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Sample records for molecule curcumin analog

  1. Synthesis and antioxidant activity of curcumin analogs.

    PubMed

    Zheng, Qu-Tong; Yang, Ze-Hua; Yu, Liu-Ying; Ren, Yu-Yan; Huang, Qiu-Xia; Liu, Qiu; Ma, Xiang-Yu; Chen, Zi-Kang; Wang, Zong-Bao; Zheng, Xing

    2017-05-01

    Numerous biological activities including antioxidant, antitumor, anti-inflammation, and antivirus of the natural product curcumin were reported. However, the clinical application of it was significantly limited by its instability, poor solubility, less body absorbing, and low bioavailability. This review focuses on the structure modification and antioxidant activity evaluation of curcumin. To study the structure-activity relationship (SAR), five series of curcumin analogs were synthesized and their antioxidant activity were evaluated in vitro. The results showed that electron-donating groups, especially the phenolic hydroxyl group are an essential component to improve the antioxidant activity.

  2. 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.

  3. Eliminating the heart from the curcumin molecule: monocarbonyl curcumin mimics (MACs).

    PubMed

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

    2014-12-24

    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.

  4. 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

  5. Current prospects of synthetic curcumin analogs and chalcone derivatives against mycobacterium tuberculosis.

    PubMed

    Bukhari, Syed Nasir Abbas; Franzblau, Scott G; Jantan, Ibrahim; Jasamai, Malina

    2013-11-01

    Tuberculosis, caused by Mycobacterium tuberculosis, is amongst the foremost infectious diseases. Treatment of tuberculosis is a complex process due to various factors including a patient's inability to persevere with a combined treatment regimen, the difficulty in eradicating the infection in immune-suppressed patients, and multidrug resistance (MDR). Extensive research circumscribing molecules to counteract this disease has led to the identification of many inhibitory small molecules. Among these are chalcone derivatives along with curcumin analogs. In this review article, we summarize the reported literature regarding anti tubercular activity of chalcone derivatives and synthetic curcumin analogs. Our goal is to provide an analysis of research to date in order to facilitate the synthesis of superior antitubercular chalcone derivatives and curcumin analogs.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Inhibition of HIV-1 by curcumin A, a novel curcumin analog

    PubMed Central

    Kumari, Namita; Kulkarni, Amol A; Lin, Xionghao; McLean, Charlee; Ammosova, Tatiana; Ivanov, Andrey; Hipolito, Maria; Nekhai, Sergei; Nwulia, Evaristus

    2015-01-01

    Despite the remarkable success of combination antiretroviral therapy at curtailing HIV progression, emergence of drug-resistant viruses, chronic low-grade inflammation, and adverse effects of combination antiretroviral therapy treatments, including metabolic disorders collectively present the impetus for development of newer and safer antiretroviral drugs. Curcumin, a phytochemical compound, was previously reported to have some in vitro anti-HIV and anti-inflammatory activities, but poor bioavailability has limited its clinical utility. To circumvent the bioavailability problem, we derivatized curcumin to sustain retro-aldol decomposition at physiological pH. The lead compound derived, curcumin A, showed increased stability, especially in murine serum where it was stable for up to 25 hours, as compared to curcumin that only had a half-life of 10 hours. Both curcumin and curcumin A showed similar inhibition of one round of HIV-1 infection in cultured lymphoblastoid (also called CEM) T cells (IC50=0.7 μM). But in primary peripheral blood mononuclear cells, curcumin A inhibited HIV-1 more potently (IC50=2 μM) compared to curcumin (IC50=12 μM). Analysis of specific steps of HIV-1 replication showed that curcumin A inhibited HIV-1 reverse transcription, but had no effect on HIV-1 long terminal repeat basal or Tat-induced transcription, or NF-κB-driven transcription at low concentrations that affected reverse transcription. Finally, we showed curcumin A induced expression of HO-1 and decreased cell cycle progression of T cells. Our findings thus indicate that altering the core structure of curcumin could yield more stable compounds with potent antiretroviral and anti-inflammatory activities. PMID:26366056

  12. 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

  13. 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

  14. Cellular uptake, retention and bioabsorption of HO-3867, a fluorinated curcumin analog with potential antitumor properties

    PubMed Central

    Dayton, Alex; Selvendiran, Karuppaiyah; Kuppusamy, M Lakshmi; Rivera, Brian K; Meduru, Sarath; Kálai, Tamás; Hideg, Kálmán

