles (AuNPs). The AuNPs were synthesized by the direct reduction of HAuCl(4) using curcumin in the aqueous phase, without the use of any other reducing agents. We found that curcumin acts both as a reducing and capping agent, stabilizing the gold sol for many months. Moreover, these curcumin-capped AuNPs also show good antioxidant activity which was confirmed by the DPPH (2,2-diphenyl-l-picrylhydrazyl) radical test. Thus, the surface functionalization of AuNPs with curcumin may pave a new way of using the curcuminoids towards possible drug delivery and therapeutics. Apart from the experimental study, a detailed quantum chemical calculation using density functional theory (DFT) has been performed, in order to investigate the formation of a complex of curcumin with Au(3+) ions in different possible conformational isomeric forms. Our theoretical calculations indicate the evidence of electron transfer from curcumin into the Au center and essentially indicate that as a consequence of complexation, Au(3+) ions are reduced to Au(0). Our theoretical results also propose that it is the breakage of intramolecular H-bonding that probably leads to the increased availability of curcumin in the presence of gold ions and water molecules.

  3. The Essential Medicinal Chemistry of Curcumin

    PubMed Central

    2017-01-01

    Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed. PMID:28074653

  4. Therapeutic actions of curcumin in bone disorders

    PubMed Central

    Rohanizadeh, Ramin; Deng, Yi; Verron, Elise

    2016-01-01

    Curcumin is the active component of turmeric extract derived from the Curcuma longa plant. In the last decade, curcumin has raised a considerable interest in medicine owing to its negligible toxicity and multiple therapeutic actions including anti-cancer, anti-inflammatory and anti-microbial activities. Among the various molecular targets of curcumin, some are involved in bone remodeling, which strongly suggests that curcumin can affect the skeletal system. The review sheds light on the current and potential applications of curcumin to treat bone disorders characterized by an excessive resorption activity. Within the scope of this review, the novel formulations of curcumin to overcome its physico-chemical and pharmacokinetic constraints are also discussed. PMID:26962450

  5. Curcumin Enhances the Anti-Trypanosoma cruzi Activity of Benznidazole-Based Chemotherapy in Acute Experimental Chagas Disease.

    PubMed

    Novaes, Rômulo Dias; Sartini, Marcus Vinicius Pessoa; Rodrigues, João Paulo Ferreira; Gonçalves, Reggiani Vilela; Santos, Eliziária Cardoso; Souza, Raquel Lopes Martins; Caldas, Ivo Santana

    2016-06-01

    Although curcumin can increase the effectiveness of drugs against malaria, combination therapies using the molecule have never been investigated in Chagas disease (ChD). Therefore, we evaluated the efficacy of curcumin as a complementary strategy to benznidazole (Bz)-based chemotherapy in mice acutely infected with Trypanosoma cruzi Eighty-four 12-week-old Swiss mice were equally randomized into seven groups: uninfected (NI), T. cruzi infected and untreated (INF), infected and treated with 100 mg/kg of body weight Bz (B100), 50 mg/kg Bz (B50), 100 mg/kg curcumin (C100), 100 mg/kg Bz plus 100 mg/kg curcumin (B100 plus C100), and 50 mg/kg Bz plus 100 mg/kg curcumin (B50 plus C100). After microscopic identification of blood trypomastigotes (4 days after inoculation), both drugs were administered by gavage once a day for 20 days. Curcumin showed limited antiparasitic, anti-inflammatory, and antioxidant effects when administered alone. When curcumin and Bz were combined, there was a drastic reduction in parasitemia, parasite load, mortality, anti-T. cruzi IgG reactivity, circulating levels of cytokines (gamma interferon [IFN-γ], interleukin 4 [IL-4], and MIP1-α), myocardial inflammation, and morphological and oxidative cardiac injury; these results exceeded the isolated effects of Bz. The combination of Bz and curcumin was also effective at mitigating liver toxicity triggered by Bz, increasing the parasitological cure rate, and preventing infection recrudescence in noncured animals, even when the animals were treated with 50% of the recommended therapeutic dose of Bz. By limiting the toxic effects of Bz and enhancing its antiparasitic efficiency, the combination of the drug with curcumin may be a relevant therapeutic strategy that is possibly better tolerated in ChD treatment than Bz-based monotherapy.

  6. The modulation of erythrocyte Na(+)/K(+)-ATPase activity by curcumin.

    PubMed

    Singh, Prabhakar; Kesharwani, Rajesh Kumar; Misra, Krishna; Rizvi, Syed Ibrahim

    2015-11-01

    Curcumin, an active biphenolic molecule present in turmeric (Curcuma longa), has been reported to elicit plethora of health protective effects. The present study was carried out in vitro, in vivo and in silico to investigate the modulatory effects of curcumin on erythrocyte membrane Na(+)/K(+)-ATPase activity. In vitro curcumin (10(-) (5) M to 10(-) (8) M) was incubated with human erythrocytes membrane. In vivo curcumin (340 mg/kg b.w. and 170 mg/kg b.w.) was supplemented to wistar rats for 21 days. In silico, catalytic unit α of Na(+)/K(+)-ATPase (3b8e.pdb) protein was used as a receptor for the natural ligand ATP to study curcumin-mediated docking simulation using AutoDock4. The in vitro effect of curcumin on the Na(+)/K(+)-ATPase activity in human erythrocytes was biphasic. An inhibitory response was observed at 10(-) (5) M (p < 0.001). An activation of the Na(+)/K(+)-ATPase activity was observed at 10(-) (7) and 10(-) (8) M (p < 0.001 and p < 0.01). In vivo, curcumin supplementation to rats increased the Na(+)/K(+)-ATPase activity at doses 340 mg/kg b.w. (p < 0.001) as well as at 170 mg/kg b.w., (p < 0.01). AutoDock4 docking simulation study showed that both ligands curcumin and ATP actively interacted with amino acids Glu214, Ser215, Glu216, Thr371, Asn377, Arg378, Met379, Arg438, Val440, Ala444, Lys451 and Asp586 at the catalytic cavity of Na+/K+-ATPase. ATP had more H bonding and hydrophobic interaction with active site amino acid residues compared to curcumin. These finding may explain some of the health beneficial properties of curcumin associated with deregulated Na(+)/K(+)-ATPase activity or ions homeostasis.

  7. 3,3'-OH curcumin causes apoptosis in HepG2 cells through ROS-mediated pathway.

    PubMed

    Liu, Guo-Yun; Sun, Yong-Zheng; Zhou, Na; Du, Xiu-Mei; Yang, Jie; Guo, Shang-Jing

    2016-04-13

    In this paper, we synthesized a series of curcumin analogs and evaluated their cytotoxicity against HepG2 cells. The results exhibited that the hydroxyl group at 3,3'-position play an essential role in enhancing their anti-proliferation activity. More importantly, 3,3'-hydroxy curcumin (1b) caused apoptosis in HepG2 cells with the ROS generation, which may be mainly composed of hydroxyl radicals (HO) and H2O2. The more cytotoxic activity and ROS-generating ability of 1b may be due to the more stable in (RPMI)-1640 medium and more massive uptake than curcumin. Then the generation of ROS can disrupt the intracellular redox balance, induce lipid peroxidation, cause the collapse of the mitochondrial membrane potential and ultimately lead to apoptosis. The results not only suggest that 3,3'-hydroxy curcumin (1b) may cause HepG2 cells apoptosis through ROS-mediated pathway, but also offer an important information for design of curcumin analog.

  8. Future of nano bisdemethoxy curcumin analog: guaranteeing safer intravenous delivery.

    PubMed

    Francis, Arul Prakash; Ganapathy, Selvam; Palla, Venkata Rajsekhar; Murthy, Prakhya Balakrishna; Devasena, Thiyagarajan

    2015-01-01

    The present study deals with the toxicity assessment of NBDMCA in vitro using red cell model and in vivo using rat model. Hemolysis was used as toxicity index in red blood cells. Different concentrations of NBDMCA viz., 20, 40, 60, 80, 100μg/ml in PBS were incubated with the red blood cells of rat. NBDMCA was found to induce less than 3% hemolysis in intact erythrocytes which was far lesser than the accepted threshold of 5%. Hematological cum biochemical parameters along with histopathological analysis and hemolysis were used as toxicity indices in rats. Whole blood of the NBDMCA-treated rats and control rats were analyzed for hematological parameters: erythrocyte count, leukocyte count, leukocyte differential count, hemoglobin, hematocrit, mean cell volume (MCV), mean corpuscular hemoglobin (MCH) using fully automated hematology analyzer. All hematological parameters analyzed were within the normal values in both the groups. Plasma samples were analyzed for biochemical parameters including glucose, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine (Cre), albumin (Alb), total protein (TP), calcium (Ca) and phosphorus (P) using fully automated biochemistry analyzer. Invariably, all the biochemical parameters are significantly similar in both the groups. Gross examination of vital organs like lung, heart, kidney, spleen and brain reveals no detectable abnormalities in NBDMCA-treated animals. Internal organs like heart, brain, lung, liver, spleen and kidneys of the experimental animals were collected and fixed in 10% formalin, processed in vacuum infiltration tissue processor, embedded with paraffin wax and sectioned at approximately 5μm thick, stained with hematoxylin and eosin. The sections were examined and imaged through light microscopy. NBDMCA did not produce any significant changes in the histoarchitecture of all the organs studied. Heart, aorta, brain, lung, liver, kidney and spleen showed normal pathology report. The histopathological data correlated with the biochemical results indicating normal hepatocellular and nephrotic function. Our investigation clearly revealed that NBDMCA is hemocompatible in vitro and also safe to vital organs in vivo. We conclude that NBDMCA is non-toxic and safe and can be promoted as an ideal therapeutic tool for human use.

  9. Development of curcumin nanocrystal: physical aspects.

    PubMed

    Rachmawati, Heni; Al Shaal, Loaye; Müller, Rainer H; Keck, Cornelia M

    2013-01-01

    Curcumin, a naturally occuring polyphenolic phytoconstituent, is isolated from the rhizomes of Curcuma longa Linn. (Zingiberaceae). It is water insoluble under acidic or neutral conditions but dissolves in alkaline environment. In neutral or alkaline conditions, curcumin is highly unstable undergoing rapid hydrolytic degradation to feruloyl methane and ferulic acid. Thus, the use of curcumin is limited by its poor aqueous solubility in acidic or neutral conditions and instability in alkaline pH. In the present study, curcumin nanocrystals were prepared using high-pressure homogenization, to improve its solubility. Five different stabilizers [polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), sodium dodecyl sulfate (SDS), carboxymethylcellulose sodium salt] possessing different stabilization mechanism were investigated. The nanoparticles were characterized with regard to size, surface charge, shape and morphology, thermal property, and crystallinity. A short-term stability study was performed storing the differently stabilized nanoparticles at 4°C and room temperature. PVA, PVP, TPGS, and SDS successfully produced curcumin nanoparticle with the particle size in the range of 500-700 nm. PVA, PVP, and TPGS showed similar performance in preserving the curcumin nanosuspension stability. However, PVP is the most efficient polymer to stabilize curcumin nanoparticle. This study illustrates that the developed curcumin nanoparticle held great potential as a possible approach to improve the curcumin solubility then enhancing bioavailability.

  10. Chalcone and curcumin derivatives: a way ahead for malarial treatment.

    PubMed

    Kumar, Dileep; Kumar, Manish; Kumar, Ashok; Singh, Sushil Kumar

    2013-12-01

    Malaria has been a major cause of morbidity and mortality in developing countries, particularly in Sub-Saharan Africa and South Asia. The global malaria situation is increasingly being challenging owing to lack of credible malaria vaccine and the emergence of drug resistance to most of the available antimalarials. They demand search for novel generation of drugs. Versatility and flexibility for structural modification of natural and synthetic analogues of curcumin and chalcone have been explored extensively for designing new antimalarial agent. Recent advances to our knowledge of parasite biology as well as the availability of the genome sequence, have opened up new vista in the firmament of antimalarial drug designing for identifying novel molecular targets. Curcumin and chalcones has been reported to exert anti-malarial effect by binding directly to numerous signaling molecules, such as histone acetyltransferase, histone deacetylase, sarco (endo) plasmic reticulum Ca(2+)-ATPase, cysteine proteases etc. This review highlights insights the more recent antimalarial activities of these compounds, their mechanisms of action, molecular targets and relevant structureactivity relationship studies. Natural lead compounds like chalcone and curcumin have shown good and optimal binding to many enzymes present in parasite and can be explored as molecular targets for in silico studies to develop new, affordable and effective antimalarial drugs. With no credible malaria vaccine in sight, there is an imperative need to develop new drugs with different mechanisms of action to help preclude issues of cross-resistance.

  11. Curcumin prevents cisplatin-induced decrease in the tight and adherens junctions: relation to oxidative stress.

    PubMed

    Trujillo, Joyce; Molina-Jijón, Eduardo; Medina-Campos, Omar Noel; Rodríguez-Muñoz, Rafael; Reyes, José Luis; Loredo, María L; Barrera-Oviedo, Diana; Pinzón, Enrique; Rodríguez-Rangel, Daniela Saraí; Pedraza-Chaverri, José

    2016-01-01

    Curcumin is a polyphenol and cisplatin is an antineoplastic agent that induces nephrotoxicity associated with oxidative stress, apoptosis, fibrosis and decrease in renal tight junction (TJ) proteins. The potential effect of curcumin against alterations in TJ structure and function has not been evaluated in cisplatin-induced nephrotoxicity. The present study explored whether curcumin is able to prevent the cisplatin-induced fibrosis and decreased expression of the TJ and adherens junction (AJ) proteins occludin, claudin-2 and E-cadherin in cisplatin-induced nephrotoxicity. Curcumin (200 mg kg(-1)) was administered in three doses, and rats were sacrificed 72 h after cisplatin administration. Curcumin was able to scavenge, in a concentration-dependent way, superoxide anion, hydroxyl radical, peroxyl radical, singlet oxygen, peroxynitrite anion, hypochlorous acid and hydrogen peroxide. Cisplatin-induced renal damage was associated with alterations in plasma creatinine, expression of neutrophil gelatinase-associated lipocalin and of kidney injury molecule-1, histological damage, increase in apoptosis, fibrosis (evaluated by transforming growth factor β1, collagen I and IV and α-smooth muscle actin expressions), increase in oxidative/nitrosative stress (evaluated by Hsp70/72 expression, protein tyrosine nitration, superoxide anion production in isolated glomeruli and proximal tubules, and protein levels of NADPH oxidase subunits p47(phox) and gp91(phox), protein kinase C β2, and Nrf2) as well as by decreased expression of occludin, claudin-2, β-catenin and E-cadherin. Curcumin treatment prevented all the above-described alterations. The protective effect of curcumin against cisplatin-induced fibrosis and decreased proteins of the TJ and AJ was associated with the prevention of glomerular and proximal tubular superoxide anion production induced by NADPH oxidase activity.

  12. AIDS-protective HLA-B*27/B*57 and chimpanzee MHC class I molecules target analogous conserved areas of HIV-1/SIVcpz.

    PubMed

    de Groot, Natasja G; Heijmans, Corrine M C; Zoet, Yvonne M; de Ru, Arnoud H; Verreck, Frank A; van Veelen, Peter A; Drijfhout, Jan W; Doxiadis, Gaby G M; Remarque, Edmond J; Doxiadis, Ilias I N; van Rood, Jon J; Koning, Frits; Bontrop, Ronald E

    2010-08-24

    In the absence of treatment, most HIV-1-infected humans develop AIDS. However, a minority are long-term nonprogressors, and resistance is associated with the presence of particular HLA-B*27/B*57 molecules. In contrast, most HIV-1-infected chimpanzees do not contract AIDS. In comparison with humans, chimpanzees experienced an ancient selective sweep affecting the MHC class I repertoire. We have determined the peptide-binding properties of frequent chimpanzee MHC class I molecules, and show that, like HLA-B*27/B*57, they target similar conserved areas of HIV-1/SIV(cpz). In addition, many animals appear to possess multiple molecules targeting various conserved areas of the HIV-1/SIV(cpz) Gag protein, a quantitative aspect of the immune response that may further minimize the chance of viral escape. The functional characteristics of the contemporary chimpanzee MHC repertoire suggest that the selective sweep was caused by a lentiviral pandemic.

  13. Determining the Effects of Lipophillic Drugs on Membrane Structure by Solid-State NMR Spectroscopy– The Case of the Antioxidant Curcumin

    PubMed Central

    Barry, Jeffrey; Fritz, Michelle; Brender, Jeffrey R.; Smith, Pieter E.S.; Lee, Dong-Kuk; Ramamoorthy, Ayyalusamy

    2009-01-01

    Curcumin is the active ingredient of the turmeric powder, a natural spice used for generations in traditional medicines. Curcumin’s broad spectrum of anti-oxidant, anti-carcinogenic, anti-mutagenic, and anti-inflammatory properties makes it particularly interesting for the development of pharmaceutical compounds. Due to curcumin’s various effects on the function of numerous unrelated membrane proteins, it has been suggested that it affects the properties of the bilayer itself. However, a detailed atomic-level study of the interaction of curcumin with membranes has not been attempted. A combination of solid-state NMR and differential scanning calorimetry experiments shows curcumin has a strong effect on membrane structure at low concentrations. Curcumin inserts deep into the membrane in a transbilayer orientation, anchored by hydrogen bonding to the phosphate group of lipids in a manner analogous to cholesterol. Like cholesterol, curcumin induces segmental ordering in the membrane. Analysis of the concentration dependence of the order parameter profile derived from NMR results suggests curcumin forms higher order oligomeric structures in the membrane that span and likely thin the bilayer. Curcumin promotes the formation of the highly curved inverted hexagonal phase which may influence exocytotic and membrane fusion processes within the cell. The experiments outlined here show promise for understanding the action of other drugs such as capsaicin in which drug-induced alterations of membrane structure have strong pharmacological effects. PMID:19256547

  14. Direct chemical grafted curcumin on halloysite nanotubes as dual-responsive prodrug for pharmacological applications.

    PubMed

    Massaro, M; Amorati, R; Cavallaro, G; Guernelli, S; Lazzara, G; Milioto, S; Noto, R; Poma, P; Riela, S

    2016-04-01

    Covalently functionalized halloysite nanotubes (HNTs) were successfully employed as dual-responsive nanocarriers for curcumin (Cur). Particularly, we synthesized HNT-Cur prodrug with a controlled curcumin release on dependence of both intracellular glutathione (GSH) and pH conditions. In order to obtain HNT-Cur produgs, halloysite was firstly functionalized with cysteamine through disulphide linkage. Afterwards, curcumin molecules were chemically conjugated to the amino end groups of halloysite via Schiff's base formation. The successful functionalization of halloysite was proved by thermogravimetric analysis, FT-IR spectroscopy, dynamic light scattering and scanning electron microscopy. Experimental data confirmed the presence of curcumin on HNT external surface. Moreover, we investigated the kinetics of curcumin release by UV-vis spectroscopy, which highlighted that HNT-Cur prodrug possesses dual stimuli-responsive ability upon exposure to GSH-rich or acidic environment. In vitro antiproliferative and antioxidant properties of HNT-Cur prodrug were studied with the aim to explore their potential applications in pharmaceutics. This work puts forward an efficient strategy to prepare halloysite based nanocarriers with controlled drug delivery capacity through direct chemical grafting with stimuli-responsive linkage.

  15. Experimental and computational studies on the inhibition of acetylcholinesterase by curcumin and some of its derivatives.

    PubMed

    Tello-Franco, Veronica; Lozada-García, Maria Concepcion; Soriano-García, Manuel

    2013-06-01

    Recent studies have demonstrated several biological activities of curcumin with therapeutic potential against Alzheimer's disease, among them the inhibition of the enzyme acetylcholinesterase (AChE). Aiming at identifying the chemical features relevant for this activity, the inhibition of curcumin and a set of 7 derivatives against AChE of E. electricus was measured. These derivatives presented lower activity than curcumin, allowing for the identification of possible unfavorable enzyme-inhibitor interactions. Our computational approach was to dock the molecules to the active site of AChE, followed by an analysis of hydrogen bonds and close contacts to relevant aromatic amino acid residues. To account for inhibitory activity, we sought to define the common structural features between known acetylcholinesterase inhibitors and the tested derivatives. A pharmacophore model was generated, which consisted of two hydrophobic, one aromatic and one hydrogen bond acceptor features. We conclude that the presence of two aromatic rings and the distance between them, allows curcumin and its derivatives to favorably interact with both the quaternary and peripheral sites of AChE. Hydrogen bonds can be formed with the quaternary and acyl sites, which should further stabilize the complex. The acylation of the hydroxyl groups and the reduction of the conjugated double bonds lowered the inhibitory activity, pointing to the modification of the keto-enol moiety as the best alternative for the design of more potent curcumin derivatives as acetylcholinesterase inhibitors.

  16. Curcumin binding to DNA and RNA.

    PubMed

    Nafisi, Shohreh; Adelzadeh, Maryam; Norouzi, Zeinab; Sarbolouki, Mohammad Nabi

    2009-04-01

    Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical with a variety of biological activities. The ongoing research and clinical trials have proved that this natural phenolic compound has great and diverse pharmacological potencies. Beside its effective antioxidant, antiinflammatory, and antimicrobial/antiviral properties, curcumin is also considered as a cancer chemopreventive agent. While the antioxidant activity of curcumin is well documented, its interaction with DNA and RNA is not fully investigated. This study was designed to examine the interactions of curcumin with calf thymus DNA and yeast RNA in aqueous solution at physiological conditions, using constant DNA and RNA concentration (6.25 mM) and various curcumin/polynucleotide (phosphate) ratios of 1/120, 1/80, 1/40, 1/20, and 1/10. Fourier transform infrared (FTIR) and UV-visible spectroscopic methods were used to determine the ligand binding modes, the binding constants, and the stability of curcumin-DNA and curcumin-RNA complexes in aqueous solution. Spectroscopic evidence showed that curcumin binds to the major and minor grooves of DNA duplex and to RNA bases as well as to the back bone phosphate group with overall binding constants of K(curcumin-DNA) = 4.255 x 10(4) M(-1) and K(curcumin-RNA) = 1.262 x 10(4) M(-1). Major DNA and RNA aggregation occurred at high pigment concentration. No conformational changes were observed upon curcumin interaction with these biopolymers; that is, DNA remains in the B, and RNA retains its A-family structure.

  17. Clinical utility of curcumin extract.

    PubMed

    Asher, Gary N; Spelman, Kevin

    2013-01-01

    Turmeric root has been used medicinally in China and India for thousands of years. The active components are thought to be the curcuminoids, primarily curcumin, which is commonly available worldwide as a standardized extract. This article reviews the pharmacology of curcuminoids, their use and efficacy, potential adverse effects, and dosage and standardization. Preclinical studies point to mechanisms of action that are predominantly anti-inflammatory and antineoplastic, while early human clinical trials suggest beneficial effects for dyspepsia, peptic ulcer, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, uveitis, orbital pseudotumor, and pancreatic cancer. Curcumin is well-tolerated; the most common side effects are nausea and diarrhea. Theoretical interactions exist due to purported effects on metabolic enzymes and transport proteins, but clinical reports do not support any meaningful interactions. Nonetheless, caution, especially with chemotherapy agents, is advised. Late-phase clinical trials are still needed to confirm most beneficial effects.

  18. Effects of curcumin on HDL functionality.

    PubMed

    Ganjali, Shiva; Blesso, Christopher N; Banach, Maciej; Pirro, Matteo; Majeed, Muhammed; Sahebkar, Amirhossein

    2017-02-10

    Curcumin, a bioactive polyphenol, is a yellow pigment of the Curcuma longa (turmeric) plant. Curcumin has many pharmacologic effects including antioxidant, anti-carcinogenic, anti-obesity, anti-angiogenic and anti-inflammatory properties. Recently, it has been found that curcumin affects lipid metabolism, and subsequently, may alleviate hyperlipidemia and atherosclerosis. Plasma HDL cholesterol (HDL-C) is an independent negative risk predictor of cardiovascular disease (CVD). However, numerous clinical and genetic studies have yielded disappointing results about the therapeutic benefit of raising plasma HDL-C levels. Therefore, research efforts are now focused on improving HDL functionality, independent of HDL-C levels. The quality of HDL particles can vary considerably due to heterogeneity in composition. Consistent with its complexity in composition and metabolism, a wide range of biological activities is reported for HDL, including antioxidant, anti-glycation, anti-inflammatory, anti-thrombotic, anti-apoptotic and immune modulatory activities. Protective properties of curcumin may influence HDL functionality; therefore, we reviewed the literature to determine whether curcumin can augment HDL function. In this review, we concluded that curcumin may modulate markers of HDL function, such as apo-AI, CETP, LCAT, PON1, MPO activities and levels. Curcumin may subsequently improve conditions in which HDL is dysfunctional and may have potential as a therapeutic drug in future. Further clinical trials with bioavailability-improved formulations of curcumin are warranted to examine its effects on lipid metabolism and HDL function.

  19. Curcumin derivatives as HIV-1 protease inhibitors

    SciTech Connect

    Sui, Z.; Li, J.; Craik, C.S.; Ortiz de Montellano, P.R.

    1993-12-31

    Curcumin, a non-toxic natural compound from Curcuma longa, has been found to be an HIV-1 protease inhibitor. Some of its derivatives were synthesized and their inhibitory activity against the HIV-1 protease was tested. Curcumin analogues containing boron enhanced the inhibitory activity. At least of the the synthesized compounds irreversibly inhibits the HIV-1 protease.

  20. Curcumin binds to the pre-fibrillar aggregates of Cu/Zn superoxide dismutase (SOD1) and alters its amyloidogenic pathway resulting in reduced cytotoxicity.

    PubMed

    Bhatia, Nidhi K; Srivastava, Ankit; Katyal, Nidhi; Jain, Nidhi; Khan, M Ashhar I; Kundu, Bishwajit; Deep, Shashank

    2015-05-01

    Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that affects motor neurons. Unfortunately, effective therapeutics against this disease is still not available. Almost 20% of familial ALS (fALS) is suggested to be associated with pathological deposition of superoxide dismutase (SOD1). Evidences suggest that SOD1-containing pathological inclusions in ALS exhibit amyloid like properties. An effective strategy to combat ALS may be to inhibit amyloid formation of SOD1 using small molecules. In the present study, we observed the fibrillation of one of the premature forms of SOD1 (SOD1 with reduced disulfide) in the presence of curcumin. Using ThT binding assay, AFM, TEM images and FTIR, we demonstrate that curcumin inhibits the DTT-induced fibrillation of SOD1 and favors the formation of smaller and disordered aggregates of SOD1. The enhancement in curcumin fluorescence on the addition of oligomers and pre-fibrillar aggregates of SOD1 suggests binding of these species to curcumin. Docking studies indicate that putative binding site of curcumin may be the amyloidogenic regions of SOD1. Further, there is a significant increase in SOD1 mediated toxicity in the regime of pre-fibrillar and fibrillar aggregates which is not evident in curcumin containing samples. All these data suggest that curcumin reduces toxicity by binding to the amyloidogenic regions of the species on the aggregation pathway and blocking the formation of the toxic species. Nanoparticles of curcumin with higher aqueous solubility show similar aggregation control as that of curcumin bulk. This suggests a potential role for curcumin in the treatment of ALS.

  1. Investigation on Curcumin nanocomposite for wound dressing.

    PubMed

    Venkatasubbu, G Devanand; Anusuya, T

    2017-02-03

    Curcuma longa (turmeric) has a long history of use in medicine as a treatment for inflammatory conditions. The primary active constituent of turmeric and the one responsible for its vibrant yellow color is curcumin. Curcumin is used for treatment of wound and inflammation. It had antimicrobial and antioxidant property. It has low intrinsic toxicity and magnificent properties like with comparatively lesser side-effects. Cotton cloth is one of the most successful wound dressings which utilize the intrinsic properties of cotton fibers. Modern wound dressings, however, require other properties such as antibacterial and moisture maintaining capabilities. In this study, conventional cotton cloth was coated with Curcumin composite for achieving modern wound dressing properties. Curcumin nanocomposite is characterized. The results show that coated cotton cloth with Curcumin nanocomposite has increased drying time (74%) and water absorbency (50%). Furthermore, they show antibacterial efficiency against bacterial species present in wounds.

  2. Enhancement of curcumin oral absorption and pharmacokinetics of curcuminoids and curcumin metabolites in mice

    PubMed Central

    Zhongfa, Liu; Chiu, Ming; Wang, Jiang; Chen, Wei; Yen, Winston; Fan-Havard, Patty; Yee, Lisa D.; Chan, Kenneth K.

    2012-01-01

    Purpose Curcumin has shown a variety of biological activity for various human diseases including cancer in preclinical setting. Its poor oral bioavailability poses significant pharmacological barriers to its clinical application. Here, we established a practical nano-emulsion curcumin (NEC) containing up to 20% curcumin (w/w) and conducted the pharmacokinetics of curcuminoids and curcumin metabolites in mice. Methods This high loading NEC was formulated based on the high solubility of curcumin in polyethylene glycols (PEGs) and the synergistic enhancement of curcumin absorption by PEGs and Cremophor EL. The pharmacokinetics of curcuminoids and curcumin metabolites was characterized in mice using a LC–MS/MS method, and the pharmacokinetic parameters were determined using WinNonlin computer software. Results A tenfold increase in the AUC0→24h and more than 40-fold increase in the Cmax in mice were observed after an oral dose of NEC compared with suspension curcumin in 1% methylcellulose. The plasma pharmacokinetics of its two natural congeners, demethoxycurcumin and bisdemethoxycurcumin, and three metabolites, tetrahydrocurcumin (THC), curcumin-O-glucuronide, and curcumin-O-sulfate, was characterized for the first time in mice after an oral dose of NEC. Conclusion This oral absorption enhanced NEC may provide a practical formulation to conduct the correlative study of the PK of curcuminoids and their pharmacodynamics, e.g., hypomethylation activity in vivo. PMID:21968952

  3. Curcumin enhances paraquat-induced apoptosis of N27 mesencephalic cells via the generation of reactive oxygen species.

    PubMed

    Ortiz-Ortiz, Miguel A; Morán, José M; Bravosanpedro, Jose M; González-Polo, Rosa A; Niso-Santano, Mireia; Anantharam, Vellareddy; Kanthasamy, Anumantha G; Soler, Germán; Fuentes, José M

    2009-11-01

    Curcumin, the active compound of the rhizome of Curcuma longa has anti-inflammatory, antioxidant and antiproliferative activities. This agent has been shown to regulate numerous transcription factors, cytokines, protein kinases, adhesion molecules, redox status and enzymes that have been linked to inflammation. While curcumin has been identified as an activator of apoptosis in several cell lines, the mechanism by which it initiates apoptosis, however, remains poorly understood. We considered curcumin from the point of view of its ability to protect against oxidative stress, the latter being one factor strongly implicated in the development of Parkinson's disease. Although the etiology of Parkinson's disease remains unknown, epidemiological studies have linked exposure to pesticides such paraquat to an increased risk of developing the condition. Analysis of the neurotoxic properties of these pesticide compounds has been focused on their ability to induce oxidative stress in neural cells. Given curcumin's capacity to protect against oxidative stress, it has been considered as a potential therapeutic agent for neurodegenerative diseases such as Parkinson's disease that involve an oxidative stress component. In the present report we describe the effect of curcumin in paraquat-mediated apoptosis of N27 mesencepahlic cells. We show that subtoxic concentrations of curcumin sensitize N27 mesencephalic cells to paraquat-mediated apoptosis.

  4. Phytosomal curcumin: A review of pharmacokinetic, experimental and clinical studies.

    PubMed

    Mirzaei, Hamed; Shakeri, Abolfazl; Rashidi, Bahman; Jalili, Amin; Banikazemi, Zarrin; Sahebkar, Amirhossein

    2017-01-01

    Curcumin, a hydrophobic polyphenol, is the principal constituent extracted from dried rhizomes of Curcuma longa L. (turmeric). Curcumin is known as a strong anti-oxidant and anti-inflammatory agent that has different pharmacological effects. In addition, several studies have demonstrated that curcumin is safe even at dosages as high as 8g per day; however, instability at physiological pH, low solubility in water and rapid metabolism results in a low oral bioavailability of curcumin. The phytosomal formulation of curcumin (a complex of curcumin with phosphatidylcholine) has been shown to improve curcumin bioavailability. Existence of phospholipids in phytosomes leads to specific physicochemical properties such as amphiphilic nature that allows dispersion in both hydrophilic and lipophilic media. The efficacy and safety of curcumin phytosomes have been shown against several human diseases including cancer, osteoarthritis, diabetic microangiopathy and retinopathy, and inflammatory diseases. This review focuses on the pharmacokinetics as well as pharmacological and clinical effects of phytosomal curcumin.

  5. Curcumin implants, not curcumin diet, inhibit estrogen-induced mammary carcinogenesis in ACI rats.

    PubMed

    Bansal, Shyam S; Kausar, Hina; Vadhanam, Manicka V; Ravoori, Srivani; Pan, Jianmin; Rai, Shesh N; Gupta, Ramesh C

    2014-04-01

    Curcumin is widely known for its antioxidant, anti-inflammatory, and antiproliferative activities in cell-culture studies. However, poor oral bioavailability limited its efficacy in animal and clinical studies. Recently, we developed polymeric curcumin implants that circumvent oral bioavailability issues, and tested their potential against 17β-estradiol (E2)-mediated mammary tumorigenesis. Female Augustus Copenhagen Irish (ACI) rats were administered curcumin either via diet (1,000 ppm) or via polymeric curcumin implants (two 2 cm; 200 mg each; 20% drug load) 4 days before grafting a subcutaneous E2 silastic implant (1.2 cm, 9 mg E2). Curcumin implants were changed after 4.5 months to provide higher curcumin dose at the appearance of palpable tumors. The animals were euthanized after 3 weeks, 3 months, and after the tumor incidence reached >80% (~6 months) in control animals. The curcumin administered via implants resulted in significant reduction in both the tumor multiplicity (2 ± 1 vs. 5 ± 3; P = 0.001) and tumor volume (184 ± 198 mm(3) vs. 280 ± 141 mm(3); P = 0.0283); the dietary curcumin, however, was ineffective. Dietary curcumin increased hepatic CYP1A and CYP1B1 activities without any effect on CYP3A4 activity, whereas curcumin implants increased both CYP1A and CYP3A4 activities but decreased CYP1B1 activity in the presence of E2. Because CYP1A and CYP3A4 metabolize most of the E2 to its noncarcinogenic 2-OH metabolite, and CYP1B1 produces potentially carcinogenic 4-OH metabolite, favorable modulation of these CYPs via systemically delivered curcumin could be one of the potential mechanisms. The analysis of plasma and liver by high-performance liquid chromatography showed substantially higher curcumin levels via implants versus the dietary route despite substantially higher dose administered.

  6. Studies on curcumin and curcuminoids. XXIX. Photoinduced cytotoxicity of curcumin in selected aqueous preparations.

    PubMed

    Bruzell, Ellen M; Morisbak, Else; Tønnesen, Hanne Hjorth

    2005-07-01

    Natural curcumin was evaluated as a potential photosensitizer for oral applications. The photocytotoxicity of curcumin on salivary gland acinar cells (SM 10-12) was investigated in five aqueous preparations consisting of 5% DMSO, non-ionic micelles, cyclodextrin, liposomes, or a hydrophilic polymer. The difference in phototoxic effects between natural curcumin and synthetic curcumin was examined. Cytotoxicity in SM 10-12 cells exposed to curcumin in the concentration range 0.4-13.5 microM was investigated by MTT test, a fluorescence-staining microscopic test, and by Western immunoblotting techniques. The potential formation of a photoreaction product, hydrogen peroxide, was evaluated by a fluorescence assay. The light source was a halogen lamp used in the dental clinic, emitting mainly in the blue part of the spectrum. The phototoxic effect on SM 10-12 cells was dependent on curcumin concentration, the light dose and the type of preparation. Natural and synthetic curcumin induced phototoxicity to the same extent. Significant effects on the cells were obtained at low curcumin concentrations (< or =0.5 microM) and at a low light dose (< or =6 J cm(-2)), after 3 h incubation. Neither the activation of caspases-3, -7, -8 or -9, nor the formation of hydrogen peroxide could be detected in cells exposed to curcumin and light. The liposome preparation was the most efficient vehicle for curcumin to induce cell death. The phototoxic effect induced by curcumin is highly dependent on the type of preparation. Curcumin might be a potential photosensitizer in the treatment of oral lesions and cancers provided careful selection of the vehicle.

  7. Analog earthquakes

    SciTech Connect

    Hofmann, R.B.

    1995-09-01

    Analogs are used to understand complex or poorly understood phenomena for which little data may be available at the actual repository site. Earthquakes are complex phenomena, and they can have a large number of effects on the natural system, as well as on engineered structures. Instrumental data close to the source of large earthquakes are rarely obtained. The rare events for which measurements are available may be used, with modfications, as analogs for potential large earthquakes at sites where no earthquake data are available. In the following, several examples of nuclear reactor and liquified natural gas facility siting are discussed. A potential use of analog earthquakes is proposed for a high-level nuclear waste (HLW) repository.

  8. Curcumin as therapeutics for the treatment of head and neck squamous cell carcinoma by activating SIRT1.

    PubMed

    Hu, An; Huang, Jing-Juan; Li, Rui-Lin; Lu, Zhao-Yang; Duan, Jun-Li; Xu, Wei-Hua; Chen, Xiao-Ping; Fan, Jing-Ping

    2015-08-24

    SIRT1 is one of seven mammalian homologs of Sir2 that catalyzes NAD(+)-dependent protein deacetylation. The aim of the present study is to explore the effect of SIRT1 small molecule activator on the anticancer activity and the underlying mechanism. We examined the anticancer activity of a novel oral agent, curcumin, which is the principal active ingredient of the traditional Chinese herb Curcuma Longa. Treatment of FaDu and Cal27 cells with curcumin inhibited growth and induced apoptosis. Mechanistic studies showed that anticancer activity of curcumin is associated with decrease in migration of HNSCC and associated angiogenesis through activating of intrinsic apoptotic pathway (caspase-9) and extrinsic apoptotic pathway (caspase-8). Our data demonstrating that anticancer activity of curcumin is linked to the activation of the ATM/CHK2 pathway and the inhibition of nuclear factor-κB. Finally, increasing SIRT1 through small molecule activator curcumin has shown beneficial effects in xenograft mouse model, indicating that SIRT1 may represent an attractive therapeutic target. Our studies provide the preclinical rationale for novel therapeutics targeting SIRT1 in HNSCC.

  9. Curcumin-Eudragit® E PO solid dispersion: A simple and potent method to solve the problems of curcumin.

    PubMed

    Li, Jinglei; Lee, Il Woo; Shin, Gye Hwa; Chen, Xiguang; Park, Hyun Jin

    2015-08-01

    Using a simple solution mixing method, curcumin was dispersed in the matrix of Eudragit® E PO polymer. Water solubility of curcumin in curcumin-Eudragit® E PO solid dispersion (Cur@EPO) was greatly increased. Based on the results of several tests, curcumin was demonstrated to exist in the polymer matrix in amorphous state. The interaction between curcumin and the polymer was investigated through Fourier transform infrared spectroscopy and (1)H NMR which implied that OH group of curcumin and carbonyl group of the polymer involved in the H bonding formation. Cur@EPO also provided protection function for curcumin as verified by the pH challenge and UV irradiation test. The pH value influenced curcumin release profile in which sustained release pattern was revealed. Additionally, in vitro transdermal test was conducted to assess the potential of Cur@EPO as a vehicle to deliver curcumin through this alternative administration route.

  10. Microwave-assisted preparation of the quorum-sensing molecule 2-heptyl-3-hydroxy-4(1H)-quinolone and structurally related analogs.

    PubMed

    Hodgkinson, James T; Galloway, Warren R J D; Welch, Martin; Spring, David R

    2012-05-24

    An optimized procedure for the efficient preparation of 2-heptyl-3-hydroxy-4(1H)-quinolone (Pseudomonas quinolone signal or PQS) and a diverse range of structurally related 2-alkyl-4-quinolones with biological activity is presented. The two-step synthesis begins with the formation of α-chloro ketones by the coupling of a Weinreb amide (2-chloro-N-methoxy-N-methylacetamide) and an appropriate Grignard reagent. The resulting α-chloro ketones can be reacted with commercially available anthranilic acids under microwave irradiation conditions to furnish the desired 2-alkyl-4-quinolone products. As a typical example, the synthesis of PQS, a molecule involved in quorum sensing in the pathogenic bacterium Pseudomonas aeruginosa, is described in detail. The first step of this process (α-chloro ketone formation) takes ∼10 h in total to complete from commercially available bromoheptane and 2-chloro-N-methoxy-N-methylacetamide. The second step (microwave-assisted reaction with anthranilic acid) takes ∼14 h in total to complete (the reaction typically proceeds in ∼30 min, with work-up and purification requiring ∼13 h).

  11. Curcumin nanoformulations: a future nanomedicine for cancer

    PubMed Central

    Yallapu, Murali M; Jaggi, Meena; Chauhan, Subhash C

    2011-01-01

    Curcumin, a natural diphenolic compound derived from turmeric Curcuma longa, has proven to be a modulator of intracellular signaling pathways that control cancer cell growth, inflammation, invasion, apoptosis and cell death, revealing its anticancer potential. In this review, we focus on the design and development of nanoparticles, self-assemblies, nanogels, liposomes and complex fabrication for sustained and efficient curcumin delivery. We also discuss the anticancer applications and clinical benefits of nanocurcumin formulations. Only a few novel multifunctional and composite nanosystem strategies offer simultaneous therapy as well as imaging characteristics. We also summarize the challenges to developing curcumin delivery platforms and up-to-date solutions for improving curcumin bioavailability and anticancer potential for therapy. PMID:21959306

  12. Differential modulation of ROS signals and other mitochondrial parameters by the antioxidants MitoQ, resveratrol and curcumin in human adipocytes.

    PubMed

    Hirzel, Estelle; Lindinger, Peter W; Maseneni, Swarna; Giese, Maria; Rhein, Véronique Virginie; Eckert, Anne; Hoch, Matthias; Krähenbühl, Stephan; Eberle, Alex N

    2013-10-01

    Mitochondrial reactive oxygen species (ROS) have been demonstrated to play an important role as signaling and regulating molecules in human adipocytes. In order to evaluate the differential modulating roles of antioxidants, we treated human adipocytes differentiated from human bone marrow-derived mesenchymal stem cells with MitoQ, resveratrol and curcumin. The effects on ROS, viability, mitochondrial respiration and intracellular ATP levels were examined. MitoQ lowered both oxidizing and reducing ROS. Resveratrol decreased reducing and curcumin oxidizing radicals only. All three substances slightly decreased state III respiration immediately after addition. After 24 h of treatment, MitoQ inhibited both basal and uncoupled oxygen consumption, whereas curcumin and resveratrol had no effect. Intracellular ATP levels were not altered. This demonstrates that MitoQ, resveratrol and curcumin exert potent modulating effects on ROS signaling in human adipocyte with marginal effects on metabolic parameters.

  13. Modulation of arachidonic acid metabolism by curcumin and related beta-diketone derivatives: effects on cytosolic phospholipase A(2), cyclooxygenases and 5-lipoxygenase.

    PubMed

    Hong, Jungil; Bose, Mousumi; Ju, Jihyeung; Ryu, Jae-Ha; Chen, Xiaoxin; Sang, Shengmin; Lee, Mao-Jung; Yang, Chung S

    2004-09-01

    -inflammatory and anticarcinogenic actions of curcumin and its analogs.

  14. Wound Healing Effect of Curcumin: A Review.

    PubMed

    Tejada, Silvia; Manayi, Azadeh; Daglia, Maria; Nabavi, Seyed Fazel; Sureda, Antoni; Hajheydari, Zohreh; Gortzi, Olga; Pazoki-Toroudi, Hamidreza; Nabavi, Seyed Mohammad

    2016-07-21

    Wound healing is a complex process that consists of several phases that range from coagulation, inflammation, accumulation of radical substances, to proliferation, formation of fibrous tissues and collagen, contraction of wound with formation of granulation tissue and scar. Since antiquity, vegetable substances have been used as phytotherapeutic agents for wound healing, and more recently natural substances of vegetable origin have been studied with the attempt to show their beneficial effect on wound treatment. Curcumin, the most active component of rhizome of Curcuma longa L. (common name: turmeric), has been studied for many years due to its bio-functional properties, especially antioxidant, radical scavenger, antimicrobial and anti-inflammatory activities, which play a crucial role in the wound healing process. Moreover, curcumin stimulated the production of the growth factors involved in the wound healing process, and so curcumin also accelerated the management of wound restoration. The aim of the present review is collecting and evaluating the literature data regarding curcumin properties potentially relevant for wound healing. Moreover, the investigations on the wound healing effects of curcumin are reported. In order to produce a more complete picture, the chemistry and sources of curcumin are also discussed.

  15. Modulation of transcription factors by curcumin.

    PubMed

    Shishodia, Shishir; Singh, Tulika; Chaturvedi, Madan M

    2007-01-01

    Curcumin is the active ingredient of turmeric that has been consumed as a dietary spice for ages. Turmeric is widely used in traditional Indian medicine to cure biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. Extensive investigation over the last five decades has indicated that curcumin reduces blood cholesterol, prevents low-density lipoprotein oxidation, inhibits platelet aggregation, suppresses thrombosis and myocardial infarction, suppresses symptoms associated with type II diabetes, rheumatoid arthritis, multiple sclerosis, and Alzheimer's disease, inhibits HIV replication, enhances wound healing, protects from liver injury, increases bile secretion, protects from cataract formation, and protects from pulmonary toxicity and fibrosis. Evidence indicates that the divergent effects of curcumin are dependent on its pleiotropic molecular effects. These include the regulation of signal transduction pathways and direct modulation of several enzymatic activities. Most of these signaling cascades lead to the activation of transcription factors. Curcumin has been found to modulate the activity of several key transcription factors and, in turn, the cellular expression profiles. Curcumin has been shown to elicit vital cellular responses such as cell cycle arrest, apoptosis, and differentiation by activating a cascade of molecular events. In this chapter, we briefly review the effects of curcumin on transcription factors NF-KB, AP-1, Egr-1, STATs, PPAR-gamma, beta-catenin, nrf2, EpRE, p53, CBP, and androgen receptor (AR) and AR-related cofactors giving major emphasis to the molecular mechanisms of its action.

  16. Triptycene analogs

    NASA Technical Reports Server (NTRS)

    Hua, Duy (Inventor); Perchellet, Jean-Pierre (Inventor)

    2004-01-01

    This invention provides analogs of triptycene which are useful as anticancer drugs, as well as for other uses. The potency of these compounds is in a similar magnitude as daunomycin, a currently used anticancer drug. Each compound of the invention produces one or more desired effects (blocking nucleoside transport, inhibiting nucleic acid or protein syntheses, decreasing the proliferation and viability of cancer cells, inducing DNA fragmentation or retaining their effectiveness against multidrug-resistant tumor cells).

  17. Cyber Analogies

    DTIC Science & Technology

    2014-02-28

    including the time for reviewing instructions , searching existing data sources, gathering and maintaining the data needed, and completing and reviewing... CONTENTS 1 Introduction Emily O. Goldman & John Arquilla 7 The Cyber Pearl Harbor James J. Wirtz 15 Applying the Historical Lessons of Surprise Attack...As H.G. Wells put it, “History is a race between education and catastrophe.” SURPRISE ATTACK The primarily history- based analogies contained herein

  18. Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats

    SciTech Connect

    Rashid, Kahkashan; Sil, Parames C.

    2015-02-01

    The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus. - Highlights: • STZ induced cellular stress plays a vital role in pancreatic dysfunction. • Cellular stress causes inflammation, pancreatic islet cell death and diabetes. • Deregulation of Nrf-2

  19. Modulating the vascular behavior of metastatic breast cancer cells by curcumin treatment

    PubMed Central

    Palange, Anna L.; Mascolo, Daniele Di; Singh, Jaykrishna; Franceschi, Maria S. De; Carallo, Claudio; Gnasso, Agostino; Decuzzi, Paolo

    2012-01-01

    The spreading of tumor cells to secondary sites (tumor metastasis) is a complex process that involves multiple, sequential steps. Vascular adhesion and extravasation of circulating tumor cells (CTCs) is one, critical step. Curcumin, a natural compound extracted from Curcuma longa, is known to have anti-tumoral, anti-proliferative, anti-inflammatory properties and affect the expression of cell adhesion molecules, mostly by targeting the NF-κB transcription factor. Here, upon treatment with curcumin, the vascular behavior of three different estrogen receptor negative (ER–) breast adenocarcinoma cell lines (SK-BR-3, MDA-MB-231, MDA-MB-468) is analyzed using a microfluidic system. First, the dose response to curcumin is characterized at 24, 48, and 72 h using a XTT assay. For all three cell lines, an IC50 larger than 20 µM is observed at 72 h; whereas no significant reduction in cell viability is detected for curcumin concentrations up to 10 µM. Upon 24 h treatment at 10 µM of curcumin, SK-BR3 and MDA-MB-231 cells show a decrease in adhesion propensity of 40% (p = 0.02) and 47% (p = 0.001), respectively. No significant change is documented for the less metastatic MDA-MB-468 cells. All three treated cell lines show a 20% increase in rolling velocity from 48.3 to 58.7 µm/s in SK-BR-3, from 64.1 to 73.77 µm/s in MDA-MB-231, and from 57.5 to 74.4 µm/s in MDA-MB-468. Collectively, these results suggest that mild curcumin treatments could limit the metastatic potential of these adenocarcinoma cell lines, possibly by altering the expression of adhesion molecules, and the organization and stiffness of the cell cytoskeleton. Future studies will elucidate the biophysical mechanisms regulating this curcumin-induced behavior and further explore the clinical relevance of these findings. PMID:23162792

  20. Structural and Spectral Properties of Curcumin and Metal- Curcumin Complex Derived from Turmeric (Curcuma longa)

    NASA Astrophysics Data System (ADS)

    Bich, Vu Thi; Thuy, Nguyen Thi; Binh, Nguyen Thanh; Huong, Nguyen Thi Mai; Yen, Pham Nguyen Dong; Luong, Tran Thanh

    Structural and spectral properties of curcumin and metal- curcumin complex derived from turmeric (Curcuma longa) were studied by SEM and vibrational (FTIR and Raman) techniques. By comparison between curcumin commercial, fresh turmeric and a yellow powder obtained via extraction and purification of turmeric, we have found that this insoluble powder in water is curcumin. The yellow compound could complex with certain ion metal and this metal-curcumin coloring complex is water soluble and capable of producing varying hues of the same colors and having antimicrobial, cytotoxicity activities for use in foodstuffs and pharmacy. The result also demonstrates that Micro-Raman spec-troscopy is a valuable non-destructive tool and fast for investigation of a natural plant even when occurring in low concentrations.

  1. Gum arabic-curcumin conjugate micelles with enhanced loading for curcumin delivery to hepatocarcinoma cells.

    PubMed

    Sarika, P R; James, Nirmala Rachel; Kumar, P R Anil; Raj, Deepa K; Kumary, T V

    2015-12-10

    Curcumin is conjugated to gum arabic, a highly water soluble polysaccharide to enhance the solubility and stability of curcumin. Conjugation of curcumin to gum arabic is confirmed by (1)H NMR, fluorescence and UV spectroscopy studies. The conjugate self assembles to spherical nano-micelles (270 ± 5 nm) spontaneously, when dispersed in aqueous medium. Spherical morphology of the self assembled conjugate is evidenced by field emission scanning electron microscopy and transmission electron microscopy. The self assembly of the amphiphilic conjugate into micelle in aqueous medium significantly enhances the solubility (900 fold of that of free curcumin) and stability of curcumin in physiological pH. The anticancer activity of the conjugate micelles is found to be higher in human hepatocellular carcinoma (HepG2) cells than in human breast carcinoma (MCF-7) cells. The conjugate exhibits enhanced accumulation and toxicity in HepG2 cells due to the targeting efficiency of the galactose groups present in gum arabic.