    2010-01-01

    Curcumin, a naturally-occurring compound found in the rhizome of Curcuma longa plant, is known for its antitumor activities. However, its clinical efficacy is limited due to poor bioabsorption. A new class of synthetic analogs of curcumin, namely diarylidenylpiperidone (DAP), has been developed with substantially higher anticancer activity than curcumin. However, its cellular uptake and bioabsorption have not been evaluated. In this study we have determined the absorption of a representative DAP compound, HO-3867, using optical and electron paramagnetic resonance spectrometry. The cellular uptake of HO-3867 was measured in a variety of cancer cell lines. HO-3867 was taken in cells within 15 minutes of exposure and its uptake was more than 100-fold higher than curcumin. HO-3867 was also retained in cells in an active form for 72 hours and possibly longer. HO-3867 was substantially cytotoxic to all the cancer cells tested. However, there was no direct correlation between cellular uptake and cytotoxicity suggesting that the cytotoxic mechanisms could be cell-type specific. When administered to rats by intraperitoneal injection, significantly high levels of HO-3867 were found in the liver, kidney, stomach and blood after 3 hours. Also, significant accumulation of HO-3867 was found in murine tumor xenografts with a dose-dependent inhibition of tumor growth. The results suggest that the curcumin analog has substantially higher bioabsorption when compared to curcumin. PMID:20798598

  15. Curcumin.

    PubMed

    Lestari, Maria L A D; Indrayanto, Gunawan

    2014-01-01

    Curcumin and its two related compounds, that is, demethoxycurcumin and bis-demethoxycurcumin (curcuminoids) are the main secondary metabolites of Curcuma longa and other Curcuma spp. Curcumin is commonly used as coloring agent as well as food additive; curcumin has also shown some therapeutic activities. This review summarizes stability of curcumin in solutions, spectroscopy characteristics of curcumin (UV, IR, Raman, MS, and NMR), polymorphism forms, method of analysis in both of biological and nonbiological samples, and metabolite studies of curcumin. For analysis of curcumin and its related compounds in complex matrices, application of LC-MS/MS is recommended. © 2014 Elsevier Inc. All rights reserved.

  16. 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

  17. 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

  18. 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.

  19. 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

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

    PubMed

    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

    2015-03-06

    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. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. Ultrasound-assisted synthesis of curcumin analogs promoted by activated chicken eggshells

    NASA Astrophysics Data System (ADS)

    Mardiana, L.; Ardiansah, B.; Septiarti, A.; Bakri, R.; Kosamagi, G.

    2017-07-01

    Curcumin has been widely known as a multifunctional natural product which has many biological activities. However, the biggest limitation for the large scale application of curcumin is its poor bioavailability. This research presented a cheap, mild and efficient solvent-free synthesis of monocarbonyl analogs of curcumin via Aldol condensation using activated chicken eggshells (ACE). Dibenzalpropanone as a product of Aldol condensation was prepared by mixing benzaldehyde and acetone using a simple glass tube in the presence of ACE under ultrasound irradiation (78 % yield), while dibenzalcyclohexanone was produced from the reaction of benzaldehyde with cyclohenxanone (81 %). The products have been characterized by FTIR, UV-Vis spectrophotometer and GC-MS instruments. The FTIR spectra show a significant absorption of carbonyl group that attached to the double bond in α,β-position at 1630-1660 cm-1. The molecular cation of m/z of 234 and 274 is in agreement with the products structures.

  2. 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.

  3. 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

    2017-04-01

    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.

  4. 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.

  5. 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

  6. Synthetic Analogs of Curcumin Modulate the Function of Multidrug Resistance-Linked ATP-Binding Cassette Transporter ABCG2.

    PubMed

    Murakami, Megumi; Ohnuma, Shinobu; Fukuda, Michihiro; Chufan, Eduardo E; Kudoh, Katsuyoshi; Kanehara, Keigo; Sugisawa, Norihiko; Ishida, Masaharu; Naitoh, Takeshi; Shibata, Hiroyuki; Iwabuchi, Yoshiharu; Ambudkar, Suresh V; Unno, Michiaki

    2017-11-01

    Multidrug resistance (MDR) caused by the overexpression of ATP-binding cassette (ABC) transporters in cancer cells is a major obstacle in cancer chemotherapy. Previous studies have shown that curcumin, a natural product and a dietary constituent of turmeric, inhibits the function of MDR-related ABC transporters, including ABCB1, ABCC1, and especially ABCG2. However, the limited bioavailability of curcumin prevents its use for modulation of the function of these transporters in the clinical setting. In this study, we investigated the effects of 24 synthetic curcumin analogs with increased bioavailability on the transport function of ABCG2. The screening of the 24 synthetic analogs by means of flow cytometry revealed that four of the curcumin analogs (GO-Y030, GO-Y078, GO-Y168, and GO-Y172) significantly inhibited the efflux of the ABCG2 substrates, mitoxantrone and pheophorbide A, from ABCG2-overexpressing K562/breast cancer resistance protein (BCRP) cells. Biochemical analyses showed that GO-Y030, GO-Y078, and GO-Y172 stimulated the ATPase activity of ABCG2 at nanomolar concentrations and inhibited the photolabeling of ABCG2 with iodoarylazidoprazosin, suggesting that these analogs interact with the substrate-binding sites of ABCG2. In addition, when used in cytotoxicity assays, GO-Y030 and GO-Y078 were found to improve the sensitivity of the anticancer drug, SN-38, in K562/BCRP cells. Taken together, these results suggest that nontoxic synthetic curcumin analogs with increased bioavailability, especially GO-Y030 and GO-Y078, inhibit the function of ABCG2 by directly interacting at the substrate-binding site. These synthetic curcumin analogs could therefore be developed as potent modulators to overcome ABCG2-mediated MDR in cancer cells. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  7. 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.

  8. 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

  9. 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

  10. Chemosensitizing effects of synthetic curcumin analogs on human multi-drug resistance leukemic cells.

    PubMed

    Mapoung, Sariya; Pitchakarn, Pornsiri; Yodkeeree, Supachai; Ovatlarnporn, Chitchamai; Sakorn, Natee; Limtrakul, Pornngarm

    2016-01-25

    Curcumin analogs were synthesized and their multi-drug resistance (MDR) reversing properties were determined in human MDR leukemic (K562/Adr) cells. Four analogs, 1,7-bis-(3,4-dimethoxy-phenyl)-hepta-1,6-diene-3,5-dione (1J), 2,6-bis-(4-hydroxy-3-methoxy-benzylidene)-cyclohexanone (2A), 2,6-bis-(3,4-dihydroxy-benzylidene)-cyclohexanone (2F) and 2,6-bis-(3,4-dimethoxy-benzylidene)-cyclohexanone (2J) markedly increased the sensitivity of K562/Adr cells to paclitaxel (PTX) for 8-, 2-, 8- and 16- folds, respectively and vinblastine (Vin) for 5-, 3-, 12- and 30- folds, respectively. The accumulation of P-gp substrates, Calcein-AM, Rhodamine 123 and Doxorubicin, was significantly increased by 1J (up to 6-, 11- and 22- folds, respectively) and 2J (up to 7-, 12- and 17- folds, respectively). Besides 2A, 2F and 2J dramatically decreased P-gp expression in K562/Adr cells. These results could be summarized in the following way. Analog 1J inhibited only P-gp function, while 2A and 2F inhibited only P-gp expression. Interestingly, 2J exerts inhibition of both P-gp function and expression. The combination index (CI) of combination between 2J and PTX (0.09) or Vin (0.06) in K562/Adr cells indicated strong synergistic effects, which likely due to its MDR reversing activity. Moreover, these analogs showed less cytotoxicity to peripheral mononuclear cells (human) and red blood cells (human and rat) suggesting the safety of analogs for further animal and clinical studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Antitumor Agents 250.† Design and Synthesis of New Curcumin Analogs as Potential Anti-Prostate Cancer Agents

    PubMed Central

    Lin, Li; Shi, Qian; Nyarko, Alexander K.; Bastow, Kenneth F.; Wu, Chin-Chung; Su, Ching-Yuan; Shih, Charles C.-Y; Lee, Kuo-Hsiung