  2. Curcumin directly inhibits the transport activity of GLUT1.

    PubMed

    Gunnink, Leesha K; Alabi, Ola D; Kuiper, Benjamin D; Gunnink, Stephen M; Schuiteman, Sam J; Strohbehn, Lauren E; Hamilton, Kathryn E; Wrobel, Kathryn E; Louters, Larry L

    2016-06-01

    Curcumin, a major ingredient in turmeric, has a long history of medicinal applications in a wide array of maladies including treatment for diabetes and cancer. Seemingly counterintuitive to the documented hypoglycemic effects of curcumin, however, a recent report indicates that curcumin directly inhibits glucose uptake in adipocytes. The major glucose transporter in adipocytes is GLUT4. Therefore, this study investigates the effects of curcumin in cell lines where the major transporter is GLUT1. We report that curcumin has an immediate inhibitory effect on basal glucose uptake in L929 fibroblast cells with a maximum inhibition of 80% achieved at 75 μM curcumin. Curcumin also blocks activation of glucose uptake by azide, glucose deprivation, hydroxylamine, or phenylarsine oxide. Inhibition does not increase with exposure time and the inhibitory effects reverse within an hour. Inhibition does not appear to involve a reaction between curcumin and the thiol side chain of a cysteine residue since neither prior treatment of cells with iodoacetamide nor curcumin with cysteine alters curcumin's inhibitory effects. Curcumin is a mixed inhibitor reducing the Vmax of 2DG transport by about half with little effect on the Km. The inhibitory effects of curcumin are not additive to the effects of cytochalasin B and 75 μM curcumin actually reduces specific cytochalasin B binding by 80%. Taken together, the data suggest that curcumin binds directly to GLUT1 at a site that overlaps with the cytochalasin B binding site and thereby inhibits glucose transport. A direct inhibition of GLUT proteins in intestinal epithelial cells would likely reduce absorption of dietary glucose and contribute to a hypoglycemic effect of curcumin. Also, inhibition of GLUT1 activity might compromise cancer cells that overexpress GLUT1 and be another possible mechanism for the documented anticancer effects of curcumin.

  3. Curcumin Based Drug Screening for Inhibitors of NF kappa B in a Cell Model of Prostate Cancer Progression

    DTIC Science & Technology

    2008-02-01

    West Society of Toxicology in Breckenridge, CO in September 2007: “Identification of Curcumin Analogs Toxic against Prostate Cancer Cells Through...quantitative structure-activity relationship ( QSAR ) and ligand-based virtual screening (LBVS) to explore the possibility of improving their efficacy...Student in my laboratory has presented part of this data at the 25th Annual Meeting of the Mountain West Society of Toxicology in Breckenridge, CO in

  4. Interaction of Curcumin with PEO-PPO-PEO block copolymers: a molecular dynamics study.

    PubMed

    Samanta, Susruta; Roccatano, Danilo

    2013-03-21

    Curcumin, a naturally occurring drug molecule, has been extensively investigated for its various potential usages in medicine. Its water insolubility and high metabolism rate require the use of drug delivery systems to make it effective in the human body. Among various types of nanocarriers, block copolymer based ones are the most effective. These polymers are broadly used as drug-delivery systems, but the nature of this process is poorly understood. In this paper, we propose a molecular dynamics simulation study of the interaction of Curcumin with block copolymer based on polyethylene oxide (PEO) and polypropylene oxide (PPO). The study has been conducted considering the smallest PEO and PPO oligomers and multiple chains of the block copolymer Pluronic P85. Our study shows that the more hydrophobic 1,2-dimethoxypropane (DMP) molecules and PPO block preferentially coat the Curcumin molecule. In the case of the Pluronic P85, simulation shows formation of a drug-polymer aggregate within 50 ns. This process leaves exposed the PEO part of the polymers, resulting in better solvation and stability of the drug in water.

  5. Mechanisms for the activity of heterocyclic cyclohexanone curcumin derivatives in estrogen receptor negative human breast cancer cell lines.

    PubMed

    Somers-Edgar, Tiffany J; Taurin, Sebastien; Larsen, Lesley; Chandramouli, Anupama; Nelson, Mark A; Rosengren, Rhonda J

    2011-02-01

    Estrogen receptor (ER)-negative breast cancer is an aggressive form that currently requires more drug treatment options. Thus, we have further modified cyclohexanone derivatives of curcumin and examined them for cytotoxicity towards ER-negative human breast cancer cells. Two of the analogs screened elicited increased cytotoxic potency compared to curcumin and other previously studied derivatives. Specifically, 2,6-bis(pyridin-3-ylmethylene)-cyclohexanone (RL90) and 2,6-bis(pyridin-4-ylmethylene)-cyclohexanone (RL91) elicited EC(50) values of 1.54 and 1.10 µM, respectively, in MDA-MB-231 cells and EC(50) values of 0.51 and 0.23 in SKBr3 cells. All other new compounds examined were less potent than curcumin, which elicited EC(50) values of 7.6 and 2.4 µM in MDA-MB-231 and SKBr3 cells, respectively. Mechanistic analyses demonstrated that RL90 and RL91 significantly induced G(2)/M-phase cell cycle arrest and apoptosis. RL90 and RL91 also modulated the expression of key cell signaling proteins, specifically, in SKBr3 cells, protein levels of Her-2, Akt, and NFκB were decreased in a time-dependent manner, while activity of stress kinases JNK1/2 and P38 MAPK were increased. Signaling events in MDA-MB-231 cells were differently implicated, as EGFR protein levels were decreased and activity of GSK-3β transiently decreased, while β-catenin protein level and activity of P38 MAPK, Akt, and JNK1/2 were transiently increased. In conclusion replacement of the phenyl group of cyclohexanone derived curcumin derivatives with heterocyclic rings forms a class of second-generation analogs that are more potent than both curcumin and other derivatives. These new derivatives provide a platform for the further development of drugs for the treatment of ER-negative breast cancer.

  6. Curcumin directly inhibits the transport activity of GLUT1

    PubMed Central

    Gunnink, Leesha K.; Alabi, Ola D.; Kuiper, Benjamin D.; Gunnink, Stephen M.; Schuiteman, Sam J.; Strohbehn, Lauren E.; Hamilton, Kathryn E.; Wrobel, Kathryn E.; Louters, Larry L.

    2016-01-01

    Curcumin, a major ingredient in turmeric, has a long history of medicinal applications in a wide array of maladies including treatment for diabetes and cancer. Seemingly counterintuitive to the documented hypoglycemic effects of curcumin, however, a recent report indicates that curcumin directly inhibits glucose uptake in adipocytes. The major glucose transporter in adipocytes is GLUT4. Therefore, this study investigates the effects of curcumin in cell lines where the major transporter is GLUT1. We report that curcumin has an immediate inhibitory effect on basal glucose uptake in L929 fibroblast cells with a maximum inhibition of 80% achieved at 75 μM curcumin. Curcumin also blocks activation of glucose uptake by azide, glucose deprivation, hydroxylamine, or phenylarsine oxide. Inhibition does not increase with exposure time and the inhibitory effects reverse within an hour. Inhibition does not appear to involve a reaction between curcumin and the thiol side chain of a cysteine residue since neither prior treatment of cells with iodoacetamide nor curcumin with cysteine alters curcumin’s inhibitory effects. Curcumin is a mixed inhibitor reducing the Vmax of 2DG transport by about half with little effect on the Km. The inhibitory effects of curcumin are not additive to the effects of cytochalasin B and 75 μM curcumin actually reduces specific cytochalasin B binding by 80%. Taken together, the data suggest that curcumin binds directly to GLUT1 at a site that overlaps with the cytochalasin B binding site and thereby inhibits glucose transport. A direct inhibition of GLUT proteins in intestinal epithelial cells would likely reduce absorption of dietary glucose and contribute to a hypoglycemic effect of curcumin. Also, inhibition of GLUT1 activity might compromise cancer cells that overexpress GLUT1 and be another possible mechanism for the documented anticancer effects of curcumin. PMID:27039889

  7. A critical examination of studies on curcumin for depression.

    PubMed

    Andrade, Chittaranjan

    2014-10-01

    Curcumin, an ingredient of turmeric, is widely available as a nutritional supplement. Curcumin has biological properties that suggest its use for a large number of health-related conditions, including depression. Curcumin is effective in animal models of depression. However, controlled clinical trials provide no convincing evidence that patients with major depressive illness fare better with different extracts of curcumin (dosed at 500-1,000 mg/d) than with placebo (or no treatment) after 5-8 weeks of monotherapy or antidepressant-augmentation therapy. At present, therefore, there is insufficient evidence to encourage depressed patients to consider curcumin as a possible alternative to standard antidepressant therapy.

  8. Solvent dependent photophysical properties of dimethoxy curcumin

    NASA Astrophysics Data System (ADS)

    Barik, Atanu; Indira Priyadarsini, K.

    2013-03-01

    Dimethoxy curcumin (DMC) is a methylated derivative of curcumin. In order to know the effect of ring substitution on photophysical properties of curcumin, steady state absorption and fluorescence spectra of DMC were recorded in organic solvents with different polarity and compared with those of curcumin. The absorption and fluorescence spectra of DMC, like curcumin, are strongly dependent on solvent polarity and the maxima of DMC showed red shift with increase in solvent polarity function (Δf), but the above effect is prominently observed in case of fluorescence maxima. From the dependence of Stokes' shift on solvent polarity function the difference between the excited state and ground state dipole moment was estimated as 4.9 D. Fluorescence quantum yield (ϕf) and fluorescence lifetime (τf) of DMC were also measured in different solvents at room temperature. The results indicated that with increasing solvent polarity, ϕf increased linearly, which has been accounted for the decrease in non-radiative rate by intersystem crossing (ISC) processes.

  9. Nanoprecipitation and Spectroscopic Characterization of Curcumin-Encapsulated Polyester Nanoparticles.

    PubMed

    Leung, Mandy H M; Harada, Takaaki; Dai, Sheng; Kee, Tak W

    2015-10-27

    Curcumin-encapsulated polyester nanoparticles (Cur-polyester NPs) of approximately 100 nm diameter with a negatively charged surface were prepared using a one-step nanoprecipitation method. The Cur-polyester NPs were prepared using polylactic acid, poly(D,L-lactic-co-glycolic acid) and poly(ϵ-caprolactone) without any emulsifier or surfactant. The encapsulation of curcumin in these polyester NPs greatly suppresses curcumin degradation in the aqueous environment due to its segregation from water. In addition, the fluorescence of curcumin in polyester NPs has a quantum yield of 4 to 5%, which is higher than that of curcumin in micellar systems and comparable to those in organic solvents, further supporting the idea that the polyester NPs are capable of excluding water from curcumin. Furthermore, the results from femtosecond fluorescence upconversion spectroscopy reveal that there is a decrease in the signal amplitude corresponding to solvent reorganization of excited state curcumin in the polyester NPs compared with curcumin in micellar systems. The Cur-polyester NPs also show a lack of deuterium isotope effect in the fluorescence lifetime. These results indicate that the interaction between curcumin and water in the polyester NPs is significantly weaker than that in micelles. Therefore, the aqueous stability of curcumin is greatly improved due to highly effective segregation from water. The overall outcome suggests that the polyester NPs prepared using the method reported herein are an attractive system for encapsulating and stabilizing curcumin in the aqueous environment.

  10. Curcumin nanoemulsion for transdermal application: formulation and evaluation.

    PubMed

    Rachmawati, Heni; Budiputra, Dewa Ken; Mauludin, Rachmat

    2015-04-01

    The aim of this work is to develop a curcumin nanoemulsion for transdermal delivery. The incorporation of curcumin inside a nanoglobul should improve curcumin stability and permeability. A nanoemulsion was prepared by the self-nanoemulsification method, using an oil phase of glyceryl monooleate, Cremophor RH40 and polyethylene glycol 400. Evaluation of the nanoemulsion included analysis of particle size, polydispersity index, zeta potential, physical stability, Raman spectrum and morphology. In addition, the physical performance of the nanoemulsion in Viscolam AT 100P gel was studied. A modified vertical diffusion cell and shed snake skin of Python reticulatus were used to study the in vitro permeation of curcumin. A spontaneously formed stable nanoemulsion has a loading capacity of 350 mg curcumin/10 g of oil phase. The mean droplet diameter, polydispersity index and zeta potential of optimized nanoemulsion were 85.0 ± 1.5 nm, 0.18 ± 0.0 and -5.9 ± 0.3 mV, respectively. Curcumin in a nanoemulsion was more stable than unencapsulated curcumin. Furthermore, nanoemulsification significantly improved the permeation flux of curcumin from the hydrophilic matrix gel; the release kinetic of curcumin changed from zero order to a Higuchi release profile. Overall, the developed nanoemulsion system not only improved curcumin permeability but also protected the curcumin from chemical degradation.

  11. Curcumin attenuates surgery-induced cognitive dysfunction in aged mice.

    PubMed

    Wu, Xiang; Chen, Huixin; Huang, Chunhui; Gu, Xinmei; Wang, Jialing; Xu, Dilin; Yu, Xin; Shuai, Chu; Chen, Liping; Li, Shun; Xu, Yiguo; Gao, Tao; Ye, Mingrui; Su, Wei; Liu, Haixiong; Zhang, Jinrong; Wang, Chuang; Chen, Junping; Wang, Qinwen; Cui, Wei

    2017-02-21

    Post-operative cognitive dysfunction (POCD) is associated with elderly patients undergoing surgery. However, pharmacological treatments for POCD are limited. In this study, we found that curcumin, an active compound derived from Curcuma longa, ameliorated the cognitive dysfunction following abdominal surgery in aged mice. Further, curcumin prevented surgery-induced anti-oxidant enzyme activity. Curcumin also increased brain-derived neurotrophic factor (BDNF)-positive area and expression of pAkt in the brain, suggesting that curcumin activated BDNF signaling in aged mice. Furthermore, curcumin neutralized cholinergic dysfunction involving choline acetyltransferase expression induced by surgery. These results strongly suggested that curcumin prevented cognitive impairments via multiple targets, possibly by increasing the activity of anti-oxidant enzymes, activation of BDNF signaling, and neutralization of cholinergic dysfunction, concurrently. Based on these novel findings, curcumin might be a potential agent in POCD prophylaxis and treatment.

  12. Curcumin Protects Intestinal Mucosal Barrier Function of Rat Enteritis via Activation of MKP-1 and Attenuation of p38 and NF-κB Activation

    PubMed Central

    Meng, Fan-Su; Zhang, Qing-Hua; Zeng, Jian-Ying; Xiao, Li-Ping; Yu, Xin-Pei; Peng, Dan-dan; Su, Lei; Xiao, Bing; Zhang, Zhen-Shu

    2010-01-01

    Background Intestinal mucosa barrier (IMB) dysfunction results in many notorious diseases for which there are currently few effective treatments. We studied curcumin's protective effect on IMB and examined its mechanism by using methotrexate (MTX) induced rat enteritis model and lipopolysaccharide (LPS) treated cell death model. Methodology/Principal Findings Curcumin was intragastrically administrated from the first day, models were made for 7 days. Cells were treated with curcumin for 30 min before exposure to LPS. Rat intestinal mucosa was collected for evaluation of pathological changes. We detected the activities of D-lactate and diamine oxidase (DAO) according to previous research and measured the levels of myeloperoxidase (MPO) and superoxide dismutase (SOD) by colorimetric method. Intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were determined by RT-PCR and IL-10 production was determined by ELISA. We found Curcumin decreased the levels of D-lactate, DAO, MPO, ICAM-1, IL-1β and TNF-α, but increased the levels of IL-10 and SOD in rat models. We further confirmed mitogen-activated protein kinase phosphatase-1 (MKP-1) was activated but phospho-p38 was inhibited by curcumin by western blot assay. Finally, NF-κB translocation was monitored by immunofluorescent staining. We showed that curcumin repressed I-κB and interfered with the translocation of NF-κB into nucleus. Conclusions/Significance The effect of curcumin is mediated by the MKP-1-dependent inactivation of p38 and inhibition of NF-κB-mediated transcription. Curcumin, with anti-inflammatory and anti-oxidant activities may be used as an effective reagent for protecting intestinal mucosa barrier and other related intestinal diseases. PMID:20885979

  13. Efficient separation of curcumin, demethoxycurcumin, and bisdemethoxycurcumin from turmeric using supercritical fluid chromatography: From analytical to preparative scale.

    PubMed

    Song, Wei; Qiao, Xue; Liang, Wen-fei; Ji, Shuai; Yang, Lu; Wang, Yuan; Xu, Yong-wei; Yang, Ying; Guo, De-an; Ye, Min

    2015-10-01

    Curcumin is the major constituent of turmeric (Curcuma longa L.). It has attracted widespread attention for its anticancer and anti-inflammatory activities. The separation of curcumin and its two close analogs, demethoxycurcumin and bisdemethoxycurcumin, has been challenging by conventional techniques. In this study, an environmentally friendly method based on supercritical fluid chromatography was established for the rapid and facile separation of the three curcuminoids directly from the methanol extract of turmeric. The method was first developed and optimized by ultra performance convergence chromatography, and was then scaled up to preparative supercritical fluid chromatography. Eluted with supercritical fluid CO2 containing 8-15% methanol (containing 10 mM oxalic acid) at a flow rate of 80 mL/min, curcumin, demethoxycurcumin and bisdemethoxycurcumin could be well separated on a Viridis BEH OBD column (Waters, 250 mm × 19 mm, 5 μm) within 6.5 min. As a result, 20.8 mg of curcumin (97.9% purity), 7.0 mg of demethoxycurcumin (91.1%), and 4.6 mg of bisdemethoxycurcumin (94.8%) were obtained after a single step of supercritical fluid chromatography separation with a mean recovery of 76.6%. Showing obvious advantages in low solvent consumption, large sample loading, and easy solvent removal, supercritical fluid chromatography was proved to be a superior technique for the efficient separation of natural products.

  14. Curcumin and diabetes: a systematic review.

    PubMed

    Zhang, Dong-Wei; Fu, Min; Gao, Si-Hua; Liu, Jun-Li

    2013-01-01

    Turmeric (Curcuma longa), a rhizomatous herbaceous perennial plant of the ginger family, has been used for the treatment of diabetes in Ayurvedic and traditional Chinese medicine. The active component of turmeric, curcumin, has caught attention as a potential treatment for diabetes and its complications primarily because it is a relatively safe and inexpensive drug that reduces glycemia and hyperlipidemia in rodent models of diabetes. Here, we review the recent literature on the applications of curcumin for glycemia and diabetes-related liver disorders, adipocyte dysfunction, neuropathy, nephropathy, vascular diseases, pancreatic disorders, and other complications, and we also discuss its antioxidant and anti-inflammatory properties. The applications of additional curcuminoid compounds for diabetes prevention and treatment are also included in this paper. Finally, we mention the approaches that are currently being sought to generate a "super curcumin" through improvement of the bioavailability to bring this promising natural product to the forefront of diabetes therapeutics.

  15. Therapeutic potential of curcumin in gastrointestinal diseases

    PubMed Central

    Rajasekaran, Sigrid A

    2011-01-01

    Curcumin, also known as diferuloylmethane, is derived from the plant Curcuma longa and is the active ingredient of the spice turmeric. The therapeutic activities of curcumin for a wide variety of diseases such as diabetes, allergies, arthritis and other chronic and inflammatory diseases have been known for a long time. More recently, curcumin’s therapeutic potential for preventing and treating various cancers is being recognized. As curcumin’s therapeutic promise is being explored more systematically in various diseases, it has become clear that, due to its increased bioavailability in the gastrointestinal tract, curcumin may be particularly suited to be developed to treat gastrointestinal diseases. This review summarizes some of the current literature of curcumin’s anti-inflammatory, anti-oxidant and anti-cancer potential in inflammatory bowel diseases, hepatic fibrosis and gastrointestinal cancers. PMID:21607160

  16. Antioxidant activities of curcumin in allergic rhinitis.

    PubMed

    Altıntoprak, Niyazi; Kar, Murat; Acar, Mustafa; Berkoz, Mehmet; Muluk, Nuray Bayar; Cingi, Cemal

    2016-11-01

    We investigated the antioxidant effects of curcumin in an experimental rat model of allergic rhinitis (AR). Female Wistar albino rats (n = 34) were divided randomly into four groups: healthy rats (control group, n = 8), AR with no treatment (AR + NoTr group, n = 10), AR with azelastine HCl treatment (AR + Aze group, n = 8), and AR with curcumin treatment (AR + Curc group, n = 8). On day 28, total blood IgE levels were measured. For measurement of antioxidant activity, the glutathione (GSH) level and catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities were measured in both inferior turbinate tissue and serum. Malondialdehyde (MDA) levels were measured only in inferior turbinate tissue, and paraoxonase (PON) and arylesterase (ARE) activities were measured only in serum. Statistically significant differences were found for all antioxidant measurements (GSH levels and CAT, SOD, GSH-Px activities in the serum and tissue, MDA levels in the tissue, and PON and ARE activities in the serum) between the four groups. In the curcumin group, serum SOD, ARE, and PON and tissue GSH values were higher than the control group. Moreover, tissue GSH levels and serum GSH-Px activities in the curcumin group were higher than in the AR + NoTr group. In the azelastine group, except MDA, antioxidant measurement values were lower than in the other groups. Curcumin may help to increase antioxidant enzymes and decrease oxidative stress in allergic rhinitis. We recommend curcumin to decrease oxidative stress in allergic rhinitis.

  17. The effect of the water on the curcumin tautomerism: A quantitative approach

    NASA Astrophysics Data System (ADS)

    Manolova, Yana; Deneva, Vera; Antonov, Liudmil; Drakalska, Elena; Momekova, Denitsa; Lambov, Nikolay

    2014-11-01

    The tautomerism of curcumin has been investigated in ethanol/water binary mixtures by using UV-Vis spectroscopy and advanced quantum-chemical calculations. The spectral changes were processed by using advanced chemometric procedure, based on resolution of overlapping bands technique. As a result, molar fractions of the tautomers and their individual spectra have been estimated. It has been shown that in ethanol the enol-keto tautomer only is presented. The addition of water leads to appearance of a new spectral band, which was assigned to the diketo tautomeric form. The results show that in 90% water/10% ethanol the diketo form is dominating. The observed shift in the equilibrium is explained by the quantum chemical calculations, which show that water molecules stabilize diketo tautomer through formation of stable complexes. To our best knowledge we report for the first time quantitative data for the tautomerism of curcumin and the effect of the water.

  18. Transformation of curcumin from food additive to multifunctional medicine: nanotechnology bridging the gap.

    PubMed

    Ahmad, Mohammad Zaki; Akhter, Shabib; Mohsin, Nehal; Abdel-Wahab, Basel A; Ahmad, Javed; Warsi, Musarrat Husain; Rahman, Mahfoozur; Mallick, Neha; Ahmad, Farhan Jalees

    2014-01-01

    Curcumin (CUR) is a yellow-coloured polyphenolic compound obtained from the rhizomes of Curcuma longa. In-depth pharmacological screening of curcumin has given the evidence that CUR persuades shielding and curative effects against various cancers, cardiovascular, wound healing effect and neuro disorders etc owning to anti-oxidant, antiproliferative, anti-inflammatory, anti-angiogenic and antimicrobial activities. However, miserable bioavailability due to poor aqueous solubility limits the application of CUR in various ailments. Different methodologies including the nanoparticle technology have been reported for the bioavailability enhancement of CUR. Nanoparticles exhibit not only the improvement in the solubility of CUR and alike lipophilic molecules (resulted in improved bioavailability) but also giving the opportunity for the disease specific cellular and organ targeting. Improved bioavailability and disease based site specific delivery of CUR is more likely to bring it as a safe multifunctional medicine.

  19. Transdermal delivery of curcumin via microemulsion.

    PubMed

    Sintov, Amnon C

    2015-03-15

    The objective of this study was to evaluate the transdermal delivery potential of a new curcumin-containing microemulsion system. Three series of experiments were carried out to comprehend the system characteristics: (a) examining the influence of water content on curcumin permeation, (b) studying the effect of curcumin loading on its permeability, and (c) assessing the contribution of the vesicular nature of the microemulsion on permeability. The skin permeability of curcumin from microemulsions, which contained 5%, 10%, and 20% of water content (1% curcumin), was measured in vitro using excised rat skin. It has been shown that the permeability coefficient of CUR in a formulation containing 10% aqueous phase (ME-10) was twofold higher than the values obtained for formulations with 5% and 20% water (Papp=0.116 × 10(-3)± 0.052 × 10(-3)vs. 0.043 × 10(-3)± 0.022 × 10(-3) and 0.047 × 10(-3)± 0.025 × 10(-3)cm/h, respectively. A reasonable explanation for this phenomenon may be the reduction of both droplet size and droplets' concentration in the microemulsion as the aqueous phase decreased from 20% to 5%. It has also been shown that a linear correlation exists between the decrease in droplet size and the increase of curcumin loading in the microemulsion. In addition, it has been demonstrated that a micellar system, S/O-mix, and a plain solution of curcumin resulted in a significantly lower curcumin permeation relative to that presented by the microemulsion, Papp=0.018 × 10(-3)± 0.011 × 10(-3), 0.005 × 10(-3)± 0.002 × 10(-3), and 0.002 × 10(-3)± 0.000 × 10(-3)cm/h, respectively, vs. 0.110 × 10(-3)± 0.021 × 10(-3)cm/h for the microemulsion. The enhancement ratio (ER=Jss-ME/Jss-solution) of CUR permeated via 1% loaded microemulsion was 55.

  20. Hydrophobic hydration driven self-assembly of curcumin in water: Similarities to nucleation and growth under large metastability, and an analysis of water dynamics at heterogeneous surfaces

    NASA Astrophysics Data System (ADS)

    Hazra, Milan Kumar; Roy, Susmita; Bagchi, Biman

    2014-11-01

    As the beneficial effects of curcumin have often been reported to be limited to its small concentrations, we have undertaken a study to find the aggregation properties of curcumin in water by varying the number of monomers. Our molecular dynamics simulation results show that the equilibrated structure is always an aggregated state with remarkable structural rearrangements as we vary the number of curcumin monomers from 4 to 16 monomers. We find that the curcumin monomers form clusters in a very definite pattern where they tend to aggregate both in parallel and anti-parallel orientation of the phenyl rings, often seen in the formation of β-sheet in proteins. A considerable enhancement in the population of parallel alignments is observed with increasing the system size from 12 to 16 curcumin monomers. Due to the prevalence of such parallel alignment for large system size, a more closely packed cluster is formed with maximum number of hydrophobic contacts. We also follow the pathway of cluster growth, in particular the transition from the initial segregated to the final aggregated state. We find the existence of a metastable structural intermediate involving a number of intermediate-sized clusters dispersed in the solution. We have constructed a free energy landscape of aggregation where the metatsable state has been identified. The course of aggregation bears similarity to nucleation and growth in highly metastable state. The final aggregated form remains stable with the total exclusion of water from its sequestered hydrophobic core. We also investigate water structure near the cluster surface along with their orientation. We find that water molecules form a distorted tetrahedral geometry in the 1st solvation layer of the cluster, interacting rather strongly with the hydrophilic groups at the surface of the curcumin. The dynamics of such quasi-bound water molecules near the surface of curcumin cluster is considerably slower than the bulk signifying a restricted

  1. Encapsulation of curcumin in cyclodextrin-metal organic frameworks: Dissociation of loaded CD-MOFs enhances stability of curcumin.

    PubMed

    Moussa, Zeinab; Hmadeh, Mohamad; Abiad, Mohamad G; Dib, Omar H; Patra, Digambara

    2016-12-01

    Curcumin has been successfully encapsulated in cyclodextrin-metal organic frameworks (CD-MOFs) without altering their crystallinity. The interaction between curcumin and CD-MOFs is strong through hydrogen bond type interaction between the OH group of cyclodextrin of CD-MOFs and the phenolic hydroxyl group of the curcumin. Interestingly, dissolving the curcumin loaded CD-MOFs crystals in water results in formation of a unique complex between curcumin, γCD and potassium cations. In fact, the initial interaction between curcumin and CD-MOF is crucial for the formation of the latter. This new complex formed in alkaline media at pH 11.5 has maximum absorbance at 520nm and emittance at 600nm. Most importantly, the stability of curcumin in this complex was enhanced by at least 3 orders of magnitude compared to free curcumin and curcumin:γ-CD at pH 11.5. These results suggest a promising benign system of CD-MOFs, which can be used to store and stabilize curcumin for food applications.

  2. Supramolecular curcumin-barium prodrugs for formulating with ceramic particles.

    PubMed

    Kamalasanan, Kaladhar; Anupriya; Deepa, M K; Sharma, Chandra P

    2014-10-01

    A simple and stable curcumin-ceramic combined formulation was developed with an aim to improve curcumin stability and release profile in the presence of reactive ceramic particles for potential dental and orthopedic applications. For that, curcumin was complexed with barium (Ba(2+)) to prepare curcumin-barium (BaCur) complex. Upon removal of the unbound curcumin and Ba(2+) by dialysis, a water-soluble BaCur complex was obtained. The complex was showing [M+1](+) peak at 10,000-20,000 with multiple fractionation peaks of MALDI-TOF-MS studies, showed that the complex was a supramolecular multimer. The (1)H NMR and FTIR studies revealed that, divalent Ba(2+) interacted predominantly through di-phenolic groups of curcumin to form an end-to-end complex resulted in supramolecular multimer. The overall crystallinity of the BaCur was lower than curcumin as per XRD analysis. The complexation of Ba(2+) to curcumin did not degrade curcumin as per HPLC studies. The fluorescence spectrum was blue shifted upon Ba(2+) complexation with curcumin. Monodisperse nanoparticles with size less than 200dnm was formed, out of the supramolecular complex upon dialysis, as per DLS, and upon loading into pluronic micelles the size was remaining in similar order of magnitude as per DLS and AFM studies. Stability of the curcumin was improved greater than 50% after complexation with Ba(2+) as per UV/Vis spectroscopy. Loading of the supramloecular nanoparticles into pluronic micelles had further improved the stability of curcumin to approx. 70% in water. These BaCur supramolecule nanoparticles can be considered as a new class of prodrugs with improved solubility and stability. Subsequently, ceramic nanoparticles with varying chemical composition were prepared for changing the material surface reactivity in terms of the increase in, degradability, surface pH and protein adsorption. Further, these ceramic particles were combined with curcumin prodrug formulations and optimized the curcumin release

  3. Biological evaluation of curcumin and related diarylheptanoids.

    PubMed

    Abas, Faridah; Hui, Lim Siang; Ahmad, Syahida; Stanslas, Johnson; Israf, D A; Shaari, Khozirah; Lajis, Nordin H

    2006-01-01

    Nine derivatives of three natural diarylheptanoids, curcumin, demethoxycurcumin and bisdemethoxycurcumin, were prepared. Their antioxidant, free radical scavenging, nitric oxide (NO) inhibitory and cytotoxic activities were evaluated and compared with those of the respective natural compounds. Curcumin (1), demethoxycurcumin (2), demethyldemethoxy-curcumin (C3), diacetyldemethoxycurcumin (AC2) and triacetyldemethylcurcumin (AC5) exhibited higher antioxidant activity than quercetin while products from demethylation of 1 and 2 exhibited higher free radical scavenging activity. Compounds AC2 and AC5 were found to be most active in inhibiting breast cancer cells (MCF-7) proliferation with IC50 values of 6.7 and 3.6 microM, respectively. The activity of AC2 is almost doubled and of AC5 almost tripled as compared to curcumin. Their selectivity towards different cell lines is also more noticeable. Compounds AC2 and AC5 also showed increased activity against a human prostate cancer cell line (DU-145) and non-small lung cancer cell line (NCI-H460) with IC50 values of 20.4, 16.3 and 18.3, 10.7 microM, respectively.

  4. Reversal of hypermethylation and reactivation of glutathione S-transferase pi 1 gene by curcumin in breast cancer cell line.

    PubMed

    Kumar, Umesh; Sharma, Ujjawal; Rathi, Garima

    2017-02-01

    One of the mechanisms for epigenetic silencing of tumor suppressor genes is hypermethylation of cytosine residue at CpG islands at their promoter region that contributes to malignant progression of tumor. Therefore, activation of tumor suppressor genes that have been silenced by promoter methylation is considered to be very attractive molecular target for cancer therapy. Epigenetic silencing of glutathione S-transferase pi 1, a tumor suppressor gene, is involved in various types of cancers including breast cancer. Epigenetic silencing of tumor suppressor genes can be reversed by several molecules including natural compounds such as polyphenols that can act as a hypomethylating agent. Curcumin has been found to specifically target various tumor suppressor genes and alter their expression. To check the effect of curcumin on the methylation pattern of glutathione S-transferase pi 1 gene in MCF-7 breast cancer cell line in dose-dependent manner. To check the reversal of methylation pattern of hypermethylated glutathione S-transferase pi 1, MCF-7 breast cancer cell line was treated with different concentrations of curcumin for different time periods. DNA and proteins of treated and untreated cell lines were isolated, and methylation status of the promoter region of glutathione S-transferase pi 1 was analyzed using methylation-specific polymerase chain reaction assay, and expression of this gene was analyzed by immunoblotting using specific antibodies against glutathione S-transferase pi 1. A very low and a nontoxic concentration (10 µM) of curcumin treatment was able to reverse the hypermethylation and led to reactivation of glutathione S-transferase pi 1 protein expression in MCF-7 cells after 72 h of treatment, although the IC50 value of curcumin was found to be at 20 µM. However, curcumin less than 3 µM of curcumin could not alter the promoter methylation pattern of glutathione S-transferase pi 1. Treatment of breast cancer MCF-7 cells with curcumin causes

  5. The pharmacology of curcumin: is it the degradation products?

    PubMed

    Shen, Liang; Ji, Hong-Fang

    2012-03-01

    The natural product curcumin has gained considerable attention in recent years for its multiple pharmacological activities, but more efforts are needed to understand how curcumin can have these pharmacological effects considering its low bioavailability. In addition, it is unclear how curcumin exerts inhibitory effects against numerous enzymes, especially those that cannot accommodate curcumin within recognized binding pockets. By analyzing the similarities between the biological activities of curcumin and its degradation products against diseases such as Alzheimer's disease and cancer, as well as the preferential inhibition of some enzymes by degradation products, it appears that the bioactive degradation products may contribute to the pharmacological effects of curcumin. This possibility should be given full attention when elucidating the pharmacology of this promising natural product for various diseases.

  6. Plasma proteins interaction with curcumin nanoparticles: implications in cancer therapeutics.

    PubMed

    Yallapu, Murali M; Ebeling, Mara C; Jaggi, Meena; Chauhan, Subhash C

    2013-05-01

    Curcumin, a natural bioactive polyphenol, has been widely investigated as a conventional medicine for centuries. Over the past two decades, major pre-clinical and clinical trials have demonstrated its safe therapeutic profile but clinical translation has been hampered due to rapid degradation, poor water solubility, bioavailability and pharmaco-kinetics. To overcome such translational issues, many laboratories have focused on developing curcumin nanoformulations for cancer therapeutics. In this review, we discuss the evolution of curcumin nanomedicine in cancer therapeutics, the possible interactions between the surface of curcumin nanoparticles and plasma proteins, the role of nanoparticle-protein complex architecture parameters, and the rational design of clinically useful curcumin nanoformulations. Considering all the biologically relevant phenomena, curcumin nanoformulations can be developed as a new neutraceutical or pharmaceutical agent.

  7. Curcumin prevents human dendritic cell response to immune stimulants

    SciTech Connect

    Shirley, Shawna A.; Montpetit, Alison J.; Lockey, R.F.; Mohapatra, Shyam S.

    2008-09-26

    Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory and immunomodulatory properties, though the mechanism remains unclear. Dendritic cells (DCs) are important to generating an immune response and the effect of curcumin on human DCs has not been explored. The role curcumin in the DC response to bacterial and viral infection was investigated in vitro using LPS and Poly I:C as models of infection. CD14{sup +} monocytes, isolated from human peripheral blood, were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs. Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and functional assays were performed. Curcumin prevents DCs from responding to immunostimulants and inducing CD4{sup +} T cell proliferation by blocking maturation marker, cytokine and chemokine expression and reducing both migration and endocytosis. These data suggest a therapeutic role for curcumin as an immune suppressant.

  8. Curcumin/xanthan-galactomannan hydrogels: rheological analysis and biocompatibility.

    PubMed

    Da-Lozzo, Eneida Janiscki; Moledo, Ricardo Cambaúva Andrukaisti; Faraco, Cloris Ditzel; Ortolani-Machado, Claudia Feijó; Bresolin, Tania Mari Bellé; Silveira, Joana Léa Meira

    2013-03-01

    Curcumin, a lipophilic compound found in the plant Curcuma longa L., exhibits a wide range of pharmacological activity; however, its therapeutic use has been limited because of its low bioavailability following oral administration. The aim of this study was to evaluate the viscoelastic characteristics and biocompatibility of a curcumin/xanthan:galactomannan hydrogel (X:G) system after topical application on chick embryo chorioallantoic membrane (CAM), a system established with a view toward curcumin nasal or topical pharmaceutical applications or possible administration in cosmetics or foods. A rheological analysis indicated that incorporation of curcumin did not alter the viscoelastic characteristics of the X:G hydrogel, suggesting that there was no change in the structure of the gel network. X:G hydrogels did not induce CAM tissue injury and the curcumin/X:G hydrogel system was also highly biocompatible. We conclude that the X:G hydrogel represents a potential matrix for curcumin formulations.

  9. Antidotal Effects of Curcumin Against Agents-Induced Cardiovascular Toxicity.

    PubMed

    Farkhondeh, Tahereh; Samarghandian, Saeed

    Curcumin, the major phenolic compound in turmeric, shows preventive effects in various diseases. Curcumin is commonly found in rhizome of the Curcuma species and traditionally used in herbal medicine. Numeros studies has indicated that curcumin posses protective effects against toxic agents in various systems including cardiovascular. This study found that curcumin may be effective in cardiovascular diseases induced by toxic agents including Streptozotocin, Doxorubicin, Cyclosporin A, Methotrexate, Isoproterenol, Cadmium, Diesel exhaust particle, Nicotine, Hydrogen peroxide, and tert- Butyl hydroperoxide. However, due to the lake of information on human, further studies are needed to determine the efficacy of curcumin as an antidote agent. The present study aimed to critically review the recent literature data from that regarding the protective effects of curcumin against agents-induced cardiovascular toxicity.

  10. Curcumin: From ancient medicine to current clinical trials

    PubMed Central

    Hatcher, H.; Planalp, R.; Cho, J.; Torti, S. V.

    2015-01-01

    Curcumin is the active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa). Curcumin has a surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. The pleiotropic activities of curcumin derive from its complex chemistry as well as its ability to influence multiple signaling pathways, including survival pathways such as those regulated by NF-κB, Akt, and growth factors; cytoprotective pathways dependent on Nrf2; and metastatic and angiogenic pathways. Curcumin is a free radical scavenger and hydrogen donor, and exhibits both pro- and antioxidant activity. It also binds metals, particularly iron and copper, and can function as an iron chelator. Curcumin is remarkably non-toxic and exhibits limited bioavailability. Curcumin exhibits great promise as a therapeutic agent, and is currently in human clinical trials for a variety of conditions, including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer, psoriasis and Alzheimer’s disease. PMID:18324353

  11. Enhanced solubilization of curcumin in mixed surfactant vesicles.

    PubMed

    Kumar, Arun; Kaur, Gurpreet; Kansal, S K; Chaudhary, Ganga Ram; Mehta, S K

    2016-05-15

    Self-assemblies of equimolar double and single chain mixed ionic surfactants, with increasing numbers of carbon atoms of double chain surfactant, were analyzed on the basis of fluorescence and conductivity results. Attempts were also made to enhance the solubilization of curcumin in aqueous equimolar mixed surfactant systems. Mixed surfactant assembly was successful in retarding the degradation of curcumin in alkaline media (only 25-28 40% degraded in 10h at pH 13). Fluorescence spectroscopy and fluorescence quenching methods were employed to predict the binding position and mechanism of curcumin with self-assemblies. Results indicate that the interactions take place according to both dynamic and static quenching mechanisms and curcumin was distributed in a palisade layer of mixed aggregates. Antioxidant activity (using DPPH radical) and biocompatibility (using calf-thymus DNA) of curcumin-loaded mixed surfactant formulations were also evaluated. The prepared systems improved the stability, solubility and antioxidant activity of curcumin and additionally are biocompatible.

  12. Antioxidant and radical scavenging properties of curcumin.

    PubMed

    Ak, Tuba; Gülçin, Ilhami

    2008-07-10

    Curcumin (diferuoyl methane) is a phenolic compound and a major component of Curcuma longa L. In the present paper, we determined the antioxidant activity of curcumin by employing various in vitro antioxidant assays such as 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH*) scavenging, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging activity, N,N-dimethyl-p-phenylenediamine dihydrochloride (DMPD) radical scavenging activity, total antioxidant activity determination by ferric thiocyanate, total reducing ability determination by the Fe(3+)-Fe(2+) transformation method, superoxide anion radical scavenging by the riboflavin/methionine/illuminate system, hydrogen peroxide scavenging and ferrous ions (Fe(2+)) chelating activities. Curcumin inhibited 97.3% lipid peroxidation of linoleic acid emulsion at 15 microg/mL concentration (20 mM). On the other hand, butylated hydroxyanisole (BHA, 123 mM), butylated hydroxytoluene (BHT, 102 mM), alpha-tocopherol (51 mM) and trolox (90 mM) as standard antioxidants indicated inhibition of 95.4, 99.7, 84.6 and 95.6% on peroxidation of linoleic acid emulsion at 45 microg/mL concentration, respectively. In addition, curcumin had an effective DPPH* scavenging, ABTS*(+) scavenging, DMPD*(+) scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, ferric ions (Fe(3+)) reducing power and ferrous ions (Fe(2+)) chelating activities. Also, BHA, BHT, alpha-tocopherol and trolox, were used as the reference antioxidant and radical scavenger compounds. According to the present study, curcumin can be used in the pharmacological and food industry because of these properties.

  13. Curcumin: a novel therapeutic for burn pain and wound healing

    DTIC Science & Technology

    2013-08-01

    curcumin delivery to cancer cells was increased by a factor of 2 -- 3 by the PEG-zein nanoparticles compared to free curcumin. Finally, the effective... cancer chemoprevention. Cancer Res 2010;70:4443-52 59. Thangapazham RL, Puri A, Tele S, et al. Evaluation of a nanotechnology -based carrier for...of these studies have been performed using identical wound models, routes of curcumin administration or in vitro tests , one common conclusion emerges

  14. Cytotoxic Effects of Curcumin in Human Retinal Pigment Epithelial Cells

    PubMed Central

    Hollborn, Margrit; Chen, Rui; Wiedemann, Peter; Reichenbach, Andreas; Bringmann, Andreas; Kohen, Leon

    2013-01-01

    Backround Curcumin from turmeric is an ingredient in curry powders. Due to its antiinflammatory, antioxidant and anticarcinogenic effects, curcumin is a promising drug for the treatment of cancer and retinal diseases. We investigated whether curcumin alters the viability and physiological properties of human retinal pigment epithelial (RPE) cells in vitro. Methodology/Principal Findings Cellular proliferation was investigated with a bromodeoxy-uridine immunoassay, and chemotaxis was investigated with a Boyden chamber assay. Cell viability was determined by trypan blue exclusion. Apoptosis and necrosis rates were determined with a DNA fragmentation ELISA. Gene expression was determined by real-time PCR, and secretion of VEGF and bFGF was examined with ELISA. The phosphorylation level of proteins was revealed by Western blotting. The proliferation of RPE cells was slightly increased by curcumin at 10 µM and strongly reduced by curcumin above 50 µM. Curcumin at 50 µM increased slightly the chemotaxis of the cells. Curcumin reduced the expression and secretion of VEGF under control conditions and abolished the VEGF secretion induced by PDGF and chemical hypoxia. Whereas low concentrations of curcumin stimulated the expression of bFGF and HGF, high concentrations caused downregulation of both factors. Curcumin decreased dose-dependently the viability of RPE cells via induction of early necrosis (above 10 µM) and delayed apoptosis (above 1 µM). The cytotoxic effect of curcumin involved activation of caspase-3 and calpain, intracellular calcium signaling, mitochondrial permeability, oxidative stress, increased phosphorylation of p38 MAPK and decreased phosphorylation of Akt protein. Conclusion It is concluded that curcumin at concentrations described to be effective in the treatment of tumor cells and in inhibiting death of retinal neurons (∼10 µM) has adverse effects on RPE cells. It is suggested that, during the intake of curcumin as concomitant therapy of

  15. Curcumin inhibits apoptosis by regulating intracellular calcium release, reactive oxygen species and mitochondrial depolarization levels in SH-SY5Y neuronal cells.

    PubMed

    Uğuz, Abdülhadi Cihangir; Öz, Ahmi; Nazıroğlu, Mustafa

    2016-08-01

    Neurological diseases such as Alzheimer's and Parkinson's diseases are incurable progressive neurological disorders caused by the degeneration of neuronal cells and characterized by motor and non-motor symptoms. Curcumin, a turmeric product, is an anti-inflammatory agent and an effective reactive oxygen and nitrogen species scavenging molecule. Hydrogen peroxide (H2O2) is the main source of oxidative stress, which is claimed to be the major source of neurological disorders. Hence, in this study we aimed to investigate the effect of curcumin on Ca(2+) signaling, oxidative stress parameters, mitochondrial depolarization levels and caspase-3 and -9 activities that are induced by the H2O2 model of oxidative stress in SH-SY5Y neuronal cells. SH-SY5Y neuronal cells were divided into four groups namely, the control, curcumin, H2O2, and curcumin + H2O2 groups. The dose and duration of curcumin and H2O2 were determined from published data. The cells in the curcumin, H2O2, and curcumin + H2O2 groups were incubated for 24 h with 5 µM curcumin and 100 µM H2O2. Lipid peroxidation and cytosolic free Ca(2+) concentrations were higher in the H2O2 group than in the control group; however, their levels were lower in the curcumin and curcumin + H2O2 groups than in the H2O2 group alone. Reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) values were lower in the H2O2 group although they were higher in the curcumin and curcumin + H2O2 groups than in the H2O2 group. Caspase-3 activity was lower in the curcumin group than in the H2O2 group. In conclusion, curcumin strongly induced modulator effects on oxidative stress, intracellular Ca(2+) levels, and the caspase-3 and -9 values in an experimental oxidative stress model in SH-SY5Y cells.

  16. Curcumin recognizes a unique binding site of tubulin.

    PubMed

    Chakraborti, Soumyananda; Das, Lalita; Kapoor, Neha; Das, Amlan; Dwivedi, Vishnu; Poddar, Asim; Chakraborti, Gopal; Janik, Mark; Basu, Gautam; Panda, Dulal; Chakrabarti, Pinak; Surolia, Avadhesha; Bhattacharyya, Bhabatarak

    2011-09-22

    Although curcumin is known for its anticarcinogenic properties, the exact mechanism of its action or the identity of the target receptor is not completely understood. Studies on a series of curcumin analogues, synthesized to investigate their tubulin binding affinities and tubulin self-assembly inhibition, showed that: (i) curcumin acts as a bifunctional ligand, (ii) analogues with substitution at the diketone and acetylation of the terminal phenolic groups of curcumin are less effective, (iii) a benzylidiene derivative, compound 7, is more effective than curcumin in inhibiting tubulin self-assembly. Cell-based studies also showed compound 7 to be more effective than curcumin. Using fluorescence spectroscopy we show that curcumin binds tubulin 32 Å away from the colchicine-binding site. Docking studies also suggests that the curcumin-binding site to be close to the vinblastine-binding site. Structure-activity studies suggest that the tridented nature of compound 7 is responsible for its higher affinity for tubulin compared to curcumin.

  17. Curcumin improves liver damage in male mice exposed to nicotine

    PubMed Central

    Salahshoor, Mohammadreza; Mohamadian, Sabah; Kakabaraei, Seyran; Roshankhah, Shiva; Jalili, Cyrus

    2015-01-01

    The color of turmeric (薑黃 jiāng huáng) is because of a substance called curcumin. It has different pharmacological effects, such as antioxidant and anti-inflammatory properties. Nicotine is a major pharmacologically active substance in cigarette smoke. It is mainly metabolized in the liver and causes devastating effects. This study was designed to evaluate the protective role of curcumin against nicotine on the liver in mice. Forty-eight mice were equally divided into eight groups; control (normal saline), nicotine (2.5 mg/kg), curcumin (10, 30, and 60 mg/kg) and curcumin plus nicotine-treated groups. Curcumin, nicotine, and curcumin plus nicotine (once a day) were intraperitoneally injected for 4 weeks. The liver weight and histology, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and serum nitric oxide levels have been studied. The results indicated that nicotine administration significantly decreased liver weight and increased the mean diameter of hepatocyte, central hepatic vein, liver enzymes level, and blood serum nitric oxide level compared with the saline group (p < 0.05). However, curcumin and curcumin plus nicotine administration substantially increased liver weight and decreased the mean diameter of hepatocyte, central hepatic vein, liver enzymes, and nitric oxide levels in all groups compared with the nicotine group (p < 0.05). Curcumin demonstrated its protective effect against nicotine-induced liver toxicity. PMID:27114942

  18. Recombinant IκBα-loaded curcumin nanoparticles for improved cancer therapeutics.

    PubMed

    Banerjee, Subhamoy; Sahoo, Amaresh Kumar; Chattopadhyay, Arun; Ghosh, Siddhartha Sankar

    2014-08-29

    The field of recombinant protein therapeutics has been evolving rapidly, making significant impact on clinical applications for several diseases, including cancer. However, the functional aspects of proteins rely exclusively on their structural integrity, in which nanoparticle mediated delivery offers unique advantages over free proteins. In the present work, a novel strategy has been developed where the nanoparticles (NPs) used for the delivery of the recombinant protein could contribute to enhancing the therapeutic efficacy of the recombinant protein. The transcription factor, NFκB, involved in cell growth and its inhibitor, IκBα, regulates its proliferation. Another similar naturally available molecule, which inhibits the function of NFκB, is curcumin. Hence, we have developed a 'green synthesis' method for preparing water-soluble curcumin nanoparticles to stabilize recombinant IκBα protein. The NPs were characterized by UV-vis and fluorescence spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering before administration into human cervical carcinoma (HeLa) and glioblastoma (U87MG) cells. Experimental results demonstrated that this combined module had enhanced therapeutic efficacy, causing apoptotic cell death, which was confirmed by cytotoxicity assay and flowcytometry analyses. The expression of apoptotic genes studied by semi-quantitative reverse transcription PCR delineated the molecular pathways involved in cell death. Thus, our study revealed that the functional delivery of recombinant IκBα-loaded curcumin NPs has promise as a natural-product-based protein therapeutics against cancer cells.