    2008-01-01

    In a continuing study of curcumin analogs as potential drug candidates to treat prostate cancer at both androgen-dependent and androgen-refractory stages, we designed and synthesized over 40 new analogs classified into four series: monophenyl analogs (series A), heterocycle-containing analogs (series B), analogs bearing various substituents on the phenyl rings (series C) and analogs with various linkers (series D). These new compounds were tested for cytotoxicity against two human prostate cancer cell lines, androgen-dependent LNCaP and androgen-independent PC-3. Antiandrogenic activity was also evaluated in LNCaP cells and PC-3 cells transfected with wild-type androgen receptor. Ten compounds possessed potent cytotoxicity against both LNCaP and PC-3 cells; seven only against LNCaP; and one solely against PC-3. This study established an advanced structure-activity relationship (SAR), and these correlations will guide the further design of new curcumin analogs with better anti-prostate cancer activity. PMID:16789753

  12. Safe and targeted anticancer therapy for ovarian cancer using a novel class of curcumin analogs

    PubMed Central

    2013-01-01

    A diagnosis of advanced ovarian cancer is the beginning of a long and arduous journey for a patient. Worldwide, approximately half of the individuals undergoing therapy for advanced cancer will succumb to the disease, or consequences of treatment. Well-known and widely-used chemotherapeutic agents such as cisplatin, paclitaxel, 5-fluorouracil, and doxorubicin are toxic to both cancer and non-cancerous cells, and have debilitating side effects Therefore, development of new targeted anticancer therapies that can selectively kill cancer cells while sparing the surrounding healthy tissues is essential to develop more effective therapies. We have developed a new class of synthetic curcumin analogs, diarylidenyl-piperidones (DAPs), which have higher anticancer activity and enhanced bio-absorption than curcumin. The DAP backbone structure exhibits cytotoxic (anticancer) activity, whereas the N-hydroxypyrroline (-NOH) moiety found on some variants functions as a cellular- or tissue-specific modulator (antioxidant) of cytotoxicity. The anticancer activity of the DAPs has been evaluated using a number of ovarian cancer cell lines, and the safety has been evaluated in a number of non-cancerous cell lines. Both variations of the DAP compounds showed similar levels of cell death in ovarian cancer cells, however the compounds with the -NOH modification were less toxic to non-cancerous cells. The selective cytotoxicity of the DAP–NOH compounds suggests that they will be useful as safe and effective anticancer agents. This article reviews some of the key findings of our work with the DAP compounds, and compares this to some of the targeted therapies currently used in ovarian cancer therapy. PMID:23663277

  13. Potent trypanocidal curcumin analogs bearing a monoenone linker motif act on trypanosoma brucei by forming an adduct with trypanothione.

    PubMed

    Alkhaldi, Abdulsalam A M; Creek, Darren J; Ibrahim, Hasan; Kim, Dong-Hyun; Quashie, Neils B; Burgess, Karl E; Changtam, Chatchawan; Barrett, Michael P; Suksamrarn, Apichart; de Koning, Harry P

    2015-01-01

    We have previously reported that curcumin analogs with a C7 linker bearing a C4-C5 olefinic linker with a single keto group at C3 (enone linker) display midnanomolar activity against the bloodstream form of Trypanosoma brucei. However, no clear indication of their mechanism of action or superior antiparasitic activity relative to analogs with the original di-ketone curcumin linker was apparent. To further investigate their utility as antiparasitic agents, we compare the cellular effects of curcumin and the enone linker lead compound 1,7-bis(4-hydroxy-3-methoxyphenyl)hept-4-en-3-one (AS-HK014) here. An AS-HK014-resitant line, trypanosomes adapted to AS-HK014 (TA014), was developed by in vitro exposure to the drug. Metabolomic analysis revealed that exposure to AS-HK014, but not curcumin, rapidly depleted glutathione and trypanothione in the wild-type line, although almost all other metabolites were unchanged relative to control. In TA014 cells, thiol levels were similar to untreated wild-type cells and not significantly depleted by AS-HK014. Adducts of AS-HK014 with both glutathione and trypanothione were identified in AS-HK014-exposed wild-type cells and reproduced by chemical reaction. However, adduct accumulation in sensitive cells was much lower than in resistant cells. TA014 cells did not exhibit any changes in sequence or protein levels of glutathione synthetase and γ-glutamylcysteine synthetase relative to wild-type cells. We conclude that monoenone curcuminoids have a different mode of action than curcumin, rapidly and specifically depleting thiol levels in trypanosomes by forming an adduct. This adduct may ultimately be responsible for the highly potent trypanocidal and antiparasitic activity of the monoenone curcuminoids. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  14. Structural Interactions of Curcumin Biotransformed Molecules with the N-Terminal Residues of Cytotoxic-Associated Gene A Protein Provide Insights into Suppression of Oncogenic Activities.