  19. Novel artemisinin and curcumin micellar formulations: drug solubility studies by NMR spectroscopy.

    PubMed

    Lapenna, Silvia; Bilia, Anna Rita; Morris, Gareth A; Nilsson, Mathias

    2009-10-01

    Artemisinin, a potent antimalarial drug derived from Artemisia annua L., and curcumin, a polyphenol extracted from the roots of Curcuma longa L., are reported to exert a synergistic antimalarial action, albeit manifesting a low bioavailability. In fact, both these molecules are poorly soluble in aqueous environments. In this study, we report a DOSY investigation of the solubilisation capacity of micelles of sodium dodecyl sulphate (SDS) for artemisinin and curcumin, individually and in combination. The aqueous solubility of artemisinin was enhanced approximately 25-fold by 40 mM SDS, and 50-fold by 81 mM SDS, while that of curcumin was increased to 2 mM by 81 mM SDS. In addition, we performed model studies on the use of the surface-active radical scavenger octanoyl-6-O-ascorbic acid (ASC8) to combine solubilisation with protection against oxidation for the chemically labile artemisinin. A 16-fold enhancement of artemisinin solubility was measured in a solution containing 40 mM SDS and 60 mM ASC8. Even after treatment with 60 mM hydrogen peroxide, more than a 30-fold excess, almost half the artemisinin remained, suggesting a potentially useful combination of the surface activity and antioxidant properties of the novel binary SDS:ASC8 system.

  20. Recombinant IκBα-loaded curcumin nanoparticles for improved cancer therapeutics

    NASA Astrophysics Data System (ADS)

    Banerjee, Subhamoy; Sahoo, Amaresh Kumar; Chattopadhyay, Arun; Sankar Ghosh, Siddhartha

    2014-08-01

    The field of recombinant protein therapeutics has been evolving rapidly, making significant impact on clinical applications for several diseases, including cancer. However, the functional aspects of proteins rely exclusively on their structural integrity, in which nanoparticle mediated delivery offers unique advantages over free proteins. In the present work, a novel strategy has been developed where the nanoparticles (NPs) used for the delivery of the recombinant protein could contribute to enhancing the therapeutic efficacy of the recombinant protein. The transcription factor, NFκB, involved in cell growth and its inhibitor, IκBα, regulates its proliferation. Another similar naturally available molecule, which inhibits the function of NFκB, is curcumin. Hence, we have developed a ‘green synthesis’ method for preparing water-soluble curcumin nanoparticles to stabilize recombinant IκBα protein. The NPs were characterized by UV-vis and fluorescence spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering before administration into human cervical carcinoma (HeLa) and glioblastoma (U87MG) cells. Experimental results demonstrated that this combined module had enhanced therapeutic efficacy, causing apoptotic cell death, which was confirmed by cytotoxicity assay and flowcytometry analyses. The expression of apoptotic genes studied by semi-quantitative reverse transcription PCR delineated the molecular pathways involved in cell death. Thus, our study revealed that the functional delivery of recombinant IκBα-loaded curcumin NPs has promise as a natural-product-based protein therapeutics against cancer cells.

  1. Influence of trehalose on the interaction of curcumin with surface active ionic liquid micelle and its vesicular aggregate composed of a non-ionic surfactant sorbitan stearate

    NASA Astrophysics Data System (ADS)

    Roy, Arpita; Dutta, Rupam; Sarkar, Nilmoni

    2016-11-01

    The present investigation unravels the effect of trehalose on 1-hexadecyl-3-methylimidazolium chloride ([C16mim]Cl), a cationic surface active ionic liquid (SAIL) micelle and SAIL ([C16mim]Cl)-nonionic surfactant (Sorbitan Stearate, Span 60) based vesicles. The influence of trehalose on size and morphology of the aggregates has been investigated using dynamic light scattering (DLS) and transmission electron microscopic (TEM) measurements. Besides, we have studied the dynamic properties of curcumin inside these aggregates using fluorescence spectroscopic based techniques. The results revealed that trehalose molecules play crucial role in modulation of the photophysical properties of curcumin in these organized assemblies.

  2. Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, Against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases

    PubMed Central

    Aggarwal, Bharat B.; Harikumar, Kuzhuvelil B.

    2009-01-01

    Although safe in most cases, ancient treatments are ignored because neither their active component nor their molecular targets are well defined. This is not the case, however, with curcumin, a yellow-pigment substance and component of turmeric (Curcuma longa), which was identified more than a century ago. For centuries it has been known that turmeric exhibits anti-inflammatory activity, but extensive research performed within the past two decades has shown that the this activity of turmeric is due to curcumin, a diferuloylmethane. This agent has been shown to regulate numerous transcription factors, cytokines, protein kinases, adhesion molecules, redox status and enzymes that have been linked to inflammation. The process of inflammation has been shown to play a major role in most chronic illnesses, including neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. In the current review, we provide evidence for the potential role of curcumin in the prevention and treatment of various pro-inflammatory chronic diseases. These features, combined with the pharmacological safety and negligible cost, render curcumin an attractive agent to explore further. PMID:18662800

  3. Galactosylated alginate-curcumin micelles for enhanced delivery of curcumin to hepatocytes.

    PubMed

    Sarika, P R; James, Nirmala Rachel; Kumar, P R Anil; Raj, Deepa K

    2016-05-01

    Galactosylated alginate-curcumin conjugate (LANH2-Alg Ald-Cur) is synthesized for targeted delivery of curcumin to hepatocytes exploiting asialoglycoprotein receptor (ASGPR) on hepatocytes. The synthetic procedure includes oxidation of alginate (Alg), modification of lactobionic acid (LA), grafting of targeting group (modified lactobinic acid, LANH2) and conjugation of curcumin to alginate. Alginate-curcumin conjugate (Alg-Cur) without targeting group is also prepared for the comparison of properties. LANH2-Alg Ald-Cur self assembles to micelle with diameter of 235 ± 5 nm and zeta potential of -29 mV in water. Cytotoxicity analysis demonstrates enhanced toxicity of LANH2-Alg Ald-Cur over Alg-Cur on HepG2 cells. Cellular uptake studies confirm that LANH2-Alg Ald-Cur can selectively recognize HepG2 cells and shows higher internalization than Alg-Cur conjugate. Results indicate that LANH2-Alg Ald-Cur conjugate micelles are suitable candidates for targeted delivery of curcumin to HepG2 cells.

  4. Curcumin-cyclodextrin complexes enhanced the anti-cancer effects of curcumin.

    PubMed

    Zhang, Lili; Man, Shuli; Qiu, Huanna; Liu, Zhen; Zhang, Mi; Ma, Long; Gao, Wenyuan

    2016-12-01

    Curcumin (CUR), as a yellow pigment in the spice turmeric (Curcuma longa), possessed a pleiotropic application containing cancer therapy. Due to its poor oral bioavailability, the objective of this study was to investigate the use of curcumin-cyclodextrin complexes (CD15) as an approach to cancer chemoprevention. In this study, CUR encapsulation into the β-cyclodextrin (CD) cavity was achieved by the saturated aqueous solution method. CD15 was characterized by Fourier transform infrared (FTIR) and UV spectra analyses. An optimized CD15 was evaluated by cellular uptake and anti-cancer activity. As a result, CD15 enhanced curcumin delivery and improved its therapeutic efficacy compared with free curcumin in vivo and in vitro. Therefore, through regulation of MAPK/NF-κB pathway, CD15 up-regulated p53/p21 pathway, down-regulated CyclinE-CDK2 combination and increased Bax/caspase 3 expression to induce cellar apoptosis and G1-phase arrest. In conclusion, these results suggested that CD15 formulation should be used as a system for improving curcumin delivery and its therapeutic efficacy in lung cancer.

  5. Protective effects of dendrosomal curcumin on an animal metastatic breast tumor.

    PubMed

    Farhangi, Baharak; Alizadeh, Ali Mohammad; Khodayari, Hamid; Khodayari, Saeed; Dehghan, Mohammad Javad; Khori, Vahid; Heidarzadeh, Alemeh; Khaniki, Mahmood; Sadeghiezadeh, Majid; Najafi, Farhood

    2015-07-05

    Curcumin has been shown to inhibit migration and invasion of cancer angiogenesis via interacting with key regulatory molecules like NF-κB. Rapidly metabolized and conjugated in the liver, curcumin has the limited systemic bioavailability. Previous results have shown a new light of potential biocompatibility, biodegradability, as well as anti-cancer effects of dendrosomal curcumin (DNC) in biological systems. The present study aims to deliberate the protective effects of DNC on metastatic breast tumor in vitro and in vivo. After the dosing procedure, twenty-seven female mice were divided into 40 and 80mg/kg groups of DNC, along with a control group to investigate the anti-metastatic effects of DNC on mammary tumor-bearing mice. In vitro results showed that the different concentrations of DNC reduced the migration and the adhesion of 4T1 cells after 24h (P<0.05). Under the dosing procedure, DNC was safe at 80mg/kg and lower doses. The treated DNC animals had a higher survival rate and lower metastatic signs (14%) compared to control (100%) (P<0.05). The metastatic tumors were more common in control mice than the treated groups in the lung, the liver and the sternum tissues. Animals treated with DNC had smaller tumor volume in comparison with control group (P<0.05). Final mean tumor volume reached to approximately 1.11, 0.31 and 0.27cm(3) in the control, and 40 and 80mg/kg DNC groups, respectively (P<0.05). Furthermore, suppression of NF-κB expression by DNC led to down-regulation of VEGF, COX-2, and MMP-9 expressions in the breast tumor, the lung, the brain, the spleen and the liver tissues (P<0.05). These outcomes indicate that dendrosomal curcumin has a chemoprotective effect on the breast cancer metastasis through suppression of NF-κB and its regulated gene products.

  6. Curcumin derivatives as metal-chelating agents with potential multifunctional activity for pharmaceutical applications.

    PubMed

    Ferrari, Erika; Benassi, Rois; Sacchi, Stefania; Pignedoli, Francesca; Asti, Mattia; Saladini, Monica

    2014-10-01

    Curcuminoids represent new perspectives for the development of novel therapeutics for Alzheimer's disease (AD), one probable mechanism of action is related to their metal complexing ability. In this work we examined the metal complexing ability of substituted curcuminoids to propose new chelating molecules with biological properties comparable with curcumin but with improved stability as new potential AD therapeutic agents. The K2T derivatives originate from the insertion of a -CH2COOC(CH3)3 group on the central atom of the diketonic moiety of curcumin. They retain the diketo-ketoenol tautomerism which is solvent dependent. In aqueous solution the prevalent form is the diketo one but the addition of metal ion (Ga(3+), Cu(2+)) causes the dissociation of the enolic proton creating chelate complexes and shifting the tautomeric equilibrium towards the keto-enol form. The formation of metal complexes is followed by both NMR and UV-vis spectroscopy. The density functional theory (DFT) calculations on K2T21 complexes with Ga(3+) and Cu(2+) are performed and compared with those on curcumin complexes. [Ga(K2T21)2(H2O)2](+) was found more stable than curcumin one. Good agreement is detected between calculated and experimental (1)H and (13)C NMR data. The calculated OH bond dissociation energy (BDE) and the OH proton dissociation enthalpy (PDE), allowed to predict the radical scavenging ability of the metal ion complexed with K2T21, while the calculated electronic affinity (EA) and ionization potential (IP) represent yardsticks of antioxidant properties. Eventually theoretical calculations suggest that the proton-transfer-associated superoxide-scavenging activity is enhanced after binding metal ions, and that Ga(3+) complexes display possible superoxide dismutase (SOD)-like activity.

  7. Core-Shell Soy Protein-Soy Polysaccharide Complex (Nano)particles as Carriers for Improved Stability and Sustained Release of Curcumin.

    PubMed

    Chen, Fei-Ping; Ou, Shi-Yi; Tang, Chuan-He

    2016-06-22

    Using soy protein isolate (SPI) and soy-soluble polysaccharides (SSPS) as polymer matrixes, this study reported a novel process to fabricate unique core-shell complex (nano)particles to perform as carriers for curcumin (a typical poorly soluble bioactive). In the process, curcumin-SPI nanocomplexes were first formed at pH 7.0 and then coated by SSPS. At this pH, the core-shell complex was formed in a way the SPI nanoparticles might be incorporated into the interior of SSPS molecules without distinctly affecting the size and morphology of particles. The core-shell structure was distinctly changed by adjusting pH from 7.0 to 4.0. At pH 4.0, SSPS was strongly bound to the surface of highly aggregated SPI nanoparticles, and as a consequence, much larger complexes were formed. The bioaccessibility of curcumin in the SPI-curcumin complexes was unaffected by the SSPS coating. However, the core-shell complex formation greatly improved the thermal stability and controlled release properties of encapsulated curcumin. The improvement was much better at pH 4.0 than that at pH 7.0. All of the freeze-dried core-shell complex preparations exhibited good redispersion behavior. The findings provide a simple approach to fabricate food-grade delivery systems for improved water dispersion, heat stability, and even controlled release of poorly soluble bioactives.

  8. Analog current mode analog/digital converter

    NASA Technical Reports Server (NTRS)

    Hadidi, Khayrollah (Inventor)

    1996-01-01

    An improved subranging or comparator circuit is provided for an analog-to-digital converter. As a subranging circuit, the circuit produces a residual signal representing the difference between an analog input signal and an analog of a digital representation. This is achieved by subdividing the digital representation into two or more parts and subtracting from the analog input signal analogs of each of the individual digital portions. In another aspect of the present invention, the subranging circuit comprises two sets of differential input pairs in which the transconductance of one differential input pair is scaled relative to the transconductance of the other differential input pair. As a consequence, the same resistor string may be used for two different digital-to-analog converters of the subranging circuit.

  9. Spatial localisation of curcumin and rapid screening of the chemical compositions of turmeric rhizomes (Curcuma longa Linn.) using Direct Analysis in Real Time-Mass Spectrometry (DART-MS).

    PubMed

    Rahman, A F M Motiur; Angawi, Rihab F; Kadi, Adnan A

    2015-04-15

    Curcumin is a potent antioxidant agent having versatile biological activities is present in turmeric rhizomes (Curcuma longa Linn.). Powder of turmeric rhizomes is consumes as curry spicy worldwide, especially in Asia. In this study, we demonstrate that, bioactive curcumin and its analog demethoxycurcumin are chiefly concentrated in the pith rather than the other parts of the turmeric rhizomes and it was discovered using modern atmospheric ionisation source 'Direct Analysis in Real Time' (DART) connected with an Ion Trap Mass Spectrometry. In addition, all the major components present in turmeric rhizomes were detected in positive and/or in negative ion mode using DART.

  10. Curcumin and Diabetes: A Systematic Review

    PubMed Central

    Zhang, Dong-wei; Fu, Min; Gao, Si-Hua; Liu, Jun-Li

    2013-01-01

    Turmeric (Curcuma longa), a rhizomatous herbaceous perennial plant of the ginger family, has been used for the treatment of diabetes in Ayurvedic and traditional Chinese medicine. The active component of turmeric, curcumin, has caught attention as a potential treatment for diabetes and its complications primarily because it is a relatively safe and inexpensive drug that reduces glycemia and hyperlipidemia in rodent models of diabetes. Here, we review the recent literature on the applications of curcumin for glycemia and diabetes-related liver disorders, adipocyte dysfunction, neuropathy, nephropathy, vascular diseases, pancreatic disorders, and other complications, and we also discuss its antioxidant and anti-inflammatory properties. The applications of additional curcuminoid compounds for diabetes prevention and treatment are also included in this paper. Finally, we mention the approaches that are currently being sought to generate a “super curcumin” through improvement of the bioavailability to bring this promising natural product to the forefront of diabetes therapeutics. PMID:24348712

  11. Challenges associated with curcumin therapy in Alzheimer disease.

    PubMed

    Belkacemi, Abdenour; Doggui, Sihem; Dao, Lé; Ramassamy, Charles

    2011-11-04

    Curcumin, the phytochemical agent in the spice turmeric, which gives Indian curry its yellow colour, is also a traditional Indian medicine. It has been used for millennia as a wound-healing agent and for treating a variety of ailments. The antioxidant, anti-inflammatory, antiproliferative and other properties of curcumin have only recently gained the attention of modern pharmacology. The mechanism of action of curcumin is complex and multifaceted. In part, curcumin acts by activating various cytoprotective proteins that are components of the phase II response. Over the past decade, research with curcumin has increased significantly. In vitro and in vivo studies have demonstrated that curcumin could target pathways involved in the pathophysiology of Alzheimer disease (AD), such as the β-amyloid cascade, tau phosphorylation, neuroinflammation or oxidative stress. These findings suggest that curcumin might be a promising compound for the development of AD therapy. However, its insolubility in water and poor bioavailability have limited clinical trials and its therapeutic applications. To be effective as a drug therapy, curcumin must be combined with other drugs, or new delivery strategies need to be developed.

  12. Trolox enhances curcumin's cytotoxicity through induction of oxidative stress.

    PubMed

    Zheng, Jie; Payne, Kelsey; Taggart, Jori E; Jiang, Hongchao; Lind, Stuart E; Ding, Wei-Qun

    2012-01-01

    Curcumin, a natural polyphenol in the spice turmeric, has been found to exhibit anticancer activity. Although curcumin is generally considered an antioxidant, it is also able to elicit apoptosis through the generation of ROS, thereby functioning as a pro-oxidant in cancer cells. The present study investigated the effects of antioxidant pretreatment on curcumin-induced cytotoxicity in the human cancer cell lines A2780, MCF-7, and MDA-MB-231. Cytotoxicity was enhanced by trolox, vitamin C or vitamin E; trolox, a water soluble vitamin E derivative, was the most potent. The combination of curcumin (10 μM) and trolox (10-50 μM) induced apoptosis of cancer cells as evidenced by PARP cleavage and caspase-3 activation. Furthermore, expression of the pro-apoptotic protein Bad was up-regulated and expression of the anti-apoptotic proteins Bcl-2 and Bcl-xl was down-regulated in cells that had been treated with trolox plus curcumin. ROS generation was detected in curcumin-treated cells and was significantly enhanced when cells were treated with trolox plus curcumin. Exogenous catalase or SOD1 did not alter cytotoxicity, while over-expression of either catalase or SOD1 did, pointing to the importance of intracellular hydrogen peroxide generation in cell killing. In conclusion, we demonstrated for the first time that antioxidants such as trolox can potentiate cancer cell killing by curcumin, a finding which may help in the development of novel drug combination therapies.

  13. Negative effects of curcumin on liver injury induced by alcohol.

    PubMed

    Zhao, Hai-Long; Song, Chang Ho; Chai, Ok Hee

    2012-12-01

    Curcumin is known for its antiinflammatory and antifibrotic properties in liver damage. However, the negative effects of curcumin on alcoholic liver damage are seldom reported. In this study, both advantageous and disadvantageous functions of curcumin on alcoholic liver injury were observed. In order to determine the effects of curcumin on liver fibrosis induced by alcohol, 5% ethanol and/or curcumin (1 × 10(-3) or 1 × 10(-4)  m) were injected intravenously in mice. Hematoxylin-eosin staining was performed to determine the value of liver injury by optical density analyses. Liver histology was evaluated by an experienced hepatopathologist blinded to the type of treatment received by the animals. Ethanol accelerates serum levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), liver injury, production of tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β) and nuclear factor-kappa B (NF-κB) during 5% ethanol-induced liver injury. 1 × 10(-3)  m curcumin accelerates liver injury and liver cellular edema during only 5% ethanol-induced liver injury evolution, whereas 1 × 10(-4)  m curcumin does not lead to (or protect) alcoholic liver injury. Therefore, it is suggested that curcumin may have dual effects on alcoholic liver injury depending on its concentration.

  14. Antimutagenic potential of curcumin on chromosomal aberrations in Allium cepa *

    PubMed Central

    Ragunathan, Irulappan; Panneerselvam, Natarajan

    2007-01-01

    Turmeric has long been used as a spice and food colouring agent in Asia. In the present investigation, the antimutagenic potential of curcumin was evaluated in Allium cepa root meristem cells. So far there is no report on the biological properties of curcumin in plant test systems. The root tip cells were treated with sodium azide at 200 and 300 µg/ml for 3 h and curcumin was given at 5, 10 and 20 µg/ml for 16 h, prior to sodium azide treatment. The tips were squashed after colchicine treatment and the cells were analyzed for chromosome aberration and mitotic index. Curcumin induces chromosomal aberration in Allium cepa root tip cells in an insignificant manner, when compared with untreated control. Sodium azide alone induces chromosomal aberrations significantly with increasing concentrations. The total number of aberrations was significantly reduced in root tip cells pretreated with curcumin. The study reveals that curcumin has antimutagenic potential against sodium azide induced chromosomal aberrations in Allium cepa root meristem cells. In addition, it showed mild cytotoxicity by reducing the percentage of mitotic index in all curcumin treated groups, but the mechanism of action remains unknown. The antimutagenic potential of curcumin is effective at 5 µg/ml in Allium cepa root meristem cells. PMID:17610326

  15. Curcumin ameliorates high-fat diet-induced spermatogenesis dysfunction

    PubMed Central

    Mu, Yang; Yan, Wen-Jie; Yin, Tai-Lang; Yang, Jing

    2016-01-01

    Curcumin, a type of natural active ingredient, is derived from rhizoma of Curcuma, which possesses antioxidant, antitumorigenic and anti-inflammatory activities. The present study aimed to investigate whether treatment with curcumin reduced high-fat diet (HFD)-induced spermatogenesis dysfunction. Sprague-Dawley rats fed a HFD were treated with or without curcumin for 8 weeks. The testis/body weight, histological analysis and serum hormone levels were used to evaluate the effects of curcumin treatment on spermatogenesis dysfunction induced by the HFD. In addition, the expression levels of apoptosis associated proteins, Fas, B-cell lymphoma (Bcl)-xl, Bcl-associated X protein (Bax) and cleaved-caspase 3, were determined in the testis. The results of the present study suggested that curcumin treatment attenuated decreased testis/body weight and abnormal hormone levels. Morphological changes induced by a HFD were characterized as atrophied seminiferous tubules, decreased spermatogenetic cells and interstitial cells were improved by curcumin treatment. In addition, curcumin treatment reduced apoptosis in the testis, and decreased expression of Fas, Bax and cleaved-caspase 3, as well as increased expression of Bcl-xl. In conclusion, the present study revealed that curcumin treatment reduced HFD-induced spermatogenesis dysfunction in male rats. PMID:27600729

  16. Curcumin Modulates α-Synuclein Aggregation and Toxicity

    PubMed Central

    2012-01-01

    In human beings, Parkinson’s disease (PD) is associated with the oligomerization and amyloid formation of α-synuclein (α-Syn). The polyphenolic Asian food ingredient curcumin has proven to be effective against a wide range of human diseases including cancers and neurological disorders. While curcumin has been shown to significantly reduce cell toxicity of α-Syn aggregates, its mechanism of action remains unexplored. Here, using a series of biophysical techniques, we demonstrate that curcumin reduces toxicity by binding to preformed oligomers and fibrils and altering their hydrophobic surface exposure. Further, our fluorescence and two-dimensional nuclear magnetic resonance (2D-NMR) data indicate that curcumin does not bind to monomeric α-Syn but binds specifically to oligomeric intermediates. The degree of curcumin binding correlates with the extent of α-Syn oligomerization, suggesting that the ordered structure of protein is required for effective curcumin binding. The acceleration of aggregation by curcumin may decrease the population of toxic oligomeric intermediates of α-Syn. Collectively; our results suggest that curcumin and related polyphenolic compounds can be pursued as candidate drug targets for treatment of PD and other neurological diseases. PMID:23509976

  17. Cancer-linked targets modulated by curcumin

    PubMed Central

    Hasima, Noor; Aggarwal, Bharat B

    2012-01-01

    In spite of major advances in oncology, the World Health Organization predicts that cancer incidence will double within the next two decades. Although it is well understood that cancer is a hyperproliferative disorder mediated through dysregulation of multiple cell signaling pathways, most cancer drug development remains focused on modulation of specific targets, mostly one at a time, with agents referred to as “targeted therapies,” “smart drugs,” or “magic bullets.” How many cancer targets there are is not known, and how many targets must be attacked to control cancer growth is not well understood. Although more than 90% of cancer-linked deaths are due to metastasis of the tumor to vital organs, most drug targeting is focused on killing the primary tumor. Besides lacking specificity, the targeted drugs induce toxicity and side effects that sometimes are greater problems than the disease itself. Furthermore, the cost of some of these drugs is so high that most people cannot afford them. The present report describes the potential anticancer properties of curcumin, a component of the Indian spice turmeric (Curcuma longa), known for its safety and low cost. Curcumin can selectively modulate multiple cell signaling pathways linked to inflammation and to survival, growth, invasion, angiogenesis, and metastasis of cancer cells. More clinical trials of curcumin are needed to prove its usefulness in the cancer setting. PMID:23301199

  18. Curcumin Suppressed Activation of Dendritic Cells via JAK/STAT/SOCS Signal in Mice with Experimental Colitis

    PubMed Central

    Zhao, Hai-Mei; Xu, Rong; Huang, Xiao-Ying; Cheng, Shao-Min; Huang, Min-Fang; Yue, Hai-Yang; Wang, Xin; Zou, Yong; Lu, Ai-Ping; Liu, Duan-Yong

    2016-01-01

    Dendritic cells (DCs) play a pivotal role as initiators in the pathogenesis of inflammatory bowel disease and are regulated by the JAK/STAT/SOCS signaling pathway. As a potent anti-inflammatory compound, curcumin represents a viable treatment alternative or adjunctive therapy in the management of chronic inflammatory bowel disease (IBD). The mechanism of curcumin treated IBD on DCs is not completely understood. In the present study, we explored the mechanism of curcumin treated experimental colitis by observing activation of DCs via JAK/STAT/SOCS signaling pathway in colitis mice. Experimental colitis was induced by 2, 4, 6-trinitrobenzene sulfonic acid. After 7 days treatment with curcumin, its therapeutic effect was verified by decreased colonic weight, histological scores, and remitting pathological injury. Meanwhile, the levels of major histocompatibility complex class II and DC costimulatory molecules (CD83, CD28, B7-DC, CD40, CD40 L, and TLR2) were inhibited and followed the up-regulated levels of IL-4, IL-10, and IFN-γ, and down-regulated GM-CSF, IL-12p70, IL-15, IL-23, and TGF-β1. A key finding was that the phosphorylation of the three members (JAK2, STAT3, and STAT6) of the JAK/STAT/SOCS signaling pathway was inhibited, and the three downstream proteins (SOCS1, SOCS3, and PIAS3) from this pathway were highly expressed. In conclusion, curcumin suppressed the activation of DCs by modulating the JAK/STAT/SOCS signaling pathway to restore immunologic balance to effectively treat experimental colitis. PMID:27932984

  19. Stabilisation of Laryngeal AL Amyloidosis with Long Term Curcumin Therapy

    PubMed Central

    Golombick, Terry; Diamond, Terrence H.; Manoharan, Arumugam; Ramakrishna, Rajeev

    2015-01-01

    Multiple myeloma (MM), smoldering myeloma (SMM), and monoclonal gammopathy of undetermined significance (MGUS) represent a spectrum of plasma cell dyscrasias (PCDs). Immunoglobulin light chain amyloidosis (AL) falls within the spectrum of these diseases and has a mortality rate of more than 80% within 2 years of diagnosis. Curcumin, derived from turmeric, has been shown to have a clinical benefit in some patients with PCDs. In addition to a clinical benefit in these patients, curcumin has been found to have a strong affinity for fibrillar amyloid proteins. We thus administered curcumin to a patient with laryngeal amyloidosis and smoldering myeloma and found that the patient has shown a lack of progression of his disease for a period of five years. This is in keeping with our previous findings of clinical benefits of curcumin in patients with plasma cell dyscrasias. We recommend further evaluation of curcumin in patients with primary AL amyloidosis. PMID:26199769

  20. Hydrophobic kenaf nanocrystalline cellulose for the binding of curcumin.

    PubMed

    Zainuddin, Norhidayu; Ahmad, Ishak; Kargarzadeh, Hanieh; Ramli, Suria

    2017-05-01

    Nanocrystalline cellulose (NCC) extracted from lignocellulosic materials has been actively investigated as a drug delivery excipients due to its large surface area, high aspect ratio, and biodegradability. In this study, the hydrophobically modified NCC was used as a drug delivery excipient of hydrophobic drug curcumin. The modification of NCC with a cationic surfactant, cetyl trimethylammonium bromide (CTAB) was used to modulate the loading of hydrophobic drugs that would not normally bind to NCC. The FTIR, Elemental analysis, XRD, TGA, and TEM were used to confirm the modification of NCC with CTAB. The effect of concentration of CTAB on the binding efficiency of hydrophobic drug curcumin was investigated. The amounts of curcumin bound onto the CTAB-NCC nanoparticles were analyzed by UV-vis Spectrophotometric. The result showed that the modified CTAB-NCC bound a significant amount of curcumin, in a range from 80% to 96% curcumin added. Nevertheless, at higher concentration of CTAB resulted in lower binding efficiency.

  1. Learning by Analogy: Discriminating between Potential Analogs

    ERIC Educational Resources Information Center

    Richland, Lindsey E.; McDonough, Ian M.

    2010-01-01

    The ability to successfully discriminate between multiple potentially relevant source analogs when solving new problems is crucial to proficiency in a mathematics domain. Experimental findings in two different mathematical contexts demonstrate that providing cues to support comparative reasoning during an initial instructional analogy, relative to…

  2. Telomerase: a target for therapeutic effects of curcumin and a curcumin derivative in Aβ1-42 insult in vitro.

    PubMed

    Xiao, Zijian; Zhang, Aiwu; Lin, Jianwen; Zheng, Zhenyang; Shi, Xiaolei; Di, Wei; Qi, Weiwei; Zhu, Yingting; Zhou, Guijuan; Fang, Yannan

    2014-01-01

    This study was designed to investigate whether telomerase was involved in the neuroprotective effect of curcumin and Cur1. Alzheimer's disease is a consequence of an imbalance between the generation and clearance of amyloid-beta peptide in the brain. In this study, we used Aβ1-42 (10 µg/ml) to establish a damaged cell model, and curcumin and Cur1 were used in treatment groups. We measured cell survival and cell growth, intracellular oxidative stress and hTERT expression. After RNA interference, the effects of curcumin and Cur1 on cells were verified. Exposure to Aβ1-42 resulted in significant oxidative stress and cell toxicity, and the expression of hTERT was significantly decreased. Curcumin and Cur1 both protected SK-N-SH cells from Aβ1-42 and up-regulated the expression of hTERT. Furthermore, Cur1 demonstrated stronger protective effects than curcumin. However, when telomerase was inhibited by TERT siRNA, the neuroprotection by curcumin and Cur1 were ceased. Our study indicated that the neuroprotective effects of curcumin and Cur1 depend on telomerase, and thus telomerase may be a target for therapeutic effects of curcumin and Cur1.

  3. Molecular complexation of curcumin with pH sensitive cationic copolymer enhances the aqueous solubility, stability and bioavailability of curcumin.

    PubMed

    Kumar, Sunny; Kesharwani, Siddharth S; Mathur, Himanshi; Tyagi, Mohit; Bhat, G Jayarama; Tummala, Hemachand

    2016-01-20

    Curcumin is a natural dietary compound with demonstrated potential in preventing/treating several chronic diseases in animal models. However, this success is yet to be translated to humans mainly because of its poor oral bioavailability caused by extremely low water solubility. This manuscript demonstrates that water insoluble curcumin (~1μg/ml) forms highly aqueous soluble complexes (>2mg/ml) with a safe pH sensitive polymer, poly(butyl-methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl-methacrylate) when precipitated together in water. The complexation process was optimized to enhance curcumin loading by varying several formulation factors. Acetone as a solvent and polyvinyl alcohol as a stabilizer with 1:2 ratio of drug to polymer yielded complexes with relatively high loading (~280μg/ml) and enhanced solubility (>2mg/ml). The complexes were amorphous in solid and were soluble only in buffers with pHs less than 5.0. Hydrogen bond formation and hydrophobic interactions between curcumin and the polymer were recorded by infrared spectroscopy and nuclear magnetic resonance spectroscopy, respectively. Molecular complexes of curcumin were more stable at various pHs compared to unformulated curcumin. In mice, these complexes increased peak plasma concentration of curcumin by 6 times and oral bioavailability by ~20 times. This is a simple, economic and safer strategy of enhancing the oral bioavailability of curcumin.

  4. Polyhydroxycurcuminoids but not curcumin upregulate neprilysin and can be applied to the prevention of Alzheimer’s disease

    PubMed Central

    Chen, Po-Ting; Chen, Zih-ten; Hou, Wen-Chi; Yu, Lung-Chih; Chen, Rita P.-Y.

    2016-01-01

    Neprilysin (NEP) is the most important Aβ-degrading enzyme. Its expression level decreases with age and inversely correlated with amyloid accumulation, suggesting its correlation with the late-onset of Alzheimer’s disease. Recently, many reports showed that upregulating NEP level is a promising strategy in the prevention and therapy of Alzheimer’s disease. Here, we used a sensitive fluorescence-based Aβ digestion assay to screen 25 curcumin analogs for their ability to upregulate NEP activity. To our surprise, four compounds, dihydroxylated curcumin, monohydroxylated demethoxycurcumin, and mono- and di-hydroxylated bisdemethoxycurcumin, increased NEP activity, while curcumin did not. The ability of these polyhydroxycurcuminoids to upregulate NEP was further confirmed by mRNA and protein expression levels in the cell and mouse models. Finally, feeding monohydroxylated demethoxycurcumin (also named demethylcurcumin) or dihydroxylated bisdemethoxycurcumin (also named bisdemethylcurcumin) to APPswe/PS1dE9 double transgenic mice upregulated NEP levels in the brain and reduced Aβ accumulation in the hippocampus and cortex. These polyhydroxycurcuminoids offer hope in the prevention of Alzheimer’s disease. PMID:27407064

  5. Binding sites of resveratrol, genistein, and curcumin with milk α- and β-caseins.

    PubMed

    Bourassa, P; Bariyanga, J; Tajmir-Riahi, H A

    2013-02-07

    The binding sites of antioxidant polyphenols resveratrol, genistein, and curcumin are located with milk α- and β-caseins in aqueous solution. FTIR, CD, and fluorescence spectroscopic methods and molecular modeling were used to analyze polyphenol binding sites, the binding constant, and the effects of complexation on casein stability and conformation. Structural analysis showed that polyphenols bind casein via hydrophilic and hydrophobic interactions with the number of bound polyphenol molecules (n) 1.20 for resveratrol, 1.42 for genistein, and 1.43 for curcumin with α-casein and 1.14 for resveratrol, 1.27 for genistein, and 1.27 for curcumin with β-casein. The overall binding constants of the complexes formed are K(res-α-casein) = 1.9 (±0.6) × 10(4) M(-1), K(gen-α-casein) = 1.8 (±0.4) × 10(4) M(-1), and K(cur-α-casein) = 2.8 (±0.8) × 10(4) M(-1) with α-casein and K(res-β-casein) = 2.3 (±0.3) × 10(4) M(-1), K(gen-β-casein) = 3.0 (±0.5) × 10(4) M(-1), and K(cur-β-casein) = 3.1 (±0.5) × 10(4) M(-1) for β-casein. Molecular modeling showed the participation of several amino acids in polyphenol-protein complexes, which were stabilized by the hydrogen bonding network with the free binding energy of -11.56 (resveratrol-α-casein), -12.35 (resveratrol-β-casein), -9.68 (genistein-α-casein), -9.97 (genistein-β-casein), -8.89 (curcumin-α-casein), and -10.70 kcal/mol (curcumin-β-casein). The binding sites of polyphenols are different with α- and β-caseins. Polyphenol binding altered casein conformation with reduction of α-helix, indicating a partial protein destabilization. Caseins might act as carriers to transport polyphenol in vitro.

  6. Natural derivatives of curcumin attenuate the Wnt/{beta}-catenin pathway through down-regulation of the transcriptional coactivator p300

    SciTech Connect

    Ryu, Min-Jung; Cho, Munju; Song, Jie-Young; Yun, Yeon-Sook; Choi, Il-Whan; Kim, Dong-Eun; Park, Byeoung-Soo; Oh, Sangtaek

    2008-12-26

    Curcumin, a component of turmeric (Curcuma longa), has been reported to suppress {beta}-catenin response transcription (CRT), which is aberrantly activated in colorectal cancer. However, the effects of its natural analogs (demethoxycurcumin [DMC] and bisdemethoxycurcumin [BDMC]) and metabolite (tetrahydrocurcumin [THC]) on the Wnt/{beta}-catenin pathway have not been investigated. Here, we show that DMC and BDMC suppressed CRT that was activated by Wnt3a conditioned-medium (Wnt3a-CM) without altering the level of intracellular {beta}-catenin, and inhibited the growth of various colon cancer cells, with comparable potency to curcumin. Additionally, DMC and BDMC down-regulated p300, which is a positive regulator of the Wnt/{beta}-catenin pathway. Notably, THC also inhibited CRT and cell proliferation, but to a much lesser degree than curcumin, DMC, or BDMC, indicating that the conjugated bonds in the central seven-carbon chain of curcuminoids are essential for the inhibition of Wnt/{beta}-catenin pathway and the anti-proliferative activity of curcuminoids. Thus, our findings suggest that curcumin derivatives inhibit the Wnt/{beta}-catenin pathway by decreasing the amount of the transcriptional coactivator p300.

  7. A Comparison between the cytotoxic effects of pure curcumin and curcumin-loaded PLGA-PEG nanoparticles on the MCF-7 human breast cancer cell line.

    PubMed

    Tabatabaei Mirakabad, Fatemeh Sadat; Akbarzadeh, Abolfazl; Milani, Morteza; Zarghami, Nosratollah; Taheri-Anganeh, Mortaza; Zeighamian, Vahideh; Badrzadeh, Fariba; Rahmati-Yamchi, Mohammad

    2016-01-01

    Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among women worldwide. Herbal medicines have tremendous potential as promising agents for the treatment of cancer. Curcumin is a natural polyphenol which has many anticancer effects. Because of its low aqueous solubility, low bioavailability, and quick degradation and metabolism, curcumin was released using PLGA-PEG nanoparticles. Herein, the efficiency of pure curcumin and curcumin-loaded PLGA-PEG in MCF-7 human breast cancer cell lines was studied. (1)H NMR, FT-IR and SEM demonstrated PLGA-PEG structure and curcumin loaded on nanoparticles. Subsequently, the cytotoxic effects of free curcumin and curcumin-loaded PLGA-PEG were determined via an MTT assay. Our study confirmed that curcumin-loaded PLGA-PEG has more cytotoxic effects on the MCF-7 breast cancer cell line and could be exploited as a potential source for developing novel drugs against breast cancer.

  8. Comparative analysis of protective effects of curcumin, curcumin-β-cyclodextrin nanoparticle and nanoliposomal curcumin on unsymmetrical dimethyl hydrazine poisoning in mice.

    PubMed

    Li, Wei; Zhou, Mengzhou; Xu, Ning; Hu, Yong; Wang, Chao; Li, Deyuan; Liu, Liegang; Li, Dongsheng

    2016-09-02

    The aim of this study was to compare the protective effects of curcumin, curcumin-β-cyclodextrin nanoparticle curcumin (BCD-CUR) and nanoliposomal curcumin (NLC) on unsymmetrical dimethylhydrazine (UDMH) induced poison in mice. Curcumin, BCD-CUR, and NLC were prepared and their properties of zeta potential, particle size, encapsulation efficiency, and loading capacity were characterized. Eighty-eight male ICR mice on normal chow diet were randomly divided into 11 groups, and intraperitoneally injected with UDMH alone, or together with different doses of curcumin, BCD-CUR or NLC daily for up to 10 d. Enzyme activities of serum alanine transaminase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were analyzed by fully-automatic analyzer and neurotransmitter levels were determined with high performance liquid chromatography (HPLC). 150 mg/kg curcumin treatment alone significantly reduced levels of serum ALT and LDH that were induced by UDMH and markedly increased level of γ-amino butyric acid (GABA) that were reduced by UDMH in the hippocampus. 150 mg/kg BCD-CUR not only decreased significantly the increase of ALT, LDH and glutamate (Glu) but also recovered levels of AST and GABA. 150 mg/kg NLC recovered profoundly levels of AST and GABA while decreased remarkably the UDMH induced increase of ALT, LDH, Glu and 5-hydroxytryptamine (5-HT). In addition, treatments with all tested doses of NLC significantly reduced the UMDH induced dopamine (DA), the monoamine neurotransmitter. NLC had more profound protective effects against liver and central nervous system injury induced by UDMH than a suspension of BCD-CUR or curcumin did in mice.

  9. Continuous Production of Aqueous Suspensions of Ultra-fine Particles of Curcumin using Ultrasonically Driven Mixing Device.

    PubMed

    Pandey, Komal; Chatte, Amruta B; Dalvi, Sameer V

    2017-04-03

    Developing drug formulations for poorly water soluble drugs is a major challenge for pharmaceutical industries as the poor water solubility limits bioavailability of these drugs. Production of nanoparticles/microparticles of these drugs is one of the ways to improve dissolution rates by increasing interfacial area for dissolution. Curcumin, a compound obtained from the rhizome of curcuma longa (turmeric roots), is a pharmaceutically viable molecule. However, poor aqueous solubility limits its therapeutic use. In this work, we report studies conducted to continuously produce aqueous suspensions of curcumin nano/micro particles. Influence of process parameters such as ultrasound, additives and solvent to antisolvent ratio on polymorphic outcome and morphology of precipitated particles has been investigated. Ultrasound was found to greatly influence the polymorphic form and the morphology of precipitated particles. Nucleation rates, mixing time and solid-liquid interfacial energies were also estimated to understand the effect of various processing parameters on the precipitation process.

  10. Radioactive Decay - An Analog.

    ERIC Educational Resources Information Center

    McGeachy, Frank

    1988-01-01

    Presents an analog of radioactive decay that allows the student to grasp the concept of half life and the exponential nature of the decay process. The analog is devised to use small, colored, plastic poker chips or counters. Provides the typical data and a graph which supports the analog. (YP)

  11. The Analogical Mind.

    ERIC Educational Resources Information Center

    Holyoak, Keith J.; Thagard, Paul

    1997-01-01

    The use of analogy in human thinking is examined from the perspective of a multiconstraint theory that postulates similarity, structure, and purpose as three kinds of constraints. The theory has been implemented in computational simulations of the analogical human mind using the Analogical Mapping by Constraint Satisfaction (ACME) model. (SLD)

  12. Enhanced bioavailability and bioefficacy of an amorphous solid dispersion of curcumin.

    PubMed

    Chuah, Ai Mey; Jacob, Bindya; Jie, Zhang; Ramesh, Subbarayan; Mandal, Shibajee; Puthan, Jithesh K; Deshpande, Parag; Vaidyanathan, Vadakkanchery V; Gelling, Richard W; Patel, Gaurav; Das, Tapas; Shreeram, Sathyavageeswaran

    2014-08-01

    Curcumin has been shown to have a wide variety of biological activities for various human diseases including inflammation, diabetes and cancer. However, the poor oral bioavailability of curcumin poses a significant pharmacological barrier to its use therapeutically and/or as a functional food. Here we report the evaluation of the bioavailability and bio-efficacy of curcumin as an amorphous solid dispersion (ASD) in a matrix consisting of hydroxypropyl methyl cellulose (HPMC), lecithin and isomalt using hot melt extrusion for application in food products. Oral pharmacokinetic studies in rats showed that ASD curcumin was ∼13-fold more bioavailable compared to unformulated curcumin. Evaluation of the anti-inflammatory activity of ASD curcumin in vivo demonstrated enhanced bio-efficacy compared to unformulated curcumin at 10-fold lower dose. Thus ASD curcumin provides a more potent and efficacious formulation of curcumin which may also help in masking the colour, taste and smell which currently limit its application as a functional food ingredient.

  13. Curcumin Ameliorates Diabetic Nephropathy by Suppressing NLRP3 Inflammasome Signaling.

    PubMed

    Lu, Miaomiao; Yin, Nanchang; Liu, Wei; Cui, Xiangfei; Chen, Shuo; Wang, Ermin

    2017-01-01

    Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, partly because of the lack of effective treatments for DN. Curcumin has been shown to exert strong antifibrotic effects in DN, but the underlying mechanisms are not well characterized. In this study, we sought to determine the effects of curcumin on diabetic renal disease in db/db mice and characterize the underlying mechanism of action. We administered curcumin to db/db mice for 16 weeks. In comparison to mock-treated db/db mice, curcumin-treated mice showed diminished renal hypertrophy, reduced mesangial matrix expansion, and a lower level of albuminuria. Furthermore, the upregulated protein and mRNA expressions of collagen IV and fibronectin in the renal cortices of the db/db mice were inhibited by curcumin treatment. Additionally, curcumin treatment was associated with significant reductions in mature interleukin-1β, cleaved caspase-1, and NLRP3 protein levels in the renal cortices of db/db mice as well as in HK-2 cells exposed to high glucose concentration. In summary, curcumin, a potent antifibrotic agent, is a promising treatment for DN, and its renoprotective effects appear to be mediated by the inhibition of NLRP3 inflammasome activity.

  14. Effects of curcumin (diferuloylmethane) on Eimeria tenella sporozoites in vitro.

    PubMed

    Khalafalla, Reda E; Müller, Uwe; Shahiduzzaman, Md; Dyachenko, Viktor; Desouky, Abdelrazik Y; Alber, Gottfried; Daugschies, Arwid

    2011-04-01

    The negative effects of coccidiosis on poultry health and productivity and increasing problems related to drug resistance have stimulated the search for novel and alternative methods of control. The present study evaluates the anticoccidial activity of curcumin (diferuloylmethane), a natural polyphenolic compound abundant in the rhizome of the perennial herb turmeric (Curcuma longa) which is a spice and food colorant commonly used in curries and also used as medicinal herb. Its effects were evaluated on Eimeria tenella sporozoites, including morphological alterations, sporozoite viability and infectivity to Madin-Darby bovine kidney (MDBK) cells. Morphological alterations of the sporozoites were recorded as deformation due to swelling and cell membrane corrugations. Curcumin at concentrations of 25, 50, 100, 200 and 400 μM showed considerable effects on sporozoite morphology and viability in a dose-dependent manner after incubation over 3, 6, 18 and 24 h while lower curcumin concentrations (6.25 and 12.5 μM) were not effective. In comparison to the untreated control, sporozoite infectivity was reduced at curcumin concentrations of 100 and 200 μM by 41.6% and 72.8%, respectively. Negative effects of curcumin on MDBK cells were not seen at these concentrations; however, curcumin at concentrations of 1,800, 600 and 400 μM was toxic to MDBK cells and affected cell proliferation. In conclusion, curcumin exhibited a marked inhibitory effect in vitro on E. tenella sporozoites inducing morphological changes and reducing sporozoite viability and infectivity.

  15. Curcumin Binding to Beta Amyloid: A Computational Study.

    PubMed

    Rao, Praveen P N; Mohamed, Tarek; Teckwani, Karan; Tin, Gary

    2015-10-01

    Curcumin, a chemical constituent present in the spice turmeric, is known to prevent the aggregation of amyloid peptide implicated in the pathophysiology of Alzheimer's disease. While curcumin is known to bind directly to various amyloid aggregates, no systematic investigations have been carried out to understand its ability to bind to the amyloid aggregates including oligomers and fibrils. In this study, we constructed computational models of (i) Aβ hexapeptide (16) KLVFFA(21) octamer steric-zipper β-sheet assembly and (ii) full-length Aβ fibril β-sheet assembly. Curcumin binding in these models was evaluated by molecular docking and molecular dynamics (MD) simulation studies. In both the models, curcumin was oriented in a linear extended conformation parallel to fiber axis and exhibited better stability in the Aβ hexapeptide (16) KLVFFA(21) octamer steric-zipper model (Ebinding  = -10.05 kcal/mol) compared to full-length Aβ fibril model (Ebinding  = -3.47 kcal/mol). Analysis of MD trajectories of curcumin bound to full-length Aβ fibril shows good stability with minimum Cα-atom RMSD shifts. Interestingly, curcumin binding led to marked fluctuations in the (14) HQKLVFFA(21) region that constitute the fibril spine with RMSF values ranging from 1.4 to 3.6 Å. These results show that curcumin binding to Aβ shifts the equilibrium in the aggregation pathway by promoting the formation of non-toxic aggregates.

  16. Curcumin Ameliorates Diabetic Nephropathy by Suppressing NLRP3 Inflammasome Signaling

    PubMed Central

    Yin, Nanchang; Liu, Wei; Cui, Xiangfei; Chen, Shuo; Wang, Ermin

    2017-01-01

    Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, partly because of the lack of effective treatments for DN. Curcumin has been shown to exert strong antifibrotic effects in DN, but the underlying mechanisms are not well characterized. In this study, we sought to determine the effects of curcumin on diabetic renal disease in db/db mice and characterize the underlying mechanism of action. We administered curcumin to db/db mice for 16 weeks. In comparison to mock-treated db/db mice, curcumin-treated mice showed diminished renal hypertrophy, reduced mesangial matrix expansion, and a lower level of albuminuria. Furthermore, the upregulated protein and mRNA expressions of collagen IV and fibronectin in the renal cortices of the db/db mice were inhibited by curcumin treatment. Additionally, curcumin treatment was associated with significant reductions in mature interleukin-1β, cleaved caspase-1, and NLRP3 protein levels in the renal cortices of db/db mice as well as in HK-2 cells exposed to high glucose concentration. In summary, curcumin, a potent antifibrotic agent, is a promising treatment for DN, and its renoprotective effects appear to be mediated by the inhibition of NLRP3 inflammasome activity. PMID:28194406

  17. Antibacterial Action of Curcumin against Staphylococcus aureus: A Brief Review

    PubMed Central

    Liew, Kitson; Ali, Syed A.; Khoo, Alan Soo-Beng; Peh, Suat-Cheng

    2016-01-01

    Curcumin, the major constituent of Curcuma longa L. (Zingiberaceae family) or turmeric, commonly used for cooking in Asian cuisine, is known to possess a broad range of pharmacological properties at relatively nontoxic doses. Curcumin is found to be effective against Staphylococcus aureus (S. aureus). As demonstrated by in vitro experiment, curcumin exerts even more potent effects when used in combination with various other antibacterial agents. Hence, curcumin which is a natural product derived from plant is believed to have profound medicinal benefits and could be potentially developed into a naturally derived antibiotic in the future. However, there are several noteworthy challenges in the development of curcumin as a medicine. S. aureus infections, particularly those caused by the multidrug-resistant strains, have emerged as a global health issue and urgent action is needed. This review focuses on the antibacterial activities of curcumin against both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). We also attempt to highlight the potential challenges in the effort of developing curcumin into a therapeutic antibacterial agent. PMID:27956904

  18. DNA damage in mouse lymphocytes exposed to curcumin and copper.

    PubMed

    Urbina-Cano, Patricia; Bobadilla-Morales, Lucina; Ramírez-Herrera, Mario A; Corona-Rivera, Jorge R; Mendoza-Magaña, Maria L; Troyo-Sanromán, Rogelio; Corona-Rivera, Alfredo

    2006-01-01

    Dietary polyphenolics, such as curcumin, have shown antioxidant and anti-inflammatory effects. Some antioxidants cause DNA strand breaks in excess of transition metal ions, such as copper. The aim of this study was to evaluate the in vitro effect of curcumin in the presence of increasing concentrations of copper to induce DNA damage in murine leukocytes by the comet assay. Balb-C mouse lymphocytes were exposed to 50 microM curcumin and various concentrations of copper (10 microM, 100 microM and 200 microM). Cellular DNA damage was detected by means of the alkaline comet assay. Our results show that 50 microM curcumin in the presence of 100-200 microM copper induced DNA damage in murine lymphocytes. Curcumin did not inhibit the oxidative DNA damage caused by 50 microM H2O2 in mouse lymphocytes. Moreover, 50 microM curcumin alone was capable of inducing DNA strand breaks under the tested conditions. The increased DNA damage by 50 mM curcumin was observed in the presence of various concentrations of copper, as detected by the alkaline comet assay.

  19. The Potential of Curcumin in Treatment of Spinal Cord Injury

    PubMed Central

    Sanivarapu, Raghavendra; Vallabhaneni, Vijayalakshmi; Verma, Vivek

    2016-01-01

    Current treatment for spinal cord injury (SCI) is supportive at best; despite great efforts, the lack of better treatment solutions looms large on neurological science and medicine. Curcumin, the active ingredient in turmeric, a spice known for its medicinal and anti-inflammatory properties, has been validated to harbor immense effects for a multitude of inflammatory-based diseases. However, to date there has not been a review on curcumin's effects on SCI. Herein, we systematically review all known data on this topic and juxtapose results of curcumin with standard therapies such as corticosteroids. Because all studies that compare the two show superior results for curcumin over corticosteroids, it could be true that curcumin better acts at the inflammatory source of SCI-mediated neurological injury, although this question remains unanswered in patients. Because curcumin has shown improvements from current standards of care in other diseases with few true treatment options (e.g., osteoarthritis), there is immense potential for this compound in treating SCI. We critically and systematically summarize available data, discuss clinical implications, and propose further testing of this well-tolerated compound in both the preclinical and the clinical realms. Analyzing preclinical data from a clinical perspective, we hope to create awareness of the incredible potential that curcumin shows for SCI in a patient population that direly needs improvements on current therapy. PMID:27298735

  20. New Curcumin-Loaded Chitosan Nanocapsules: In Vivo Evaluation.

    PubMed

    Marin, Edgar; Briceño, Maria Isabel; Torres, Alicia; Caballero-George, Catherina

    2017-03-06

    The medicinal applications of curcumin, the major component of Curcuma longa, are limited by its poor solubility and low oral bioavailability. In order to overcome this limitation, a method to produce nanocapsules of chitosan loaded with curcumin was developed. Three different molecular weight and deacetylation degree chitosan polymers were used in the formulation in order to prepare curcumin-loaded nanocapsules (mass ratio 1 : 1.4). The best results were achieved using chitosan-Bi with a molecular weight of 710 000 Da. A bimodal distribution was observed in samples; moreover, chitosan-Bi produced the lowest particle size (197 nm). The entrapment efficacy of all chitosan nanocapsules produced reached values between 75 and 92 %. Their rate of drug release at different pH levels (2.0 and 7.4) showed a fast onset of curcumin release. Swiss mice were used to determine oral and total bioavailability of the new curcumin-loaded nanocapsules. Remarkably, the bioavailability of curcumin nanoformulated increased 9-fold compared with no formulated curcumin. These nanocapsules have the ability to cross the blood-brain barrier, and its production is an easy to scale-up procedure using nontoxic materials.

  1. Overdose Intake of Curcumin Initiates the Unbalanced State of Bodies.

    PubMed

    Qiu, Peiyu; Man, Shuli; Li, Jing; Liu, Jing; Zhang, Liming; Yu, Peng; Gao, Wenyuan

    2016-04-06

    Curcumin is the major active component of turmeric and widely used as a spice and coloring agent in food. However, its safety evaluation has been little investigated. To evaluate the 90-day subchronic toxicity of curcumin in rats, its general observation, clinical biochemistry, pathology, and metabolomics were evaluated. The results showed that curcumin induced liver injury through the generation of the overexpression of reactive oxygen species (ROS) and pro-inflammatory cytokines IL-6 and the decreases of the levels of antioxidant enzyme SOD and detoxified enzyme GST. Meanwhile, for the self-protection of rats, curcumin treatment activated the transcription of Nrf-2 and elevated the expression of HO-1 to reduce tissue damage. Furthermore, curcumin significantly increased key mRNA levels of HK2, PKM2, LDHA, CES, Cpt1, Cpt2, FASN, and ATP5b and decreased levels of GLUT2 and ACC1 to enhance glycolysis and inhibit lipid metabolism and TCA cycle. Therefore, overdose or long-term intake of curcumin could initiate the unbalanced state of bodies through oxidative stress, inflammation, and metabolic disorders, which induces liver injury. Intermittent administration of curcumin is necessary in our daily lives.

  2. Modulation of Erythrocyte Plasma Membrane Redox System Activity by Curcumin

    PubMed Central

    Singh, Prabhakar; Kesharwani, Rajesh Kumar; Misra, Krishna; Rizvi, Syed Ibrahim

    2016-01-01

    Plasma membrane redox system (PMRS) is an electron transport chain system ubiquitously present throughout all cell types. It transfers electron from intracellular substrates to extracellular acceptors for regulation of redox status. Curcumin, isolated from Curcuma longa, has modulatory effects on cellular physiology due to its membrane interaction ability and antioxidant potential. The present study investigates the effect of curcumin on PMRS activity of erythrocytes isolated from Wistar rats in vitro and in vivo and validated through an in silico docking simulation study using Molegro Virtual Docker (MVD). Effects of curcumin were also evaluated on level of glutathione (GSH) and the oxidant potential of plasma measured in terms of plasma ferric equivalent oxidative potentials (PFEOP). Results show that curcumin significantly (p < 0.01) downregulated the PMRS activity in a dose-dependent manner. Molecular docking results suggest that curcumin interacts with amino acids at the active site cavity of cytochrome b5 reductase, a key constituent of PMRS. Curcumin also increased the GSH level in erythrocytes and plasma while simultaneously decreasing the oxidant potential (PFEOP) of plasma. Altered PMRS activity and redox status are associated with the pathophysiology of several health complications including aging and diabetes; hence, the above finding may explain part of the role of curcumin in health beneficial effects. PMID:26904287

  3. Modulatory effect of curcumin on survival of irradiated human intestinal microvascular endothelial cells: role of Akt/mTOR and NF-κB

    PubMed Central

    Binion, David G.; Wellner, Michael; Behmaram, Behnaz; Floer, Martin; Mitton, Elizabeth; Nie, Linghui; Zhang, Zhihong; Otterson, Mary F.

    2010-01-01

    Radiation therapy is an essential modality in the treatment of colorectal cancers. Radiation exerts an antiangiogenic effect on tumors, inhibiting endothelial proliferation and survival in the tumor microvasculature. However, damage from low levels of irradiation can induce a paradoxical effect, stimulating survival in endothelial cells. We used human intestinal microvascular endothelial cells (HIMEC) to define effects of radiation on these gut-specific endothelial cells. Low-level irradiation (1–5 Gy) activates NF-κB and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which is involved in cell cycle reentry and cell survival in HIMEC. A downstream target of PI3K/Akt is mammalian target of rapamycin (mTOR), which contributes to endothelial proliferation and angiogenesis. The aim of this study was to investigate the signaling molecules involved in the radiosensitizing effects of curcumin on HIMEC subjected to low levels of irradiation. We have demonstrated that exposure of HIMEC to low levels of irradiation induced Akt and mTOR phosphorylation, which was attenuated by curcumin, rapamycin, LY294002, and mTOR small interference RNA (siRNA). Activation of NF-κB by low levels of irradiation was inhibited by curcumin, SN-50, and mTOR siRNA. Curcumin also induced apoptosis by induction of caspase-3 cleavage in irradiated HIMEC. In conclusion, curcumin significantly inhibited NF-κB and attenuated the effect of irradiation-induced prosurvival signaling through the PI3K/Akt/mTOR and NF-κB pathways in these gut-specific endothelial cells. Curcumin may be a potential radiosensitizing agent for enhanced antiangiogenic effect in colorectal cancer radiation therapy. PMID:20299603

  4. Curcumin counteracts loss of force and atrophy of hindlimb unloaded rat soleus by hampering neuronal nitric oxide synthase untethering from sarcolemma

    PubMed Central

    Vitadello, Maurizio; Germinario, Elena; Ravara, Barbara; Libera, Luciano Dalla; Danieli-Betto, Daniela; Gorza, Luisa

    2014-01-01

    Antioxidant administration aimed to antagonize the development and progression of disuse muscle atrophy provided controversial results. Here we investigated the effects of curcumin, a vegetal polyphenol with pleiotropic biological activity, because of its ability to upregulate glucose-regulated protein 94 kDa (Grp94) expression in myogenic cells. Grp94 is a sarco-endoplasmic reticulum chaperone, the levels of which decrease significantly in unloaded muscle. Rats were injected intraperitoneally with curcumin and soleus muscle was analysed after 7 days of hindlimb unloading or standard caging. Curcumin administration increased Grp94 protein levels about twofold in muscles of ambulatory rats (P < 0.05) and antagonized its decrease in unloaded ones. Treatment countered loss of soleus mass and myofibre cross-sectional area by approximately 30% (P ≤ 0.02) and maintained a force–frequency relationship closer to ambulatory levels. Indexes of muscle protein and lipid oxidation, such as protein carbonylation, revealed by Oxyblot, and malondialdehyde, measured with HPLC, were significantly blunted in unloaded treated rats compared to untreated ones (P = 0.01). Mechanistic involvement of Grp94 was suggested by the disruption of curcumin-induced attenuation of myofibre atrophy after transfection with antisense grp94 cDNA and by the drug-positive effect on the maintenance of the subsarcolemmal localization of active neuronal nitric oxide synthase molecules, which were displaced to the sarcoplasm by unloading. The absence of additive effects after combined administration of a neuronal nitric oxide synthase inhibitor further supported curcumin interference with this pro-atrophic pathway. In conclusion, curcumin represents an effective and safe tool to upregulate Grp94 muscle levels and to maintain muscle function during unweighting. PMID:24710058

  5. Curcumin-induced degradation of ErbB2: A role for the E3 ubiquitin ligase CHIP and the Michael reaction acceptor activity of curcumin.

    PubMed

    Jung, Yunjin; Xu, Wanping; Kim, Heejung; Ha, Namchul; Neckers, Len

    2007-03-01

    We investigated the molecular mechanism underlying curcumin depletion of ErbB2 protein. Curcumin induced ErbB2 ubiquitination but pretreatment with proteasome inhibitors neither prevented curcumin depletion of ErbB2 protein nor further accumulated ubiquitinated ErbB2. Curcumin increased association of endogenous and ectopically expressed CHIP, a chaperone-dependent ubiquitin ligase, with ErbB2. In COS7 cells cotransfected with ErbB2 and various CHIP plasmids followed by curcumin treatment, CHIP-H260Q (a mutant lacking ubiquitin ligase activity) promoted less curcumin-induced ErbB2 ubiquitination than did wild type CHIP, and CHIP-K30A (a mutant incapable of binding Hsp90 and Hsp70) neither associated with ErbB2 nor promoted its ubiquitination. ErbB2 mutants lacking the kinase domain failed to associate with CHIP and were completely resistant to ubiquitination and depletion induced by curcumin. Finally, curcumin's Michael reaction acceptor functionality was required for both covalent association of curcumin with ErbB2 and curcumin-mediated ErbB2 depletion. These data suggest (1) that CHIP-dependent ErbB2 ubiquitination is implicated in curcumin-stimulated ErbB2 depletion, and (2) that covalent modification of ErbB2 by curcumin is the proximal signal which initiates this process.

  6. Parenterally administrable nano-micelles of 3,4-difluorobenzylidene curcumin for treating pancreatic cancer.

    PubMed

    Kesharwani, Prashant; Banerjee, Sanjeev; Padhye, Subhash; Sarkar, Fazlul H; Iyer, Arun K

    2015-08-01

    Pancreatic cancer remains one of the most devastating diseases in terms of patient mortality rates for which current treatment options are very limited. 3,4-Difluorobenzylidene curcumin (CDF) is a nontoxic analog of curcumin (CMN) developed in our laboratory, which exhibits extended circulation half-life, while maintaining high anticancer activity and improved pancreas specific accumulation in vivo, compared with CMN. CDF however has poor aqueous solubility and its dose escalation for systemic administration remains challenging. We have engineered self-assembling nano-micelles of amphiphilic styrene-maleic acid copolymer (SMA) with CDF by non-covalent hydrophobic interactions. The SMA-CDF nano-micelles were characterized for size, charge, drug loading, release, serum stability, and in vitro anticancer activity. The SMA-CDF nano-micelles exhibited tunable CDF loading from 5 to 15% with excellent aqueous solubility, stability, favorable hemocompatibility and sustained drug release characteristics. The outcome of cytotoxicity testing of SMA-CDF nano-micelles on MiaPaCa-2 and AsPC-1 pancreatic cancer cell lines revealed pronounced antitumor response due to efficient intracellular trafficking of the drug loaded nano-micelles. Additionally, the nano-micelles are administrable via the systemic route for future in vivo studies and clinical translation. The currently developed SMA based nano-micelles thus portend to be a versatile carrier for dose escalation and targeted delivery of CDF, with enhanced therapeutic margin and safety.

  7. Protective role of curcumin in oxidative stress of breast cells.

    PubMed

    Calaf, Gloria M; Echiburú-Chau, Carlos; Roy, Debasish; Chai, Yunfei; Wen, Gengyun; Balajee, Adayabalam S

    2011-10-01

    Curcumin (diferuloylmethane) is a well known antioxidant that exerts anti-proliferative and apoptotic effects. The effects of curcumin were evaluated in a breast cancer model that was developed with the immortalized breast epithelial cell line, MCF-10F after exposure to low doses of high LET (linear energy transfer) α particles (150 keV/µm) of radiation, and subsequently cultured in the presence of 17β-estradiol (estrogen). This model consisted of human breast epithelial cells in different stages of transformation: i) a control cell line, MCF-10F, ii) an estrogen-treated cell line, named Estrogen, iii) a malignant cell line, named Alpha3 and iv) a malignant and tumorigenic, cell line named Alpha5. Curcumin decreased the formation of hydrogen peroxide in the control MCF-10F, Estrogen and Alpha5 cell lines in comparison to their counterparts. Curcumin had little effect on NFκB (50 kDa) but decreased the protein expression in the Estrogen cell line in comparison to their counterparts. Curcumin enhanced manganese superoxide dismutase (MnSOD) protein expression in the MCF-10F and Alpha3 cell lines. Results indicated that catalase protein expression increased in curcumin treated-Alpha3 and Alpha5 cell lines. Curcumin slightly decreased lipid peroxidation in the MCF-10F cell lines, but significantly (P<0.05) decreased it in the Alpha5 cell line treated with curcumin in comparison to their counterparts as demonstrated by the 8-iso-prostaglandin F2α (8-iso-PGF2α) levels. It can be concluded that curcumin acted upon oxidative stress in human breast epithelial cells transformed by the effect of radiation in the presence of estrogen.

  8. Curcumin shows excellent therapeutic effect on psoriasis in mouse model.

    PubMed

    Kang, Di; Li, Bowen; Luo, Lei; Jiang, Wenbing; Lu, Qiumin; Rong, Mingqing; Lai, Ren

    2016-04-01

    Curcumin is an active herbal ingredient possessing surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. Recently, it has been reported to exhibit inhibitory activity on potassium channel subtype Kv1.3. As Kv1.3 channels are mainly expressed in T cells and play a key role in psoriasis, the effects of curcumin were investigated on inflammatory factors secretion in T cells and psoriasis developed in keratin (K) 14-vascular endothelial growth factor (VEGF) transgenic mouse model. Results showed that, 10 μM of curcumin significantly inhibited secretion of inflammatory factors including interleukin (IL)-17,IL-22, IFN-γ, IL-2, IL-8 and TNF-α in T cells by 30-60% in vitro. Notably, more than 50% of T cells proliferation was inhibited by application of 100 μM curcumin. Compared with severe psoriatic symptoms observed in the negative control mice, all psoriasis indexes including ear redness, weight, thickness and lymph node weight were significantly improved by oral application of curcumin in treatment mouse group. Histological examination indicated that curcumin had anti-inflammatory function in the experimental animals. More than 50% level of inflammatory factors including TNF-α, IFN-γ, IL-2, IL-12, IL-22 and IL-23 in mouse serum was decreased by curcumin treatment as well as cyclosporine. Compared with renal fibrosis observed in the mouse group treated by cyclosporine, no obvious side effect in mouse kidney was found after treated by curcumin. Taken together, curcumin, with high efficacy and safety, has a great potential to treat psoriasis.

  9. Synthetic analogs of bacterial quorum sensors

    SciTech Connect

    Iyer, Rashi S.; Ganguly, Kumkum; Silks, Louis A.

    2013-01-08

    Bacterial quorum-sensing molecule analogs having the following structures: ##STR00001## and methods of reducing bacterial pathogenicity, comprising providing a biological system comprising pathogenic bacteria which produce natural quorum-sensing molecule; providing a synthetic bacterial quorum-sensing molecule having the above structures and introducing the synthetic quorum-sensing molecule into the biological system comprising pathogenic bacteria. Further is provided a method of targeted delivery of an antibiotic, comprising providing a synthetic quorum-sensing molecule; chemically linking the synthetic quorum-sensing molecule to an antibiotic to produce a quorum-sensing molecule-antibiotic conjugate; and introducing the conjugate into a biological system comprising pathogenic bacteria susceptible to the antibiotic.

  10. Synthetic analogs of bacterial quorum sensors

    SciTech Connect

    Iyer, Rashi; Ganguly, Kumkum; Silks, Louis A

    2011-12-06

    Bacterial quorum-sensing molecule analogs having the following structures: ##STR00001## and methods of reducing bacterial pathogenicity, comprising providing a biological system comprising pathogenic bacteria which produce natural quorum-sensing molecule; providing a synthetic bacterial quorum-sensing molecule having the above structures and introducing the synthetic quorum-sensing molecule into the biological system comprising pathogenic bacteria. Further is provided a method of targeted delivery of an antibiotic, comprising providing a synthetic quorum-sensing molecule; chemically linking the synthetic quorum-sensing molecule to an antibiotic to produce a quorum-sensing molecule-antibiotic conjugate; and introducing the conjugate into a biological system comprising pathogenic bacteria susceptible to the antibiotic.

  11. Gelsolin Amyloidogenesis Is Effectively Modulated by Curcumin and Emetine Conjugated PLGA Nanoparticles

    PubMed Central

    Goel, Surbhi; Kundu, Bishwajit; Mishra, Prashant; Fnu, Ashish

    2015-01-01

    Small molecule based therapeutic intervention of amyloids has been limited by their low solubility and poor pharmacokinetic characteristics. We report here, the use of water soluble poly lactic-co-glycolic acid (PLGA)-encapsulated curcumin and emetine nanoparticles (Cm-NPs and Em-NPs, respectively), as potential modulators of gelsolin amyloidogenesis. Using the amyloid-specific dye Thioflavin T (ThT) as an indicator along with electron microscopic imaging we show that the presence of Cm-NPs augmented amyloid formation in gelsolin by skipping the pre-fibrillar assemblies, while Em-NPs induced non-fibrillar aggregates. These two types of aggregates differed in their morphologies, surface hydrophobicity and secondary structural signatures, confirming that they followed distinct pathways. In spite of differences, both these aggregates displayed reduced toxicity against SH-SY5Y human neuroblastoma cells as compared to control gelsolin amyloids. We conclude that the cytotoxicity of gelsolin amyloids can be reduced by either stalling or accelerating its fibrillation process. In addition, Cm-NPs increased the fibrillar bulk while Em-NPs defibrillated the pre-formed gelsolin amyloids. Moreover, amyloid modulation happened at a much lower concentration and at a faster rate by the PLGA encapsulated compounds as compared to their free forms. Thus, besides improving pharmacokinetic and biocompatible properties of curcumin and emetine, PLGA conjugation elevates the therapeutic potential of both small molecules against amyloid fibrillation and toxicity. PMID:25996685

  12. Bioavailability of a Sustained Release Formulation of Curcumin

    PubMed Central

    Madhavi, Doddabele; Kagan, Daniel

    2014-01-01

    Context Curcumin has a number of beneficial effects, such as functioning as a potent antioxidant,1 anti-inflammatory, 2 and anticancer agent. Because of its poor oral bioavailability, very high oral doses and repeated dosing have been used to obtain effective plasma levels, with mixed results. High doses of curcumin may cause gastric disturbance, often resulting in poor patient compliance. Objective The objective of this study was to compare the relative bioavailability of MicroActive Curcumin—an advanced, micronized formulation of curcumin that is 25% curcuminoids in a sustained release matrix—with that of an unformulated, 95% pure curcumin powder. Design A dissolution study compared the solubility of the formulated and the unformulated curcumin. The research team also performed a single-dose, 12-h, crossover uptake study with 10 participants and a high-dose tolerability and accumulation study with 3 participants, comparing the 2 forms of curcumin. Setting The study was done in MAZE Laboratories (Purchase, NY, USA). Participants Ten healthy male and female volunteers, aged 21–66 y, took part in the single-dose study. Three participants, 2 female and 1 male aged 40–55 y, took part in the tolerability and accumulation study. The participants were people from the community. Intervention For the dissolution study, the research team filled hard gelatin capsules with unformulated 95% curcumin powder and the MicroActive Curcumin powder to the equivalent of 25 mg curcuminoids. For the single-dose study, participants received 500 mg of curcumin in 2 forms. MicroActive Curcumin capsules were administered after breakfast, and blood samples were drawn at 1, 2, 4, 8, and 12 h postdose. After a 7-d washout period, the protocol was repeated for unformulated, 95% curcumin powder capsules. For the tolerability study, the unformulated, 95% curcumin powder was given at a dose that provided 2 g of curcumin for 7 d followed by 5 g of curcumin for an additional 7 d. After a

  13. Recent Developments in Delivery, Bioavailability, Absorption and Metabolism of Curcumin: the Golden Pigment from Golden Spice

    PubMed Central

    Prasad, Sahdeo; Tyagi, Amit K.

    2014-01-01

    Curcumin (diferuloylmethane) is a yellow pigment present in the spice turmeric (Curcuma longa) that has been associated with antioxidant, anti-inflammatory, anticancer, antiviral, and antibacterial activities as indicated by over 6,000 citations. In addition, over one hundred clinical studies have been carried out with curcumin. One of the major problems with curcumin is perceived to be the bioavailability. How curcumin should be delivered in vivo, how bioavailable is it, how well curcumin is absorbed and how it is metabolized, is the focus of this review. Various formulations of curcumin that are currently available are also discussed. PMID:24520218

  14. Curcumin Reduces the Motility of Salmonella enterica Serovar Typhimurium by Binding to the Flagella, Thereby Leading to Flagellar Fragility and Shedding

    PubMed Central

    Balakrishnan, Arjun; Negi, Vidya Devi; Sakorey, Deepika; Chandra, Nagasuma

    2016-01-01

    ABSTRACT One of the important virulence properties of the pathogen is its ability to travel to a favorable environment, cross the viscous mucus barrier (intestinal barrier for enteric pathogens), and reach the epithelia to initiate pathogenesis with the help of an appendage, like flagella. Nonetheless, flagella can act as an “Achilles heel,” revealing the pathogen's presence to the host through the stimulation of innate and adaptive immune responses. We assessed whether curcumin, a dietary polyphenol, could alter the motility of Salmonella, a foodborne pathogen. It reduced the motility of Salmonella enterica serovar Typhimurium by shortening the length of the flagellar filament (from ∼8 μm to ∼5 μm) and decreasing its density (4 or 5 flagella/bacterium instead of 8 or 9 flagella/bacterium). Upon curcumin treatment, the percentage of flagellated bacteria declined from ∼84% to 59%. However, no change was detected in the expression of the flagellin gene and protein. A fluorescence binding assay demonstrated binding of curcumin to the flagellar filament. This might make the filament fragile, breaking it into smaller fragments. Computational analysis predicted the binding of curcumin, its analogues, and its degraded products to a flagellin molecule at an interface between domains D1 and D2. Site-directed mutagenesis and a fluorescence binding assay confirmed the binding of curcumin to flagellin at residues ASN120, ASP123, ASN163, SER164, ASN173, and GLN175. IMPORTANCE This work, to our knowledge the first report of its kind, examines how curcumin targets flagellar density and affects the pathogenesis of bacteria. We found that curcumin does not affect any of the flagellar synthesis genes. Instead, it binds to the flagellum and makes it fragile. It increases the torsional stress on the flagellar filament that then breaks, leaving fewer flagella around the bacteria. Flagella, which are crucial ligands for Toll-like receptor 5, are some of the most important

  15. Sonodynamic action of curcumin on foodborne bacteria Bacillus cereus and Escherichia coli.

    PubMed

    Wang, Xinna; Ip, Margaret; Leung, Albert Wingnang; Yang, Zhengrong; Wang, Pan; Zhang, Baoting; Ip, Siupo; Xu, Chuanshan

    2015-09-01

    Bacterial contamination is an important cause of foodborne diseases. The present study aimed to investigate sonodynamic action of curcumin on foodborne bacteria Bacillus cereus (B. cereus) and Escherichia coli (E. coli). The uptake of curcumin was measured for optimizing the concentration incubation time before ultrasound sonication, and colony forming units (CFU) were counted after ultrasound treatment. The chromosomal DNA fragmentation of bacteria was analyzed and the effect of hypoxic condition on the antibacterial efficacy of sonodynamic action of curcumin was also assessed in this study. The results showed that the maximum uptake of curcumin in B. cereus and E. coli occurred in 50min after curcumin incubation. Curcumin had sonodynamic bactericidal activity in a curcumin dose-dependent manner, and 5.6-log reduction in CFU of B. cereus was observed after curcumin treatment (2.0μM), however, only 2-log reduction in CFU of E. coli after 40μM curcumin treatment. No significant change in chromosomal DNA was found after the combined treatment of curcumin and ultrasound. The survival of B. cereus and E. coli after sonodynamic treatment in hypoxic group was significantly higher than that in normal oxygen group. These findings indicated that sonodynamic action of curcumin had significant inactivation effect on foodborne bacteria, and B. cereus was more sensitive to sonodynamic treatment of curcumin than E. coli. Sonodynamic antibacterial activity of curcumin might be dependent on the oxygen environment.

  16. Construction and characterization of curcumin nanoparticles system

    NASA Astrophysics Data System (ADS)

    Sun, Weitong; Zou, Yu; Guo, Yaping; Wang, Lu; Xiao, Xue; Sun, Rui; Zhao, Kun

    2014-03-01

    This study was aimed at developing a nanoparticles system for curcumin, a widely used traditional Chinese medicine, but with the disadvantage of poor aqueous solubility. The objective was intended to improve in vitro release characteristics, enhance blood and gastrointestinal stability, increase bioavailability and pharmacological activities. Curcumin nanoparticles system (Cur-NS) was prepared by ionotropic gelation technique. Cur-NS was characterized by particle size, zeta potential, drug entrapment efficiency, drug loading, and physical stability, respectively. Cur-NS presented controlled release properties, and the release properties of Cur from NS were fit non-Fickian mechanism, controlled by the expected diffusional release and the erosion or solubilization from the crosslink layer of polymer carrier. In addition, the pharmacokinetic study in rats revealed a notable improved oral bioavailability of Cur, and the anti-tumor activity in vivo of Cur-NS on tumor growth was investigated. Cur-NS significantly inhibited tumor effect compared with non-vehicle group, thus making it a potential candidate for cancer therapy.

  17. Curcumin Nanoformulation for Cervical Cancer Treatment

    PubMed Central

    Zaman, Mohd S.; Chauhan, Neeraj; Yallapu, Murali M.; Gara, Rishi K.; Maher, Diane M.; Kumari, Sonam; Sikander, Mohammed; Khan, Sheema; Zafar, Nadeem; Jaggi, Meena; Chauhan, Subhash C.

    2016-01-01

    Cervical cancer is one of the most common cancers among women worldwide. Current standards of care for cervical cancer includes surgery, radiation, and chemotherapy. Conventional chemotherapy fails to elicit therapeutic responses and causes severe systemic toxicity. Thus, developing a natural product based, safe treatment modality would be a highly viable option. Curcumin (CUR) is a well-known natural compound, which exhibits excellent anti-cancer potential by regulating many proliferative, oncogenic, and chemo-resistance associated genes/proteins. However, due to rapid degradation and poor bioavailability, its translational and clinical use has been limited. To improve these clinically relevant parameters, we report a poly(lactic-co-glycolic acid) based curcumin nanoparticle formulation (Nano-CUR). This study demonstrates that in comparison to free CUR, Nano-CUR effectively inhibits cell growth, induces apoptosis, and arrests the cell cycle in cervical cancer cell lines. Nano-CUR treatment modulated entities such as miRNAs, transcription factors, and proteins associated with carcinogenesis. Moreover, Nano-CUR effectively reduced the tumor burden in a pre-clinical orthotopic mouse model of cervical cancer by decreasing oncogenic miRNA-21, suppressing nuclear β-catenin, and abrogating expression of E6/E7 HPV oncoproteins including smoking compound benzo[a]pyrene (BaP) induced E6/E7 and IL-6 expression. These superior pre-clinical data suggest that Nano-CUR may be an effective therapeutic modality for cervical cancer. PMID:26837852

  18. Fiber-mesh photonic molecule

    NASA Astrophysics Data System (ADS)

    Mishra, Subodha; Satpathy, Sashi

    2008-03-01

    Analogous to the photonic crystal, we introduce the concept of a fiber-mesh photonic molecule made up of optical fibers and study its transmission characteristics. We consider a specific example of a photonic molecule, inspired by the well-known C60 molecule, with the arms of the molecule formed out of single-moded optical fibers. The transmittance consists of sharp peaks determined by the pole structure of the scattering matrix in the complex energy plane. A molecule can be designed to control the positions and the widths of the transmission peaks, opening up the possibility of building new photonic devices such as high quality band-pass filters.

  19. Formulation of nanotized curcumin and demonstration of its antimalarial efficacy

    PubMed Central

    Ghosh, Aparajita; Banerjee, Tanushree; Bhandary, Suman; Surolia, Avadhesha

    2014-01-01

    Aim The present study was conducted to overcome the disadvantages associated with the poor water solubility and low bioavailability of curcumin by synthesizing nanotized curcumin and demonstrating its efficacy in treating malaria. Materials and methods Nanotized curcumin was prepared by a modified emulsion-diffusion-evaporation method and was characterized by means of transmission electron microscopy, atomic force microscopy, dynamic light scattering, Zetasizer, Fourier transform infrared spectroscopy, and differential thermal analysis. The novelty of the prepared nanoformulation lies in the fact that it was devoid of any polymeric matrices used in conventional carriers. The antimalarial efficacy of the prepared nanotized curcumin was then checked both in vitro and in vivo. Results The nanopreparation was found to be non-toxic and had a particle size distribution of 20–50 nm along with improved aqueous dispersibility and an entrapment efficiency of 45%. Nanotized curcumin (half maximal inhibitory concentration [IC50]: 0.5 μM) was also found to be ten-fold more effective for growth inhibition of Plasmodium falciparum in vitro as compared to its native counterpart (IC50: 5 μM). Oral bioavailability of nanotized curcumin was found to be superior to that of its native counterpart. Moreover, when Plasmodium berghei-infected mice were orally treated with nanotized curcumin, it prolonged their survival by more than 2 months with complete clearance of parasites in comparison to the untreated animals, which survived for 8 days only. Conclusion Nanotized curcumin holds a considerable promise in therapeutics as demonstrated here for treating malaria as a test system. PMID:25484584

  20. Analog without fear

    NASA Technical Reports Server (NTRS)

    Delagrange, A. D.

    1977-01-01

    Analog circuitry, also referred to as Linear, has been nearly run over by the digital/computer bandwagon. This is unfortunate because tremendous advances are being made in the field of analog integrated circuitry. Each year's progress raises the state-of-the-art, bringing achievements not possible even the year before. Many of the traditional prejudices against analog circuitry are no longer valid. This report attempts to summarize what is available now and what can (and can't) be done with analog integrated circuitry.

  1. Analog synthetic biology.

    PubMed

    Sarpeshkar, R

    2014-03-28

    We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog-digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA-protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations.

  2. Nonvolatile Analog Memory

    NASA Technical Reports Server (NTRS)

    MacLeod, Todd C. (Inventor)

    2007-01-01

    A nonvolatile analog memory uses pairs of ferroelectric field effect transistors (FFETs). Each pair is defined by a first FFET and a second FFET. When an analog value is to be stored in one of the pairs, the first FFET has a saturation voltage applied thereto, and the second FFET has a storage voltage applied thereto that is indicative of the analog value. The saturation and storage voltages decay over time in accordance with a known decay function that is used to recover the original analog value when the pair of FFETs is read.

  3. Curcumin: a natural product for diabetes and its complications.

    PubMed

    Nabavi, Seyed Fazel; Thiagarajan, Raman; Rastrelli, Luca; Daglia, Maria; Sobarzo-Sánchez, Eduardo; Alinezhad, Heshmatollah; Nabavi, Seyed Mohammad

    2015-01-01

    Curcumin is the yellow-colored bioactive constituent of the perennial plant, Curcuma longa L., which possesses a wide range of physiological and pharmacological properties such as antioxidant, anti-inflammatory, anticancer, neuroprotective and anti-diabetic activities. Anti-diabetic activity of curcumin may be due to its potent ability to suppress oxidative stress and inflammation. Moreover, it shows a beneficial role on the diabetesinduced endothelial dysfunction and induces a down-regulation of nuclear factor-kappa B. Curcumin possesses a protective role against advanced glycation as well as collagen crosslinking and through this way, mitigates advanced glycation end products-induced complications of diabetes. Curcumin also reduces blood glucose, and the levels of glycosylated hemoglobin in diabetic rat through the regulation of polyol pathway. It also suppresses increased bone resorption through the inhibition of osteoclastogenesis and expression of the AP-1 transcription factors, c-fos and c-jun, in diabetic animals. Overall, scientific literature shows that curcumin possesses anti-diabetic effects and mitigates diabetes complications. Here we report a systematical discussion on the beneficial role of curcumin on diabetes and its complications with emphasis on its molecular mechanisms of actions.

  4. Curcumin AntiCancer Studies in Pancreatic Cancer.

    PubMed

    Bimonte, Sabrina; Barbieri, Antonio; Leongito, Maddalena; Piccirillo, Mauro; Giudice, Aldo; Pivonello, Claudia; de Angelis, Cristina; Granata, Vincenza; Palaia, Raffaele; Izzo, Francesco

    2016-07-16

    Pancreatic cancer (PC) is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC.

  5. Molecular Mechanisms of Anti-metastatic Activity of Curcumin.

    PubMed

    Deng, Y I; Verron, Elise; Rohanizadeh, Ramin

    2016-11-01

    Cancer is the leading cause of death worldwide. Although cancer occurs as a localized disease, its morbidity and mortality rates remain high due to the ability of cancer cells to break-off from the primary tumor and spread to distant organs. Currently, chemotherapy is the main treatment for cancer; however, the increase in proportion of drug-resistant cancer cells and unpleasant side-effects of chemotherapy are still the major challenges in cancer therapy. Curcumin is a natural polyphenol compound and the main bioactive constituent of Indian spice turmeric, widely used in Indian and Chinese medicines. Curcumin has well-known therapeutic actions, including anti-inflammatory, anti-microbial, anti-oxidant and anti-cancer properties. Curcumin induces cancer cell apoptosis through regulating various signaling pathways and arresting tumor cell cycle. Curcumin's therapeutic/ preventative actions on metastatic cancers have not been yet fully understood and studied. The present review explores the potential anti-metastatic mechanisms of curcumin, including inhibition of transcription factors and their signaling pathways (e.g., NF-κB, ApP-1 and STAT3), inflammatory cytokines (e.g., CXCL1, CXCL2, IL-6, IL-8), multiple proteases (e.g., uPA, MMPs), multiple protein kinases (e.g., MAPKs, FAK), regulation of miRNAs (e.g., miR21, miR181b) and heat shock proteins (HLJ1). In addition, possible synergistic actions of combination therapy of curcumin with current chemotherapies are discussed in this review.

  6. The effect of curcumin (turmeric) on Alzheimer's disease: An overview

    PubMed Central

    Mishra, Shrikant; Palanivelu, Kalpana

    2008-01-01

    This paper discusses the effects of curcumin on patients with Alzheimer's disease (AD). Curcumin (Turmeric), an ancient Indian herb used in curry powder, has been extensively studied in modern medicine and Indian systems of medicine for the treatment of various medical conditions, including cystic fibrosis, haemorrhoids, gastric ulcer, colon cancer, breast cancer, atherosclerosis, liver diseases and arthritis. It has been used in various types of treatments for dementia and traumatic brain injury. Curcumin also has a potential role in the prevention and treatment of AD. Curcumin as an antioxidant, anti-inflammatory and lipophilic action improves the cognitive functions in patients with AD. A growing body of evidence indicates that oxidative stress, free radicals, beta amyloid, cerebral deregulation caused by bio-metal toxicity and abnormal inflammatory reactions contribute to the key event in Alzheimer's disease pathology. Due to various effects of curcumin, such as decreased Beta-amyloid plaques, delayed degradation of neurons, metal-chelation, anti-inflammatory, antioxidant and decreased microglia formation, the overall memory in patients with AD has improved. This paper reviews the various mechanisms of actions of curcumin in AD and pathology. PMID:19966973

  7. Curcumin-Loaded PLA Nanoparticles: Formulation and Physical Evaluation

    PubMed Central

    Rachmawati, Heni; Yanda, Yulia L.; Rahma, Annisa; Mase, Nobuyuki

    2016-01-01

    Curcumin is a polyphenolic compound derived from Curcuma domestica (Zingiberaceae) that possesses diverse pharmacological effects including anti-inflammatory, antioxidant, antimicrobial, and anticarcinogenic activities. Although phase I clinical trials have shown curcumin as a safe drug even at high doses (12 g/day) in humans, poor bioavaibility largely limits its pharmacological activity. Nanoencapsulation in biodegradable polymers is a promising alternative to improve curcumin bioavaibility. In this study, curcumin was encapsulated in biodegradable polymer poly-(lactic acid) (PLA) nanoparticles via the emulsification-solvent evaporation method. Optimization of selected parameters of this method including the type of solvent, surfactant concentration, drug loading, sonication time, and centrifugation speed, were performed to obtain polymeric nano-carriers with optimum characteristics. Dichloromethane was used as the solvent and vitamin E polyethylene glycol succinate (TPGS) was used as the surfactant. Four minutes of sonication time and centrifugation at 10500 rpm were able to produce spherical nanoparticles with average size below 300 nm. The highest encapsulation efficiency was found on PLA nanoparticles containing 5% of curcumin at 89.42 ± 1.04%. The particle size, polydispersity index, zeta potential of 5% curcumin-PLA nanoparticles were 387.50 ± 58.60 nm, 0.289 ± 0.047, and −1.12 mV, respectively. Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) studies showed partial interaction between the drug and polymer. PMID:27110509

  8. Curcumin AntiCancer Studies in Pancreatic Cancer

    PubMed Central

    Bimonte, Sabrina; Barbieri, Antonio; Leongito, Maddalena; Piccirillo, Mauro; Giudice, Aldo; Pivonello, Claudia; de Angelis, Cristina; Granata, Vincenza; Palaia, Raffaele; Izzo, Francesco

    2016-01-01

    Pancreatic cancer (PC) is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC. PMID:27438851

  9. Wound Healing Effects of Curcumin: A Short Review.

    PubMed

    Tejada, Silvia; Manayi, Azadeh; Daglia, Maria; Nabavi, Seyed F; Sureda, Antoni; Hajheydari, Zohreh; Gortzi, Olga; Pazoki-Toroudi, Hamidreza; Nabavi, Seyed M

    Wound healing is a complex process that consists of several phases that range from coagulation, inflammation, accumulation of radical substances, to proliferation, formation of fibrous tissues and collagen, contraction of wound with formation of granulation tissue and scar. Since antiquity, vegetable substances have been used as phytotherapeutic agents for wound healing, and more recently natural substances of vegetable origin have been studied with the attempt to show their beneficial effect on wound treatment. Curcumin, the most active component of rhizome of Curcuma longa L. (common name: turmeric), has been studied for many years due to its bio-functional properties, especially antioxidant, radical scavenger, antimicrobial and anti-inflammatory activities, which play a crucial role in the wound healing process. Moreover, curcumin stimulated the production of the growth factors involved in the wound healing process, and so curcumin also accelerated the management of wound restoration. The aim of the present review is collecting and evaluating the literature data regarding curcumin properties potentially relevant for wound healing. Moreover, the investigations on the wound healing effects of curcumin are reported. In order to produce a more complete picture, the chemistry and sources of curcumin are also discussed.

  10. Mechanism of the Anti-inflammatory Effect of Curcumin: PPAR-γ Activation

    PubMed Central

    Jacob, Asha; Wu, Rongqian; Zhou, Mian; Wang, Ping

    2007-01-01

    Curcumin, the phytochemical component in turmeric, is used as a dietary spice and a topical ointment for the treatment of inflammation in India for centuries. Curcumin (diferuloylmethane) is relatively insoluble in water, but dissolves in acetone, dimethylsulphoxide, and ethanol. Commercial grade curcumin contains 10–20% curcuminoids, desmethoxycurcumin, and bisdesmethoxycurcumin and they are as effective as pure curcumin. Based on a number of clinical studies in carcinogenesis, a daily oral dose of 3.6 g curcumin has been efficacious for colorectal cancer and advocates its advancement into Phase II clinical studies. In addition to the anticancer effects, curcumin has been effective against a variety of disease conditions in both in vitro and in vivo preclinical studies. The present review highlights the importance of curcumin as an anti-inflammatory agent and suggests that the beneficial effect of curcumin is mediated by the upregulation of peroxisome proliferator-activated receptor-γ (PPAR-γ) activation. PMID:18274631

  11. Synthesis of novel steroidal curcumin derivatives as anti-Alzheimer's disease candidates: Evidences-based on in vivo study.

    PubMed

    Elmegeed, Gamal A; Ahmed, Hanaa H; Hashash, Maher A; Abd-Elhalim, Mervat M; El-kady, Dina S

    2015-09-01

    Alzheimer's disease (AD) is a complex disease in which a single monofunctional 'targeted' drug is uneffective for management. Hybrid drugs that impact multiple targets simultaneously are better at controlling such complex disease systems. Hybrid agents were synthesized through the combination of the steroid moiety with curcumin molecule. Also novel curcumin analogues containing promising heterocyclic nucleus fused to the essential pharmacophoric feature of the curcumin moiety, were synthesized. The aim of the present study was extended to elucidate the efficacy of these novel synthesized compounds in the regression of AD induced in adult female albino rats. The results revealed that treatment of AD groups with compounds 3, 5, 8c or rivastigmin experienced significant increase in brain Ach, GSH, paraoxenase and BCL2 levels with respect to untreated group associated with significant decrease in brain AchE activity, urinary 8-OHG level, serum Caspase-3 level and brain P53 level relative to the untreated group. Immunohistochemical investigation revealed that the selected treatments caused marked increase in ChAT positive cells. These findings were documented by the histological investigation of the brain tissue. The activity of tested compounds showed gradual increase from compound b followed by compound 8c then compound 5. The anti-cholinesterase potential, anti-oxidant properties and anti-apoptotic activity are responsible for the anti-Alzheimer's disease potential of these compounds.

  12. pH-sensitive micelles for the intracellular co-delivery of curcumin and Pluronic L61 unimers for synergistic reversal effect of multidrug resistance

    PubMed Central

    Hong, Wei; Shi, Hong; Qiao, Mingxi; Zhang, Zehui; Yang, Wenting; Dong, Lingying; Xie, Fucheng; Zhao, Chunpeng; Kang, Li

    2017-01-01

    Pluronic L61 unimers, which are biomacromolecular modulators, and curcumin, a small-molecule modulator, were co-formulated into pH-sensitive micelles to reveal the full synergistic potential of combination drug treatments to reverse multidrug resistance (MDR). Compared to monotherapy, combined therapy significantly improved the cytotoxicity, cellular uptake and apoptotic effects of doxorubicin (DOX) against MCF-7/ADR cells. In mechanistic studies, both L61 and curcumin enhanced the cytotoxic effect by acting on mitochondrial signalling pathways. The compounds selectively accumulated in the mitochondria and disabled the mitochondria by dissipating the mitochondrial membrane potential, decreasing the ATP levels, and releasing cytochrome c, which initiated a cascade of caspase-9 and caspase-3 reactions. Furthermore, both curcumin and L61 down-regulated the expression and function of P-gp in response to drug efflux from the MCF-7/ADR cells. In the MCF-7/ADR tumour-bearing mouse model, intravenous administration of the combined therapy directly targeted the tumour, as revealed by the accumulation of DiR in the tumour site, which led to a significant inhibition of tumour growth without measurable side effects. In conclusion, co-formulation consisting of L61 and curcumin in pH-sensitive micelles induced significant synergistic effects on the reversal of MDR. Therefore, the intracellular co-delivery of various MDR modulators has great potential to reverse MDR in tumours. PMID:28195164

  13. Curcumin targets the TFEB-lysosome pathway for induction of autophagy

    PubMed Central

    Xu, Jian; Lu, Yuanqiang; Jiang, Jiukun; Wang, Liming; Shen, Han-Ming; Xia, Dajing

    2016-01-01

    Curcumin is a hydrophobic polyphenol derived from the herb Curcumalonga and its wide spectrum of pharmacological activities has been widely studied. It has been reported that Curcumin can induce autophagy through inhibition of the Akt-mTOR pathway. However, the effect of Curcumin on lysosome remains largely elusive. In this study, we first found that Curcumin treatment enhances autophagic flux in both human colon cancer HCT116 cells and mouse embryonic fibroblasts (MEFs). Moreover, Curcumin treatment promotes lysosomal function, evidenced by the increased lysosomal acidification and enzyme activity. Second, Curcumin is capable of suppressing the mammalian target of rapamycin (mTOR). Interestingly, Curcumin fails to inhibit mTOR and to activate lysosomal function in Tsc2−/−MEFs with constitutive activation of mTOR, indicating that Curcumin-mediated lysosomal activation is achieved via suppression of mTOR. Third, Curcumin treatment activates transcription factor EB (TFEB), a key nuclear transcription factor in control of autophagy and lysosome biogenesis and function, based on the following observations: (i) Curcumin directly binds to TFEB, (ii) Curcumin promotes TFEB nuclear translocation; and (iii) Curcumin increases transcriptional activity of TFEB. Finally, inhibition of autophagy and lysosome leads to more cell death in Curcumin-treated HCT116 cells, suggesting that autophagy and lysosomal activation serves as a cell survival mechanism to protect against Curcumin-mediated cell death. Taken together, data from our study provide a novel insight into the regulatory mechanisms of Curcumin on autophagy and lysosome, which may facilitate the development of Curcumin as a potential cancer therapeutic agent. PMID:27689333

  14. Curcumin Suppresses Soluble Tau Dimers and Corrects Molecular Chaperone, Synaptic, and Behavioral Deficits in Aged Human Tau Transgenic Mice*

    PubMed Central

    Ma, Qiu-Lan; Zuo, Xiaohong; Yang, Fusheng; Ubeda, Oliver J.; Gant, Dana J.; Alaverdyan, Mher; Teng, Edmond; Hu, Shuxin; Chen, Ping-Ping; Maiti, Panchanan; Teter, Bruce; Cole, Greg M.; Frautschy, Sally A.

    2013-01-01

    The mechanisms underlying Tau-related synaptic and cognitive deficits and the interrelationships between Tau species, their clearance pathways, and synaptic impairments remain poorly understood. To gain insight into these mechanisms, we examined these interrelationships in aged non-mutant genomic human Tau mice, with established Tau pathology and neuron loss. We also examined how these interrelationships changed with an intervention by feeding mice either a control diet or one containing the brain permeable beta-amyloid and Tau aggregate binding molecule curcumin. Transgene-dependent elevations in soluble and insoluble phospho-Tau monomer and soluble Tau dimers accompanied deficits in behavior, hippocampal excitatory synaptic markers, and molecular chaperones (heat shock proteins (HSPs)) involved in Tau degradation and microtubule stability. In human Tau mice but not control mice, HSP70, HSP70/HSP72, and HSP90 were reduced in membrane-enriched fractions but not in cytosolic fractions. The synaptic proteins PSD95 and NR2B were reduced in dendritic fields and redistributed into perikarya, corresponding to changes observed by immunoblot. Curcumin selectively suppressed levels of soluble Tau dimers, but not of insoluble and monomeric phospho-Tau, while correcting behavioral, synaptic, and HSP deficits. Treatment increased PSD95 co-immunoprecipitating with NR2B and, independent of transgene, increased HSPs implicated in Tau clearance. It elevated HSP90 and HSC70 without increasing HSP mRNAs; that is, without induction of the heat shock response. Instead curcumin differentially impacted HSP90 client kinases, reducing Fyn without reducing Akt. In summary, curcumin reduced soluble Tau and elevated HSPs involved in Tau clearance, showing that even after tangles have formed, Tau-dependent behavioral and synaptic deficits can be corrected. PMID:23264626

  15. Challenges in Using Analogies

    ERIC Educational Resources Information Center

    Lin, Shih-Yin; Singh, Chandralekha

    2011-01-01

    Learning physics requires understanding the applicability of fundamental principles in a variety of contexts that share deep features. One way to help students learn physics is via analogical reasoning. Students can be taught to make an analogy between situations that are more familiar or easier to understand and another situation where the same…

  16. Analogies for Avogadro's Number.

    ERIC Educational Resources Information Center

    Poskozim, Paul S.; And Others

    1986-01-01

    Reviews analogies used to try to capture the concept of the magnitude of Avogadro's number, including analogies related to small/tiny objects, counting, people, water, and money. Also presents several new ones which are based on modern computers and printers. (JN)

  17. Hydraulic Capacitor Analogy

    ERIC Educational Resources Information Center

    Baser, Mustafa

    2007-01-01

    Students have difficulties in physics because of the abstract nature of concepts and principles. One of the effective methods for overcoming students' difficulties is the use of analogies to visualize abstract concepts to promote conceptual understanding. According to Iding, analogies are consistent with the tenets of constructivist learning…

  18. Analog pulse processor

    DOEpatents

    Wessendorf, Kurt O.; Kemper, Dale A.

    2003-06-03

    A very low power analog pulse processing system implemented as an ASIC useful for processing signals from radiation detectors, among other things. The system incorporates the functions of a charge sensitive amplifier, a shaping amplifier, a peak sample and hold circuit, and, optionally, an analog to digital converter and associated drivers.

  19. Administration of Biosimilar Insulin Analogs: Role of Devices.

    PubMed

    Heinemann, Lutz; Fritz, Ingo; Khatami, Hootan; Edelman, Steven V

    2017-02-01

    With the expiration of patent protection for several originator insulin analog molecules, the availability of insulin analog copies is set to increase. Many regulatory authorities have developed, and continue to refine, guidelines for the approval of biosimilar insulin analogs. Aspects such as the structure, pharmacokinetics and pharmacodynamics, efficacy, safety, and immunogenicity of biosimilar insulin analogs are extensively addressed in these guidelines, but how the biosimilar insulin analog is administered to people with diabetes is not usually a topic. The aim of this article is to highlight that the delivery device-drug combination is of particular importance. Regulatory, legal, and practical aspects of the delivery device, be it a syringe, pen, or pump, have to be considered in the context of biosimilar insulin analogs. Although the safety and efficacy of biosimilar insulin analogs per se are of primary importance for physicians and people with diabetes, functions and features of the devices used for administration also require attention from a practical point of view. Unfortunately, although there are several clinical studies investigating the technical aspects of and patient preference for the originator insulin analog pens, there are currently very little published data for nonoriginator or biosimilar insulin analog pens. In addition, it is not known if it is safe to assume that a biosimilar insulin analog cartridge is compatible with an existing originator insulin analog pen. We believe that there is a need for more discussion on the role of devices for administration of biosimilar insulin analogs.