    PubMed

    Srivastava, Akhileshwar Kumar; Singh, Divya; Roy, Bijoy Krishna

    2017-03-01

    Curcumin as a natural product has drawn considerable attention in recent years for its multiple pharmacological activities against various diseases, but more studies are required to understand the curcumin pharmacological action considering its low bioavailability. Though numerous reasons contribute to the low bioavailability of curcumin, one of the important reasons is associated with biotransformation of curcumin through either conjugation or reduction depending on curcumin administration route. The orally administered curcumin (CUR) is metabolised into curcumin glucuronidase (CUR-GLR) and curcumin sulphate by conjugation, whereas dihydroxycurcumin, tetrahydrocurcumin, and hexahydrocurcumin (HHC) are formed by reduction after intraperitoneal administration of curcumin. The main aim of the current study was to investigate the pharmacological properties of curcumin and its biotransformed molecules and its inhibitory potential against CagA (cytotoxic-associated gene A) oncoprotein of Helicobacter pylori. All lead molecules followed the Lipinski's five rules for biological activities, except CUR-GLR, whereas druglikeness scores were obtained for all molecules. Subsequently, molecular docking was employed to analyse the binding affinity of molecules with CagA. The docking studies revealed that CUR-GLR has highest binding affinity with CagA, whereas less interactive affinity was observed in HHC. From the virtual screening and docking studies, the current study suggests that the biotransformation of curcumin through conjugation has more potential for inhibition of oncogenic activities of CagA+ H. pylori than reduction.

  15. Synthesis of 86 species of 1,5-diaryl-3-oxo-1,4-pentadienes analogs of curcumin can yield a good lead in vivo

    PubMed Central

    2011-01-01

    Background Curcumin is known to possess many anti-tumor properties such as inhibition of tumor growth and induction of apotosis. However, limited bioavailability of curcumin prevents its clinical application. A synthesized curcumin analog, 1,5-diaryl-3-oxo-1,4-pentadiene such as GO-Y030, has the improved anti-tumor potential in vitro as well as in mouse model of colorectal carcinogenesis. Results These compounds were divided into two groups; one is the higher anti-proliferative group, in which 79.7% of 1,5-diaryl-3-oxo-1,4-pentadienes were clustered. One of the 1,5-diaryl-3-oxo-1,4-pentadiene analogs, GO-Y078 has the most enhanced growth inhibition, and its solubility was improved, compared with curcumin. GO-Y078 inhibits NF-κB transactivation, as well as expression of TP53 and DR5 more effectively than curcumin. In a mouse model, GO-Y078 presented 1.4 fold more survival elongation that was not achieved by curcumin and GO-Y030. Conclusions The 1,5-diaryl-3-oxo-1,4-pentadiene analogs can yield good lead compounds for cancer chemotherapy, to overcome low bioavailability of curcumin. PMID:21619659

  16. 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

  17. Bis-demethoxy curcumin analog nanoparticles: synthesis, characterization, and anticancer activity in vitro.

    PubMed

    Francis, Arul Prakash; Murthy, Prakhya Balakishna; Devas, Thiyagarajan

    2014-07-01

    We have optimized a protocol for the preparation of bisdemethoxy curcumin analog nanoparticles (BDMCA-NP) by the solvent assisted process. The structural similarities between bulk and nano BDMCA were determined by Co-TLC, NMR and F-TIR. This shows that our synthesis protocol enhanced the dispersibility and reduce the size of BDMCA without altering the integrity of functional moieties and structure, which is crucial for anticancer and antioxidant activities. The morphology and size of BDMCA-NP as determined by SEM, HRTEM and DLS was found to be around 80 nm. BDMCA-NP treated breast cancer cell lines (MCF 7) showed cell death as characterized by MTT assay. Flow cytometric analysis of BDMCA-NP treated MCF 7 cell lines showed an increase of cell count in G2/M phase indicates the cell cycle arrest. Western blot analysis revealed the presence of caspase 3, caspase 9, cleaved fragments of PARP and Bax proteins in the BDMCA-NP treated MCF 7 cell lines, but not in untreated cell lines. To recap, we have prepared BDMCA-NP by solvent assisted process, which exerted anticancer activity against breast cancer cells, which may be due to (i) enhanced dispersibility and surface: volume ratio, (ii) apoptosis (iii) mitochondrial pathway induced cell death, (iv) G2/M phase cell cycle arrest and (v) disassembly of mitotic spindle of the cancer cells. Thus, nano BDMCA can be used as a potent anticancer agent.