  20. Curcumin-Combretastatin Nanocells as Breast Cancer Cytotoxic and Antiangiogenic Agent

    DTIC Science & Technology

    2008-09-01

    walled carbon nanotubes (SWCNT) and the colloidal nanogels, and loaded them with curcumin. We have demonstrated that while the nanocarriers...receptors. 15. SUBJECT TERMS Nanotechnology-based cancer therapeutics, natural anticancer compounds, curcumin, single-walled carbon nanotubes ...carbon nanotubes (SWCNT) and polymeric nanogels, were selected for loading with curcumin. SWCNT have been shown to shuttle various cargoes across

  1. Curcumin-supplemented diets increase superoxide dismutase activity and mean lifespan in Drosophila

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Curcumin is an antioxidant extracted from the root of the turmeric plant. We examined the antioxidant effect and lifespan extension of curcumin in Drosophila. To ascertain the antioxidant effects of curcumin with regard to lifespan extension and the response to reactive oxygen species, female and ma...

  2. MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells

    SciTech Connect

    Yu, Teng; Ji, Jiang; Guo, Yong-li

    2013-11-08

    Highlights: •Curcumin activates MST1 in melanoma cells. •MST1 mediates curcumin-induced apoptosis of melanoma cells. •ROS production is involved in curcumin-induced MST1 activation. •MST1 mediates curcumin-induced JNK activation in melanoma cells. •MST1 mediates curcumin-induced Foxo3a nuclear translocation and Bim expression. -- Abstract: Different groups including ours have shown that curcumin induces melanoma cell apoptosis, here we focused the role of mammalian Sterile 20-like kinase 1 (MST1) in it. We observed that curcumin activated MST1-dependent apoptosis in cultured melanoma cells. MST1 silencing by RNA interference (RNAi) suppressed curcumin-induced cell apoptosis, while MST1 over-expressing increased curcumin sensitivity. Meanwhile, curcumin induced reactive oxygen species (ROS) production in melanoma cells, and the ROS scavenger, N-acetyl-cysteine (NAC), almost blocked MST1 activation to suggest that ROS might be required for MST1 activation by curcumin. c-Jun N-terminal protein kinase (JNK) activation by curcumin was dependent on MST1, since MST1 inhibition by RNAi or NAC largely inhibited curcumin-induced JNK activation. Further, curcumin induced Foxo3 nuclear translocation and Bim-1 (Foxo3 target gene) expression in melanoma cells, such an effect by curcumin was inhibited by MST1 RNAi. In conclusion, we suggested that MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells.

  3. Binding of curcumin with bovine serum albumin in the presence of ι-carrageenan and implications on the stability and antioxidant activity of curcumin.

    PubMed

    Yang, Mingling; Wu, Yue; Li, Jinbing; Zhou, Haibo; Wang, Xiaoyong

    2013-07-24

    This work studied the influences of formation of BSA/ι-carrageenan complexes on the binding, stability, and antioxidant activity of curcumin. In the presence of BSA and ι-carrageenan, curcumin gives higher intensities of absorption and fluorescence than free curcumin and curcumin only combined with BSA. The added ι-carrageenan is observed to promote curcumin for quenching the instrinsic fluorescence of BSA. These results are explained in terms of the formation of BSA/ι-carrageenan complexes, which help to stabilize the folded structure of BSA for providing curcumin with a more hydrophobic microenvironment. The small difference in anisotropy values of curcumin with BSA alone and of BSA/ι-carrageenan complexes suggests that ι-carrageenan acts as outer stretch conformation in BSA/ι-carrageenan complexes but does not directly disturb the hydrophobic pockets inside BSA, where curcumin is hydrophobically located. The determined values of the binding constant are higher for curcumin with BSA/ι-carrageenan complexes than with BSA alone. Moreover, BSA/ι-carrageenan complexes are found to be superior to single BSA for enhancing the stability and DPPH radical-scavenging ability of curcumin.

  4. Anticandidal activity of curcumin and methyl cinnamaldehyde.

    PubMed

    Khan, Neelofar; Shreaz, Sheikh; Bhatia, Rimple; Ahmad, Sheikh Imran; Muralidhar, Sumathi; Manzoor, Nikhat; Khan, Luqman Ahmad

    2012-04-01

    Cinnamaldehyde, its derivatives and curcumin are reported to have strong antifungal activity. In this work we report and compare anticandidal activity of curcumin (CUR) and α-methyl cinnamaldehyde (MCD) against 38 strains of Candida (3; standard, fluconazole sensitive, 24; clinical, fluconazole sensitive, 11; clinical, fluconazole resistant). The minimum inhibitory concentrations (MIC₉₀) of CUR ranged from 250 to 650 μg/ml for sensitive strains and from 250 to 500 μg/ml for resistant strains. MIC₉₀ of MCD varied between 100 and 250 μg/ml and 100-200 μg/ml for sensitive and resistant strains, respectively. Higher activity of MCD as compared to CUR was further reinforced by spot assays and growth curve studies. At their respective MIC₉₀ values, in the presence of glucose, average inhibition of H+-efflux caused by CUR and MCD against standard, clinical and resistant isolates was 24%, 31%, 32% and 54%, 52%, 54%, respectively. Inhibition of H+-extrusion leads to intracellular acidification and cell death, average pHi for control, CUR and MCD exposed cells was 6.68, 6.39 and 6.20, respectively. Scanning electron micrographs of treated cells show more extensive damage in case of MCD. Haemolytic activity of CUR and MCD at their highest MIC was 11.45% and 13.00%, respectively as against 20% shown by fluconazole at typical MIC of 30 μg/ml. In conclusion, this study shows significant anticandidal activity of CUR and MCD against both azole-resistant and sensitive clinical isolates, MCD is found to be more effective.

  5. Zn(II)-curcumin protects against hemorheological alterations, oxidative stress and liver injury in a rat model of acute alcoholism.

    PubMed

    Yu, Chuan; Mei, Xue-Ting; Zheng, Yan-Ping; Xu, Dong-Hui

    2014-03-01

    Curcumin can chelate metal ions, forming metallocomplexes. We compared the effects of Zn(II)-curcumin with curcumin against hemorheological alterations, oxidative stress and liver injury in a rat model of acute alcoholism. Oral administration of Zn(II)-curcumin dose-dependently prevented the ethanol-induced elevation of serum malondialdehyde (MDA) content and reductions in glutathione level and superoxide dismutase (SOD) activity. Zn(II)-curcumin also inhibited ethanol-induced liver injury. Additionally, Zn(II)-curcumin dose-dependently inhibited hemorheological abnormalities, including the ethanol-induced elevation of whole blood viscosity, plasma viscosity, blood viscosity at corrected hematocrit (45%), erythrocyte aggregation index, erythrocyte rigidity index and hematocrit. Compared to curcumin at the same dose, Zn(II)-curcumin more effectively elevated SOD activity, ameliorated liver injury and improved hemorheological variables. These results suggest that Zn(II)-curcumin protected the rats from ethanol-induced liver injury and hemorheological abnormalities via the synergistic effect of curcumin and zinc.

  6. Curcumin and insulin resistance-Molecular targets and clinical evidences.

    PubMed

    Jiménez-Osorio, Angélica Saraí; Monroy, Adriana; Alavez, Silvestre

    2016-11-12

    Curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), the main component of the Indian spice turmeric, has been used in traditional medicine to improve diabetes and its comorbidities. Since the last two decades, scientific research has shown that in addition to its antioxidant properties, curcumin could also work as protein homeostasis regulator and it is able to modulate other intracellular pathways. Curcumin supplementation has been proposed to improve insulin resistance (IR) through the activation of the insulin receptor and its downstream pathways in several experimental models, pointing out that its clinical use may be a good and innocuous strategy to improve IR-related diseases. IR is associated with many diseases and syndromes like carbohydrate intolerance, diabetes, metabolic syndrome, and cardiovascular disease. Therefore, it is imperative to identify safe therapeutic interventions aimed to reduce side effects that could lead the patient to leave the treatment. To date, many clinical trials have been carried out using turmeric and curcumin to improve metabolic syndrome, carbohydrate intolerance, diabetes, and obesity in individuals with IR. Results so far are inconclusive because dose, time of treatment, and type of curcumin can change the study outcome significantly. However, there is some clinical evidence suggesting a beneficial effect of curcumin on IR. In this review, we discuss the factors that could influence curcumin effects in clinical trials aimed to improve IR and related diseases, and the conclusions that can be drawn from results obtained so far. © 2016 BioFactors, 42(6):561-580, 2016.

  7. Encapsulation of curcumin in polyelectrolyte nanocapsules and their neuroprotective activity

    NASA Astrophysics Data System (ADS)

    Szczepanowicz, Krzysztof; Jantas, Danuta; Piotrowski, Marek; Staroń, Jakub; Leśkiewicz, Monika; Regulska, Magdalena; Lasoń, Władysław; Warszyński, Piotr

    2016-09-01

    Poor water solubility and low bioavailability of lipophilic drugs can be potentially improved with the use of delivery systems. In this study, encapsulation of nanoemulsion droplets was utilized to prepare curcumin nanocarriers. Nanosize droplets containing the drug were encapsulated in polyelectrolyte shells formed by the layer-by-layer (LbL) adsorption of biocompatible polyelectrolytes: poly-L-lysine (PLL) and poly-L-glutamic acid (PGA). The size of synthesized nanocapsules was around 100 nm. Their biocompatibility and neuroprotective effects were evaluated on the SH-SY5Y human neuroblastoma cell line using cell viability/toxicity assays (MTT reduction, LDH release). Statistically significant toxic effect was clearly observed for PLL coated nanocapsules (reduction in cell viability about 20%-60%), while nanocapsules with PLL/PGA coating did not evoke any detrimental effects on SH-SY5Y cells. Curcumin encapsulated in PLL/PGA showed similar neuroprotective activity against hydrogen peroxide (H2O2)-induced cell damage, as did 5 μM curcumin pre-dissolved in DMSO (about 16% of protection). Determination of concentration of curcumin in cell lysate confirmed that curcumin in nanocapsules has cell protective effect in lower concentrations (at least 20 times) than when given alone. Intracellular mechanisms of encapsulated curcumin-mediated protection engaged the prevention of the H2O2-induced decrease in mitochondrial membrane potential (MMP) but did not attenuate Reactive Oxygen Species (ROS) formation. The obtained results indicate the utility of PLL/PGA shell nanocapsules as a promising, alternative way of curcumin delivery for neuroprotective purposes with improved efficiency and reduced toxicity.

  8. Encapsulation of curcumin in polyelectrolyte nanocapsules and their neuroprotective activity.

    PubMed

    Szczepanowicz, Krzysztof; Jantas, Danuta; Piotrowski, Marek; Staroń, Jakub; Leśkiewicz, Monika; Regulska, Magdalena; Lasoń, Władysław; Warszyński, Piotr

    2016-09-02

    Poor water solubility and low bioavailability of lipophilic drugs can be potentially improved with the use of delivery systems. In this study, encapsulation of nanoemulsion droplets was utilized to prepare curcumin nanocarriers. Nanosize droplets containing the drug were encapsulated in polyelectrolyte shells formed by the layer-by-layer (LbL) adsorption of biocompatible polyelectrolytes: poly-L-lysine (PLL) and poly-L-glutamic acid (PGA). The size of synthesized nanocapsules was around 100 nm. Their biocompatibility and neuroprotective effects were evaluated on the SH-SY5Y human neuroblastoma cell line using cell viability/toxicity assays (MTT reduction, LDH release). Statistically significant toxic effect was clearly observed for PLL coated nanocapsules (reduction in cell viability about 20%-60%), while nanocapsules with PLL/PGA coating did not evoke any detrimental effects on SH-SY5Y cells. Curcumin encapsulated in PLL/PGA showed similar neuroprotective activity against hydrogen peroxide (H2O2)-induced cell damage, as did 5 μM curcumin pre-dissolved in DMSO (about 16% of protection). Determination of concentration of curcumin in cell lysate confirmed that curcumin in nanocapsules has cell protective effect in lower concentrations (at least 20 times) than when given alone. Intracellular mechanisms of encapsulated curcumin-mediated protection engaged the prevention of the H2O2-induced decrease in mitochondrial membrane potential (MMP) but did not attenuate Reactive Oxygen Species (ROS) formation. The obtained results indicate the utility of PLL/PGA shell nanocapsules as a promising, alternative way of curcumin delivery for neuroprotective purposes with improved efficiency and reduced toxicity.

  9. Meat analog: a review.

    PubMed

    Malav, O P; Talukder, S; Gokulakrishnan, P; Chand, S

    2015-01-01

    The health-conscious consumers are in search of nutritious and convenient food item which can be best suited in their busy life. The vegetarianism is the key for the search of such food which resembles the meat in respect of nutrition and sensory characters, but not of animal origin and contains vegetable or its modified form, this is the point when meat analog evolved out and gets shape. The consumers gets full satisfaction by consumption of meat analog due to its typical meaty texture, appearance and the flavor which are being imparted during the skilled production of meat analog. The supplement of protein in vegetarian diet through meat alike food can be fulfilled by incorporating protein-rich vegetative food grade materials in meat analog and by adopting proper technological process which can promote the proper fabrication of meat analog with acceptable meat like texture, appearance, flavor, etc. The easily available vegetables, cereals, and pulses in India have great advantages and prospects to be used in food products and it can improve the nutritional and functional characters of the food items. The various form and functional characters of food items are available world over and attracts the meat technologists and the food processors to bring some innovativeness in meat analog and its presentation and marketability so that the acceptability of meat analog can be overgrown by the consumers.

  10. PEGylated exendin-4, a modified GLP-1 analog exhibits more potent cardioprotection than its unmodified parent molecule on a dose to dose basis in a murine model of myocardial infarction.

    PubMed

    Sun, Zhongchan; Tong, Guang; Kim, Tae Hyung; Ma, Nan; Niu, Gang; Cao, Feng; Chen, Xiaoyuan

    2015-01-01

    A Site-specifically PEGylated exendin-4 (denoted as PEG-Ex4) is an exendin-4 (denoted as Ex4) analog we developed by site-specific PEGylation of exendin-4 with a high molecular weight trimeric poly(ethylene glycol) (tPEG). It has been shown to possess prolonged half-life in vivo with similar receptor binding affinity compared to unmodified exendin-4 by our previous work. This study is sought to test whether PEG-Ex4 is suitable for treating myocardial infarction (MI). In the MI model, PEG-Ex4 was administered every 3 days while equivalent amount of Ex4 was administered every 3 days or twice daily. Animal survival rate, heart function, remodeling and neoangiogenesis were evaluated and compared. Tube formation was examined in endothelial cells. In addition, Western blotting and histology were performed to determine the markers of cardiac hypertrophy and angiogenesis and to explore the possible molecular mechanism involved. PEG-Ex4 and Ex4 showed comparable binding affinity to GLP-1 receptor. In MI mice, PEG-Ex4 given at 3 days interval achieved similar extent of protection as Ex4 given twice daily, while Ex4 given at 3 days interval failed to produce protection. PEG-Ex4 elevated endothelial tube formation in vitro and capillary density in the border area of MI. PEG-Ex4 increased Akt activity and VEGF production in a GLP-1R dependent manner in endothelial cells and antagonism of GLP-1R, Akt or VEGF abolished the protection of PEG-Ex4 in the MI model. PEG-Ex4 is a potent long-acting GLP-1 receptor agonist for the treatment of chronic heart disease. Its protection might be attributed to enhanced angiogenesis mediated by the activation of Akt and VEGF.

  11. Liposome encapsulation of curcumin: physico-chemical characterizations and effects on MCF7 cancer cell proliferation.

    PubMed

    Hasan, M; Belhaj, N; Benachour, H; Barberi-Heyob, M; Kahn, C J F; Jabbari, E; Linder, M; Arab-Tehrany, E

    2014-01-30

    The role of curcumin (diferuloylmethane), for cancer treatment has been an area of growing interest. However, due to its low absorption, the poor bioavailability of curcumin limits its clinical use. In this study, we reported an approach of encapsulation a curcumin by nanoliposome to achieve an improved bioavailability of a poorly absorbed hydrophobic compound. We demonstrated that liposomal preparations to deliver curcumin increase its bioavailability. Liposomes composed of salmon's lecithin also improved curcumin bioavailability compared to those constituted of rapeseed and soya lecithins. A real-time label-free cell analysis system based on real-time cell impedance monitoring was used to investigate the in vitro cytotoxicity of liposomal preparations.

  12. A Computational Study of Structure and Reactivity of N-Substitued-4-Piperidones Curcumin Analogues and Their Radical Anions.

    PubMed

    Martínez-Cifuentes, Maximiliano; Weiss-López, Boris; Araya-Maturana, Ramiro

    2016-12-02

    In this work, a computational study of a series of N-substitued-4-piperidones curcumin analogues is presented. The molecular structure of the neutral molecules and their radical anions, as well as their reactivity, are investigated. N-substituents include methyl and benzyl groups, while substituents on the aromatic rings cover electron-donor and electron-acceptor groups. Substitutions at the nitrogen atom do not significantly affect the geometry and frontier molecular orbitals (FMO) energies of these molecules. On the other hand, substituents on the aromatic rings modify the distribution of FMO. In addition, they influence the capability of these molecules to attach an additional electron, which was studied through adiabatic (AEA) and vertical electron affinities (VEA), as well as vertical detachment energy (VDE). To study electrophilic properties of these structures, local reactivity indices, such as Fukui (f⁺) and Parr (P⁺) functions, were calculated, and show the influence of the aromatic rings substituents on the reactivity of α,β-unsaturated ketones towards nucleophilic attack. This study has potential implications for the design of curcumin analogues based on a 4-piperidone core with desired reactivity.

  13. Involvement of ROS in Curcumin-induced Autophagic Cell Death.

    PubMed

    Lee, Youn Ju; Kim, Nam-Yi; Suh, Young-Ah; Lee, Chuhee

    2011-02-01

    Many anticancer agents as well as ionizing radiation have been shown to induce autophagy which is originally described as a protein recycling process and recently reported to play a crucial role in various disorders. In HCT116 human colon cancer cells, we found that curcumin, a polyphenolic phytochemical extracted from the plant Curcuma longa, markedly induced the conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II and degradation of sequestome-1 (SQSTM1) which is a marker of autophagosome degradation. Moreover, we found that curcumin caused GFP-LC3 formation puncta, a marker of autophagosome, and decrease of GFP-LC3 and SQSTM1 protein level in GFP-LC3 expressing HCT116 cells. It was further confirmed that treatment of cells with hydrogen peroxide induced increase of LC3 conversion and decrease of GFP-LC3 and SQSTM1 levels, but these changes by curcumin were almost completely blocked in the presence of antioxidant, N-acetylcystein (NAC), indicating that curcumin leads to reactive oxygen species (ROS) production, which results in autophagosome development and autolysosomal degradation. In parallel with NAC, SQSTM1 degradation was also diminished by bafilomycin A, a potent inhibitor of autophagosome-lysosome fusion, and cell viability assay was further confirmed that cucurmin-induced cell death was partially blocked by bafilomycin A as well as NAC. We also observed that NAC abolished curcumin-induced activation of extracelluar signal-regulated kinases (ERK) 1/2 and p38 mitogen-activated protein kinases (MAPK), but not Jun N-terminal kinase (JNK). However, the activation of ERK1/2 and p38 MAPK seemed to have no effect on the curcumin-induced autophagy, since both the conversion of LC3 protein and SQSTM1 degradation by curcumin was not changed in the presence of NAC. Taken together, our data suggest that curcumin induced ROS production, which resulted in autophagic activation and concomitant cell death in HCT116 human colon cancer cell

  14. Involvement of ROS in Curcumin-induced Autophagic Cell Death

    PubMed Central

    Lee, Youn Ju; Kim, Nam-Yi; Suh, Young-Ah

    2011-01-01

    Many anticancer agents as well as ionizing radiation have been shown to induce autophagy which is originally described as a protein recycling process and recently reported to play a crucial role in various disorders. In HCT116 human colon cancer cells, we found that curcumin, a polyphenolic phytochemical extracted from the plant Curcuma longa, markedly induced the conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II and degradation of sequestome-1 (SQSTM1) which is a marker of autophagosome degradation. Moreover, we found that curcumin caused GFP-LC3 formation puncta, a marker of autophagosome, and decrease of GFP-LC3 and SQSTM1 protein level in GFP-LC3 expressing HCT116 cells. It was further confirmed that treatment of cells with hydrogen peroxide induced increase of LC3 conversion and decrease of GFP-LC3 and SQSTM1 levels, but these changes by curcumin were almost completely blocked in the presence of antioxidant, N-acetylcystein (NAC), indicating that curcumin leads to reactive oxygen species (ROS) production, which results in autophagosome development and autolysosomal degradation. In parallel with NAC, SQSTM1 degradation was also diminished by bafilomycin A, a potent inhibitor of autophagosome-lysosome fusion, and cell viability assay was further confirmed that cucurmin-induced cell death was partially blocked by bafilomycin A as well as NAC. We also observed that NAC abolished curcumin-induced activation of extracelluar signal-regulated kinases (ERK) 1/2 and p38 mitogen-activated protein kinases (MAPK), but not Jun N-terminal kinase (JNK). However, the activation of ERK1/2 and p38 MAPK seemed to have no effect on the curcumin-induced autophagy, since both the conversion of LC3 protein and SQSTM1 degradation by curcumin was not changed in the presence of NAC. Taken together, our data suggest that curcumin induced ROS production, which resulted in autophagic activation and concomitant cell death in HCT116 human colon cancer cell

  15. Molecular targets of curcumin for cancer therapy: an updated review.

    PubMed

    Kasi, Pandima Devi; Tamilselvam, Rajavel; Skalicka-Woźniak, Krystyna; Nabavi, Seyed Fazel; Daglia, Maria; Bishayee, Anupam; Pazoki-Toroudi, Hamidreza; Nabavi, Seyed Mohammad

    2016-10-01

    In recent years, natural edible products have been found to be important therapeutic agents for the treatment of chronic human diseases including cancer, cardiovascular disease, and neurodegeneration. Curcumin is a well-known diarylheptanoid constituent of turmeric which possesses anticancer effects under both pre-clinical and clinical conditions. Moreover, it is well known that the anticancer effects of curcumin are primarily due to the activation of apoptotic pathways in the cancer cells as well as inhibition of tumor microenvironments like inflammation, angiogenesis, and tumor metastasis. In particular, extensive studies have demonstrated that curcumin targets numerous therapeutically important cancer signaling pathways such as p53, Ras, PI3K, AKT, Wnt-β catenin, mTOR and so on. Clinical studies also suggested that either curcumin alone or as combination with other drugs possess promising anticancer effect in cancer patients without causing any adverse effects. In this article, we critically review the available scientific evidence on the molecular targets of curcumin for the treatment of different types of cancer. In addition, we also discuss its chemistry, sources, bioavailability, and future research directions.

  16. Trypanocidal activity of free and nanoencapsulated curcumin on Trypanosoma evansi.

    PubMed

    Gressler, L T; Oliveira, C B; Coradini, K; Dalla Rosa, L; Grando, T H; Baldissera, M D; Zimmermann, C E; Da Silva, A S; Almeida, T C; Hermes, C L; Wolkmer, P; Silva, C B; Moreira, K L S; Beck, R C R; Moresco, R N; Da Veiga, M L; Stefani, L M; Monteiro, S G

    2015-03-01

    This study aimed to evaluate in vitro and in vivo trypanocidal activity of free and nanoencapsulated curcumin against Trypanosoma evansi. In vitro efficacy of free curcumin (CURC) and curcumin-loaded in lipid-core nanocapsules (C-LNCs) was evaluated to verify their lethal effect on T. evansi. To perform the in vivo tests, T. evansi-infected animals were treated with CURC (10 and 100 mg kg(-1), intraperitoneally [i.p.]) and C-LNCs (10 mg kg(-1), i.p.) during 6 days, with the results showing that these treatments significantly attenuated the parasitaemia. Infected untreated rats showed protein peroxidation and an increase of nitrites/nitrates, whereas animals treated with curcumin showed a reduction on these variables. As a result, the activity of antioxidant enzymes (superoxide dismutase and catalase) differs between groups (P<0.05). Infected animals and treated with CURC exhibited a reduction in the levels of alanine aminotransferase and creatinine, when compared with the positive control group. The use of curcumin in vitro resulted in a better parasitaemia control, an antioxidant activity and a protective effect on liver and kidney functions of T. evansi-infected adult male Wistar rats.

  17. Enhanced apoptotic effect of curcumin loaded solid lipid nanoparticles.

    PubMed

    Vandita, Kakkar; Shashi, Bhushan; Santosh, Kumar Guru; Pal, Kaur Indu

    2012-12-03

    Curcumin is reported to show potent in vitro anticancer effects in a surfeit of human cancer cell lines and majorly in the carcinogenesis of GIT, in animals. Its poor pharmacokinetics and stability limit its vivo clinical efficacy for the other systemic cancers. We recently reported on a 32-155 times enhancement in bioavailability of curcumin when incorporated into solid lipid nanoparticles (C-SLNs). Presently we report on a 54-85% reduction in IC 50 values with developed C-SLNs in comparison to free curcumin against a panel of human cancer cell lines (HL-60, A549, and PC3). Results demonstrate mechanisms similar to those claimed for free curcumin, including induction of cellular apoptosis by activation of caspases, release of cyctochrome c, loss of membrane potential, blockade of nuclear factor kappa B (NF-κB) activation, and upregulation of TNF-R for C-SLNs. However, the extent of cell death provided by C-SLNs in all these tests was significantly higher (p < 0.001). This may be attributed to the presentation of curcumin in a dispersible/soluble form which enhanced permeability across the cell surface. The display of significantly better in vitro anticancer effect coupled with high in vivo bioavailability points toward a great potential of using C-SLNs for cancer therapeutics.

  18. Curcumin alleviates oxidative stress and mitochondrial dysfunction in astrocytes.

    PubMed

    Daverey, Amita; Agrawal, Sandeep K

    2016-10-01

    Oxidative stress plays a critical role in various neurodegenerative diseases, thus alleviating oxidative stress is a potential strategy for therapeutic intervention and/or prevention of neurodegenerative diseases. In the present study, alleviation of oxidative stress through curcumin is investigated in A172 (human glioblastoma cell line) and HA-sp (human astrocytes cell line derived from the spinal cord) astrocytes. H2O2 was used to induce oxidative stress in astrocytes (A172 and HA-sp). Data show that H2O2 induces activation of astrocytes in dose- and time-dependent manner as evident by increased expression of GFAP in A172 and HA-sp cells after 24 and 12h respectively. An upregulation of Prdx6 was also observed in A172 and HA-sp cells after 24h of H2O2 treatment as compared to untreated control. Our data also showed that curcumin inhibits oxidative stress-induced cytoskeleton disarrangement, and impedes the activation of astrocytes by inhibiting upregulation of GFAP, vimentin and Prdx6. In addition, we observed an inhibition of oxidative stress-induced inflammation, apoptosis and mitochondria fragmentation after curcumin treatment. Therefore, our results suggest that curcumin not only protects astrocytes from H2O2-induced oxidative stress but also reverses the mitochondrial damage and dysfunction induced by oxidative stress. This study also provides evidence for protective role of curcumin on astrocytes by showing its effects on attenuating reactive astrogliosis and inhibiting apoptosis.

  19. Curcumin Reduces the Noise-Exposed Cochlear Fibroblasts Apoptosis

    PubMed Central

    Haryuna, Tengku Siti Hajar; Riawan, Wibi; Nasution, Ardyansyah; Ma'at, Suprapto; Harahap, Juliandi; Adriztina, Indri

    2016-01-01

    Introduction The structural changes underlying permanent noise-induced hearing loss (NIHL) include loss of the sensory hair cells, damage to their stereocilia, and supporting tissues within the cochlear lateral wall. Objective The objective of this study is to demonstrate curcumin as a safe and effective therapeutic agent in the prevention and treatment for fibroblasts damage within the cochlear supporting tissues and lateral wall through cell death pathway. Methods We divided 24 Rattus norvegicus into 4 groups, Group 1: control; Group 2: noise (+); Group 3: noise (+), 50 mg/day curcumin (+); Group 4: noise (+), 100 mg/day curcumin (+). We provided the noise exposure dose at 100 dB SPL for two hours over two weeks and administered the curcumin orally over two weeks. We examined all samples for the expressions of calcineurin, nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and apoptotic index of cochlear fibroblasts. Results We found significant differences for the expressions of calcineurin (p < 0.05) in all groups, significant differences for the expressions of NFATc1 (p < 0.05) in all groups, except in Groups 1 and 4, and significant differences for the apoptotic index (p < 0.05) in all groups. Conclusion Curcumin proved to be potentially effective in the prevention and treatment for fibroblasts damage within the cochlear supporting tissues and lateral wall regarding the decreased expression of calcineurin, NFATc1, and apoptotic index of cochlear fibroblasts. PMID:27746842

  20. Lipid Based Nanosystems for Curcumin: Past, Present and Future.

    PubMed

    Nayak, Aditya P; Mills, Tom; Norton, Ian

    2016-01-01

    Curcumin is one of the principle bioactive compounds used in the ayurvedic medicine system that has the history of over 5000 years for human use. Curcumin an "Indian Gold" is used to treat simple ailments like the common cold to severe life threatening diseases like cancer, and HIV. Though its contribution is immense for the health protection and disease prevention, its clinical use is limited due to its susceptible nature to alkaline pH, high temperature, presence of oxygen and light. Hence it becomes extremely difficult to maintain its bioactivity during processing, storage and consumption. Recent advancements in the application of nanotechnology to curcumin offer an opportunity to enhance its stability, bioactivity and to overcome its pharmacokinetic mismatch. This in turn helps to bridge the gaps that exist between its bench top research data to its clinical findings. Among the various types of nano/micro delivery systems, lipid based delivery systems are well studied and are the best suited delivery systems to enhance the stability and pharmacokinetic profile of curcumin both for pharma and the food application. In the current review, effort will be made to recapitulate the work done in the past to use lipid based delivery systems (liposomes, solid lipid nanoparticles, and emulsions) to enhance the application of curcumin for health promotion and disease prevention. Further, future prospects for the utilization of these lipid-based delivery systems will be discussed in detail.

  1. Synthesis and characterization of chitosan/curcumin blends based polyurethanes.

    PubMed

    Zia, Fatima; Zia, Khalid Mahmood; Zuber, Mohammad; Rehman, Saima; Tabasum, Shazia; Sultana, Salma

    2016-11-01

    In this work, new hexamethylene diisocyanate (HMDI) and hyroxylterminated polybutadiene (HTPB) based polyurethanes (PUs) were prepared following step growth polymerization by the introduction of varying mole ratio of chitosan (CH) and curcumin (CUR). Structural study of blends through infrared spectroscopy confirmed the incorporation of CH and CUR into the backbone of the PU. The scanning electron microscopic (SEM) study confirmed the well dispersion of incorporated chitosan/curcumin and homogeneity of surface of synthesized samples. Thermogravimetric analysis (TGA) of PU blends indicated a better thermal stability with 0.25M:0.75M of chitosan to curcumin. Mechanical properties such as modulus and tensile strength of PU blends were found to be better with higher contents of chitosan and curcumin. The same extender composition (1mol BDO, 075mol chitosan and 0.25mol curcumin) based PU showed higher substantial of antimicrobial activity as compared to the all other PUs. On the whole, this work is actually a step towards the generation of novel biocompatible materials preferably useful for biomedical applications.

  2. Fatty acid analogs

    DOEpatents

    Elmaleh, David R.; Livni, Eli

    1985-01-01

    In one aspect, a radioactively labeled analog of a fatty acid which is capable of being taken up by mammalian tissue and which exhibits an in vivo beta-oxidation rate below that with a corresponding radioactively labeled fatty acid.

  3. Challenges in Using Analogies

    NASA Astrophysics Data System (ADS)

    Lin, Shih-Yin; Singh, Chandralekha

    2011-11-01

    Learning physics requires understanding the applicability of fundamental principles in a variety of contexts that share deep features.1-7 One way to help students learn physics is via analogical reasoning. Students can be taught to make an analogy between situations that are more familiar or easier to understand and another situation where the same physics principle is involved but that is more difficult to handle. Here, we examine introductory physics students' ability to use analogies in solving problems involving Newton's second law. Students enrolled in an algebra-based introductory physics course were given a solved problem involving tension in a rope and were then asked to solve another problem for which the physics is very similar but involved a frictional force. They were asked to point out the similarities between the two problems and then use the analogy to solve the friction problem.

  4. Curcumin-induced autophagy contributes to the decreased survival of oral cancer cells.

    PubMed

    Kim, Ji Young; Cho, Tae Jin; Woo, Bok Hee; Choi, Kyung Un; Lee, Chang Hun; Ryu, Mi Heon; Park, Hae Ryoun

    2012-08-01

    Curcumin, a major active component of turmeric Curcuma longa, has been shown to have inhibitory effects on cancers. In vitro studies suggest that curcumin inhibits cancer cell growth by activating apoptosis, but the mechanism underlying the anticancer effects of curcumin is unclear. Recently, it has been suggested that autophagy may play an important role in cancer therapy. However, little data are available regarding the role of autophagy in oral cancers. In this study, we have shown that curcumin has anticancer activity against oral squamous cell carcinoma (OSCC). Induction of autophagy, marked by autophagic vacuoles formation, was detected by acridine orange staining and monodansylcadaverine (MDC) dye after exposure to curcumin. Conversion of LC3-I to LC3-II, a marker of active autophagosome formation, was also detectable by Western blot following curcumin treatment. We have also observed that curcumin induced reactive oxygen species (ROS) production and autophagic vacuoles formation by curcumin was almost completely blocked in the presence of N-acetylcystein (NAC), an antioxidant. Rescue experiments using an autophagy inhibitor suppressed curcumin-induced cell death in OSCC, confirming that autophagy acts as a pro-death signal. Furthermore, curcumin shows anticancer activity against OSCC via both autophagy and apoptosis. These findings suggest that curcumin may potentially contribute to oral cancer treatment and provide useful information for the development of a new therapeutic agent.

  5. Protective effects of curcumin on amyloid-β-induced neuronal oxidative damage.

    PubMed

    Huang, Han-Chang; Chang, Ping; Dai, Xue-Ling; Jiang, Zhao-Feng

    2012-07-01

    To investigate the protective effects of curcumin against amyloid-β (Aβ)-induced neuronal damage. Primary rat cortical neurons were cultured with different treatments of Aβ and curcumin. Neuronal morphologies, viability and damage were assessed. Neuronal oxidative stress was assessed, including extracellular hydrogen peroxide and intracellular reactive oxygen species. The abilities of curcumin to scavenge free radicals and to inhibit Aβ aggregation and β-sheeted formation are further assessed and discussed. Curcumin preserves cell viability, which is decreased by Aβ. The results of changed morphology, released Lactate dehydrogenases and cell viability assays indicate that curcumin protects Aβ-induced neuronal damage. Curcumin depresses Aβ-induced up-regulation of neuronal oxidative stress. The treatment sequence impacts the protective effect of curcumin on Aβ-induced neuronal damage. Curcumin shows a more protective effect on neuronal oxidative damage when curcumin was added into cultured neurons not later than Aβ, especially prior to Aβ. The abilities of curcumin to scavenge free radicals and to inhibit the formation of β-sheeted aggregation are both beneficial to depress Aβ-induced oxidative damage. Curcumin prevents neurons from Aβ-induced oxidative damage, implying the therapeutic usage for the treatment of Alzheimer's disease patients.

  6. Study on interaction between curcumin and pepsin by spectroscopic and docking methods.

    PubMed

    Ying, Ming; Huang, Fengwen; Ye, Haidong; Xu, Hong; Shen, Liangliang; Huan, Tianwen; Huang, Shitong; Xie, Jiangfeng; Tian, Shengli; Hu, Zhangli; He, Zhendan; Lu, Jun; Zhou, Kai

    2015-08-01

    The interaction between curcumin and pepsin was investigated by fluorescence, synchronous fluorescence, UV-vis absorption, circular dichroism (CD), and molecular docking. Under physiological pH value in stomach, the fluorescence of pepsin can be quenched effectively by curcumin via a combined quenching process. Binding constant (Ka) and binding site number (n) of curcumin to pepsin were obtained. According to the theory of Förster's non-radiation energy transfer, the distance r between pepsin and curcumin was found to be 2.45 nm within the curcumin-pepsin complex, which implies that the energy transfer occurs between curcumin and pepsin, leading to the quenching of pepsin fluorescence. Fluorescence experiments also suggest that curcumin is located more closely to tryptophan residues than tyrosine residues. CD spectra together with UV-vis absorbance studies show that binding of curcumin to pepsin results in the extension of peptide strands of pepsin with loss of some β-sheet structures. Thermodynamic parameters calculated from the binding constants at different temperatures reveal that hydrophobic force plays a major role in stabilizing the curcumin-pepsin complex. In addition, docking results support the above experimental findings and suggest the possible hydrogen bonds of curcumin with Thr-77, Thr-218, and Glu-287 of pepsin, which help further stabilize the curcumin-pepsin complex.

  7. Localization and dynamics of the anticarcinogenic curcumin with GM1 and other miceller assemblies.

    PubMed

    Patra, Malay; Mandal, Manoj; Chakrabarti, Abhijit; Mukhopadhyay, Chaitali

    2017-04-01

    Structural transitions involving shape changes play an important role in cellular physiology and enhance the bioavailability of the natural food like curcumin in surfactant aggregates. In this work, we have studied the localization, dynamics and stability of curcumin in various miceller assemblies using a combination of absorbance and fluorescence spectroscopic approaches. The measurements of absorption and fluorescence spectra of curcumin revealed that the nature of interactions of ionic and nonionic surfactants and the glycosphingolipid, GM1 with curcumin is significantly different with surfactant concentrations. At low concentrations of SDS and the GM1 the head group of SDS and GM1 binds to the central β-diketone group of curcumin to form SDS-curcumin or GM1-curcumin complexes. At high concentrations, both formed micelles with curcumin completely solubilized inside. Cucurmin is solubilized in the stern layer of SDS micelles. Compared to spherical micelles, rod shaped micelles allow more curcumin to bind through hydrophobic interactions indicated by higher absorption and fluorescence, enhanced partition coefficient and stability. Whereas curcumin associates with GM1 micelles with lower partition coefficient, solubility and remain closer to aqueous phase decreasing its bioavailability and stability. While cucurmin is solubilized in the palisade layer of deoxycholate and octyl glucopyranoside micelles through the alkyl chains providing more hydrophobic microenvironment to curcumin with enhanced stability and bioavailability. Graphical abstract Schematic diagram of the two different types of detergent micelles and larger GM1 micelles.

  8. Antimicrobial activity of curcumin-loaded myristic acid microemulsions against Staphylococcus epidermidis.

    PubMed

    Liu, Chi-Hsien; Huang, Hsin-Ying

    2012-01-01

    The bactericidal properties of myristic acid and curcumin were revealed in a number of studies. However, whether curcumin-loaded myristic acid microemulsions can be used to inhibit Staphylococcus epidermidis, which causes nosocomial infections, has not been reported. Our aim was to develop curcumin-loaded myristic acid microemulsions to inhibit S. epidermidis on the skin. The interfacial tension, size distribution, and viscosity data of the microemulsions were characterized to elucidate the physicochemical properties of the curcumin microemulsions. Curcumin distribution in neonate pig skin was visualized using confocal laser scanning microscopy. Dermal curcumin accumulation (326 µg/g skin) and transdermal curcumin penetration (87 µg/cm(2)/d) were obtained with the microemulsions developed herein. Curcumin at the concentration of 0.86 µg/mL in the myristic acid microemulsion could inhibit 50% of the bacterial growth, which was 12 times more effective than curcumin dissolved in dimethyl sulfoxide (DMSO). The cocktail combination of myristic acid and curcumin in the microemulsion carrier synergistically inhibited the growth of S. epidermidis. The results we obtained highlight the potential of using curcumin-loaded microemulsions as an alternative treatment for S. epidermidis-associated diseases and acne vulgaris.

  9. FGF growth factor analogs

    DOEpatents

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  10. A Potential Role of the Curry Spice Curcumin in Alzheimer’s Disease

    PubMed Central

    Ringman, John M.; Frautschy, Sally A.; Cole, Gregory M.; Masterman, Donna L.; Cummings, Jeffrey L.

    2005-01-01

    There is substantial in-vitro data indicating that curcumin has antioxidant, anti-inflammatory, and anti-amyloid activity. In addition, studies in animal models of Alzheimer’s disease (AD) indicate a direct effect of curcumin in decreasing the amyloid pathology of AD. As the widespread use of curcumin as a food additive and relatively small short-term studies in humans suggest safety, curcumin is a promising agent in the treatment and/or prevention of AD. Nonetheless, important information regarding curcumin bioavailability, safety and tolerability, particularly in an elderly population is lacking. We are therefore performing a study of curcumin in patients with AD to gather this information in addition to data on the effect of curcumin on biomarkers of AD pathology. PMID:15974909

  11. Discovery of a new function of curcumin which enhances its anticancer therapeutic potency

    NASA Astrophysics Data System (ADS)

    Nagahama, Koji; Utsumi, Tomoya; Kumano, Takayuki; Maekawa, Saeko; Oyama, Naho; Kawakami, Junji

    2016-08-01

    Curcumin has received immense attention over the past decades because of its diverse biological activities and recognized as a promising drug candidate in a large number of diseases. However, its clinical application has been hindered due to extremely low aqueous solubility, chemical stability, and cellular uptake. In this study, we discovered quite a new function of curcumin, i.e. pH-responsive endosomal disrupting activity, derived from curcumin’s self-assembly. We selected anticancer activity as an example of biological activities of curcumin, and investigated the contribution of pH-responsive property to its anticancer activity. As a result, we demonstrated that the pH-responsive property significantly enhances the anticancer activity of curcumin. Furthermore, we demonstrated a utility of the pH-responsive property of curcumin as delivery nanocarriers for doxorubicin toward combination cancer therapy. These results clearly indicate that the smart curcumin assemblies act as promising nanoplatform for development of curcumin-based therapeutics.

  12. Synergic Antibacterial Effect of Curcumin with Ampicillin; Free Drug Solutions in Comparison with SLN Dispersions.

    PubMed

    Alihosseini, Faezeh; Azarmi, Shirzad; Ghaffari, Solmaz; Haghighat, Setareh; Rezayat Sorkhabadi, Seyed Mahdi

    2016-09-01

    Purpose: This study was designed to investigate benefit of using nanotechnology on increasing of synergic antibacterial effect of natural and chemical antibacterial agents. Methods: At first the MIC and MBC of Curcumin and Ampicillin as selected antibacterial agents was determined, after that Solid Lipid Nanoparticles (SLNs) of each active ingredients as well as Curcumin-Ampicillin loaded SLNs were prepared using high pressure homogenization technique. Characterization of prepared SLNs was done, then MIC, MBC and contact killing time were investigated for Curcumin-Ampicillin loaded SLNs in comparison with free Curcumin and Ampicillin solutions as well as Ampicillin and Curcumin SLNs. Results: Based on results nanoparticles with the size of 150 nm show much more decreased MIC and MBC when Ampicillin and Curcumin were loaded together on SLNs than solutions in which free Ampicillin and Curcumin were mixed. Conclusion: It seems that using nanotechnology could cause decrease the dosage of antibiotics and risk of having antibiotic resistance bacteria strains.

  13. Curcumin Reduces Amyloid Fibrillation of Prion Protein and Decreases Reactive Oxidative Stress

    PubMed Central

    Lin, Chi-Fen; Yu, Kun-Hua; Jheng, Cheng-Ping; Chung, Raymond; Lee, Cheng-I

    2013-01-01

    Misfolding and aggregation into amyloids of the prion protein (PrP) is responsible for the development of fatal transmissible neurodegenerative diseases. Various studies on curcumin demonstrate promise for the prevention of Alzheimer’s disease and inhibition of PrPres accumulation. To evaluate the effect of curcumin on amyloid fibrillation of prion protein, we first investigated the effect of curcumin on mouse prion protein (mPrP) in a cell-free system. Curcumin reduced the prion fibril formation significantly. Furthermore, we monitored the change in apoptosis and reactive oxygen species (ROS) level upon curcumin treatment in mouse neuroblastoma cells (N2a). Curcumin effectively rescues the cells from apoptosis and decreases the ROS level caused by subsequent co-incubation with prion amyloid fibrils. The assays in cell-free mPrP and in N2a cells of this work verified the promising effect of curcumin on the prevention of transmissible neurodegenerative diseases. PMID:25437204

  14. A potential role of the curry spice curcumin in Alzheimer's disease.

    PubMed

    Ringman, John M; Frautschy, Sally A; Cole, Gregory M; Masterman, Donna L; Cummings, Jeffrey L

    2005-04-01

    There is substantial in-vitro data indicating that curcumin has antioxidant, anti-inflammatory, and anti-amyloid activity. In addition, studies in animal models of Alzheimer's disease (AD) indicate a direct effect of curcumin in decreasing the amyloid pathology of AD. As the widespread use of curcumin as a food additive and relatively small short-term studies in humans suggest safety, curcumin is a promising agent in the treatment and/or prevention of AD. Nonetheless, important information regarding curcumin bioavailability, safety and tolerability, particularly in an elderly population is lacking. We are therefore performing a study of curcumin in patients with AD to gather this information in addition to data on the effect of curcumin on biomarkers of AD pathology.

  15. Synergic Antibacterial Effect of Curcumin with Ampicillin; Free Drug Solutions in Comparison with SLN Dispersions

    PubMed Central

    Alihosseini, Faezeh; Azarmi, Shirzad; Ghaffari, Solmaz; Haghighat, Setareh; Rezayat Sorkhabadi, Seyed Mahdi

    2016-01-01

    Purpose: This study was designed to investigate benefit of using nanotechnology on increasing of synergic antibacterial effect of natural and chemical antibacterial agents. Methods: At first the MIC and MBC of Curcumin and Ampicillin as selected antibacterial agents was determined, after that Solid Lipid Nanoparticles (SLNs) of each active ingredients as well as Curcumin-Ampicillin loaded SLNs were prepared using high pressure homogenization technique. Characterization of prepared SLNs was done, then MIC, MBC and contact killing time were investigated for Curcumin-Ampicillin loaded SLNs in comparison with free Curcumin and Ampicillin solutions as well as Ampicillin and Curcumin SLNs. Results: Based on results nanoparticles with the size of 150 nm show much more decreased MIC and MBC when Ampicillin and Curcumin were loaded together on SLNs than solutions in which free Ampicillin and Curcumin were mixed. Conclusion: It seems that using nanotechnology could cause decrease the dosage of antibiotics and risk of having antibiotic resistance bacteria strains. PMID:27766232

  16. Extraction of Curcumin Pigment from Indonesian Local Turmeric with Its Infrared Spectra and Thermal Decomposition Properties

    NASA Astrophysics Data System (ADS)

    Nandiyanto, A. B. D.; Wiryani, A. S.; Rusli, A.; Purnamasari, A.; Abdullah, A. G.; Ana; Widiaty, I.; Hurriyati, R.

    2017-03-01

    Curcumin is one of the pigments which is used as a spice in Asian cuisine, traditional cosmetic, and medicine. Therefore, process for getting curcumin has been widely studied. Here, the purpose of this study was to demonstrate the simple method for extracting curcumin from Indonesian local turmeric and investigate the infrared spectra and thermal decomposition properties. In the experimental procedure, the washed turmeric was dissolved into an ethanol solution, and then put into a rotary evaporator to enrich curcumin concentration. The result showed that the present method is effective to isolate curcumin compound from Indonesian local turmeric. Since the process is very simple, this method can be used for home industrial application. Further, understanding the thermal decomposition properties of curcumin give information, specifically relating to the selection of treatment when curcumin must face the thermal-related process.

  17. Electrical Circuits and Water Analogies

    ERIC Educational Resources Information Center

    Smith, Frederick A.; Wilson, Jerry D.

    1974-01-01

    Briefly describes water analogies for electrical circuits and presents plans for the construction of apparatus to demonstrate these analogies. Demonstrations include series circuits, parallel circuits, and capacitors. (GS)

  18. Curcumin suppresses proliferation of colon cancer cells by targeting CDK2.

    PubMed

    Lim, Tae-Gyu; Lee, Sung-Young; Huang, Zunnan; Lim, Do Young; Chen, Hanyong; Jung, Sung Keun; Bode, Ann M; Lee, Ki Won; Dong, Zigang

    2014-04-01

    Curcumin, the yellow pigment of turmeric found in Southeast Indian food, is one of the most popular phytochemicals for cancer prevention. Numerous reports have demonstrated modulation of multiple cellular signaling pathways by curcumin and its molecular targets in various cancer cell lines. To identify a new molecular target of curcumin, we used shape screening and reverse docking to screen the Protein Data Bank against curcumin. Cyclin-dependent kinase 2 (CDK2), a major cell-cycle protein, was identified as a potential molecular target of curcumin. Indeed, in vitro and ex vivo kinase assay data revealed a dramatic suppressive effect of curcumin on CDK2 kinase activity. Furthermore, curcumin induced G1 cell-cycle arrest, which is regulated by CDK2 in HCT116 cells. Although the expression levels of CDK2 and its regulatory subunit, cyclin E, were not changed, the phosphorylation of retinoblastoma (Rb), a well-known CDK2 substrate, was reduced by curcumin. Because curcumin induced cell-cycle arrest, we investigated the antiproliferative effect of curcumin on HCT116 colon cancer cells. In this experiment, curcumin suppressed HCT116 cell proliferation effectively. To determine whether CDK2 is a direct target of curcumin, CDK2 expression was knocked down in HCT116 cells. As expected, HCT116 sh-CDK2 cells exhibited G1 arrest and reduced proliferation. Because of the low levels of CDK2 in HCT116 sh-CDK2 cells, the effects of curcumin on G1 arrest and cell proliferation were not substantially relative to HCT116 sh-control cells. From these results, we identified CDK2 as a direct target of curcumin in colon cancer cells.

  19. Polymeric nanogel formulations of nucleoside analogs

    PubMed Central

    Vinogradov, Serguei V

    2008-01-01

    Nanogels are colloidal microgel carriers that have been introduced recently as a prospective drug delivery system for nucleotide therapeutics. The crosslinked protonated polymer network of nanogels binds oppositely charged drug molecules, encapsulating them into submicron particles with a core-shell structure. The nanogel network also provides a suitable template for chemical engineering, surface modification and vectorisation. This review reveals recent attempts to develop novel drug formulations of nanogels with antiviral and antiproliferative nucleoside analogs in the active form of 5′-triphosphates; discusses structural approaches to the optimisation of nanogel properties, and; discusses the development of targeted nanogel drug formulations for systemic administration. Notably, nanogels can improve the CNS penetration of nucleoside analogs that are otherwise restricted from passing across the blood–brain barrier. The latest findings reviewed here demonstrate an efficient intracellular release of nucleoside analogs, encouraging further applications of nanogel carriers for targeted drug delivery. PMID:17184158

  20. Insights into the importance for designing curcumin-inspired anticancer agents by a prooxidant strategy: The case of diarylpentanoids.

    PubMed

    Dai, Fang; Liu, Guo-Yun; Li, Yan; Yan, Wen-Jing; Wang, Qi; Yang, Jie; Lu, Dong-Liang; Ding, De-Jun; Lin, Dong; Zhou, Bo

    2015-08-01

    Developing anticancer agents by a prooxidant strategy has attracted increasing attention in recent years, although it is not conventional in medicinal chemistry and is completely opposite to antioxidant therapy. In this work, a panel of diarylpentanoids as the curcumin mono-carbonyl analogs were designed and synthesized, and their cytotoxic and proapoptotic mechanisms against human lung cancer A549 cells were investigated at the frontiers of chemistry and biology. It was found that compared with curcumin, the compounds (A1, B1, and C1) bearing two ortho substituents on the aromatic rings, especially A1, exhibit significantly increased cytotoxic and proapoptotic activities through a Michael acceptor unit-dependent prooxidant-mediated mechanism. The prooxidative ability is governed not only by their electrophilicity but also by their geometry, cellular uptake and metabolic stability, and TrxR-inhibitory activity. Mechanistic investigation reveals that the compound A1 could effectively and irreversibly modify the TrxR by virtue of the above optimal biochemical parameters, and convert this antioxidant enzyme into a reactive oxygen species (ROS) promoter, resulting in a burst of the intracellular ROS including H2O2 and O2(-)•. The ROS generation is associated with falling apart in the redox buffering system, and subsequently induces increases in Ca(2+) influx and oxidative stress, collapse of mitochondrial membrane potential, and activation of caspase-9 and caspase-3, ultimately leading to cell apoptosis. This work highlights the feasibility in designing curcumin-inspired anticancer agents by a prooxidant strategy, and gives us useful information on how to design them.

  1. Controlled release of curcumin from curcumin-loaded nanomicelles to prevent peritendinous adhesion during Achilles tendon healing in rats.

    PubMed

    Zhang, Weizhong; Li, Xuanyi; Comes Franchini, Mauro; Xu, Ke; Locatelli, Erica; Martin, Robert C; Monaco, Ilaria; Li, Yan; Cui, Shusen

    2016-01-01

    We introduced curcumin-loaded nanomicelles into a tendon-healing model to evaluate their effects on tendon healing and adhesion. Three groups consisting of 36 rats underwent rupture and repair of the Achilles tendon. The treatment group received an injection of curcumin-loaded nanomicelles (gold nanorods [GNRs]-1/curcumin in polymeric nanomicelles [curc@PMs] at a dosage of 0.44 mg curcumin/kg in 0.1 mL saline) into the surgical site and exposed to laser postoperatively at weeks 1, 2, and 3, for three times 10 seconds each, on the surgical site in the rats that underwent tendon rupture and repair, while the other two groups received 0.44 mg curcumin/kg in 0.1 mL saline and 0.1 mL of saline, respectively. The specimens were harvested at 4 weeks and subjected to biomechanical and histological evaluation. The scoring results of tendon adhesion indicated that GNRs-1/curc@PMs group was in the lowest grade of peritendinous adhesions compared to the other groups. Histological assessment further confirmed the preventive effect of GNRs-1/curc@PMs on tendon adhesion. These findings indicated greater tendon strength with less adhesion in the group treated with GNRs-1/curc@PMs combined with laser exposure, and that nanoparticle-based therapy may be applied to prevent adhesion in clinical patients.

  2. Controlled release of curcumin from curcumin-loaded nanomicelles to prevent peritendinous adhesion during Achilles tendon healing in rats

    PubMed Central

    Zhang, Weizhong; Li, Xuanyi; Comes Franchini, Mauro; Xu, Ke; Locatelli, Erica; Martin, Robert C; Monaco, Ilaria; Li, Yan; Cui, Shusen

    2016-01-01

    We introduced curcumin-loaded nanomicelles into a tendon-healing model to evaluate their effects on tendon healing and adhesion. Three groups consisting of 36 rats underwent rupture and repair of the Achilles tendon. The treatment group received an injection of curcumin-loaded nanomicelles (gold nanorods [GNRs]-1/curcumin in polymeric nanomicelles [curc@PMs] at a dosage of 0.44 mg curcumin/kg in 0.1 mL saline) into the surgical site and exposed to laser postoperatively at weeks 1, 2, and 3, for three times 10 seconds each, on the surgical site in the rats that underwent tendon rupture and repair, while the other two groups received 0.44 mg curcumin/kg in 0.1 mL saline and 0.1 mL of saline, respectively. The specimens were harvested at 4 weeks and subjected to biomechanical and histological evaluation. The scoring results of tendon adhesion indicated that GNRs-1/curc@PMs group was in the lowest grade of peritendinous adhesions compared to the other groups. Histological assessment further confirmed the preventive effect of GNRs-1/curc@PMs on tendon adhesion. These findings indicated greater tendon strength with less adhesion in the group treated with GNRs-1/curc@PMs combined with laser exposure, and that nanoparticle-based therapy may be applied to prevent adhesion in clinical patients. PMID:27382278

  3. Curcumin, resveratrol and flavonoids as anti-inflammatory, cyto- and DNA-protective dietary compounds.

    PubMed

    Bisht, Kavita; Wagner, Karl-Heinz; Bulmer, Andrew C

    2010-11-28

    Numerous dietary compounds, ubiquitous in fruits, vegetables and spices have been isolated and evaluated during recent years for their therapeutic potential. These compounds include flavonoid and non-flavonoid polyphenols, which describe beneficial effects against a variety of ailments. The notion that these plant products have health promoting effects emerged because their intake was related to a reduced incidence of cancer, cardiovascular, neurological, respiratory, and age-related diseases. Exposure of the body to a stressful environment challenges cell survival and increases the risk of chronic disease developing. The polyphenols afford protection against various stress-induced toxicities through modulating intercellular cascades which inhibit inflammatory molecule synthesis, the formation of free radicals, nuclear damage and induce antioxidant enzyme expression. These responses have the potential to increase life expectancy. The present review article focuses on curcumin, resveratrol, and flavonoids and seeks to summarize their anti-inflammatory, cytoprotective and DNA-protective properties.

  4. Controlled release of curcumin from poly(HEMA-MAPA) membrane.

    PubMed

    Caka, Müşerref; Türkcan, Ceren; Aktaş Uygun, Deniz; Uygun, Murat; Akgöl, Sinan; Denizli, Adil

    2017-05-01

    In this work, poly(HEMA-MAPA) membranes were prepared by UV-polymerization technique. These membranes were characterized by SEM, FTIR, and swelling studies. Synthesized membranes had high porous structure. These membranes were used for controlled release of curcumin which is already used as folk remedy and used as drug for some certain diseases and cancers. Curcumin release was investigated for various pHs and temperatures. Optimum drug release yield was found to be as 70% at pH 7.4 and 37 °C within 2 h period. Time-depended release of curcumin was also investigated and its slow release from the membrane demonstrated within 48 h.

  5. Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

    PubMed Central

    Klinger, Neil V.

    2016-01-01

    Brain malignancies currently carry a poor prognosis despite the current multimodal standard of care that includes surgical resection and adjuvant chemotherapy and radiation. As new therapies are desperately needed, naturally occurring chemical compounds have been studied for their potential chemotherapeutic benefits and low toxicity profile. Curcumin, found in the rhizome of turmeric, has extensive therapeutic promise via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown it to be an effective treatment for brain tumors including glioblastoma multiforme. These effects are potentiated by curcumin's ability to induce G2/M cell cycle arrest, activation of apoptotic pathways, induction of autophagy, disruption of molecular signaling, inhibition of invasion, and metastasis and by increasing the efficacy of existing chemotherapeutics. Further, clinical data suggest that it has low toxicity in humans even at large doses. Curcumin is a promising nutraceutical compound that should be evaluated in clinical trials for the treatment of human brain tumors. PMID:27807473

  6. Effect of Curcumin Against Oxidation of Biomolecules by Hydroxyl Radicals

    PubMed Central

    Mahendra, Jaideep; Gurumurthy, Prema; Jayamathi; Iqbal, Shabeer S; Mahendra, Little

    2014-01-01

    Background: Among various reactive oxygen species, hydroxyl radicals have the strongest chemical activity, which can damage a wide range of essential biomolecules such as lipids, proteins, and DNA. Objective: The objective of this study was to investigate the beneficial effects of curcumin on prevention of oxidative damage of biomolecules by hydroxyl radicals generated in in vitro by a Fenton like reaction. Materials and Methods: We have incubated the serum, plasma and whole blood with H2O2/Cu2+/ Ascorbic acid system for 4 hours at 37 0C and observed the oxidation of biomolecules like albumin, lipids, proteins and DNA. Results: Curcumin at the concentrations of 50,100 and 200 μmoles, prevented the formation of ischemia modified albumin, MDA, protein carbonyls, oxidized DNA and increased the total antioxidant levels and GSH significantly. Conclusion: These observations suggest the hydroxyl radical scavenging potentials of curcumin and protective actions to prevent the oxidation of biomolecules by hydroxyl radicals. PMID:25478334

  7. Microencapsulation of curcumin in PLGA microcapsules by coaxial flow focusing

    NASA Astrophysics Data System (ADS)

    Lei, Fan; Si, Ting; Luo, Xisheng; Xu, Ronald X.

    2014-03-01

    Curcumin-loaded PLGA microcapsules are fabricated by a liquid-driving coaxial flow focusing device. In the process, a stable coaxial cone-jet configuration is formed under the action of a coflowing liquid stream and the coaxial liquid jet eventually breaks up into microcapsules because of flow instability. This process can be well controlled by adjusting the flow rates of three phases including the driving PVA water solution, the outer PLGA ethyl acetate solution and the inner curcumin propylene glycol solution. Confocal and SEM imaging methods clearly indicate the core-shell structure of the resultant microcapsules. The encapsulation rate of curcumin in PLGA is measured to be more than 70%, which is much higher than the tranditional methods such as emulsion. The size distribution of resultant microcapsules under different conditions is presented and compared. An in vitro release simulation platform is further developed to verify the feasibility and reliability of the method.

  8. Combining the rapid MTT formazan exocytosis assay and the MC65 protection assay led to the discovery of carbazole analogs as small molecule inhibitors of Abeta oligomer-induced cytotoxicity.

    PubMed

    Hong, Hyun-Seok; Maezawa, Izumi; Yao, Nianhuan; Xu, Bailing; Diaz-Avalos, Ruben; Rana, Sandeep; Hua, Duy H; Cheng, R Holland; Lam, Kit S; Jin, Lee-Way

    2007-01-26

    The discovery of small molecule inhibitors of cytotoxicity induced by amyloid-beta (Abeta) oligomers, either applied extracellularly or accumulated intraneuronally, is an important goal of drug development for Alzheimer's disease (AD), but has been limited by the lack of efficient screening methods. Here we describe our approach using two cell-based methods. The first method takes advantage of the unique ability of extracellularly applied Abeta oligomers to rapidly induce the exocytosis of formazan formed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). We employed a short protocol to quantify this toxicity, and quickly identified two novel inhibitors, code-named CP2 and A5, from two compound libraries. A second independent screen of the same libraries using our previously published MC65 protection assay, which identifies inhibitors of toxicity related to intracellular Abeta oligomers, also selected the same two leads, suggesting that both assays select for the same anti-Abeta oligomer properties displayed by these compounds. We further demonstrated that A5 attenuated the progressive aggregation of existing Abeta oligomers, reduced the level of intracellular Abeta oligomers, and prevented the Abeta oligomer-induced death of primary cortical neurons, effects similar to those demonstrated by CP2. Our results suggest that, when combined, the two methods would generate fewer false results and give a high likelihood of identifying leads that show promises in ameliorating Abeta oligomer-induced toxicities within both intraneuronal and extracellular sites. Both assays are simple, suitable for rapid screening of a large number of medicinal libraries, and amenable for automation.

  9. New Dendrimer-Based Nanoparticles Enhance Curcumin Solubility.

    PubMed

    Falconieri, Maria Cristina; Adamo, Mauro; Monasterolo, Claudio; Bergonzi, Maria Camilla; Coronnello, Marcella; Bilia, Anna Rita

    2017-03-01

    Curcumin, the main curcuminoid of the popular Indian spice turmeric, is a potent chemopreventive agent and useful in many different diseases. A major limitation of applicability of curcumin as a health promoting and medicinal agent is its extremely low bioavailability due to efficient first pass metabolism, poor gastrointestinal absorption, rapid elimination, and poor aqueous solubility. In the present study, nanotechnology was selected as a choice approach to enhance the bioavailability of the curcuminis. A new polyamidoamine dendrimer (G0.5) was synthesized, characterized, and tested for cytotoxicity in human breast cancer cells (MCF-7). No cytotoxicity of G0.5 was found in the range between 10(-3) and 3 × 10(-8) M. Consequently, G0.5 was used to prepare spherical nanoparticles of ca. 150 nm, which were loaded with curcumin [molar ratio G0.5/curcumin 1 : 1 (formulation 1) and 1 : 0.5 (formulation 2)]. Remarkably, the occurrence of a single population of nanoparticles having an excellent polydispersity index (< 0.20) was found in both formulations. Formulation 1 was selected to test in vitro drug release because it was superior in terms of encapsulation efficiency (62 %) and loading capacity (32 %). The solubility of curcumin was increased ca. 415 and 150 times with respect to the unformulated drug, respectively, for formulation 1 and formulation 2. The release of curcumin from the nanoparticles showed an interesting prolonged and sustained release profile.

  10. Acetal-linked polymeric prodrug micelles for enhanced curcumin delivery.

    PubMed

    Li, Man; Gao, Min; Fu, Yunlan; Chen, Chao; Meng, Xuan; Fan, Aiping; Kong, Deling; Wang, Zheng; Zhao, Yanjun

    2016-04-01

    On-demand curcumin delivery via stimuli-responsive micellar nanocarriers holds promise for addressing its solubility and stability problem. Polymer-curcumin prodrug conjugate micelle is one of such nanosystems. The diversity of linker and conjugation chemistry enabled the generation and optimization of different curcumin micelles with tunable stimuli-responsiveness and delivery efficiency. The aim of the current work was to generate and assess acetal-linked polymeric micelles to enrich the pH-responsive curcumin delivery platforms. Curcumin was slightly modified prior to conjugating to amphiphilic methoxy poly(ethylene glycol)-poly(lactic acid) (mPEG-PLA) copolymer via an acetal bond, whereas an ester bond-linked conjugate was used as the control. The acetal-containing micelles showed a hydrodynamic diameter of 91.1 ± 2.9(nm) and the accompanying core size of 63.5 ± 7.1 (nm) with a zeta potential of -10.9 ± 0.7(mV). Both control and pH-labile micelles displayed similar critical micelle concentration at 1.6 μM. The acetal-containing nanocarriers exhibited a pH-dependent drug release behavior, which was faster at lower pH values. The cytotoxicity study in HepG2 cells revealed a significantly lower IC50 at 51.7 ± 9.0(μM) for acetal-linked micelles in contrast to the control at 103.0 ± 17.8(μM), but the polymer residue showed no cytotoxicity upon drug release. The acetal-linked micellar nanocarrier could be a useful addition to the spectrum of currently available stimuli-responsive curcumin nano-formulations.

  11. Enhanced anti-cancer and antimicrobial activities of curcumin nanoparticles.

    PubMed

    Adahoun, Mo'ath Ahmad; Al-Akhras, Mohammed-Ali Hassan; Jaafar, Mohamad Suhaimi; Bououdina, Mohamed

    2017-02-01

    Background Curcumin (diferuloylmethane) is a polyphenol derived from the plant Curcuma longa, commonly called turmeric. Extensive research over the last 50 years has demonstrated that these polyphenols play an important role in the maintenance of health and prevention of diseases, in addition to its therapeutic benefits such as anti-tumor, anti-inflammatory, and anti-oxidant activities. Materials and methods This study is devoted to the enhancement of the solubility and bioavailability of curcumin nanoparticles prepared by a process based on a wet-milling technique and then examine in vitro against prostate cancer cell line 3 (PC3), human embryonic kidney cell line (HEK), human erythrocytes (red blood cells (RBCs)), and against fourth different bacterial strains two gram-positive (Micrococcus luteus ATCC 9341, Staphylococcus aureus ATCC 29213), two gram-negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853). Results The cell viability curve, the half maximal inhibitory concentration (IC50), and the minimum bactericidal concentration (MBC) were evaluated. Nanocurcumin displayed significant activity against cancer cell line (PC3) and low toxicity against normal cells (HEK) compared with parent curcumin in favor of PC3 (P < 0.05). In addition, it was found that the efficiency of toxicity for nanocurcumin against PC3 (E% = 59.66%) was much better than HEK (E% = 36.07%) compared with parent curcumin. The results also demonstrate that, although nanocurcumin has a little more ability to lays RBCs than parent curcumin after incubated 60 min, but the hemolysis % remained very low and there was no significant difference between hemolysis % of nanocurcumin and parent curcumin (P > 0.05). On the other hand, the results demonstrate that, the MBCs of nanocurcumin were lower than curcumin for all different bacterial strains. Moreover, the selected gram-positive bacteria had higher sensitivity than the selected gram-negative bacteria for both

  12. Molecule nanoweaver

    DOEpatents

    Gerald, II; Rex E.; Klingler, Robert J.; Rathke, Jerome W.; Diaz, Rocio; Vukovic, Lela

    2009-03-10

    A method, apparatus, and system for constructing uniform macroscopic films with tailored geometric assemblies of molecules on the nanometer scale. The method, apparatus, and system include providing starting molecules of selected character, applying one or more force fields to the molecules to cause them to order and condense with NMR spectra and images being used to monitor progress in creating the desired geometrical assembly and functionality of molecules that comprise the films.

  13. Solubility and stability of curcumin in solutions containing alginate and other viscosity modifying macromolecules. Studies of curcumin and curcuminoids. XXX.

    PubMed

    Tønnesen, H Hjorth

    2006-08-01

    The solubility, chemical- and photochemical stability of curcumin in aqueous solutions containing alginate, gelatin or other viscosity modifying macromolecules have been investigated in order to obtain an alternative to the use of surfactants or cyclodextrins. The solubility of curcumin in aqueous solution at pH 5 increased by a factor > or = 10(4) in the presence of 0.5% (w/v) alginate (various qualities) or gelatin compared to plain buffer, while propylene glycol alginate ester, cesapectin and sodium carboxymethyl cellulose did not have a similar solubilizing effect. The solubilization was slightly influenced by pH, ionic strength and type and concentration of buffer salts. The macromolecules do, however, not stabilize towards hydrolytic- or photolytic degradation of curcumin.

  14. Synthetic Biology: A Unifying View and Review Using Analog Circuits.

    PubMed

    Teo, Jonathan J Y; Woo, Sung Sik; Sarpeshkar, Rahul

    2015-08-01

    We review the field of synthetic biology from an analog circuits and analog computation perspective, focusing on circuits that have been built in living cells. This perspective is well suited to pictorially, symbolically, and quantitatively representing the nonlinear, dynamic, and stochastic (noisy) ordinary and partial differential equations that rigorously describe the molecular circuits of synthetic biology. This perspective enables us to construct a canonical analog circuit schematic that helps unify and review the operation of many fundamental circuits that have been built in synthetic biology at the DNA, RNA, protein, and small-molecule levels over nearly two decades. We review 17 circuits in the literature as particular examples of feedforward and feedback analog circuits that arise from special topological cases of the canonical analog circuit schematic. Digital circuit operation of these circuits represents a special case of saturated analog circuit behavior and is automatically incorporated as well. Many issues that have prevented synthetic biology from scaling are naturally represented in analog circuit schematics. Furthermore, the deep similarity between the Boltzmann thermodynamic equations that describe noisy electronic current flow in subthreshold transistors and noisy molecular flux in biochemical reactions has helped map analog circuit motifs in electronics to analog circuit motifs in cells and vice versa via a `cytomorphic' approach. Thus, a body of knowledge in analog electronic circuit design, analysis, simulation, and implementation may also be useful in the robust and efficient design of molecular circuits in synthetic biology, helping it to scale to more complex circuits in the future.

  15. Effect of curcumin-associated and lipid ligand-functionalized nanoliposomes on aggregation of the Alzheimer's Aβ peptide.

    PubMed

    Taylor, Mark; Moore, Susan; Mourtas, Spyridon; Niarakis, Anna; Re, Francesca; Zona, Cristiano; La Ferla, Barbara; Nicotra, Francesco; Masserini, Massimo; Antimisiaris, Sophia G; Gregori, Maria; Allsop, David

    2011-10-01

    The effect of various types of nanoliposomes (associated with curcumin, phosphatidic acid, cardiolipin, or GM1 ganglioside) on the aggregation of the amyloid-β(1-42) (Aβ(1-42)) peptide was investigated. Nanoliposomes incorporating curcumin (curcumin-liposomes) were prepared by adding curcumin in the lipid phase during liposome preparation, whereas curcumin surface-decorated liposomes were prepared by using a curcumin-lipid conjugate (lipid-S-curcumin liposomes) or by attaching a curcumin derivative on preformed liposomes by click chemistry (click-curcumin liposomes). The lipid ligands (phosphatidic acid, cardiolipin, or GM1) were also incorporated into nanoliposomes during their formation. All nanoliposomes with curcumin, or the curcumin derivative, were able to inhibit the formation of fibrillar and/or oligomeric Aβ in vitro. Of the three forms of curcumin liposomes tested, the click-curcumin type was by far the most effective. Liposomes with lipid ligands only inhibited Aβ fibril and oligomer formation at a very high ratio of liposome to peptide. Curcumin-based liposomes could be further developed as a novel treatment for Alzheimer's disease.

  16. Curcumin micelles improve mitochondrial function in neuronal PC12 cells and brains of NMRI mice - Impact on bioavailability.

    PubMed

    Hagl, Stephanie; Kocher, Alexa; Schiborr, Christina; Kolesova, Natalie; Frank, Jan; Eckert, Gunter P

    2015-10-01

    Curcumin, a polyphenolic compound abundant in the rhizome of Curcuma longa, has been reported to have various beneficial biological and pharmacological activities. Recent research revealed that curcumin might be valuable in the prevention and therapy of numerous disorders including neurodegenerative diseases like Alzheimer's disease. Due to its low absorption and quick elimination from the body, curcumin bioavailability is rather low which poses major problems for the use of curcumin as a therapeutic agent. There are several approaches to ameliorate curcumin bioavailability after oral administration, amongst them simultaneous administration with secondary plant compounds, micronization and micellation. We examined bioavailability in vivo in NMRI mice and the effects of native curcumin and a newly developed curcumin micelles formulation on mitochondrial function in vitro in PC12 cells and ex vivo in isolated mouse brain mitochondria. We found that curcumin micelles improved bioavailability of native curcumin around 10- to 40-fold in plasma and brain of mice. Incubation with native curcumin and curcumin micelles prevented isolated mouse brain mitochondria from swelling, indicating less mitochondrial permeability transition pore (mPTP) opening and prevention of injury. Curcumin micelles proved to be more efficient in preventing mitochondrial swelling in isolated mouse brain mitochondria and protecting PC12 cells from nitrosative stress than native curcumin. Due to their improved effectivity, curcumin micelles might be a suitable formulation for the prevention of mitochondrial dysfunction in brain aging and neurodegeneration.

  17. Resveratrol and curcumin synergistically induces apoptosis in cigarette smoke condensate transformed breast epithelial cells through a p21(Waf1/Cip1) mediated inhibition of Hh-Gli signaling.

    PubMed

    Mohapatra, Purusottam; Satapathy, Shakti Ranjan; Siddharth, Sumit; Das, Dipon; Nayak, Anmada; Kundu, Chanakya Nath

    2015-09-01

    Combination therapy using two or more small molecule inhibitors of aberrant signaling cascade in aggressive breast cancers is a promising therapeutic strategy over traditional monotherapeutic approaches. Here, we have studied the synergistic mechanism of resveratrol and curcumin induced apoptosis using in vitro (cigarette smoke condensate mediated transformed breast epithelial cell, MCF-10A-Tr) and in vivo (tumor xenograft mice) model system. Resveratrol exposure increased the intracellular uptake of curcumin in a dose dependent manner and caused apoptosis in MCF-10A-Tr cells. Approximately, ten fold lower IC50 value was noted in cells treated with the combination of resveratrol (3μM) and curcumin (3μM) in comparison to 30μM of resveratrol or curcumin alone. Resveratrol+curcumin combination caused apoptosis by increasing Bax/Bcl-xL ratio, Cytochrome C release, cleaved product of PARP and caspase 3 in cells. Interestingly, this combination unaltered the protein expressions of WNT-TCF and Notch signaling components, β-catenin and cleaved notch-1 val1744, respectively. Furthermore, the combination also significantly decreased the intermediates of Hedgehog-Gli cascade including SMO, SHH, Gli-1, c-MYC, Cyclin-D1, etc. and increased the level of p21(Waf/Cip1) in vitro and in vivo. A significant reduction of Gli- promoter activity was noted in combinational drug treated cells in comparison to individual drug treatment. Un-alteration of the expressions of the above proteins and Gli1 promoter activity in p21(Waf/Cip1) knockout cells suggests this combination caused apoptosis through p21(Waf/Cip1). Thus, our findings revealed resveratrol and curcumin synergistically caused apoptosis in cigarette smoke induced breast cancer cells through p2(Waf/Cip1) mediated inhibition of Hedgehog-Gli cascade.

  18. Retro-Curcuminoids as Mimics of Dehydrozingerone and Curcumin: Synthesis, NMR, X-ray, and Cytotoxic Activity.

    PubMed

    Obregón-Mendoza, Marco A; Estévez-Carmona, María Mirian; Hernández-Ortega, Simón; Soriano-García, Manuel; Ramírez-Apan, María Teresa; Orea, Laura; Pilotzi, Hugo; Gnecco, Dino; Cassani, Julia; Enríquez, Raúl G

    2016-12-29

    Curcumin and its derivatives have been extensively studied for their remarkable medicinal properties, and their chemical synthesis has been an important step in the optimization of well-controlled laboratory production. A family of new compounds that mimic the structure of curcumin and curcuminoids, here named retro-curcuminoids (7-14), was synthesized and characterized using 1D ¹H- and (13)C-NMR, IR, and mass spectrometry; the X-ray structure of 7, 8, 9, 10, 12, 13, and 14 are reported here for the first time. The main structural feature of these compounds is the reverse linkage of the two aromatic moieties, where the acid chloride moiety is linked to the phenolic group while preserving α, β-unsaturated ketone functionality. The cytotoxic screening of 7, 8, 9, and 10 at 50 and 10 µg/mL was carried out with human cancer cell lines K562, MCF-7, and SKLU-1. Lipid peroxidation on rat brain was also tested for compounds 7 and 10. Compounds 7, 8, and 10 showed relevant cytotoxic activity against these cancer cell lines, and 10 showed a protective effect against lipid peroxidation. The molecular resemblance to curcuminoids and analogs with ortho substituents suggests a potential source of useful bioactive compounds.

  19. Targeting thyroid diseases with TSH receptor analogs.

    PubMed

    Galofré, Juan C; Chacón, Ana M; Latif, Rauf

    2013-12-01

    The thyroid-stimulating hormone (TSH) receptor (TSHR) is a major regulator of thyroid function and growth, and is the key antigen in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Various effective treatment strategies are currently available for many of these clinical conditions such as antithyroid drugs or radioiodine therapy, but they are not devoid of side effects. In addition, treatment of complications of Graves' disease such as Graves' ophthalmopathy is often difficult and unsatisfactory using current methods. Recent advances in basic research on both in vitro and in vivo models have suggested that TSH analogs could be used for diagnosis and treatment of some of the thyroid diseases. The advent of high-throughput screening methods has resulted in a group of TSH analogs called small molecules, which have the potential to be developed as promising drugs. Small molecules are low molecular weight compounds with agonist, antagonist and, in some cases, inverse agonist activity on TSHR. This short review will focus on current advances in development of TSH analogs and their potential clinical applications. Rapid advances in this field may lead to the conduct of clinical trials of small molecules related to TSHR for the management of Graves' disease, thyroid cancer, and thyroid-related osteoporosis in the coming years.

  20. Digital and analog communication systems

    NASA Technical Reports Server (NTRS)

    Shanmugam, K. S.

    1979-01-01

    The book presents an introductory treatment of digital and analog communication systems with emphasis on digital systems. Attention is given to the following topics: systems and signal analysis, random signal theory, information and channel capacity, baseband data transmission, analog signal transmission, noise in analog communication systems, digital carrier modulation schemes, error control coding, and the digital transmission of analog signals.

  1. Analogical Reasoning in Geometry Education

    ERIC Educational Resources Information Center

    Magdas, Ioana

    2015-01-01

    The analogical reasoning isn't used only in mathematics but also in everyday life. In this article we approach the analogical reasoning in Geometry Education. The novelty of this article is a classification of geometrical analogies by reasoning type and their exemplification. Our classification includes: analogies for understanding and setting a…

  2. Electrical analogous in viscoelasticity

    NASA Astrophysics Data System (ADS)

    Ala, Guido; Di Paola, Mario; Francomano, Elisa; Li, Yan; Pinnola, Francesco P.

    2014-07-01

    In this paper, electrical analogous models of fractional hereditary materials are introduced. Based on recent works by the authors, mechanical models of materials viscoelasticity behavior are firstly approached by using fractional mathematical operators. Viscoelastic models have elastic and viscous components which are obtained by combining springs and dashpots. Various arrangements of these elements can be used, and all of these viscoelastic models can be equivalently modeled as electrical circuits, where the spring and dashpot are analogous to the capacitance and resistance, respectively. The proposed models are validated by using modal analysis. Moreover, a comparison with numerical experiments based on finite difference time domain method shows that, for long time simulations, the correct time behavior can be obtained only with modal analysis. The use of electrical analogous in viscoelasticity can better reveal the real behavior of fractional hereditary materials.

  3. Curcumin induces apoptosis and protective autophagy in castration-resistant prostate cancer cells through iron chelation

    PubMed Central

    Yang, Chunguang; Ma, Xueyou; Wang, Zhihua; Zeng, Xing; Hu, Zhiquan; Ye, Zhangqun; Shen, Guanxin

    2017-01-01

    Background Curcumin induces apoptosis and autophagy in different cancer cells. Moreover, chemical and biological experiments have evidenced that curcumin is a biologically active iron chelator and induces cytotoxicity through iron chelation. We thus hypothesized that curcumin may induce apoptosis and autophagy in castration-resistant prostate cancer (CRPC) cells through its iron-chelating properties. Materials and methods CRPC cells were loaded with curcumin alone or in combination with ferric ammonium citrate (FAC). Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was assessed by flow cytometry, terminal deoxynucleotidyl transferase nick end labeling (TUNEL) assay and caspase activity. Autophagy status was analyzed by the detection of autophagosomes and light chain 3-II (LC3-II) using transmission electron microscopy and Western blot. Iron-binding activity of curcumin was assessed by spectrophotometry and MTT assay. The expression levels of transferrin receptor 1 (TfR1) and iron regulatory protein 1 (IRP1) were examined by Western blot. Results Curcumin induced apoptosis and autophagy in CRPC cells. Combining curcumin with autophagy inhibitors (3-methyladenine [3-MA]) synergized the apoptotic effect of curcumin. Moreover, curcumin bound to FAC at a ratio of ~1:1, as assessed by spectrophotometry and MTT assay. Apoptosis and autophagy induced by curcumin were counteracted by equal amounts of FAC. At apoptosis- and autophagy-inducing concentrations, curcumin enhanced the expression levels of TfR1 and IRP1, indicative of iron deprivation induced by curcumin. Conclusion Together, our results indicate that curcumin induces apoptosis and protective autophagy in CRPC cells, which are at least partially dependent on its iron-chelating properties. PMID:28243065

  4. Analog Optical Links

    NASA Astrophysics Data System (ADS)

    Cox, Charles H., III

    2004-05-01

    Unlike books that focus on the devices used in links, such as lasers and photodiodes, among others, this text focuses on the next level. It covers the collection of devices that form a link, how the individual device performance affects the link performance, or the reverse. Analog links are used for the distribution of cable TV signals, and in conveying the signals to and from antennas (so called antenna remoting). The design of analog links differs significantly from digital links which are primarily used in telecommunications.

  5. Arterial Pressure Analog.

    ERIC Educational Resources Information Center

    Heusner, A. A.; Tracy, M. L.

    1980-01-01

    Describes a simple hydraulic analog which allows students to explore some physical aspects of the cardiovascular system and provides them with a means to visualize and conceptualize these basic principles. Simulates the behavior of arterial pressure in response to changes in heart rate, stroke volume, arterial compliance, and peripheral…

  6. Reasoning through Instructional Analogies

    ERIC Educational Resources Information Center

    Kapon, Shulamit; diSessa, Andrea A.

    2012-01-01

    This article aims to account for students' assessments of the plausibility and applicability of analogical explanations, and individual differences in these assessments, by analyzing properties of students' underlying knowledge systems. We developed a model of explanation and change in explanation focusing on knowledge elements that provide a…

  7. An Interesting Analogy

    ERIC Educational Resources Information Center

    Pacheco, Jose M.; Fernandez, Isabel

    2002-01-01

    The aim of this note is to give some insight into the formal unity of a very applicable area of mathematics by showing an interesting analogy between the weak part of the Rouche-Frobenius theorem and the existence result for the initial value problem for the general first-order linear two-dimensional PDE.

  8. Analogy, explanation, and proof.

    PubMed

    Hummel, John E; Licato, John; Bringsjord, Selmer

    2014-01-01

    People are habitual explanation generators. At its most mundane, our propensity to explain allows us to infer that we should not drink milk that smells sour; at the other extreme, it allows us to establish facts (e.g., theorems in mathematical logic) whose truth was not even known prior to the existence of the explanation (proof). What do the cognitive operations underlying the inference that the milk is sour have in common with the proof that, say, the square root of two is irrational? Our ability to generate explanations bears striking similarities to our ability to make analogies. Both reflect a capacity to generate inferences and generalizations that go beyond the featural similarities between a novel problem and familiar problems in terms of which the novel problem may be understood. However, a notable difference between analogy-making and explanation-generation is that the former is a process in which a single source situation is used to reason about a single target, whereas the latter often requires the reasoner to integrate multiple sources of knowledge. This seemingly small difference poses a challenge to the task of marshaling our understanding of analogical reasoning to understanding explanation. We describe a model of explanation, derived from a model of analogy, adapted to permit systematic violations of this one-to-one mapping constraint. Simulation results demonstrate that the resulting model can generate explanations for novel explananda and that, like the explanations generated by human reasoners, these explanations vary in their coherence.

  9. Quantum Analog Computing

    NASA Technical Reports Server (NTRS)

    Zak, M.

    1998-01-01

    Quantum analog computing is based upon similarity between mathematical formalism of quantum mechanics and phenomena to be computed. It exploits a dynamical convergence of several competing phenomena to an attractor which can represent an externum of a function, an image, a solution to a system of ODE, or a stochastic process.

  10. Are Scientific Analogies Metaphors?

    DTIC Science & Technology

    1981-02-01

    psychospiritual processes. A more modern example of unclarified analogy is Freud’s (1973; reprinted from 1955) discussion of anal- eroticism , in which...299-304. Freud, S. On transformations of instinct as exemplified in anal eroticism . In J. Strachey (Ed.), The standard 37 edition of the complete

  11. Analogy, explanation, and proof

    PubMed Central

    Hummel, John E.; Licato, John; Bringsjord, Selmer

    2014-01-01

    People are habitual explanation generators. At its most mundane, our propensity to explain allows us to infer that we should not drink milk that smells sour; at the other extreme, it allows us to establish facts (e.g., theorems in mathematical logic) whose truth was not even known prior to the existence of the explanation (proof). What do the cognitive operations underlying the inference that the milk is sour have in common with the proof that, say, the square root of two is irrational? Our ability to generate explanations bears striking similarities to our ability to make analogies. Both reflect a capacity to generate inferences and generalizations that go beyond the featural similarities between a novel problem and familiar problems in terms of which the novel problem may be understood. However, a notable difference between analogy-making and explanation-generation is that the former is a process in which a single source situation is used to reason about a single target, whereas the latter often requires the reasoner to integrate multiple sources of knowledge. This seemingly small difference poses a challenge to the task of marshaling our understanding of analogical reasoning to understanding explanation. We describe a model of explanation, derived from a model of analogy, adapted to permit systematic violations of this one-to-one mapping constraint. Simulation results demonstrate that the resulting model can generate explanations for novel explananda and that, like the explanations generated by human reasoners, these explanations vary in their coherence. PMID:25414655

  12. Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.

    PubMed

    Sankrityayan, Himanshu; Majumdar, Anuradha S

    2016-01-01

    Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 μg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels.

  13. The Chemistry of Curcumin, the Health Promoting Ingredient in Turmeric

    ERIC Educational Resources Information Center

    Dewprashad, Brahmadeo

    2010-01-01

    Case studies pertaining to the health benefits of foods can be particularly effective in engaging students and in teaching core concepts in science (Heidemann and Urquart 2005). This case study focuses on the chemistry of curcumin, the health-promoting ingredient in turmeric. The case was developed to review core concepts in organic chemistry and…

  14. Novel Therapeutic Approach for the Treatment of Periodontitis by Curcumin

    PubMed Central

    Bhatia, Madhu; Pentyala, Kishore Babu; Urolagin, Sarvesh Basavaraj; K B, Menaka; Bhoi, Shreedevi

    2014-01-01

    Aims and objectives: The aim of the present study was to evaluate the clinical and microbiological efficacy of locally delivered 1% curcumin gel as an adjunct to scaling and root planing in the treatment of chronic periodontitis. Materials and Methods: The study group consisted of 25 patients, belonging to both sex, aged between 21-45 years. All patients diagnosed as chronic periodontitis with periodontal pockets of depth >5mm bilaterally were randomly selected. A split mouth design was followed and the patients received a complete prophylaxis including scaling and root planing. Examination of plaque index, bleeding index, probing pocket depth and clinical attachment level were measured for each patient. The test group received 1% curcumin gel along with scaling and root planing whereas the control group received scaling and root planing alone followed by microbiological samples taken at baseline, 1, 3 and 6 months interval. Results: The 1% curcumin gel appeared to provide significant improvements in clinical parameters. Microbiological counts of Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum and capnocytophaga showed significant reduction in periopathogens at the test sites after six months when compared with that of control sites. Conclusion: Locally delivered 1% curcumin gel was more effective in inhibiting the growth of oral bacteria when used as an adjunct to SRP in the treatment of chronic periodontitis. PMID:25654035

  15. Synthesis, characterization and fluorescent properties of water-soluble glycopolymer bearing curcumin pendant residues.

    PubMed

    Zhang, Haisong; Yu, Meng; Zhang, Hailei; Bai, Libin; Wu, Yonggang; Wang, Sujuan; Ba, Xinwu

    2016-08-01

    Curcumin is a potential natural anticancer drug with low oral bioavailability because of poor water solubility. The aqueous solubility of curcumin is enhanced by means of modification with the carbohydrate units. Polymerization of the curcumin-containing monomer with carbohydrate-containing monomer gives the water-soluble glycopolymer bearing curcumin pendant residues. The obtained copolymers (P1 and P2) having desirable water solubility were well-characterized by infrared spectroscopy (IR), nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), UV-Vis absorption spectroscopy, and photoluminescence spectroscopy. The copolymer P2 with a molar ratio of 1:6 (curcumin/carbohydrate) calculated from the proton NMR results exhibits a similar anticancer activity compared to original curcumin, which may serve as a potential chemotherapeutic agent in the field of anticancer medicine.

  16. Mechanism of curcumin-induced trypsin inhibition: Computational and experimental studies

    NASA Astrophysics Data System (ADS)

    Wang, Yan-Qing; Zhang, Hong-Mei; Kang, Yi-Jun; Gu, Yun-Lan; Cao, Jian

    2016-03-01

    In the present study, the experimental and theoretical methods were used to analyze the binding interaction of food dye, curcumin with trypsin. The results of fluorescence spectroscopic measurements indicated that curcumin binding resulted in the obviously intrinsic fluorescence quenching with the increase concentration of curcumin. This binding interaction is a spontaneous process with the estimated enthalpy and entropy changes being -15.70 kJ mol-1 and 40.25 J mol-1 K-1, respectively. Hydrogen bonds and hydrophobic forces played an important role in the complex formation between curcumin and trypsin. Moreover, curcumin could enter into the primary substrate-binding pocket and makes the activity of trypsin decrease remarkably with the increasing concentration of curcumin.

  17. Curcumin encapsulation in submicrometer spray-dried chitosan/Tween 20 particles.

    PubMed

    O'Toole, Martin G; Henderson, Richard M; Soucy, Patricia A; Fasciotto, Brigitte H; Hoblitzell, Patrick J; Keynton, Robert S; Ehringer, William D; Gobin, Andrea S

    2012-08-13

    Optimal curcumin delivery for medicinal applications requires a drug delivery system that both solubilizes curcumin and prevents degradation. To achieve this, curcumin has been encapsulated in submicrometer chitosan/Tween 20 particles via a benchtop spray-drying process. Spray-drying parameters have been optimized using a Taguchi statistical approach to minimize particle size and to favor spheroid particles with smooth surfaces, as evaluated with scanning electron microscopy (SEM) imaging. Nearly spherical particles with 285 ± 30 nm diameter and 1.21 axial ratio were achieved. Inclusion of curcumin in the spray-drying solution results in complete encapsulation of curcumin within the chitosan/Tween 20 particles. Release studies confirm that curcumin can be released completely from the particles over a 2 h period.

  18. Effect of curcumin on the binding of cationic, anionic and nonionic surfactants with myoglobin

    NASA Astrophysics Data System (ADS)

    Mondal, Satyajit; Ghosh, Soumen

    2017-04-01

    Interaction of a globular protein, myoglobin and different surfactants has been studied in the absence and presence of curcumin in phosphate buffer at pH = 7.4 by UV-VIS spectrophotometry, fluorimetry and fluorescence polarization anisotropy methods. Results show that heme environment of myoglobin is changed by cationic cetyltrimethylammonium bromide (CTAB) and sodium N-dodecanoyl sarcosinate (SDDS). In the presence of curcumin, CTAB cannot change the heme; but SDDS can make change. Nonionic surfactant N-decanoyl-N-methylglucamine (Mega 10) cannot change the heme environment. Protein is unfolded by the surfactant. Curcumin can prevent the unfolding of protein in the low concentration region of ionic surfactants such as CTAB and SDDS. In nonionic surfactant media, curcumin accelerates the denaturation process. Due to myoglobin-curcumin complex formation, rotational motion of curcumin decreases in surfactant media and so anisotropy increases.

  19. Analysis of anti-depressant potential of curcumin against depression induced male albino wistar rats.

    PubMed

    Chang, Xue-Run; Wang, Li; Li, Jing; Wu, Dian-Shui

    2016-07-01

    The present study investigated the antidepressant potential of curcumin in olfactory bulbectomy and forced swimming test models of depression in male albino rats under chronic treatment. The experimental animals were divided into four groups, and curcumin was administered for 45 days. Our results showed that the curcumin significantly reduced olfactory bulbectomy-induced behavioral abnormalities including deficits in step-down passive avoidance, increased activity in the open area and immobility time. Chronic administration of curcumin significantly reversed levels of 3, 4-dihydroxyphenylacetic acid, noradrenaline, serotonin and 5-hydroxyindoleacetic acid in the hippocampus region of male albino rats. Also, curcumin normalizes the levels of dopamine, noradrenaline, and 5-hydroxyindoleacetic acid in the frontal cortex of rats. Taking all these results together, it may suggest that curcumin is potent compound acting against the depression in the male albino rats.

  20. Stabilization of Curcumin by Complexation with Divalent Cations in Glycerol/Water System

    PubMed Central

    Zebib, Bachar; Mouloungui, Zéphirin; Noirot, Virginie

    2010-01-01

    The purpose of present study was to stabilize curcumin food pigment by its complexation with divalent ions like (Zn2+, Cu2+, Mg2+, Se2+), in “green media” and evaluate its stability in vitro compared to curcumin alone. The curcumin complexes were prepared by mechanical mixture of curcumin and sulfate salts of each metal (metal : curcumin 1/1mol) into unconventional and nontoxic glycerol/water solvent. Two stoichiometry of complex were obtained, 1 : 1 and 1 : 2 (metal/curcumin), respectively. On evaluation of in vitro stability, all complexes were found to provide a higher stability from curcumin alone. PMID:20634909

  1. Comparative cytotoxicity and ROS generation by curcumin and tetrahydrocurcumin following visible-light irradiation or treatment with horseradish peroxidase.

    PubMed

    Atsumi, Toshiko; Tonosaki, Keiichi; Fujisawa, Seiichiro

    2007-01-01

    In order to clarify the cytotoxic mechanism of curcumin, a well-known chemopreventive agent, the cytotoxicity (by MTT method), intracellular glutathione (using GSH detection kit) and intracellular reactive oxygen species (ROS) levels (with a flow cytometer), were measured in curcumin- and tetrahydrocurcumin (TH-curcumin)-treated cancer (HSG) and normal (HGF) cells under two different oxidation conditions: irradiation with visible light (VL) and enzymatic oxidation with horseradish peroxidase (HRP)/H2O2. The cytotoxicity of curcumin was highly enhanced by VL-irradiation, whereas that of TH-curcumin was enhanced by HRP/H2O2 treatment. The cytotoxicity of curcumin against HGF cells was greater than that against HSG cells. Curcumin significantly reduced the intracellular GSH level significantly under VL-irradiation, and increased it under HRP/H2O2, whereas TH-curcumin had no effect with either oxidation treatment. HRP/H2O2 treatment of TH-curcumin enhanced generation of ROS; in contrast, VL-irradiation of curcumin was considered to produce ROS preferably. In conclusion, curcumin was highly photo-toxic, caused a decrease in GSH and mediated ROS generation. In contrast, the cytotoxicity of TH-curcumin was enhanced by enzymatic oxidation. A low-level pro-oxidant intracellular milieu induced by TH-curcumin could be effectively useful for cancer prevention.

  2. Curcumin inhibits Rift Valley fever virus replication in human cells.

    PubMed

    Narayanan, Aarthi; Kehn-Hall, Kylene; Senina, Svetlana; Lundberg, Lindsay; Van Duyne, Rachel; Guendel, Irene; Das, Ravi; Baer, Alan; Bethel, Laura; Turell, Michael; Hartman, Amy Lynn; Das, Bhaskar; Bailey, Charles; Kashanchi, Fatah

    2012-09-28

    Rift Valley fever virus (RVFV) is an arbovirus that is classified as a select agent, an emerging infectious virus, and an agricultural pathogen. Understanding RVFV-host interactions is imperative to the design of novel therapeutics. Here, we report that an infection by the MP-12 strain of RVFV induces phosphorylation of the p65 component of the NFκB cascade. We demonstrate that phosphorylation of p65 (serine 536) involves phosphorylation of IκBα and occurs through the classical NFκB cascade. A unique, low molecular weight complex of the IKK-β subunit can be observed in MP-12-infected cells, which we have labeled IKK-β2. The IKK-β2 complex retains kinase activity and phosphorylates an IκBα substrate. Inhibition of the IKK complex using inhibitors impairs viral replication, thus alluding to the requirement of an active IKK complex to the viral life cycle. Curcumin strongly down-regulates levels of extracellular infectious virus. Our data demonstrated that curcumin binds to and inhibits kinase activity of the IKK-β2 complex in infected cells. Curcumin partially exerts its inhibitory influence on RVFV replication by interfering with IKK-β2-mediated phosphorylation of the viral protein NSs and by altering the cell cycle of treated cells. Curcumin also demonstrated efficacy against ZH501, the fully virulent version of RVFV. Curcumin treatment down-regulated viral replication in the liver of infected animals. Our data point to the possibility that RVFV infection may result in the generation of novel versions of host components (such as IKK-β2) that, by virtue of altered protein interaction and function, qualify as unique therapeutic targets.

  3. Curcumin Inhibits Rift Valley Fever Virus Replication in Human Cells*

    PubMed Central

    Narayanan, Aarthi; Kehn-Hall, Kylene; Senina, Svetlana; Lundberg, Lindsay; Van Duyne, Rachel; Guendel, Irene; Das, Ravi; Baer, Alan; Bethel, Laura; Turell, Michael; Hartman, Amy Lynn; Das, Bhaskar; Bailey, Charles; Kashanchi, Fatah

    2012-01-01

    Rift Valley fever virus (RVFV) is an arbovirus that is classified as a select agent, an emerging infectious virus, and an agricultural pathogen. Understanding RVFV-host interactions is imperative to the design of novel therapeutics. Here, we report that an infection by the MP-12 strain of RVFV induces phosphorylation of the p65 component of the NFκB cascade. We demonstrate that phosphorylation of p65 (serine 536) involves phosphorylation of IκBα and occurs through the classical NFκB cascade. A unique, low molecular weight complex of the IKK-β subunit can be observed in MP-12-infected cells, which we have labeled IKK-β2. The IKK-β2 complex retains kinase activity and phosphorylates an IκBα substrate. Inhibition of the IKK complex using inhibitors impairs viral replication, thus alluding to the requirement of an active IKK complex to the viral life cycle. Curcumin strongly down-regulates levels of extracellular infectious virus. Our data demonstrated that curcumin binds to and inhibits kinase activity of the IKK-β2 complex in infected cells. Curcumin partially exerts its inhibitory influence on RVFV replication by interfering with IKK-β2-mediated phosphorylation of the viral protein NSs and by altering the cell cycle of treated cells. Curcumin also demonstrated efficacy against ZH501, the fully virulent version of RVFV. Curcumin treatment down-regulated viral replication in the liver of infected animals. Our data point to the possibility that RVFV infection may result in the generation of novel versions of host components (such as IKK-β2) that, by virtue of altered protein interaction and function, qualify as unique therapeutic targets. PMID:22847000

  4. Attenuation of arsenic neurotoxicity by curcumin in rats

    SciTech Connect

    Yadav, Rajesh S.; Sankhwar, Madhu Lata; Shukla, Rajendra K.; Chandra, Ramesh; Pant, Aditya B.; Islam, Fakhrul; Khanna, Vinay K.

    2009-11-01

    In view of continued exposure to arsenic and associated human health risk including neurotoxicity, neuroprotective efficacy of curcumin, a polyphenolic antioxidant, has been investigated in rats. A significant decrease in locomotor activity, grip strength (26%) and rota-rod performance (82%) was observed in rats treated with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) as compared to controls. The arsenic treated rats also exhibited a decrease in the binding of striatal dopamine receptors (32%) and tyrosine hydroxylase (TH) immunoreactivity (19%) in striatum. Increased arsenic levels in corpus striatum (6.5 fold), frontal cortex (6.3 fold) and hippocampus (7.0 fold) associated with enhanced oxidative stress in these brain regions, as evident by an increase in lipid perioxidation, protein carbonyl and a decrease in the levels of glutathione and activity of superoxide dismutase, catalase and glutathione peroxidase with differential effects were observed in arsenic treated rats compared to controls. Simultaneous treatment with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) and curcumin (100 mg/kg body weight, p.o., 28 days) caused an increase in locomotor activity and grip strength and improved the rota-rod performance in comparison to arsenic treated rats. Binding of striatal dopamine receptors and TH expression increased while arsenic levels and oxidative stress decreased in these brain regions in co-treated rats as compared to those treated with arsenic alone. No significant effect on any of these parameters was observed in rats treated with curcumin (100 mg/kg body weight, p.o., 28 days) alone compared to controls. A significant protection in behavioral, neurochemical and immunohistochemical parameters in rats simultaneously treated with arsenic and curcumin suggest the neuroprotective efficacy of curcumin.

  5. Curcumin inhibits activation of TRPM2 channels in rat hepatocytes

    PubMed Central

    Kheradpezhouh, E.; Barritt, G.J.; Rychkov, G.Y.