  18. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Release-Modulated Antioxidant Activity of a Composite Curcumin-Chitosan Polymer.

    PubMed

    O'Toole, Martin G; Soucy, Patricia A; Chauhan, Rajat; Raju, Mandapati V Ramakrishnam; Patel, Dhruvina N; Nunn, Betty M; Keynton, Megan A; Ehringer, William D; Nantz, Michael H; Keynton, Robert S; Gobin, Andrea S

    2016-04-11

    Curcumin is known to have immense therapeutic potential but is hindered by poor solubility and rapid degradation in solution. To overcome these shortcomings, curcumin has been conjugated to chitosan through a pendant glutaric anhydride linker using amide bond coupling chemistry. The hybrid polymer has been characterized by UV-visible, fluorescence, and infrared spectroscopies as well as zeta potential measurements and SEM imaging. The conjugation reactivity was confirmed through gel permeation chromatography and quantification of unconjugated curcumin. An analogous reaction of curcumin with glucosamine, a small molecule analogue for chitosan, was performed and the purified product characterized by mass spectrometry, UV-visible, fluorescence, and infrared spectroscopies. Conjugation of curcumin to chitosan has greatly improved curcumin aqueous solubility and stability, with no significant curcumin degradation detected after one month in solution. The absorbance and fluorescence properties of curcumin are minimally perturbed (λmax shifts of 2 and 5 nm, respectively) by the conjugation reaction. This conjugation strategy required use of one out of two curcumin phenols (one of the main antioxidant functional groups) for covalent linkage to chitosan, thus temporarily attenuating its antioxidant capacity. Hydrolysis-based release of curcumin from the polymer, however, is accompanied by full restoration of curcumin's antioxidant potential. Antioxidant assays show that curcumin radical scavenging potential is reduced by 40% after conjugation, but that full antioxidant potential is restored upon hydrolytic release from chitosan. Release studies show that curcumin is released over 19 days from the polymer and maintains a concentration of 0.23 ± 0.12 μM curcumin/mg polymer/mL solution based on 1% curcumin loading on the polymer. Release studies in the presence of carbonic anhydrase, an enzyme with known phenolic esterase activity, show no significant difference from

  20. Systematical investigation of binding interaction between novel ruthenium(II) arene complex with curcumin analogs and ctDNA.

    PubMed

    Huang, Shan; Liang, Yu; Huang, Chusheng; Su, Wei; Lei, Xiaolin; Liu, Yi; Xiao, Qi

    2016-11-01

    In this study, the interaction between a novel ruthenium(II) arene complex with curcumin analogs and calf thymus DNA (ctDNA) was investigated systematically by viscosity measurement, the DNA melting approach, multispectroscopic techniques and electrochemical methods. The absorption spectra of the ctDNA-drug complex showed a slight red shift and a weak hypochromic effect. The relative viscosity and melting temperature of ctDNA increased on addition of the drug. The evidence obtained from fluorescence competitive experiments indicated that the binding mode of the drug with ctDNA was intercalative. Using acridine orange (AO) as a fluorescence probe, the drug statically quenched the fluorescence of the ctDNA-AO complex, and hydrogen bonding and van der Waals interactions played vital roles in the binding interaction between the drug and ctDNA. The influences of ionic strength, chemical denaturants and pH on the binding interaction were also investigated. Circular dichroism and Fourier transform infrared spectra suggested that this drug might bond with the G-C base pairs of ctDNA and the right-handed B-form helicity of ctDNA remained after drug binding. The intercalative binding between the drug and ctDNA was further investigated using electrochemical techniques. All these results suggested that the biological activity of ctDNA was affected by ruthenium(II) arene complex with curcumin analogs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. 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.

  2. 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.