    2015-01-01

    Oxidative stress is a hallmark of many liver diseases including viral and drug-induced hepatitis, ischemia-reperfusion injury, and non-alcoholic steatohepatitis. One of the consequences of oxidative stress in the liver is deregulation of Ca2+ homeostasis, resulting in a sustained elevation of the free cytosolic Ca2+ concentration ([Ca2+]c) in hepatocytes, which leads to irreversible cellular damage. Recently it has been shown that liver damage induced by paracetamol and subsequent oxidative stress is, in large part, mediated by Ca2+ entry through Transient Receptor Potential Melastatin 2 (TRPM2) channels. Involvement of TRPM2 channels in hepatocellular damage induced by oxidative stress makes TRPM2 a potential therapeutic target for treatment of a range of oxidative stress-related liver diseases. We report here the identification of curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), a natural plant-derived polyphenol in turmeric spice, as a novel inhibitor of TRPM2 channel. Presence of 5 µM curcumin in the incubation medium prevented the H2O2- and paracetamol-induced [Ca2+]c rise in rat hepatocytes. Furthermore, in patch clamping experiments incubation of hepatocytes with curcumin inhibited activation of TRPM2 current by intracellular ADPR with IC50 of approximately 50 nM. These findings enhance understanding of the actions of curcumin and suggest that the known hepatoprotective properties of curcumin are, at least in part, mediated through inhibition of TRPM2 channels. PMID:26609559

  6. Curcumin inhibits activation of TRPM2 channels in rat hepatocytes.

    PubMed

    Kheradpezhouh, E; Barritt, G J; Rychkov, G Y

    2016-04-01

    Oxidative stress is a hallmark of many liver diseases including viral and drug-induced hepatitis, ischemia-reperfusion injury, and non-alcoholic steatohepatitis. One of the consequences of oxidative stress in the liver is deregulation of Ca(2+) homeostasis, resulting in a sustained elevation of the free cytosolic Ca(2+) concentration ([Ca(2+)]c) in hepatocytes, which leads to irreversible cellular damage. Recently it has been shown that liver damage induced by paracetamol and subsequent oxidative stress is, in large part, mediated by Ca(2+) entry through Transient Receptor Potential Melastatin 2 (TRPM2) channels. Involvement of TRPM2 channels in hepatocellular damage induced by oxidative stress makes TRPM2 a potential therapeutic target for treatment of a range of oxidative stress-related liver diseases. We report here the identification of curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), a natural plant-derived polyphenol in turmeric spice, as a novel inhibitor of TRPM2 channel. Presence of 5µM curcumin in the incubation medium prevented the H2O2- and paracetamol-induced [Ca(2+)]c rise in rat hepatocytes. Furthermore, in patch clamping experiments incubation of hepatocytes with curcumin inhibited activation of TRPM2 current by intracellular ADPR with IC50 of approximately 50nM. These findings enhance understanding of the actions of curcumin and suggest that the known hepatoprotective properties of curcumin are, at least in part, mediated through inhibition of TRPM2 channels.

  7. Curcumin as fluorescent probe for directly monitoring in vitro uptake of curcumin combined paclitaxel loaded PLA-TPGS nanoparticles

    NASA Astrophysics Data System (ADS)

    Nguyen, Hoai Nam; Thu Ha, Phuong; Sao Nguyen, Anh; Nguyen, Dac Tu; Doan Do, Hai; Nguyen Thi, Quy; Nhung Hoang Thi, My

    2016-06-01

    Theranostics, which is the combination of both therapeutic and diagnostic capacities in one dose, is a promising tool for both clinical application and research. Although there are many chromophores available for optical imaging, their applications are limited due to the photobleaching property or intrinsic toxicity. Curcumin, a natural compound extracted from the rhizome of curcuma longa, is well known thanks to its bio-pharmaceutical activities and strong fluorescence as biocompatible probe for bio-imaging. In this study, we aimed to fabricate a system with dual functions: diagnostic and therapeutic, based on poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) micelles co-loaded curcumin (Cur) and paclitaxel (PTX). Two kinds of curcumin nanoparticle (NP) were fabricated and characterized by Fourier transform infrared spectroscopy, field emission scanning electron microscopy and dynamic light scattering methods. The cellular uptake and fluorescent activities of curcumin in these systems were also tested by bioassay studies, and were compared with paclitaxe-oregon. The results showed that (Cur + PTX)-PLA-TPGS NPs is a potential system for cancer theranostics.

  8. Antiparasitic efficacy of curcumin from Curcuma longa against Ichthyophthirius multifiliis in grass carp.

    PubMed

    Liu, Yan-Meng; Zhang, Qi-Zhong; Xu, De-Hai; Fu, Yao-Wu; Lin, De-Jie; Zhou, Sheng-Yu; Li, Jian-Pei

    2017-03-15

    Ichthyophthirius multifiliis is a ciliated parasite that elicits great economic losses in aquaculture. In the present study, a polyphenol compound, curcumin, was obtained from the rhizome of Curcuma longa by bioassay-guided isolation based on the efficacy of anti-I. multifiliis theronts. Anti-I. multifiliis efficacy of curcumin was evaluated in vitro and in vivo. Curcumin resulted in 100% mortality of I. multifiliis theronts at a concentration of 1mg/L within 21.7±1.2min and killed all tomonts at 8mg/L within 31.0±1.0min. Curcumin at 4mg/L for 16h exposure can completely terminate the reproduction of tomonts. The pretreatment with curcumin at concentrations of 0.5, 0.25, and 0.125mg/L for 2h significantly reduced the infectivity of I. multifiliis theronts. Curcumin at 4mg/L completely cured the infected grass carp and protected naive fish from I. multifiliis infection after 10days exposure. The 4h median effective concentration (EC50) of curcumin to I. multifiliis theronts and the 5h EC50 of curcumin to I. multifiliis tomonts were 0.303mg/L and 2.891mg/L, respectively. The 96h median lethal concentration (LC50) of curcumin to grass carp was 56.8mg/L, which was approximately 187.4 times EC50 of curcumin to theronts and 19.6 times EC50 of curcumin to tomonts. The results demonstrated that curcumin has the potential to be a safe and effective therapeutant for controlling ichthyophthiriasis in aquaculture.

  9. Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Gou, Maling; Men, Ke; Shi, Huashan; Xiang, Mingli; Zhang, Juan; Song, Jia; Long, Jianlin; Wan, Yang; Luo, Feng; Zhao, Xia; Qian, Zhiyong

    2011-04-01

    Curcumin is an effective and safe anticancer agent, but its hydrophobicity inhibits its clinical application. Nanotechnology provides an effective method to improve the water solubility of hydrophobic drug. In this work, curcumin was encapsulated into monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles through a single-step nano-precipitation method, creating curcumin-loaded MPEG-PCL (Cur/MPEG-PCL) micelles. These Cur/MPEG-PCL micelles were monodisperse (PDI = 0.097 +/- 0.011) with a mean particle size of 27.3 +/- 1.3 nm, good re-solubility after freeze-drying, an encapsulation efficiency of 99.16 +/- 1.02%, and drug loading of 12.95 +/- 0.15%. Moreover, these micelles were prepared by a simple and reproducible procedure, making them potentially suitable for scale-up. Curcumin was molecularly dispersed in the PCL core of MPEG-PCL micelles, and could be slow-released in vitro. Encapsulation of curcumin in MPEG-PCL micelles improved the t1/2 and AUC of curcuminin vivo. As well as free curcumin, Cur/MPEG-PCL micelles efficiently inhibited the angiogenesis on transgenic zebrafish model. In an alginate-encapsulated cancer cell assay, intravenous application of Cur/MPEG-PCL micelles more efficiently inhibited the tumor cell-induced angiogenesisin vivo than that of free curcumin. MPEG-PCL micelle-encapsulated curcumin maintained the cytotoxicity of curcumin on C-26 colon carcinoma cellsin vitro. Intravenous application of Cur/MPEG-PCL micelle (25 mg kg-1curcumin) inhibited the growth of subcutaneous C-26 colon carcinoma in vivo (p < 0.01), and induced a stronger anticancer effect than that of free curcumin (p < 0.05). In conclusion, Cur/MPEG-PCL micelles are an excellent intravenously injectable aqueous formulation of curcumin; this formulation can inhibit the growth of colon carcinoma through inhibiting angiogenesis and directly killing cancer cells.

  10. Curcumin enhances the cytogenotoxic effect of etoposide in leukemia cells through induction of reactive oxygen species

    PubMed Central

    Papież, Monika A; Krzyściak, Wirginia; Szade, Krzysztof; Bukowska-Straková, Karolina; Kozakowska, Magdalena; Hajduk, Karolina; Bystrowska, Beata; Dulak, Jozef; Jozkowicz, Alicja

    2016-01-01

    Curcumin may exert a more selective cytotoxic effect in tumor cells with elevated levels of free radicals. Here, we investigated whether curcumin can modulate etoposide action in myeloid leukemia cells and in normal cells of hematopoietic origin. HL-60 cell line, normal myeloid progenitor cluster of differentiation (CD)-34+ cells, and granulocytes were incubated for 4 or 24 hours at different concentrations of curcumin and/or etoposide. Brown Norway rats with acute myeloid leukemia (BNML) were used to prove the influence of curcumin on etoposide action in vivo. Rats were treated with curcumin for 23 days and etoposide was administered for the final 3 days of the experiment. Curcumin synergistically potentiated the cytotoxic effect of etoposide, and it intensified apoptosis and phosphorylation of the histone H2AX induced by this cytostatic drug in leukemic HL-60 cells. In contrast, curcumin did not significantly modify etoposide-induced cytotoxicity and H2AX phosphorylation in normal CD34+ cells and granulocytes. Curcumin modified the cytotoxic action of etoposide in HL-60 cells through intensification of free radical production because preincubation with N-acetyl-l-cysteine (NAC) significantly reduced the cytotoxic effect of curcumin itself and a combination of two compounds. In contrast, NAC did not decrease the cytotoxic effect of etoposide. Thus, oxidative stress plays a greater role in the cytotoxic effect of curcumin than that of etoposide in HL-60 cells. In vitro results were confirmed in a BNML model. Pretreatment with curcumin enhanced the antileukemic activity of etoposide in BNML rats (1.57-fold tumor reduction versus etoposide alone; P<0.05) and induced apoptosis of BNML cells more efficiently than etoposide alone (1.54-fold change versus etoposide alone; P<0.05), but this treatment protected nonleukemic B-cells from apoptosis. Thus, curcumin can increase the antileukemic effect of etoposide through reactive oxygen species in sensitive myeloid leukemia

  11. Curcumin enhances the lung cancer chemopreventive efficacy of phospho-sulindac by improving its pharmacokinetics

    PubMed Central

    CHENG, KA-WING; WONG, CHI C.; MATTHEOLABAKIS, GEORGE; XIE, GANG; HUANG, LIQUN; RIGAS, BASIL

    2013-01-01

    Phospho-sulindac (PS) is a safe sulindac derivative with promising anticancer efficacy in colon cancer. We evaluated whether its combination with curcumin could enhance the efficacy in the treatment of lung cancer. Curcumin, the principal bioactive component in turmeric, has demonstrated versatile capabilities to modify the therapeutic efficacy of a wide range of anticancer agents. Here, we evaluated the effect of co-administration of curcumin on the anticancer activity of PS in a mouse xenograft model of human lung cancer. Curcumin enhanced the cellular uptake of PS in human lung and colon cancer cell lines. To assess the potential synergism between curcumin and PS in vivo, curcumin was suspended in 10% Tween-80 or formulated in micellar nanoparticles and given to mice by oral gavage prior to the administration of PS. Both formulations of curcumin significantly improved the pharmacokinetic profiles of PS, with the 10% Tween-80 suspension being much more effective than the nanoparticle formation. However, curcumin did not exhibit any significant modification of the metabolite profile of PS. Furthermore, in a mouse subcutaneous xenograft model of human lung cancer, PS (200 mg/kg) in combination with curcumin (500 mg/kg) suspended in 10% Tween-80 (51% inhibition, p<0.05) was significantly more efficacious than PS plus micelle curcumin (30%) or PS (25%) or curcumin alone (no effect). Consistent with the improved pharmacokinetics, the combination treatment group had higher levels of PS and its metabolites in the xenografts compared to PS alone. Our results show that curcumin substantially improves the pharmacokinetics of PS leading to synergistic inhibition of the growth of human lung cancer xenografts, representing a promising drug combination. PMID:23807084

  12. A Subpopulation of the K562 Cells Are Killed by Curcumin Treatment after G2/M Arrest and Mitotic Catastrophe.

    PubMed

    Martinez-Castillo, Macario; Bonilla-Moreno, Raul; Aleman-Lazarini, Leticia; Meraz-Rios, Marco Antonio; Orozco, Lorena; Cedillo-Barron, Leticia; Cordova, Emilio J; Villegas-Sepulveda, Nicolas

    2016-01-01

    Curcumin is extensively investigated as a good chemo-preventive agent in the development of many cancers and particularly in leukemia, including treatment of chronic myelogenous leukemia and it has been proposed as an adjuvant for leukemia therapies. Human chronic myeloid leukemia cells (K562), were treated with 20 μM of curcumin, and we found that a subpopulation of these cells were arrested and accumulate in the G2/M phase of the cell cycle. Characterization of this cell subpopulation showed that the arrested cells presented nuclear morphology changes resembling those described for mitotic catastrophe. Mitotic cells displayed abnormal chromatin organization, collapse of the mitotic spindle and abnormal chromosome segregation. Then, these cells died in an apoptosis dependent manner and showed diminution in the protein levels of BCL-2 and XIAP. Moreover, our results shown that a transient activation of the nuclear factor κB (NFκB) occurred early in these cells, but decreased after 6 h of the treatment, explaining in part the diminution of the anti-apoptotic proteins. Additionally, P73 was translocated to the cell nuclei, because the expression of the C/EBPα, a cognate repressor of the P73 gene, was decreased, suggesting that apoptosis is trigger by elevation of P73 protein levels acting in concert with the diminution of the two anti-apoptotic molecules. In summary, curcumin treatment might produce a P73-dependent apoptotic cell death in chronic myelogenous leukemia cells (K562), which was triggered by mitotic catastrophe, due to sustained BAX and survivin expression and impairment of the anti-apoptotic proteins BCL-2 and XIAP.

  13. A Subpopulation of the K562 Cells Are Killed by Curcumin Treatment after G2/M Arrest and Mitotic Catastrophe

    PubMed Central

    Martinez-Castillo, Macario; Bonilla-Moreno, Raul; Aleman-Lazarini, Leticia; Meraz-Rios, Marco Antonio; Orozco, Lorena; Cedillo-Barron, Leticia; Cordova, Emilio J.

    2016-01-01

    Curcumin is extensively investigated as a good chemo-preventive agent in the development of many cancers and particularly in leukemia, including treatment of chronic myelogenous leukemia and it has been proposed as an adjuvant for leukemia therapies. Human chronic myeloid leukemia cells (K562), were treated with 20 μM of curcumin, and we found that a subpopulation of these cells were arrested and accumulate in the G2/M phase of the cell cycle. Characterization of this cell subpopulation showed that the arrested cells presented nuclear morphology changes resembling those described for mitotic catastrophe. Mitotic cells displayed abnormal chromatin organization, collapse of the mitotic spindle and abnormal chromosome segregation. Then, these cells died in an apoptosis dependent manner and showed diminution in the protein levels of BCL-2 and XIAP. Moreover, our results shown that a transient activation of the nuclear factor κB (NFκB) occurred early in these cells, but decreased after 6 h of the treatment, explaining in part the diminution of the anti-apoptotic proteins. Additionally, P73 was translocated to the cell nuclei, because the expression of the C/EBPα, a cognate repressor of the P73 gene, was decreased, suggesting that apoptosis is trigger by elevation of P73 protein levels acting in concert with the diminution of the two anti-apoptotic molecules. In summary, curcumin treatment might produce a P73-dependent apoptotic cell death in chronic myelogenous leukemia cells (K562), which was triggered by mitotic catastrophe, due to sustained BAX and survivin expression and impairment of the anti-apoptotic proteins BCL-2 and XIAP. PMID:27832139

  14. Antinociceptive effects of curcumin in a rat model of postoperative pain

    PubMed Central

    Zhu, Qing; Sun, Yuehua; Yun, Xiaodi; Ou, Yuntao; Zhang, Wei; Li, Jun-Xu

    2014-01-01

    Curcumin is a principal ingredient of traditional Chinese medicine, Curcuma Longa, which possesses a variety of pharmacological activities including pain relief. Preclinical studies have demonstrated that curcumin has antinociceptive effects for inflammatory and neuropathic pain. This study examined the effects of curcumin in a rat model of postoperative pain. A surgical incision on the right hind paw induced a sustained mechanical hyperalgesia that lasted for 5 days. Acute curcumin treatment (10–40 mg/kg, p.o) significantly and dose dependently reversed mechanical hyperalgesia. In addition, repeated curcumin treatment significantly facilitated the recovery from surgery. In contrast, repeated treatment with curcumin before surgery did not impact the postoperative pain threshold and recovery rate. All the doses of curcumin did not significantly alter the spontaneous locomotor activity. Combined, these results suggested that curcumin could alleviate postoperative pain and promote recovery from the surgery, although there was no significant preventive value. This study extends previous findings and supports the application of curcumin alone or as an adjunct therapy for the management of peri-operative pain. PMID:24816565

  15. Development and performance evaluation of novel nanoparticles of a grafted copolymer loaded with curcumin.

    PubMed

    Mutalik, Srinivas; Suthar, Neelam A; Managuli, Renuka S; Shetty, Pallavi K; Avadhani, Kiran; Kalthur, Guruprasad; Kulkarni, Raghavendra V; Thomas, Ranjeny

    2016-05-01

    Inflammatory bowel disease (IBD) is an inflammatory condition with mucosal ulceration, edema and hemorrhage of gastrointestinal tract. Curcumin has been shown to mitigate colitis in animal models. However, its usefulness is reduced due to poor pharmacokinetic behavior and low oral bioavailability. To address this, novel pH-sensitive hydrolyzed polyacrylamide-grafted-xanthan gum (PAAm-g-XG) nanoparticles (NPs) loaded with curcumin were prepared for colonic delivery. Optimized nanoparticles (CN20) were spherical, with an average size of 425 nm. A negligible amount of curcumin (≈8%) was released from CN20 NPs in pH 1.2 and 4.5 solutions. When the pH was increased to 7.2, curcumin release was comparatively faster than that observed with pH 1.2 and 4.5 collectively. In pH 6.8 solution, excellent release of curcumin was observed. Highest curcumin release was observed when rat caecal contents were incorporated in pH 6.8 solution, indicating microflora-dependent drug release property of NPs. In acetic acid-induced IBD in rats, curcumin NPs reduced myeloperoxidase and nitrite levels, prevented weight loss and attenuated colonic inflammation. Curcumin was better absorbed systemically in nanoparticulate form with increased Cmax (∼3 fold) and AUC (∼2.5 fold) than when delivered as free curcumin. We demonstrate successful development of grafted co-polymeric NPs containing drug suitable for colon targeting.

  16. Fabrication of biodegradable PEG-PLA nanospheres for solubility, stabilization, and delivery of curcumin.

    PubMed

    Liang, Hongying; Friedman, Joel M; Nacharaju, Parimala

    2017-03-01

    Curcumin is an effective and safe anticancer agent, and also known to induce vasodilation, but its hydrophobicity limits its clinical application. In this study, a simple emulsion method was developed to prepare biodegradable poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) nanospheres to encapsulate curcumin to improve its solubility and stability. The nanoparticle size was around 150 nm with a narrow size distribution. Fluorescence microscopy showed that curcumin encapsulated PEG-PLA nanospheres were taken up rapidly by Hela and MDA-MB-231 cancer cells. This novel nanoparticulate carrier may improve the bioavailability of curcumin without affecting its anticancer properties.

  17. Spicy SDS-PAGE gels: curcumin/turmeric as an environment-friendly protein stain.

    PubMed

    Kurien, Biji T; Dorri, Yaser; Scofield, R Hal

    2012-01-01

    Gel proteins are commonly stained with calorimetric/fluorescent dyes. Here, we demonstrate that heat-solubilized curcumin can serve as a nontoxic and environment-friendly fluorescent/colorimetric reversible protein stain. Curcumin, the yellow pigment found in the rhizomes of the perennial herb Curcuma longa (turmeric), is insoluble in aqueous solvents. However, heat (100°C) solubilization in water renders 1.5% of curcumin soluble. Curcumin solubilized by ethanol or alkali is ineffective in staining proteins. Heat solubilized curry spice turmeric stains proteins similarly. Staining is achieved in 30 min, with a sensitivity almost equaling that of Coomassie Brilliant Blue (CBB). Destaining is not required, and excess curcumin/turmeric can be discarded into the sink. Binding of proteins by silver inhibits curcumin binding, suggesting similarity of protein binding by silver and curcumin. It costs $1.5-2.0 to stain a mini-gel with curcumin, while turmeric costs less than 0.005 cent. CBB staining/destaining costs about 2 cents. However, CBB is toxic and its use necessitates specialized disposal efforts. Curcumin/turmeric, thus, can serve as an ideal nontoxic protein stain.

  18. Injectable Sustained Release Microparticles of Curcumin: A New Concept for Cancer Chemoprevention

    PubMed Central

    Shahani, Komal; Swaminathan, Suresh Kumar; Freeman, Diana; Blum, Angela; Ma, Linan; Panyam, Jayanth

    2010-01-01

    Poor oral bioavailability limits the use of curcumin and other dietary polyphenols in the prevention and treatment of cancer. Minimally invasive strategies that can provide effective and sustained tissue concentrations of these agents will be highly valuable tools in the fight against cancer. The objective of this study was to investigate the use of an injectable sustained release microparticle formulation of curcumin as a novel approach to breast cancer chemoprevention. A biodegradable and biocompatible polymer, poly(D,L-lactide-co-glycolide) (PLGA), was used to fabricate curcumin microparticles. When injected subcutaneously in mice, a single dose of microparticles sustained curcumin levels in the blood and other tissues for nearly a month. Curcumin levels in the lungs and brain, frequent sites of breast cancer metastases, were 10-30-fold higher than that in the blood. Further, curcumin microparticles showed marked anticancer efficacy in nude mice bearing MDA-MB-231 xenografts compared to other controls. Repeated systemic injections of curcumin were not effective in inhibiting tumor growth. Treatment with curcumin microparticles resulted in diminished VEGF expression and poorly developed tumor microvessels, indicating a significant effect on tumor angiogenesis. These results suggest that sustained delivery of chemopreventives such as curcumin using polymeric microparticles is a promising new approach to cancer chemoprevention and therapy. PMID:20460537

  19. Curcumin-derived pyrazoles and isoxazoles: Swiss army knives or blunt tools for Alzheimer's disease?

    PubMed

    Narlawar, Rajeshwar; Pickhardt, Marcus; Leuchtenberger, Stefanie; Baumann, Karlheinz; Krause, Sabine; Dyrks, Thomas; Weggen, Sascha; Mandelkow, Eckhard; Schmidt, Boris

    2008-01-01

    Curcumin binds to the amyloid beta peptide (Abeta) and inhibits or modulates amyloid precursor protein (APP) metabolism. Therefore, curcumin-derived isoxazoles and pyrazoles were synthesized to minimize the metal chelation properties of curcumin. The decreased rotational freedom and absence of stereoisomers was predicted to enhance affinity toward Abeta(42) aggregates. Accordingly, replacement of the 1,3-dicarbonyl moiety with isosteric heterocycles turned curcumin analogue isoxazoles and pyrazoles into potent ligands of fibrillar Abeta(42) aggregates. Additionally, several compounds are potent inhibitors of tau protein aggregation and depolymerized tau protein aggregates at low micromolar concentrations.

  20. Curcumin loaded mesoporous silica: an effective drug delivery system for cancer treatment.

    PubMed

    Kotcherlakota, Rajesh; Barui, Ayan Kumar; Prashar, Sanjiv; Fajardo, Mariano; Briones, David; Rodríguez-Diéguez, Antonio; Patra, Chitta Ranjan; Gómez-Ruiz, Santiago

    2016-03-01

    In the present study, we report the delivery of anti-cancer drug curcumin to cancer cells using mesoporous silica materials. A series of mesoporous silica material based drug delivery systems (S2, S4 and S6) were first designed and developed through the amine functionalization of KIT-6, MSU-2 and MCM-41 followed by the loading of curcumin. The curcumin loaded materials were characterized with several physico-chemical techniques and thoroughly screened on cancer cells to evaluate their in vitro drug delivery efficacy. All the curcumin loaded silica materials exhibited higher cellular uptake and inhibition of cancer cell viability compared to pristine curcumin. The effective internalization of curcumin in cancer cells through the mesoporous silica materials initiated the generation of intracellular reactive oxygen species and the down regulation of poly ADP ribose polymerase (PARP) enzyme levels compared to free curcumin leading to the activation of apoptosis. This study shows that the anti-cancer activity of curcumin can be potentiated by loading onto mesoporous silica materials. Therefore, we strongly believe that mesoporous silica based curcumin loaded drug delivery systems may have future potential applications for the treatment of cancers.

  1. Curcumin amorphous solid dispersions: the influence of intra and intermolecular bonding on physical stability.

    PubMed

    Wegiel, Lindsay A; Zhao, Yuhong; Mauer, Lisa J; Edgar, Kevin J; Taylor, Lynne S

    2014-12-01

    We have investigated the physical stability of amorphous curcumin dispersions and the role of curcumin-polymer intermolecular interactions in delaying crystallization. Curcumin is an interesting model compound as it forms both intra and intermolecular hydrogen bonds in the crystal. A structurally diverse set of amorphous dispersion polymers was investigated; poly(vinylpyrrolidone), Eudragit E100, carboxymethyl cellulose acetate butyrate, hydroxypropyl methyl cellulose (HPMC) and HPMC-acetate succinate. Mid-infrared spectroscopy was used to determine and quantify the extent of curcumin-polymer interactions. Physical stability under different environmental conditions was monitored by powder X-ray diffraction. Curcumin chemical stability was monitored by UV-Vis spectroscopy. Isolation of stable amorphous curcumin was difficult in the absence of polymers. Polymers proved to be effective curcumin crystallization inhibitors enabling the production of amorphous solid dispersions; however, the polymers showed very different abilities to inhibit crystallization during long-term storage. Curcumin intramolecular hydrogen bonding reduced the extent of its hydrogen bonding with polymers; hence most polymers were not highly effective crystallization inhibitors. Overall, polymers proved to be crystallization inhibitors, but inhibition was limited due to the intramolecular hydrogen bonding in curcumin, which leads to a decrease in the ability of the polymers to interact at a molecular level.

  2. Protective Effects of Curcumin, Vitamin C, or their Combination on Cadmium-Induced Hepatotoxicity

    PubMed Central

    Tarasub, Naovarat; Junseecha, Thongbai; Tarasub, Chinnawat; Na Ayutthaya, Watcharaporn Devakul

    2012-01-01

    Curcumin, a biologically active compound from turmeric, and vitamin C act as a natural antioxidant and potent chemopreventive agent. The objective of the study was to investigate whether the combined pretreatment with curcumin and vitamin C offers more beneficial effects than that provided by either of them alone in reversing cadmium (Cd)- induced hepatotoxicity. For this purpose, 64 adult male Wistar rats, equally divided into control and seven treated groups, received either Cd (as CdCl2 5 mg/kg), curcumin 400 mg/kg, curcumin 200 or 400 mg/kg + CdCl2, vitamin C 100 mg/kg + CdCl2, curcumin 200 or 400 mg/kg + vitamin C + CdCl2. All groups were treated by gavage for 27 days. The results showed that Cd treatment increased significantly lipid peroxidation levels,decreased significantly the glutathione levels, increased significantly on metallothionein (MT) expressions including the degenerative changes of liver histological tissues were observed. The treatment of Cd-exposed rats with curcumin or vitamin C alone could not reverse Cd-induced the above changes. The combined treatment with curcumin along with vitamin C before Cd intoxication was more effective than that with either of them alone in reducing such changes and reverse the changes almost similar to that of control. In conclusion, the results demonstrated that the combined pretreatment with curcumin along with vitamin C could recover the alterations and offer more protection than curcumin or vitamin C alone against Cd hepatotoxicity. PMID:24826037

  3. Decomposition Behavior of Curcumin during Solar Irradiation when Contact with Inorganic Particles

    NASA Astrophysics Data System (ADS)

    Nandiyanto, A. B. D.; Wiryani, A. S.; Rusli, A.; Purnamasari, A.; Abdullah, A. G.; Riza, L. S.

    2017-03-01

    Curcumin is one of materials which have been widely used in medicine, Asian cuisine, and traditional cosmetic. Therefore, understanding the stability of curcumin has been widely studied. The purpose of this study was to investigate the stability of curcumin solution against solar irradiation when making contact with inorganic material. As a model for the inorganic material, titanium dioxide (TiO2) was used. In the experimental method, the curcumin solution was irradiated using a solar irradiation. To confirm the stability of curcumin when contact with inorganic material, we added TiO2 micro particles with different concentrations. The results showed that the concentration of curcumin decreased during solar irradiation. The less concentration of curcumin affected the more decomposition rate obtained. The decomposition rate was increased greatly when TiO2 was added, in which the more TiO2 concentration added allowed the faster decomposition rate. Based on the result, we conclude that the curcumin is relatively stable as long as using higher concentration of curcumin and is no inorganic material existed. Then, the decomposition can be minimized by avoiding contact with inorganic material.

  4. Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers.

    PubMed

    Gota, Vikram S; Maru, Girish B; Soni, Tejal G; Gandhi, Tejal R; Kochar, Nitin; Agarwal, Manish G

    2010-02-24

    Curcumin is the lipid-soluble antioxidant compound obtained from the rhizome of Curcuma longa Linn, also known as turmeric. Curcumin targets multiple chemotherapeutic and inflammatory pathways and has demonstrated safety and tolerability in humans, supporting its potential as a therapeutic agent; however, the clinical literature lacks conclusive evidence supporting its use as a therapeutic agent due to its low bioavailability in humans. The purpose of this study was to quantify plasma levels of free curcumin after dosing of a solid lipid curcumin particle (SLCP) formulation versus unformulated curcumin in healthy volunteers and to determine its tolerability and dose-plasma concentration relationship in late-stage osteosarcoma patients. Doses of 2, 3, and 4 g of SLCP were evaluated in 11 patients with osteosarcoma. Plasma curcumin levels were measured using a validated high-performance liquid chromatography method. The limit of detection of the assay was 1 ng/mL of curcumin. In healthy subjects, the mean peak concentration of curcumin achieved from dosing 650 mg of SLCP was 22.43 ng/mL, whereas plasma curcumin from dosing an equal quantity of unformulated 95% curcuminoids extract was not detected. In both healthy individuals and osteosarcoma patients, high interindividual variability in pharmacokinetics and nonlinear dose dependency was observed, suggesting potentially complex absorption kinetics. Overall, good tolerability was noted in both healthy and osteosarcoma groups.

  5. Analogy Construction versus Analogy Solution, and Their Influence on Transfer

    ERIC Educational Resources Information Center

    Harpaz-Itay, Yifat; Kaniel, Shlomo; Ben-Amram, Einat

    2006-01-01

    This study compares transfer performed by subjects trained to solve verbal analogies, with transfer by subjects trained to construct them. The first group (n = 57) received instruction in a strategy to solve verbal analogies and the second group (n = 66) was trained in strategies for constructing such analogies. Before and after intervention, all…

  6. Terrestrial Spaceflight Analogs: Antarctica

    NASA Technical Reports Server (NTRS)

    Crucian, Brian

    2013-01-01

    Alterations in immune cell distribution and function, circadian misalignment, stress and latent viral reactivation appear to persist during Antarctic winterover at Concordia Station. Some of these changes are similar to those observed in Astronauts, either during or immediately following spaceflight. Others are unique to the Concordia analog. Based on some initial immune data and environmental conditions, Concordia winterover may be an appropriate analog for some flight-associated immune system changes and mission stress effects. An ongoing smaller control study at Neumayer III will address the influence of the hypoxic variable. Changes were observed in the peripheral blood leukocyte distribution consistent with immune mobilization, and similar to those observed during spaceflight. Alterations in cytokine production profiles were observed during winterover that are distinct from those observed during spaceflight, but potentially consistent with those observed during persistent hypobaric hypoxia. The reactivation of latent herpesviruses was observed during overwinter/isolation, that is consistently associated with dysregulation in immune function.

  7. Comparison of the Effects of Glutamine, Curcumin, and Nesfatin-1 on the Gastric Serosal Surface Neomucosa Formation: An Experimental Rodent Model

    PubMed Central

    Solmaz, Ali; Yiğitbaş, Hakan; Yavuz, Erkan; Ozdogan, Kamil; Arici, Sinan; Sarac, Tulin; Çelebi, Fatih; Celik, Atilla

    2016-01-01

    Introduction. Short bowel syndrome can crop up if more than 50% of small intestine is resected or when less than 100 cm of small bowel is left. Glutamine is the main food source of enterocytes. Curcumin has protective effects on intestinal ischemia-reperfusion damage. Nesfatin-1 is a satiety molecule. It has protective effects on gastric mucosa. The primary purpose of this study is to compare effects of glutamine, curcumin, and nesfatin-1 on the gastric serosal surface neomucosa formation on rats. Materials and Methods. 24 Wistar-Hannover rats were randomly divided into 4 groups and treated with saline, glutamine, curcumin, and nesfatin-1 after ileogastric anastomosis. After 14 days all rats were euthanized, and blood was collected. En bloc resection of anastomotic part was performed for histopathological examination. Results. PDGF, TGF-β, and VEGF levels and neomucosa formation were higher in glutamine group (p = 0.003, p = 0.003, and p = 0.025). Glutamine promotes the intestinal neomucosa formation on the gastric serosal surface and augments growth factors essential for neomucosa formation on rats. Conclusion. Glutamine may be used in short bowel syndrome for increasing the absorption surface area. But that needs to be determined by adequately powered clinical trials. PMID:27525002

  8. Migration-prone glioma cells show curcumin resistance associated with enhanced expression of miR-21 and invasion/anti-apoptosis-related proteins

    PubMed Central

    Huang, Chiung-Yin; Huang, Bor-Ren; Lin, Chingju; Lu, Dah-Yuu; Wei, Kuo-Chen

    2015-01-01

    In study, the expression patterns and functional differences between an original glioma cell population (U251 and U87) and sublines (U251-P10, U87-P10) that were selected to be migration-prone were investigated. The expressions levels of VEGF and intracellular adhesion molecule-1 (ICAM-1) were increased in the migration-prone sublines as well as in samples from patients with high-grade glioma when compared to those with low-grade glioma. In addition, cells of the migration-prone sublines showed increased expression of the oncogenic microRNA. miR-21, which was also associated with more advanced clinical pathological stages in the patient tissue specimens. Treatment of U251 cells with an miR-21 mimic dramatically enhanced the migratory activity and expression of anti-apoptotic proteins. Furthermore, treatment with curcumin decreased the miR-21 level and anti-apoptotic protein expression, and increased the expression of pro-apoptosis proteins and microtubule-associated protein light chain 3-II (LC3-II) in U251 cells. The migration-prone sublines showed decreased induction of cell death markers in response to curcumin treatment. Finally, U251-P10 cells showed resistance against curcumin treatment. These results suggest that miR-21 is associated with regulation of the migratory ability and survival in human glioma cells. These findings suggest novel mechanisms of malignancy and new potential combinatorial strategies for the management of malignant glioma. PMID:26473373

  9. VIIP Bedrest Analog Roadmap

    NASA Technical Reports Server (NTRS)

    Villarreal, Jennifer D.

    2014-01-01

    The objective is to define successive bed rest campaigns leading to a potential VIIP (Vision Impairment and Intracranial Pressure) countermeasure. To determine if the analog is successful, changes need to occur in the following outcome measures (dependent variables): Intracranial pressure; Retinal nerve fiber layer; Choroidal engorgement; Globe flattening; Axial biometry; Optic nerve sheath diameter distention; Cycloplegic refraction; Visual acuity. Study parameters (independent variables) to include: CO2; Sodium; Exercise (resistive & aerobic); Strict tilt angle.

  10. Analog storage integrated circuit

    DOEpatents

    Walker, J. T.; Larsen, R. S.; Shapiro, S. L.

    1989-01-01

    A high speed data storage array is defined utilizing a unique cell design for high speed sampling of a rapidly changing signal. Each cell of the array includes two input gates between the signal input and a storage capacitor. The gates are controlled by a high speed row clock and low speed column clock so that the instantaneous analog value of the signal is only sampled and stored by each cell on coincidence of the two clocks.

  11. Antarctic analogs for Enceladus

    NASA Astrophysics Data System (ADS)

    Murray, A. E.; Andersen, D. T.; McKay, C. P.

    2014-12-01

    Enceladus is a new world for Astrobiology. The Cassini discovery of the icy plume emanating from the South Polar region indicates an active world, where detection of water, organics, sodium, and nano-particle silica in the plume strongly suggests that the source is a subsurface salty ocean reservoir. Recent gravity data from Cassini confirms the presence of a regional sea extending north to 50°S. An ocean habitat under a thick ice cover is perhaps a recurring theme in the Outer Solar System, but what makes Enceladus unique is that the plume jetting out into space is carrying samples of this ocean. Therefore, through the study of Enceladus' plumes we can gain new insights not only of a possible habitable world in the Solar Systems, but also about the formation and evolution of other icy-satellites. Cassini has been able to fly through this plume - effectively sampling the ocean. It is time to plan for future missions that do more detailed analyses, possibly return samples back to Earth and search for evidence of life. To help prepare for such missions, the need for earth-based analog environments is essential for logistical, methodological (life detection) and theoretical development. We have undertaken studies of two terrestrial environments that are close analogs to Enceladus' ocean: Lake Vida and Lake Untersee - two ice-sealed Antarctic lakes that represent physical, chemical and possibly biological analogs for Enceladus. By studying the diverse biology and physical and chemical constraints to life in these two unique lakes we will begin to understand the potential habitability of Enceladus and other icy moons, including possible sources of nutrients and energy, which together with liquid water are the key ingredients for life. Analog research such as this will also enable us to develop and test new strategies to search for evidence of life on Enceladus.

  12. Analog storage integrated circuit

    DOEpatents

    Walker, J.T.; Larsen, R.S.; Shapiro, S.L.

    1989-03-07

    A high speed data storage array is defined utilizing a unique cell design for high speed sampling of a rapidly changing signal. Each cell of the array includes two input gates between the signal input and a storage capacitor. The gates are controlled by a high speed row clock and low speed column clock so that the instantaneous analog value of the signal is only sampled and stored by each cell on coincidence of the two clocks. 6 figs.

  13. A Transiting Jupiter Analog

    NASA Astrophysics Data System (ADS)

    Kipping, D. M.; Torres, G.; Henze, C.; Teachey, A.; Isaacson, H.; Petigura, E.; Marcy, G. W.; Buchhave, L. A.; Chen, J.; Bryson, S. T.; Sandford, E.

    2016-04-01

    Decadal-long radial velocity surveys have recently started to discover analogs to the most influential planet of our solar system, Jupiter. Detecting and characterizing these worlds is expected to shape our understanding of our uniqueness in the cosmos. Despite the great successes of recent transit surveys, Jupiter analogs represent a terra incognita, owing to the strong intrinsic bias of this method against long orbital periods. We here report on the first validated transiting Jupiter analog, Kepler-167e (KOI-490.02), discovered using Kepler archival photometry orbiting the K4-dwarf KIC-3239945. With a radius of (0.91+/- 0.02) {R}{{J}}, a low orbital eccentricity ({0.06}-0.04+0.10), and an equilibrium temperature of (131+/- 3) K, Kepler-167e bears many of the basic hallmarks of Jupiter. Kepler-167e is accompanied by three Super-Earths on compact orbits, which we also validate, leaving a large cavity of transiting worlds around the habitable-zone. With two transits and continuous photometric coverage, we are able to uniquely and precisely measure the orbital period of this post snow-line planet (1071.2323 ± 0.0006d), paving the way for follow-up of this K = 11.8 mag target.

  14. Antisolvent precipitation technique: A very promising approach to crystallize curcumin in presence of polyvinyl pyrrolidon for solubility and dissolution enhancement.

    PubMed

    Sadeghi, Fatemeh; Ashofteh, Mohammad; Homayouni, Alireza; Abbaspour, Mohammadreza; Nokhodchi, Ali; Garekani, Hadi Afrasiabi

    2016-11-01

    Curcumin with a vast number of pharmacological activities is a poorly water soluble drug which its oral bioavailability is profoundly limited by its dissolution or solubility in GI tract. Curcumin could be a good anticancer drug if its solubility could be increased. Therefore, the aim of the present study was to increase the dissolution rate of curcumin by employing antisolvent crystallization technique and to investigate the effect of polyvinyl pyrrolidone K30 (PVP) as colloidal particles in crystallization medium on resultant particles. Curcumin was crystalized in the presence of different amounts of PVP by antisolvent crystallization method and their physical mixtures were prepared for comparison purposes. The samples were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and Fourier transform infrared spectroscopy (FT-IR). The solubility and dissolution of the treated and untreated curcumin were also determined. Antisolvent crystallization of curcumin led to the formation of particles with no definite geometric shape. It was interesting to note that the DSC and XRPD studies indicated the formation of a new polymorph and less crystallinity for particles crystallized in the absence of PVP. However, the crystallized curcumin in the presence of PVP was completely amorphous. All crystalized curcumin samples showed much higher dissolution rate compared to untreated curcumin. The amount of curcumin dissolved within 10 for treated curcumin in the presence of PVP (1:1 curcumin:PVP) was 7 times higher than untreated curcumin and this enhancement in the dissolution for curcumin samples crystallized in the absence of PVP was around 5 times. Overall' the results of this study showed that antisolvent crystallization method in the absence or presence of small amounts of PVP is very efficient in increasing the dissolution rate of curcumin to achieve better efficiency for curcumin.

  15. Curcumin nanoparticles ameliorate ICAM-1 expression in TNF-α-treated lung epithelial cells through p47 (phox) and MAPKs/AP-1 pathways.

    PubMed

    Yen, Feng-Lin; Tsai, Ming-Horng; Yang, Chuen-Mao; Liang, Chan-Jung; Lin, Chun-Ching; Chiang, Yao-Chang; Lee, Hui-Chun; Ko, Horng-Huey; Lee, Chiang-Wen

    2013-01-01

    Upregulation of intercellular adhesion molecule-1 (ICAM-1) involves adhesions between both circulating and resident leukocytes and the human lung epithelial cells during lung inflammatory reactions. We have previously demonstrated that curcumin-loaded polyvinylpyrrolidone nanoparticles (CURN) improve the anti-inflammatory and anti-oxidative properties of curcumin in hepatocytes. In this study, we focused on the effects of CURN on the expression of ICAM-1 in TNF-α-treated lung epithelial cells and compared these to the effects of curcumin water preparation (CURH). TNF-αinduced ICAM-1 expression, ROS production, and cell-cell adhesion were significantly attenuated by the pretreatment with antioxidants (DPI, APO, or NAC) and CURN, but not by CURH, as revealed by western blot analysis, RT-PCR, promoter assay, and ROS detection and adhesion assay. In addition, treatment of TNF-α-treated cells with CURN and antioxidants also resulted in an inhibition of activation of p47 (phox) and phosphorylation of MAPKs, as compared to that using CURH. Our findings also suggest that phosphorylation of MAPKs may eventually lead to the activation of transcription factors. We also observed that the effects of TNF-α treatment for 30 min, which includes a significant increase in the binding activity of AP-1 and phosphorylation of c-jun and c-fos genes, were reduced by CURN treatment. In vivo studies have revealed that CURN improved the anti-inflammation activities of CURH in the lung epithelial cells of TNF-α-treated mice. Our results indicate that curcumin-loaded polyvinylpyrrolidone nanoparticles may potentially serve as an anti-inflammatory drug for the treatment of respiratory diseases.

  16. The dietary polyphenols trans-resveratrol and curcumin selectively bind human CB1 cannabinoid receptors with nanomolar affinities and function as antagonists/inverse agonists.

    PubMed

    Seely, Kathryn A; Levi, Mark S; Prather, Paul L

    2009-07-01

    The dietary polyphenols trans-resveratrol [5-[(1E)-2-(4-hydroxyphenyl)ethenyl]-1,3-benzenediol; found in red wine] and curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1E,6E-heptadiene-3,5-dione] (found in curry powders) exert anti-inflammatory and antioxidant effects via poorly defined mechanisms. It is interesting that cannabinoids, derived from the marijuana plant (Cannabis sativa), produce similar protective effects via CB1 and CB2 receptors. We examined whether trans-resveratrol, curcumin, and ASC-J9 [1,7-bis(3,4-dimethoxyphenyl)-5-hydroxy-1E,4E,6E-heptatriene-3-one] (a curcumin analog) act as ligands at cannabinoid receptors. All three bind to human (h) CB1 and mouse CB1 receptors with nanomolar affinities, displaying only micromolar affinities for hCB2 receptors. Characteristic of inverse agonists, the polyphenols inhibit basal G-protein activity in membranes prepared from Chinese hamster ovary (CHO)-hCB1 cells or mouse brain that is reversed by a neutral CB1 antagonist. Furthermore, they competitively antagonize G-protein activation produced by a CB1 agonist. In intact CHO-hCB1 cells, the polyphenols act as neutral antagonists, producing no effect when tested alone, whereas competitively antagonizing CB1 agonist mediated inhibition of adenylyl cyclase activity. Confirming their neutral antagonist profile in cells, the polyphenols similarly attenuate stimulation of adenylyl cyclase activity produced by a CB1 inverse agonist. In mice, the polyphenols dose-dependently reverse acute hypothermia produced by a CB1 agonist. Upon repeated administration, the polyphenols also reduce body weight in mice similar to that produced by a CB1 antagonist/inverse agonist. Finally, trans-resveratrol and curcumin share common structural motifs with other known cannabinoid receptor ligands. Collectively, we suggest that trans-resveratrol and curcumin act as antagonists/inverse agonists at CB1 receptors at dietary relevant concentrations. Therefore, these polyphenols and their

  17. Affinity of nat/68Ga-Labelled Curcumin and Curcuminoid Complexes for β-Amyloid Plaques: Towards the Development of New Metal-Curcumin Based Radiotracers

    PubMed Central

    Rubagotti, Sara; Croci, Stefania; Ferrari, Erika; Iori, Michele; Capponi, Pier C.; Lorenzini, Luca; Calzà, Laura; Versari, Annibale; Asti, Mattia

    2016-01-01

    Curcumin derivatives labelled with fluorine-18 or technetium-99m have recently shown their potential as diagnostic tools for Alzheimer’s disease. Nevertheless, no study by exploiting the labelling with gallium-68 has been performed so far, in spite of its suitable properties (positron emitter, generator produced radionuclide). Herein, an evaluation of the affinity for synthetic β-amyloid fibrils and for amyloid plaques of three nat/68Ga-labelled curcumin analogues, namely curcumin curcumin (CUR), bis-dehydroxy-curcumin (bDHC) and diacetyl-curcumin (DAC), was performed. Affinity and specificity were tested in vitro on amyloid synthetic fibrils by using gallium-68 labelled compounds. Post-mortem brain cryosections from Tg2576 mice were used for the ex vivo visualization of amyloid plaques. The affinity of 68Ga(CUR)2+, 68Ga(DAC)2+, and 68Ga(bDHC)2+ for synthetic β-amyloid fibrils was moderate and their uptake could be observed in vitro. On the other hand, amyloid plaques could not be visualized on brain sections of Tg2576 mice after injection, probably due to the low stability of the complexes in vivo and of a hampered passage through the blood–brain barrier. Like curcumin, all nat/68Ga-curcuminoid complexes maintain a high affinity for β-amyloid plaques. However, structural modifications are still needed to improve their applicability as radiotracers in vivo. PMID:27608011

  18. Affinity of (nat/68)Ga-Labelled Curcumin and Curcuminoid Complexes for β-Amyloid Plaques: Towards the Development of New Metal-Curcumin Based Radiotracers.

    PubMed

    Rubagotti, Sara; Croci, Stefania; Ferrari, Erika; Iori, Michele; Capponi, Pier C; Lorenzini, Luca; Calzà, Laura; Versari, Annibale; Asti, Mattia

    2016-09-06

    Curcumin derivatives labelled with fluorine-18 or technetium-99m have recently shown their potential as diagnostic tools for Alzheimer's disease. Nevertheless, no study by exploiting the labelling with gallium-68 has been performed so far, in spite of its suitable properties (positron emitter, generator produced radionuclide). Herein, an evaluation of the affinity for synthetic β-amyloid fibrils and for amyloid plaques of three (nat/68)Ga-labelled curcumin analogues, namely curcumin curcumin (CUR), bis-dehydroxy-curcumin (bDHC) and diacetyl-curcumin (DAC), was performed. Affinity and specificity were tested in vitro on amyloid synthetic fibrils by using gallium-68 labelled compounds. Post-mortem brain cryosections from Tg2576 mice were used for the ex vivo visualization of amyloid plaques. The affinity of (68)Ga(CUR)₂⁺, (68)Ga(DAC)₂⁺, and (68)Ga(bDHC)₂⁺ for synthetic β-amyloid fibrils was moderate and their uptake could be observed in vitro. On the other hand, amyloid plaques could not be visualized on brain sections of Tg2576 mice after injection, probably due to the low stability of the complexes in vivo and of a hampered passage through the blood-brain barrier. Like curcumin, all (nat/68)Ga-curcuminoid complexes maintain a high affinity for β-amyloid plaques. However, structural modifications are still needed to improve their applicability as radiotracers in vivo.

  19. Spectrophotometric and electrochemical determination of the formation constants of the complexes Curcumin-Fe(III)-water and Curcumin-Fe(II)-water.

    PubMed

    Bernabé-Pineda, Marganta; Ramírez-Silva, Maria Teresa; Romero-Romo, Mario Alberto; González-Vergara, Enrique; Rojas-Hernández, Alberto

    2004-04-01

    The formation of complexes among the Curcumin, Fe(III) and Fe(II) was studied in aqueous media within the 5-11 pH range by means of UV-Vis spectrophotometry and cyclic voltammetry. When the reaction between the Curcumin and the ions present in basic media took place, the resulting spectra of the systems Curcumin-Fe(III) and Curcumin-Fe(II) presented a similar behaviour. The cyclic voltammograms in basic media indicated that a chemical reaction has taken place between the Curcumin and Fe(III) before that of the formation of complexes. Data processing with SQUAD permitted to calculate the formation constants of the complexes Curcumin-Fe(III), corresponding to the species FeCur (lob beta110 = 22.25 +/- 0.03) and FeCur(OH)- (log beta111 = 12.14 +/- 0.03), while for the complexes Curcumin-Fe(II) the corresponding formation constants of the species FeCur- (log beta110 = 9.20 +/- 0.04), FeHCur (log beta111 = 19.76 +/- 0.03), FeH2Cur+ (log beta112 = 28.11 +/- 0.02).

  20. Cellular effects of curcumin on Plasmodium falciparum include disruption of microtubules.

    PubMed

    Chakrabarti, Rimi; Rawat, Parkash S; Cooke, Brian M; Coppel, Ross L; Patankar, Swati

    2013-01-01

    Curcumin has been widely investigated for its myriad cellular effects resulting in reduced proliferation of various eukaryotic cells including cancer cells and the human malaria parasite Plasmodium falciparum. Studies with human cancer cell lines HT-29, Caco-2, and MCF-7 suggest that curcumin can bind to tubulin and induce alterations in microtubule structure. Based on this finding, we investigated whether curcumin has any effect on P. falciparum microtubules, considering that mammalian and parasite tubulin are 83% identical. IC50 of curcumin was found to be 5 µM as compared to 20 µM reported before. Immunofluorescence images of parasites treated with 5 or 20 µM curcumin showed a concentration-dependent effect on parasite microtubules resulting in diffuse staining contrasting with the discrete hemispindles and subpellicular microtubules observed in untreated parasites. The effect on P. falciparum microtubules was evident only in the second cycle for both concentrations tested. This diffuse pattern of tubulin fluorescence in curcumin treated parasites was similar to the effect of a microtubule destabilizing drug vinblastine on P. falciparum. Molecular docking predicted the binding site of curcumin at the interface of alpha and beta tubulin, similar to another destabilizing drug colchicine. Data from predicted drug binding is supported by results from drug combination assays showing antagonistic interactions between curcumin and colchicine, sharing a similar binding site, and additive/synergistic interactions of curcumin with paclitaxel and vinblastine, having different binding sites. This evidence suggests that cellular effects of curcumin are at least, in part, due to its perturbing effect on P. falciparum microtubules. The action of curcumin, both direct and indirect, on P. falciparum microtubules is discussed.

  1. Curcumin alleviates glucocorticoid-induced osteoporosis by protecting osteoblasts from apoptosis in vivo and in vitro.

    PubMed

    Chen, Zhiguang; Xue, Jinqi; Shen, Tao; Ba, Gen; Yu, Dongdong; Fu, Qin

    2016-02-01

    Curcumin, an active component of the rhizomes of Curcumin longa L., possesses broad anti-inflammation and anti-cancer properties. Curcumin was previously reported to be capable of protecting ovariectomized rats against osteoporosis. However, the effect of curcumin on glucocorticoid-induced osteoporosis (GIO) is not yet clear. The present study investigated the effects of curcumin on dexamethasone (Dex)-induced osteoporosis in vivo and Dex-induced osteoblast apoptosis in vivo and in vitro. The GIO rat model was induced by subcutaneous injection of Dex for 60 days and verified to be successful as evidenced by the significantly decreased bone mineral density (BMD) determined using dual X-ray absorptiometry. Subsequently, curcumin administration (100 mg/kg) for 60 days obviously increased BMD and bone-alkaline phosphatase, decreased carboxy-terminal collagen cross links, enhanced bone mechanical strength, and improved trabecular microstructure, thereby alleviating Dex-induced osteoporosis. Mechanically, curcumin remarkably reversed Dex-induced femoral osteoblast apoptosis in vivo. In cultured primary osteoblasts, pretreatment with curcumin concentration-dependently decreased the number of Dex-induced apoptotic osteoblasts by down-regulating the ratio of Bax/Bcl-2 as well as the levels of cleaved caspase-3 and cleaved poly ADP-ribose polymerase (PARP). Moreover, curcumin pretreatment activated extracellular signal regulated kinase (ERK) signalling in Dex-induced osteoblasts by up-regulating the expression level of p-ERK1/2. Taken together, our study demonstrated that curcumin could ameliorate GIO by protecting osteoblasts from apoptosis, which was possibly related to the activation of the ERK pathway. The results suggest that curcumin may be a promising drug for prevention and treatment of GIO.

  2. Enhancement of transport of curcumin to brain in mice by poly( n-butylcyanoacrylate) nanoparticle

    NASA Astrophysics Data System (ADS)

    Sun, Min; Gao, Yan; Guo, Chenyu; Cao, Fengliang; Song, Zhimei; Xi, Yanwei; Yu, Aihua; Li, Aiguo; Zhai, Guangxi

    2010-10-01

    Curcumin, a widely used coloring agent and spice in food, has a potential in blocking brain tumor formation and curing Alzheimer's disease. Due to the specific properties of blood-brain barrier (BBB), only traces of curcumin were transported across BBB. The aim of the present study was to design and characterize curcumin loaded polybutylcyanoacrylate nanoparticles (PBCN) coated with polysorbate 80, and to evaluate the effect of PBCN as a delivery system on carrying curcumin across BBB. Curcumin loaded nanoparticles were prepared by an anionic polymerization method, and they presented in a core-shell spherical shape under transmission electron microscopy, with an average diameter of 152.0 nm. The average drug loading was 21.1%. Physicochemical status of curcumin in the nanoparticles was confirmed with differential scanning colorimetry and Fourier transform infrared spectroscopy. The in vitro release behavior of drug from the nanoparticles was fitted to a double phase kinetics model. The studies of pharmacokinetic and bio-distribution to brain were conducted in mice after intravenous administration of the nanoparticle formulation at the dose of 5 mg/kg and curcumin solution at the dose of 10 mg/kg via the tail vein. The results showed that in plasma, the area under concentration-time curve (AUC0-∞) for curcumin loaded nanoparticles was greater than that for the control solution, moreover, the mean residence time of curcumin loaded nanoparticles was 14-fold that of the control solution. In brain, AUC0-∞ for curcumin loaded nanoparticles was 2.53-fold that for the control solution. In conclusion, the present study demonstrated that PBCN could enhance the transport of curcumin to brain and have a potential as a delivery system to cross the BBB.

  3. Curcumin attenuates oxidative stress following downhill running-induced muscle damage.

    PubMed

    Kawanishi, Noriaki; Kato, Kouki; Takahashi, Masaki; Mizokami, Tsubasa; Otsuka, Yoshihiko; Imaizumi, Atsushi; Shiva, Daisuke; Yano, Hiromi; Suzuki, Katsuhiko

    2013-11-22

    Downhill running causes muscle damage, and induces oxidative stress and inflammatory reaction. Recently, it is shown that curcumin possesses anti-oxidant and anti-inflammatory potentials. Interestingly, curcumin reduces inflammatory cytokine concentrations in skeletal muscle after downhill running of mice. However, it is not known whether curcumin affects oxidative stress after downhill running-induced muscle damage. Therefore, the purpose of this study was to investigate the effects of curcumin on oxidative stress following downhill running induced-muscle damage. We also investigated whether curcumin affects macrophage infiltration via chemokines such as MCP-1 and CXCL14. Male C57BL/6 mice were divided into four groups; rest, rest plus curcumin, downhill running, or downhill running plus curcumin. Downhill running mice ran at 22 m/min, -15% grade on the treadmill for 150 min. Curcumin (3mg) was administered in oral administration immediately after downhill running. Hydrogen peroxide concentration and NADPH-oxidase mRNA expression in the downhill running mice were significantly higher than those in the rest mice, but these variables were significantly attenuated by curcumin administration in downhill running mice. In addition, mRNA expression levels of MCP-1, CXCL14 and F4/80 reflecting presence of macrophages in the downhill running mice were significantly higher than those in the rest mice. However, MCP-1 and F4/80 mRNA expression levels were significantly attenuated by curcumin administration in downhill running mice. Curcumin may attenuate oxidative stress following downhill running-induced muscle damage.

  4. Interstellar Molecules

    ERIC Educational Resources Information Center

    Solomon, Philip M.

    1973-01-01

    Radioastronomy reveals that clouds between the stars, once believed to consist of simple atoms, contain molecules as complex as seven atoms and may be the most massive objects in our Galaxy. (Author/DF)

  5. Modeling Molecules

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The molecule modeling method known as Multibody Order (N) Dynamics, or MBO(N)D, was developed by Moldyn, Inc. at Goddard Space Flight Center through funding provided by the SBIR program. The software can model the dynamics of molecules through technology which stimulates low-frequency molecular motions and properties, such as movements among a molecule's constituent parts. With MBO(N)D, a molecule is substructured into a set of interconnected rigid and flexible bodies. These bodies replace the computation burden of mapping individual atoms. Moldyn's technology cuts computation time while increasing accuracy. The MBO(N)D technology is available as Insight II 97.0 from Molecular Simulations, Inc. Currently the technology is used to account for forces on spacecraft parts and to perform molecular analyses for pharmaceutical purposes. It permits the solution of molecular dynamics problems on a moderate workstation, as opposed to on a supercomputer.

  6. Mobius Molecules

    ERIC Educational Resources Information Center

    Eckert, J. M.

    1973-01-01

    Discusses formation of chemical molecules via Mobius strip intermediates, and concludes that many special physics-chemical properties of the fully closed circular form (1) of polyoma DNA are explainable by this topological feature. (CC)

  7. Enumerating molecules.

    SciTech Connect

    Visco, Donald Patrick, Jr.; Faulon, Jean-Loup Michel; Roe, Diana C.

    2004-04-01

    This report is a comprehensive review of the field of molecular enumeration from early isomer counting theories to evolutionary algorithms that design molecules in silico. The core of the review is a detail account on how molecules are counted, enumerated, and sampled. The practical applications of molecular enumeration are also reviewed for chemical information, structure elucidation, molecular design, and combinatorial library design purposes. This review is to appear as a chapter in Reviews in Computational Chemistry volume 21 edited by Kenny B. Lipkowitz.

  8. Neural Analog Information Processing

    NASA Astrophysics Data System (ADS)

    Hecht-Nielsen, Robert

    1982-07-01

    Neural Analog Information Processing (NAIP) is an effort to develop general purpose pattern classification architectures based upon biological information processing principles. This paper gives an overview of NAIP and its relationship to the previous work in neural modeling from which its fundamental principles are derived. It also presents a theorem concerning the stability of response of a slab (a two dimensional array of identical simple processing units) to time-invariant (spatial) patterns. An experiment (via computer emulation) demonstrating classification of a spatial pattern by a simple, but complete NAIP architecture is described. A concept for hardware implementation of NAIP architectures is briefly discussed.

  9. Analogical Processes in Learning

    DTIC Science & Technology

    1980-09-15

    CLASSICATMN OF ThIS PA5UrSfie Dule gIt.,.d ANALOGICAL PROCESSES IN LEARNING David E . Rumelhart & Donald A. Norman Program in Cognitive Science Center...for Human Information Processing University of California, San Diego La Jolla, California 92093 Copyright Q) 1980 David E . Rumelhart & Donald A. Norman...4) SEARS 7 E Ilamnp C5P Tota $.600 Aprovd.L. Figure 1. Stimuli for the two conditions of D’Andrade’s reasoning * experiment. The left panel shows the

  10. Therapeutic effect of curcumin on experimental colitis mediated by inhibiting CD8+CD11c+ cells

    PubMed Central

    Zhao, Hai-Mei; Han, Fei; Xu, Rong; Huang, Xiao-Ying; Cheng, Shao-Min; Huang, Min-Fang; Yue, Hai-Yang; Wang, Xin; Zou, Yong; Xu, Han-Lin; Liu, Duan-Yong

    2017-01-01

    AIM To verify whether curcumin (Cur) can treat inflammatory bowel disease by regulating CD8+CD11c+ cells. METHODS We evaluated the suppressive effect of Cur on CD8+CD11c+ cells in spleen and Peyer’s patches (PPs) in colitis induced by trinitrobenzene sulfonic acid. Mice with colitis were treated by 200 mg/kg Cur for 7 d. On day 8, the therapeutic effect of Cur was evaluated by visual assessment and histological examination, while co-stimulatory molecules of CD8+CD11c+ cells in the spleen and PPs were measured by flow cytometry. The levels of interleukin (IL)-10, interferon (IFN)-γ and transforming growth factor (TGF)-β1 in spleen and colonic mucosa were determined by ELISA. RESULTS The disease activity index, colon weight, weight index of colon and histological score of experimental colitis were obviously decreased after Cur treatment, while the body weight and colon length recovered. After treatment with Cur, CD8+CD11c+ cells were decreased in the spleen and PPs, and the expression of major histocompatibility complex II, CD205, CD40, CD40L and intercellular adhesion molecule-1 was inhibited. IL-10, IFN-γ and TGF-β1 levels were increased compared with those in mice with untreated colitis. CONCLUSION Cur can effectively treat experimental colitis, which is realized by inhibiting CD8+CD11c+ cells. PMID:28348486

  11. Curcumin and kaempferol prevent lysozyme fibril formation by modulating aggregation kinetic parameters.

    PubMed

    Borana, Mohanish S; Mishra, Pushpa; Pissurlenkar, Raghuvir R S; Hosur, Ramakrishna V; Ahmad, Basir

    2014-03-01

    Interaction of small molecule inhibitors with protein aggregates has been studied extensively, but how these inhibitors modulate aggregation kinetic parameters is little understood. In this work, we investigated the ability of two potential aggregation inhibiting drugs, curcumin and kaempferol, to control the kinetic parameters of aggregation reaction. Using thioflavin T fluorescence and static light scattering, the kinetic parameters such as amplitude, elongation rate constant and lag time of guanidine hydrochloride-induced aggregation reactions of hen egg white lysozyme were studied. We observed a contrasting effect of inhibitors on the kinetic parameters when aggregation reactions were measured by these two probes. The interactions of these inhibitors with hen egg white lysozyme were investigated using fluorescence quench titration method and molecular dynamics simulations coupled with binding free energy calculations. We conclude that both the inhibitors prolong nucleation of amyloid aggregation through binding to region of the protein which is known to form the core of the protein fibril, but once the nucleus is formed the rate of elongation is not affected by the inhibitors. This work would provide insight into the mechanism of aggregation inhibition by these potential drug molecules.

  12. Fe3O4-citrate-curcumin: Promising conjugates for superoxide scavenging, tumor suppression and cancer hyperthermia

    NASA Astrophysics Data System (ADS)

    Kitture, Rohini; Ghosh, Sougata; Kulkarni, Parag; Liu, X. L.; Maity, Dipak; Patil, S. I.; Jun, Ding; Dushing, Yogesh; Laware, S. L.; Chopade, B. A.; Kale, S. N.

    2012-03-01

    Fe3O4 nanoparticles have been conjugated to curcumin (CU) molecules via a citrate (CA) linker (Fe-CA-CU) and have been explored for superoxide scavenging, tumor suppression, and cancer hyperthermia. The conjugation chemistry reveals that Fe3+ ions on the nanoparticle surface readily conjugates to the available carboxyl sites on the CA molecule, which further conjugates to CU at its central enol -OH group. As seen from the UV-vis spectroscopy, the therapeutically active chromophore group of CU, which is seen at 423 nm, was intact, ensuring the activity the molecule. Magnetization measurements showed good hysteresis curves of Fe3O4 and Fe-CA-CU, indicating the presence of magnetism after conjugation. The loading percentage of citrate-curcumin was seen to be ˜10% from the thermo-gravimetric analysis. The systems when subjected to radio-frequency fields of 240 KHz, were seen to get heated up. The Fe3O4 heating exhibited better slope (1 °C/s) as compared to the Fe-CA-CU system (˜0.7 °C/s) for a sample of concentration 10 mg/ml in average time of ˜20 s to reach the required hyperthermia threshold temperature of ˜45 °C. Tumor suppression studies were done using potato assay, which showed that while only CU showed 100% suppression in 7 days, it was about 89% by the Fe-CA-CU. Upon subjecting these systems to the superoxide anion scavenging assay and superoxide radical scavenging assay (riboflavin), it was observed that the activity was enhanced in the Fe-CA-CU to 40% (from 38% in only CU) and 100% (from 5.75% in only CU). These studies promise Fe-CA-CU as a good cancer hyperthermia-cum-tumor suppressant and antioxidant agent.

  13. Nonlinear optical studies of curcumin metal derivatives with cw laser

    NASA Astrophysics Data System (ADS)

    Henari, F. Z.; Cassidy, S.

    2015-03-01

    We report on measurements of the nonlinear refractive index and nonlinear absorption coefficients for curcumin and curcumin metal complexes of boron, copper, and iron at different wavelengths using the Z-scan technique. These materials are found to be novel nonlinear media. It was found that the addition of metals slightly influences its nonlinearity. These materials show a large negative nonlinear refractive index of the order of 10-7 cm2/W and negative nonlinear absorption of the order of 10-6 cm/W. The origin of the nonlinearity was investigated by comparison of the formalism that is known as the Gaussian decomposition model with the thermal lens model. The optical limiting behavior based on the nonlinear refractive index was also investigated.

  14. Tamoxifen and curcumin binding to serum albumin. Spectroscopic study

    NASA Astrophysics Data System (ADS)

    Maciążek-Jurczyk, M.; Maliszewska, M.; Pożycka, J.; Równicka-Zubik, J.; Góra, A.; Sułkowska, A.

    2013-07-01

    Tamoxifen (TMX) is widely used for the breast cancer treatment and is known as chemopreventive agent. Curcumin (CUR) is natural phenolic compound with broad spectrum of biological activity e.g. anti-inflammatory, antimicrobial, antiviral, antifungal and chemopreventive. Combination of tamoxifen and curcumin could be more effective with lower toxicity than each agent alone in use for the treatment or chemoprevention of breast cancer. Binding of drugs to serum albumin is an important factor, which determines toxicity and therapeutic dosage of the drugs. When two drugs are administered together the competition between them for the binding site on albumin can result in a decrease in bound fraction and an increase in the concentration of free biologically active fraction of drug.

  15. Curcumin, inflammation, and chronic diseases: how are they linked?

    PubMed

    He, Yan; Yue, Yuan; Zheng, Xi; Zhang, Kun; Chen, Shaohua; Du, Zhiyun

    2015-05-20

    It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, shows strong anti-oxidative and anti-inflammatory activities when used as a remedy for the prevention and treatment of chronic diseases. How oxidative stress activates inflammatory pathways leading to the progression of chronic diseases is the focus of this review. Thus, research to date suggests that chronic inflammation, oxidative stress, and most chronic diseases are closely linked, and the antioxidant properties of curcumin can play a key role in the prevention and treatment of chronic inflammation diseases.

  16. Unraveling the Anticancer Effect of Curcumin and Resveratrol

    PubMed Central

    Pavan, Aline Renata; da Silva, Gabriel Dalio Bernardes; Jornada, Daniela Hartmann; Chiba, Diego Eidy; Fernandes, Guilherme Felipe dos Santos; Man Chin, Chung; dos Santos, Jean Leandro

    2016-01-01

    Resveratrol and curcumin are natural products with important therapeutic properties useful to treat several human diseases, including cancer. In the last years, the number of studies describing the effect of both polyphenols against cancer has increased; however, the mechanism of action in all of those cases is not completely comprehended. The unspecific effect and the ability to interfere in assays by both polyphenols make this challenge even more difficult. Herein, we analyzed the anticancer activity of resveratrol and curcumin reported in the literature in the last 11 years, in order to unravel the molecular mechanism of action of both compounds. Molecular targets and cellular pathways will be described. Furthermore, we also discussed the ability of these natural products act as chemopreventive and its use in association with other anticancer drugs. PMID:27834913

  17. Nonlinear optical studies of curcumin metal derivatives with cw laser

    SciTech Connect

    Henari, F. Z. Cassidy, S.

    2015-03-30

    We report on measurements of the nonlinear refractive index and nonlinear absorption coefficients for curcumin and curcumin metal complexes of boron, copper, and iron at different wavelengths using the Z-scan technique. These materials are found to be novel nonlinear media. It was found that the addition of metals slightly influences its nonlinearity. These materials show a large negative nonlinear refractive index of the order of 10{sup −7} cm{sup 2}/W and negative nonlinear absorption of the order of 10{sup −6} cm/W. The origin of the nonlinearity was investigated by comparison of the formalism that is known as the Gaussian decomposition model with the thermal lens model. The optical limiting behavior based on the nonlinear refractive index was also investigated.

  18. Synthesis of antisense oligonucleotides containing acyclic alkynyl nucleoside analogs and their biophysical and biological properties.

    PubMed

    Ogata, Aya; Maeda, Yusuke; Ueno, Yoshihito

    2017-04-01

    The synthesis of oligonucleotide (ON) analogs, which can be used as antisense molecules, has recently gained much attention. Here, we report the synthesis and properties of an ON analog containing acyclic thymidine and cytidine analogs with a 4-pentyl-1,2-diol instead of the d-ribofuranose moiety. The incorporation of these analogs into the ON improved its nuclease resistance to 3'-exonucleases. Furthermore, it was found that the incorporation of the acyclic thymidine analog into a DNA/RNA duplex accelerates the RNA cleavage of a DNA/RNA duplex by Escherichia coli RNase H.

  19. Anthelmintic Potential of Thymoquinone and Curcumin on Fasciola gigantica.

    PubMed

    Ullah, Rizwan; Rehman, Abdur; Zafeer, Mohd Faraz; Rehman, Lubna; Khan, Yasir A; Khan, M A Hannan; Khan, Shahper N; Khan, Asad U; Abidi, S M A

    2017-01-01

    Fasciolosis an economically important global disease of ruminants in the temperate and tropical regions, caused by Fasciola hepatica and F. gigantica, respectively, also poses a potential zoonotic threat. In India alone it causes huge losses to stakeholders. Anthelmintics including triclabendazole have been used to control this menace but the emerging resistance against the available compounds necessitates identification of novel and alternative therapeutic measures involving plant derived natural compounds for their anthelmintic potential. Thymoquinone (T) and curcumin (C), the active ingredients of Nigella sativa and Curcuma longa respectively have been used as antiparasitic agents but the information on their flukicidal effect is very limited. Adult flukes of F. gigantica were in vitro exposed to different concentrations of thymoquinone and curcumin separately for 3h at 37+ 1°C. A significant (p<0.05) reduction in the worm motility at 60 μM concentration of both T and C was observed though all the worms remained alive after 3h exposure, whereas the effect on egg shedding was statistically insignificant. Pronounced tegumental disruptions and erosion of spines in the posterior region and around the acetabulum was evident. A significant (p<0.05) decrease in glutathione-S-transferase and superoxide dismutase activity and reduced glutathione (GSH) level was observed, while protein carbonylation increased differentially. A significant inhibition of CathepsinL (CatL) gene expression in thymoquinone treated worms was also evident. Further, in silico molecular docking of T and C with CatL revealed a stronger interaction of curcumin with the involvement of higher number of amino acids as compared to thymoquinone that could be more effective in inhibiting the antioxidant enzymes of F. gigantica. It is concluded that both the compounds understudy will decrease the detoxification ability of F. gigantica, while inhibition of CatL will significantly affect their virulence

  20. Radio-protective effect of some new curcumin analogues.

    PubMed

    El-Gazzar, Marwa G; Zaher, Nashwa H; El-Hossary, Ebaa M; Ismail, Amel F M

    2016-09-01

    In the present study, novel symmetrical curcumin analogues (2-7) have been synthesized by substituting the phenolic OH of curcumin with different linkers providing additional keto-enol tautomerism, very essential for radioprotective activity. The structures of the synthesized compounds (2-7) were elucidated by elemental analysis, IR, (1)H-NMR, (13)C-NMR and mass spectral data and were found consistent with the assigned structures. The curative effect of these new compounds, against the oxidative stress due to exposure of rats to the whole body γ-irradiation (7Gy) was investigated. Gamma-irradiated rats exhibited elevations of ALT, AST activities, urea, creatinine, triglycerides, total cholesterol, malondialdehyde (MDA), nitric oxide (NO), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) and Nuclear Factor-kappa B (NF-κB) levels. Contrariwise, the total protein, albumin, total calcium level, SOD, CAT, GSH-Px, GST activities and GSH content were decreased. Treatment of gamma-irradiated rats with the new curcumin analogues (2-7) showed significant amelioration in the in-vivo antioxidant status, liver and kidney functions, as well as the anti-inflammatory markers (IL-6, TNF-α and NF-κB). Inhibition of NF-κB could be responsible for the improvement of the antioxidant and anti-inflammatory status in gamma-irradiated animals, by down-regulation of IL-1β and TNF-α level. In conclusion, the new curcumin analogues (2-7) exhibited post-protective effect on gamma-irradiation, by NF-κB inhibition.

  1. Anthelmintic Potential of Thymoquinone and Curcumin on Fasciola gigantica

    PubMed Central

    Ullah, Rizwan; Rehman, Abdur; Zafeer, Mohd Faraz; Rehman, Lubna; Khan, Yasir A.; Khan, M. A. Hannan; Khan, Shahper N.; Khan, Asad U.; Abidi, S. M. A.

    2017-01-01

    Fasciolosis an economically important global disease of ruminants in the temperate and tropical regions, caused by Fasciola hepatica and F. gigantica, respectively, also poses a potential zoonotic threat. In India alone it causes huge losses to stakeholders. Anthelmintics including triclabendazole have been used to control this menace but the emerging resistance against the available compounds necessitates identification of novel and alternative therapeutic measures involving plant derived natural compounds for their anthelmintic potential. Thymoquinone (T) and curcumin (C), the active ingredients of Nigella sativa and Curcuma longa respectively have been used as antiparasitic agents but the information on their flukicidal effect is very limited. Adult flukes of F. gigantica were in vitro exposed to different concentrations of thymoquinone and curcumin separately for 3h at 37+ 1°C. A significant (p<0.05) reduction in the worm motility at 60 μM concentration of both T and C was observed though all the worms remained alive after 3h exposure, whereas the effect on egg shedding was statistically insignificant. Pronounced tegumental disruptions and erosion of spines in the posterior region and around the acetabulum was evident. A significant (p<0.05) decrease in glutathione-S-transferase and superoxide dismutase activity and reduced glutathione (GSH) level was observed, while protein carbonylation increased differentially. A significant inhibition of CathepsinL (CatL) gene expression in thymoquinone treated worms was also evident. Further, in silico molecular docking of T and C with CatL revealed a stronger interaction of curcumin with the involvement of higher number of amino acids as compared to thymoquinone that could be more effective in inhibiting the antioxidant enzymes of F. gigantica. It is concluded that both the compounds understudy will decrease the detoxification ability of F. gigantica, while inhibition of CatL will significantly affect their virulence

  2. Antarctic Space Analog Program

    NASA Technical Reports Server (NTRS)

    Palinkas, Lawrence A; Gunderson, E. K. Eric; Johnson, Jeffrey C.; Holland, Albert W.

    1998-01-01

    The primary aim of this project was to examine group dynamics and individual performance in extreme, isolated environments and identify human factors requirements for long-duration space missions using data collected in an analog environment. Specifically, we wished to determine: 1) the characteristics of social relations in small groups of individuals living and working together in extreme, isolated environments, and 2) the environmental, social and psychological determinants of performance effectiveness in such groups. These two issues were examined in six interrelated studies using data collected in small, isolated research stations in Antarctica from 1963 to the present. Results from these six studies indicated that behavior and performance on long-duration space flights is likely to be seasonal or cyclical, situational, social, and salutogenic in nature. The project responded to two NASA program emphases for FY 1997 as described in the NRA: 1) the primary emphasis of the Behavior and Performance Program on determining long-term individual and group performance responses to space, identifying critical factors affecting those responses and understanding underlying mechanisms involved in behavior and performance, and developing and using ground-based models and analogs for studying space-related behavior and performance; and 2) the emphasis of the Data Analysis Program on extended data analysis. Results from the study were used to develop recommendations for the design and development of pre-flight crew training and in-flight psychological countermeasures for long-duration manned space missions.

  3. Autophagy inhibition improves the efficacy of curcumin/temozolomide combination therapy in glioblastomas.

    PubMed

    Zanotto-Filho, Alfeu; Braganhol, Elizandra; Klafke, Karina; Figueiró, Fabrício; Terra, Sílvia Resende; Paludo, Francis Jackson; Morrone, Maurílio; Bristot, Ivi Juliana; Battastini, Ana Maria; Forcelini, Cassiano Mateus; Bishop, Alexander James Roy; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

    2015-03-28

    Glioblastoma is a devastating primary brain tumor resistant to conventional therapies. In this study, we tested the efficacy of combining temozolomide with curcumin, a phytochemical known to inhibit glioblastoma growth, and investigated the mechanisms involved. The data showed that synergy between curcumin and temozolomide was not achieved due to redundant mechanisms that lead to activating protective autophagy both in vitro and in vivo. Autophagy preceded apoptosis, and blocking this response with autophagy inhibitors (3-methyl-adenine, ATG7 siRNA and chloroquine) rendered cells susceptible to temozolomide and curcumin alone or combinations by increasing apoptosis. While curcumin inhibited STAT3, NFκB and PI3K/Akt to affect survival, temozolomide-induced autophagy relied on the DNA damage response and repair components ATM and MSH6, as well as p38 and JNK1/2. However, the most interesting observation was that both temozolomide and curcumin required ERK1/2 to induce autophagy. Blocking this ERK1/2-mediated temozolomide and curcumin induced autophagy with resveratrol, a blood-brain barrier permeable drug, improved temozolomide/curcumin efficacy in brain-implanted tumors. Overall, the data presented demonstrate that autophagy impairs the efficacy of temozolomide/curcumin, and inhibiting this phenomenon could provide novel opportunities to improve brain tumor treatment.

  4. Curcumin reduces trabecular and cortical bone in naive and Lewis lung carcinoma-bearing mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study investigated the effects of dietary supplementation with curcumin on bone microstructural changes in female C57BL/6 mice in the presence or absence of Lewis lung carcinoma. Morphometric analysis showed that in tumor-bearing mice curcumin at 2% and 4% dietary levels (w/w) significa...

  5. Curcumin deteriorates trabecular and cortical bone in mice bearing metastatic Lewis lung carcinoma

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bone is a major target of metastasis for many malignancies; curcumin has been studied for its role in cancer prevention including early phase clinical trials for its efficacy and safe use with cancer patients. The present study investigated the effects of dietary supplementation with curcumin (2% a...

  6. Inhibitory effects of curcumin on dengue virus type 2-infected cells in vitro.

    PubMed

    Padilla-S, Leonardo; Rodríguez, Andrés; Gonzales, María M; Gallego-G, Juan C; Castaño-O, Jhon C

    2014-03-01

    Curcumin, a traditional Chinese and Indian treatment for many diseases, has recently been found to alter the in vitro infection processes of various viruses, including hepatitis C virus, human immunodeficiency virus, coxsackievirus, and Japanese encephalitis virus. The present study evaluated the cellular effects of curcumin in an in vitro (cellular) infection model of dengue virus. Within a dose range of 10 to 30 μM and a treatment period of 24 hours, the cytotoxicity of curcumin was low, as determined by MTT assays. Cells infected with dengue virus type 2 at a multiplicity of infection of 5 were treated with various concentrations of curcumin or the proteasome inhibitor MG132. Plaque assays, immunofluorescence analysis, western blots, and in-cell western assays were then performed. Treatment with 10, 15, and 20 μM curcumin decreased the number of plaques produced, caused an intracellular accumulation of viral proteins, and increased the level of Lys48 ubiquitin-conjugated proteins. At 20 μM curcumin, changes in cell and nuclear morphology and alterations in the actin cytoskeleton were also observed. Treatment with MG132 also reduced plaque production. These results show that curcumin can interfere with the infection processes of dengue virus and that this interference may not occur through direct effects on viral particle production but may result from curcumin's effects on various cellular systems such as the cytoskeleton, the ubiquitin-proteasome system, or the apoptosis process.

  7. Improving the oral bioavailability of curcumin using novel organogel-based nanoemulsions.

    PubMed

    Yu, Hailong; Huang, Qingrong

    2012-05-30

    Curcumin is a natural bioactive compound with many health-promoting benefits. Its low oral bioavailability limits its application in functional foods. In the present study, novel organogel-based nanoemulsions have been developed for oral delivery of curcumin and improvement of its bioavailability. Recently developed curcumin organogel was used as the oil phase in the curcumin nanoemulsion formulation. Tween 20 was selected as the emulsifier on the basis of maximum in vitro bioaccessibility of curcumin in the nanoemulsion. In vitro lipolysis profile revealed that the digestion of nanoemulsion was significantly faster and more complete than the organogel. Permeation experiments on Caco-2 cell monolayers suggested that digestion-diffusion was the major absorption mechanism for curcumin in the nanoemulsion. Furthermore, in vivo pharmacokinetics analysis on mice confirmed that the oral bioavailability of curcumin in the nanoemulsion was increased by 9-fold compared with unformulated curcumin. This novel formulation approach may also be used for oral delivery of other poorly soluble nutraceuticals with high loading capacity, which has significant impact in functional foods, dietary supplements and pharmaceutical industries.

  8. Increase of a group of PTC(+) transcripts by curcumin through inhibition of the NMD pathway.

    PubMed

    Feng, Dairong; Su, Ruey-Chyi; Zou, Liping; Triggs-Raine, Barbara; Huang, Shangzhi; Xie, Jiuyong

    2015-08-01

    Nonsense-mediated mRNA decay (NMD), an mRNA surveillance mechanism, eliminates premature termination codon-containing (PTC⁺) transcripts. For instance, it maintains the homeostasis of splicing factors and degrades aberrant transcripts of human genetic disease genes. Here we examine the inhibitory effect on the NMD pathway and consequent increase of PTC+ transcripts by the dietary compound curcumin. We have found that several PTC⁺ transcripts including that of serine/arginine-rich splicing factor 1 (SRSF1) were specifically increased in cells by curcumin. We also observed a similar curcumin effect on the PTC⁺ mutant transcript from a Tay-Sachs-causing HEXA allele or from a beta-globin reporter gene. The curcumin effect was accompanied by significantly reduced expression of the NMD factors UPF1, 2, 3A and 3B. Consistently, in chromatin immunoprecipitation assays, curcumin specifically reduced the occupancy of acetyl-histone H3 and RNA polymerase II at the promoter region (-376 to -247nt) of human UPF1, in a time- and dosage-dependent way. Importantly, knocking down UPF1 abolished or substantially reduced the difference of PTC(+) transcript levels between control and curcumin-treated cells. The disrupted curcumin effect was efficiently rescued by expression of exogenous Myc-UPF1 in the knockdown cells. Together, our data demonstrate that a group of PTC⁺ transcripts are stabilized by a dietary compound curcumin through the inhibition of UPF factor expression and the NMD pathway.

  9. Curcumin loaded-PLGA nanoparticles conjugated with Tet-1 peptide for potential use in Alzheimer's disease.

    PubMed

    Mathew, Anila; Fukuda, Takahiro; Nagaoka, Yutaka; Hasumura, Takashi; Morimoto, Hisao; Yoshida, Yasuhiko; Maekawa, Toru; Venugopal, Kizhikkilot; Kumar, D Sakthi

    2012-01-01

    Alzheimer's disease is a growing concern in the modern world. As the currently available medications are not very promising, there is an increased need for the fabrication of newer drugs. Curcumin is a plant derived compound which has potential activities beneficial for the treatment of Alzheimer's disease. Anti-amyloid activity and anti-oxidant activity of curcumin is highly beneficial for the treatment of Alzheimer's disease. The insolubility of curcumin in water restricts its use to a great extend, which can be overcome by the synthesis of curcumin nanoparticles. In our work, we have successfully synthesized water-soluble PLGA coated- curcumin nanoparticles and characterized it using different techniques. As drug targeting to diseases of cerebral origin are difficult due to the stringency of blood-brain barrier, we have coupled the nanoparticle with Tet-1 peptide, which has the affinity to neurons and possess retrograde transportation properties. Our results suggest that curcumin encapsulated-PLGA nanoparticles are able to destroy amyloid aggregates, exhibit anti-oxidative property and are non-cytotoxic. The encapsulation of the curcumin in PLGA does not destroy its inherent properties and so, the PLGA-curcumin nanoparticles can be used as a drug with multiple functions in treating Alzheimer's disease proving it to be a potential therapeutic tool against this dreaded disease.

  10. Drastic nickel ion removal from aqueous solution by curcumin-capped Ag nanoparticles

    NASA Astrophysics Data System (ADS)

    Bettini, S.; Pagano, R.; Valli, L.; Giancane, G.

    2014-08-01

    A completely green synthesis protocol has been adopted to obtain silver nanoaggregates capped by the natural compound (1E, 6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-diene), also known as curcumin. The synthesis has been monitored by infrared, Raman, visible and fluorescence spectroscopies. Characterization confirms that curcumin reduces and caps the nanoparticles, and such a procedure allows its solubility in water and drastically increases curcumin stability. Silver nanoparticles (AgNPs)/curcumin complex has been dispersed in a water solution containing a known nickel ion concentration. After three days, a grey precipitate is observed and nickel concentration in the solution is reduced by about 70%.A completely green synthesis protocol has been adopted to obtain silver nanoaggregates capped by the natural compound (1E, 6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-diene), also known as curcumin. The synthesis has been monitored by infrared, Raman, visible and fluorescence spectroscopies. Characterization confirms that curcumin reduces and caps the nanoparticles, and such a procedure allows its solubility in water and drastically increases curcumin stability. Silver nanoparticles (AgNPs)/curcumin complex has been dispersed in a water solution containing a known nickel ion concentration. After three days, a grey precipitate is observed and nickel concentration in the solution is reduced by about 70%. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr02583k

  11. Dietary supplementation with curcumin enhances metastatic growth of Lewis lung carcinoma in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Curcumin is a phenolic compound derived from the Curcuma longa plant, commonly known as turmeric. Curcumin has been used traditionally in Ayurvedic medicine as it has therapeutic properties including being anti-inflammatory, anti-oxidant and anti-microbial. The present study investigated the effects...

  12. Pretreatment of Adipose Derived Stem Cells with Curcumin Facilitates Myocardial Recovery via Antiapoptosis and Angiogenesis.

    PubMed

    Liu, Jianfeng; Zhu, Ping; Song, Peng; Xiong, Weiping; Chen, Haixu; Peng, Wenhui; Wang, Shuxia; Li, Shan; Fu, Zhiqing; Wang, Yutang; Wang, Haibin

    2015-01-01

    The poor survival rate of transplanted stem cells in ischemic myocardium has limited their therapeutic efficacy. Curcumin has potent antioxidant property. This study investigates whether prior curcumin treatment protects stem cells from oxidative stress injury and improves myocardial recovery following cells transplantation. Autologous Sprague-Dawley rat adipose derived mesenchymal stem cells (ADSCs) were pretreated with or without curcumin. The hydrogen peroxide/serum deprivation (H2O2/SD) medium was used to mimic the ischemic condition in vitro. Cytoprotective effects of curcumin on ADSCs were evaluated. Curcumin pretreatment significantly increased cell viability and VEGF secretion, and decreased cell injury and apoptosis via regulation of PTEN/Akt/p53 and HO-1 signal proteins expression. The therapeutic potential of ADSCs implantation was investigated in myocardial ischemia-reperfusion injury (IRI) model. Transplantation of curcumin pretreated ADSCs not only resulted in better heart function, higher cells retention, and smaller infarct size, but also decreased myocardial apoptosis, promoted neovascularization, and increased VEGF level in ischemic myocardium. Together, priming of ADSCs with curcumin improved tolerance to oxidative stress injury and resulted in enhancement of their therapeutic potential of ADSCs for myocardial repair. Curcumin pretreatment is a promising adjuvant strategy for stem cells transplantation in myocardial restoration.

  13. Reversal of Oxidative Stress in Neural Cells by an Injectable Curcumin/Thermosensitive Hydrogel.

    PubMed

    Lu, Chuan

    2016-01-01

    Curcumin as an antioxidative agent which has been widely used medicinally in India and China. However, rapid metabolism coupled with the instability of curcumin under physiological conditions has greatly limited its applications in vivo. In the present study, a thermosensitive hydrogel with high payload of curcumin was developed by using a co-precipitation method, and its reversion of oxidative stress in Neuro-2a cells was investigated. With an increase in drug loading capacity, the solgel transition temperature of the thermosensitive hydrogel decreased accordingly. The stability of curcumin in phosphate-buffered saline (PBS; pH=7.4) was greatly improved by encapsulation in the thermosensitive hydrogel, as indicated by an in vitro degradation test. An in vitro release study showed that the encapsulated curcumin was rapidly released from the hydrogel within 6 h. A curcumin/F-127 aqueous solution under the threshold concentration of 4μg/mL was non-toxic against Neuro-2a cells after 24-h incubation. A MitoSOX assay indicated that the developed curcumin formulation could attenuate the oxidative damage induced by H2O2 as compared to that of the H2O2 group. All these results suggested that the developed curcumin/thermosensitive hydrogel might have great potential application in the reversion of oxidative stress after traumatic brain injury.

  14. Curcumin increases the pathogenicity of Salmonella enterica serovar Typhimurium in murine model.

    PubMed

    Marathe, Sandhya A; Ray, Seemun; Chakravortty, Dipshikha

    2010-07-09

    Curcumin has gained immense importance for its vast therapeutic and prophylactic applications. Contrary to this, our study reveals that it regulates the defense pathways of Salmonella enterica serovar Typhimurium (S. Typhimurium) to enhance its pathogenicity. In a murine model of typhoid fever, we observed higher bacterial load in Peyer's patches, mesenteric lymph node, spleen and liver, when infected with curcumin-treated Salmonella. Curcumin increased the resistance of S. Typhimurium against antimicrobial agents like antimicrobial peptides, reactive oxygen and nitrogen species. This increased tolerance might be attributed to the up-regulation of genes involved in resistance against antimicrobial peptides--pmrD and pmrHFIJKLM and genes with antioxidant function--mntH, sodA and sitA. We implicate that iron chelation property of curcumin have a role in regulating mntH and sitA. Interestingly, we see that the curcumin-mediated modulation of pmr genes is through the PhoPQ regulatory system. Curcumin downregulates SPI1 genes, required for entry into epithelial cells and upregulates SPI2 genes required to intracellular survival. Since it is known that the SPI1 and SPI2 system can be regulated by the PhoPQ system, this common regulator could explain curcumin's mode of action. This data urges us to rethink the indiscriminate use of curcumin especially during Salmonella outbreaks.

  15. Curcumin inhibits Zika and chikungunya virus infection by inhibiting cell binding.

    PubMed

    Mounce, Bryan C; Cesaro, Teresa; Carrau, Lucia; Vallet, Thomas; Vignuzzi, Marco

    2017-03-24

    Several compounds extracted from spices and herbs exhibit antiviral effects in vitro, suggesting potential pharmacological uses. Curcumin, a component of turmeric, has been used as a food additive and herbal supplement due to its potential medicinal properties. Previously, curcumin exhibited antiviral properties against several viruses, including dengue virus and hepatitis C virus, among others. Here, we describe the antiviral effect of curcumin on Zika and chikungunya viruses, two mosquito-borne outbreak viruses. Both viruses responded to treatment of cells with up to 5 μM curumin without impacting cellular viability. We observed that direct treatment of virus with curcumin reduced infectivity of virus in a dose- and time-dependent manner for these enveloped viruses, as well as vesicular stomatitis virus. In contrast, we found no change in infectivity for Coxsackievirus B3, a non-enveloped virus. Derivatives of curcumin also exhibited antiviral activity against enveloped viruses. Further examination revealed that curcumin interfered with the binding of the enveloped viruses to cells in a dose-dependent manner, though the integrity of the viral RNA was maintained. Together, these results expand the family of viruses sensitive to curcumin and provide a mechanism of action for curcumin's effect on these enveloped viruses.

  16. RNA-Seq Analysis Reveals Candidate Targets for Curcumin against Tetranychus cinnabarinus

    PubMed Central

    Wu, Dousheng; Zhang, Yongqiang; Zhou, Hong; Lai, Ting

    2016-01-01

    Tetranychus cinnabarinus is an important agricultural pest with a broad host range. We previously identified curcumin as a promising acaricidal compound against T. cinnabarinus. However, the acaricidal mechanism of curcumin remains unknown. In this study, RNA-seq was employed to analyze the transcriptome changes in T. cinnabarinus treated with curcumin or the solvent. A total of 105,706,297 clean sequence reads were generated by sequencing, with more than 90% of the reads successfully mapped to the reference sequence. The RNA-seq identified 111 and 96 differentially expressed genes between curcumin- and solvent-treated mites at 24 and 48 h after treatment, respectively. GO enrichment analysis of differentially expressed genes showed that the cellular process was the dominant group at both time points. Finally, we screened 23 differentially expressed genes that were functionally identical or similar to the targets of common insecticide/acaricides or genes that were associated with mite detoxification and metabolism. Calmodulin, phospholipase A2, and phospholipase C were activated upon curcumin treatment suggesting that the calcium channel related genes might play important roles in mite's response to curcumin. Overall our results revealed the global transcriptional changes in T. cinnabarinus after curcumin treatment to enable further identification of the targets of curcumin in mites. PMID:27672652

  17. Intrathecal curcumin attenuates pain hypersensitivity and decreases spinal neuroinflammation in rat model of monoarthritis

    PubMed Central

    Chen, Jun-Jie; Dai, Lin; Zhao, Lin-Xia; Zhu, Xiang; Cao, Su; Gao, Yong-Jing

    2015-01-01

    Curcumin is a major component of turmeric and reportedly has anti-inflammatory and anti-oxidant effects. Neuroinflammation has been recognized to play an important role in the pathogenesis of various diseases in the central nervous system. Here we investigated the anti-nociceptive and anti-neuroinflammatory effect of curcumin on arthritic pain in rats. We found that repeated oral treatment with curcumin, either before or after complete Freund’s adjuvant (CFA) injection, dose-dependently attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, but had no effect on joint edema. Repeated intrathecal injection of curcumin reversed CFA-induced pain hypersensitivity. Furthermore, such a curcumin treatment reduced CFA-induced activation of glial cells and production of inflammatory mediators [interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and monocyte inflammatory protein-1 (MIP-1α)] in the spinal cord. Curcumin also decreased lipopolysaccharide-induced production of IL-1β, tumor necrosis factor-α, MCP-1, and MIP-1α in cultured astrocytes and microglia. Our results suggest that intrathecal curcumin attenuates arthritic pain by inhibiting glial activation and the production of inflammatory mediators in the spinal cord, suggesting a new application of curcumin for the treatment of arthritic pain. PMID:25988362

  18. Curcumin liposomes prepared with milk fat globule membrane phospholipids and soybean lecithin.

    PubMed

    Jin, Hong-Hao; Lu, Qun; Jiang, Jian-Guo

    2016-03-01

    Using thin film ultrasonic dispersion method, the curcumin liposomes were prepared with milk fat globule membrane (MFGM) phospholipids and soybean lecithins, respectively, to compare the characteristics and stability of the 2 curcumin liposomes. The processing parameters of curcumin liposomes were investigated to evaluate their effects on the encapsulation efficiency. Curcumin liposomes were characterized in terms of size distribution, ζ-potential, and in vitro release behavior, and then their storage stability under various conditions was evaluated. The curcumin liposomes prepared with MFGM phospholipids had an encapsulation efficiency of about 74%, an average particle size of 212.3 nm, and a ζ-potential of -48.60 mV. The MFGM liposomes showed higher encapsulation efficiency, smaller particle size, higher absolute value of ζ-potential, and slower in vitro release than soybean liposomes. The retention rate of liposomal curcumin was significantly higher than that of free curcumin. The stability of the 2 liposomes under different pH was almost the same, but MFGM liposomes displayed a slightly higher stability than soybean liposomes under the conditions of Fe(3+), light, temperature, oxygen, and relative humidity. In conclusion, MFGM phospholipids have potential advantages in the manufacture of curcumin liposomes used in food systems.

  19. Development and characterization of eucalyptol microemulsions for topic delivery of curcumin.

    PubMed

    Liu, Chi-Hsien; Chang, Fu-Yen

    2011-01-01

    Microemulsions have received great attention for applications in transdermal drug delivery. The use of curcumin for treating various skin diseases like scleroderma, psoriasis, and skin cancer was extensively reported. The solubility of curcumin in various oils, surfactants, and cosurfactants was studied herein in order to find the optimal components for a transdermal delivery vehicle. Microemulsion systems composed of eucalyptol, polysorbate 80, ethanol, and water were developed as transdermal delivery vehicles for curcumin. Effects of the microemulsion composition on transdermal curcumin delivery were studied using Franz diffusion cells. The transdermal curcumin flux, permeability coefficient, and enhancement ratio were analyzed to evaluate the effects of eucalyptol/water ratios in the microemulsions. Pseudo-ternary phase diagrams of the eucalyptol microemulsions with various surfactant/cosurfactant ratios (1:1-1:3) were constructed to investigate their phase behaviors. Conductivity, interfacial tension, size, and viscosity data of the microemulsions were used to characterize the physicochemical properties of transdermal vehicles. The influence of the microemulsions on skin histology and on the delivery route was analyzed using hematoxylin/eosin staining and confocal laser scanning microscopy. In conclusion, microemulsions were successfully developed for transdermal curcumin delivery after screening various components and adjusting the oil/water ratios. The curcumin permeation rate of the microemulsion developed was 15.7-fold higher than that of the control (eucalyptol only). These results indicate that an eucalyptol microemulsion system is a promising tool for the percutaneous delivery of curcumin.

  20. Preparation and anti-cancer activity of polymer-encapsulated curcumin nanoparticles

    NASA Astrophysics Data System (ADS)

    Thu Ha, Phuong; Huong Le, Mai; Nhung Hoang, Thi My; Thu Huong Le, Thi; Quang Duong, Tuan; Tran, Thi Hong Ha; Tran, Dai Lam; Phuc Nguyen, Xuan

    2012-09-01

    Curcumin (Cur) is a yellow compound isolated from rhizome of the herb curcuma longa. Curcumin possesses antioxidant, anti-inflammatory, anti-carcinogenic and antimicrobial properties, and suppresses proliferation of many tumor cells. However, the clinical application of curcumin in cancer treatment is considerably limited due to its serious poor delivery characteristics. In order to increase the hydrophilicity and drug delivery capability, we encapsulated curcumin into copolymer PLA-TPGS, 1,3-beta-glucan (Glu), O-carboxymethyl chitosan (OCMCs) and folate-conjugated OCMCs (OCMCs-Fol). These polymer-encapsulated curcumin nanoparticles (Cur-PLA-TPGS, Cur-Glu, Cur-OCMCs and Cur-OCMCs-Fol) were characterized by infrared (IR), fluorescence (FL), photoluminescence (PL) spectra, field emission scanning electron microscopy (FE-SEM), and found to be spherical particles with an average size of 50-100 nm, being suitable for drug delivery applications. They were much more soluble in water than not only free curcumin but also other biodegradable polymer-encapsulated curcumin nanoparticles. The anti-tumor promoting assay was carried out, showing the positive effects of Cur-Glu and Cur-PLA-TPGS on tumor promotion of Hep-G2 cell line in vitro. Confocal microscopy revealed that the nano-sized curcumin encapsulated by polymers OCMCs and OCMCs-Fol significantly enhanced the cellular uptake (cancer cell HT29 and HeLa).

  1. A systemic administration of liposomal curcumin inhibits radiation pneumonitis and sensitizes lung carcinoma to radiation

    PubMed Central

    Shi, Hua-shan; Gao, Xiang; Li, Dan; Zhang, Qiong-wen; Wang, Yong-sheng; Zheng, Yu; Cai, Lu-Lu; Zhong, Ren-ming; Rui, Ao; Li, Zhi-yong; Zheng, Hao; Chen, Xian-cheng; Chen, Li-juan

    2012-01-01

    Radiation pneumonitis (RP) is an important dose-limiting toxicity during thoracic radiotherapy. Previous investigations have shown that curcumin is used for the treatment of inflammatory conditions and cancer, suggesting that curcumin may prevent RP and sensitize cancer cells to irradiation. However, the clinical advancement of curcumin is limited by its poor water solubility and low bioavailability after oral administration. Here, a water-soluble liposomal curcumin system was developed to investigate its prevention and sensitizing effects by an intravenous administration manner in mice models. The results showed that liposomal curcumin inhibited nuclear factor-κB pathway and downregulated inflammatory factors including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and transforming growth factor-β induced by thoracic irradiation. Furthermore, the combined treatment with liposomal curcumin and radiotherapy increased intratumoral apoptosis and microvessel responses to irradiation in vivo. The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2) model. There were no obvious toxicities observed in mice. The current results indicate that liposomal curcumin can effectively mitigate RP, reduce the fibrosis of lung, and sensitize LL/2 cells to irradiation. This study also suggests that the systemic administration of liposomal curcumin is safe and deserves to be investigated for further clinical application. PMID:22679371

  2. Curcumin increases exosomal TCF21 thus suppressing exosome-induced lung cancer

    PubMed Central

    Zeng, Chao; Wu, Da; Mu, Zhimin; Chen, Baokun; Xie, Yuancai; Ye, Yiwang; Liu, Jixian

    2016-01-01

    Curcumin is a novel drug for lung cancer treatment. However, the mechanism underlying the anti-tumor effect of curcumin remains elusive. Previous evidences indicated that, the methylating transferase DNMT1 is downregulated by