  3. Lesson Learned from Nature for the Development of Novel Anti-Cancer Agents: Implication of Isoflavone, Curcumin, and their Synthetic Analogs

    PubMed Central

    Sarkar, Fazlul H.; Li, Yiwei; Wang, Zhiwei; Padhye, Subhash

    2011-01-01

    In recent years, naturally occurring dietary compounds have received greater attention in the field of cancer prevention and treatment research. Among them, isoflavone genistein and curcumin are very promising anti-cancer agents because of their non-toxic and potent anti-cancer properties. However, it is important to note that the low water solubility, poor in vivo bioavailability and unacceptable pharmacokinetic profile of these natural compounds limit their efficacy as anti-cancer agents for solid tumors. Therefore, the development of synthetic analogs of isoflavone and curcumin based on the structure-activity assay, and the encapsulation of isoflavone and curcumin with liposome or nanoparticle for enhancing the anti-tumor activity of these natural agents, is an exciting area of research. Emerging in vitro and in vivo studies clearly suggest that these analogs and formulations of natural compounds could be much more potent for the prevention and/or treatment of various cancers. In this review article, we will summarize the current knowledge regarding the anti-cancer effect of natural compounds and their analogs, the regulation of cell signaling by these agents, and the structure-activity relationship for better design of novel anti-cancer agents, which could open newer avenues for the prevention of tumor progression and/or treatment of human malignancies. PMID:20345353

  4. 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.

  5. Isothiouronium modification empowers pyrimidine-substituted curcumin analogs potent cytotoxicity and Golgi localization.

    PubMed

    Tong, Sheng; Zhang, Meng; Wang, Shixi; Yin, Ruijuan; Yu, Rilei; Wan, Shengbiao; Jiang, Tao; Zhang, Lijuan

    2016-11-10

    Most of protein post-translational modifications occur in the Golgi and many human diseases are associated with abnormal Golgi function or improper post translational modifications of proteins in the Golgi. In this study, we designed and synthesized 4 × 6 series of novel isothiouronium-modified (E,E)-4,6-bis(styryl)-pyrimidine analogs and found that they localized at the Golgi as visualized by the intrinsic fluorescence of the analogs. The isothiouronium-modified analogs had potent cytotoxicity in both normal (Chinese Hamster Ovary or CHO) and cancer cells. Furthermore, permethylated isothiouronium-modified analogs showed cancer cell-selective cytotoxicity. The molecular mechanisms underlying Golgi localization of isothiouronium-modified compounds were investigated using 7 CHO and 4 human cancer cell lines and the results indicated that the compounds had binding partners in the Golgi. Thus, isothiouronium-modified analogs might be promising anticancer agents, novel Golgi staining reagents, and useful research tools for studying Golgi functions in normal or cancer cells and in Golgi-related human diseases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  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 DM-1 in Monotherapy or Combinatory Treatment with Dacarbazine as a Strategy to Inhibit In Vivo Melanoma Progression

    PubMed Central

    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. PMID:25742310

  8. Curcumin Resource Database

    PubMed Central

    Kumar, Anil; Chetia, Hasnahana; Sharma, Swagata; Kabiraj, Debajyoti; Talukdar, Narayan Chandra; Bora, Utpal

    2015-01-01

    Curcumin is one of the most intensively studied diarylheptanoid, Curcuma longa being its principal producer. This apart, a class of promising curcumin analogs has been generated in laboratories, aptly named as Curcuminoids which are showing huge potential in the fields of medicine, food technology, etc. The lack of a universal source of data on curcumin as well as curcuminoids has been felt by the curcumin research community for long. Hence, in an attempt to address this stumbling block, we have developed Curcumin Resource Database (CRDB) that aims to perform as a gateway-cum-repository to access all relevant data and related information on curcumin and its analogs. Currently, this database encompasses 1186 curcumin analogs, 195 molecular targets, 9075 peer reviewed publications, 489 patents and 176 varieties of C. longa obtained by extensive data mining and careful curation from numerous sources. Each data entry is identified by a unique CRDB ID (identifier). Furnished with a user-friendly web interface and in-built search engine, CRDB provides well-curated and cross-referenced information that are hyperlinked with external sources. CRDB is expected to be highly useful to the researchers working on structure as well as ligand-based molecular design of curcumin analogs. Database URL: http://www.crdb.in PMID:26220923

  9. 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

  10. 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.

  11. 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.

  12. Effect of dehydrozingerone, a half analog of curcumin on dexamethasone-delayed wound healing in albino rats.

    PubMed

    Rao, Mallikarjuna C; Sudheendra, Arun T; Nayak, Pawan G; Paul, Piya; Kutty, Gopalan N; Shenoy, Rekha R

    2011-09-01

    Oxidative stress is triggered by the wound which results in the production of reactive oxygen species (ROS), thereby delaying normal wound repair. Therefore, it is important to reduce the level of ROS to improve healing. A known antioxidant, dehydrozingerone (DHZ) was synthesized and selected for the study. The authors aimed to investigate the wound healing action of topical (100 mg/wound) and systemic (100 mg/kg, p. o.). DHZ on different wound models in normal and dexamethasone (DEX)-suppressed healing. Topical DHZ showed a significant (P < 0.05) rise in tensile strength when compared to control in normal healing. Significant (P < 0.05) wound closure was observed from 3 to 9 days in DHZ oral and gel treated groups. There was a significant (P < 0.05) rise in hydroxyproline content with the DHZ treated groups when compared to control. Systemic DHZ exhibited a significant (P < 0.05) increase in lysyl oxidase (LO) levels of 3.73 ± 0.15 nmol of H(2)O(2) when compared to control. In DEX-suppressed healing, showed good pro-healing activity with respect to the parameters mentioned above. DHZ treatment exhibited a parabolic dose response of ROS inhibition with a plateau effect at 75 μM. There was a steady and constant increase in the % NO inhibition with increasing doses of DHZ. Oral DHZ is effective in accelerating the healing process in both normal and dexamethasone-suppressed wounds. Our study suggests that DHZ (half analog of curcumin) supplementation reduces the steroid-induced delay in wound healing.

  13. 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).

  14. 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.

  15. Curcumin in Alzheimer's disease: Can we think to new strategies and perspectives for this molecule?

    PubMed

    Serafini, Melania Maria; Catanzaro, Michele; Rosini, Michela; Racchi, Marco; Lanni, Cristina

    2017-10-01

    Population aging is an irreversible global trend with economic and socio-political consequences. One of the most invalidating outcomes of aging in the elderly is cognitive decline, leading to dementia and often related to neurodegenerative disorders. Among these latter, Alzheimer's disease (AD) is the major cause of dementia, affecting more than 30 million of individuals worldwide. To date, the treatment of AD remains a challenge because of an incomplete understanding of the events that lead to the selective neurodegeneration typical of Alzheimer's brains. There is an enormous global demand for new effective therapies and researchers are investigating new fields. One promising strategy is the use of nutraceuticals as integrative, complementary and preventive therapy. Curcumin is one example of natural product with anti-AD properties, with promising potential for prevention, treatment and diagnostic. The limitations in the use of curcumin as therapeutic are represented by its pharmacokinetics profile and the low bioavailability after oral administration. However, curcumin has been the focus of intense research for new drug development. Here we analyzed some new approaches that have been applied in the attempt to improve its use, particularly new formulations, changes in the way of administration, nanotechnology-based delivery systems and the hybridization strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. MC37, a new mono-carbonyl curcumin analog, induces G2/M cell cycle arrest and mitochondria-mediated apoptosis in human colorectal cancer cells.

    PubMed

    Liang, Baoxia; Liu, Ziyi; Cao, Yingnan; Zhu, Cuige; Zuo, Yinglin; Huang, Lei; Wen, Gesi; Shang, Nana; Chen, Yu; Yue, Xin; Du, Jun; Li, Baojian; Zhou, Binhua; Bu, Xianzhang

    2017-02-05

    (E)-1-(3'-fluoro-[1,1'-biphenyl-3-yl)-3-(3-hydroxy-4-methoxyphenyl)prop-2-en-1-one) (MC37), a novel mono-carbonyl curcumin analog, was previously synthesized in our laboratory as a nuclear factor kappa B (NF-κB) inhibitor with excellent cytotoxicity against several cancer cell lines. In this study, our further investigations showed that the potent growth inhibitory activity of MC37 in human colorectal cancer cells was associated with the arrest of cell cycle progression and the induction of apoptosis. As a multi-targeted agent, MC37 inhibited the intracellular microtubule assembly, altered the expression of cyclin-dependent kinase 1 (CDK1), and ultimately induced G2/M cell cycle arrest. Moreover, MC37 collapsed the mitochondrial membrane potential (MMP), increased the Bax/Bcl-2 ratio, activated the caspase-9/3 cascade, and finally led to cancer cells apoptosis, suggesting that the mitochondrial-mediated apoptotic pathway was involved in MC37-induced apoptosis. In conclusion, these observations demonstrated that mono-carbonyl curcumin analogs would serve as multi-targeted lead for promising anti-colorectal cancer agent development. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. 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.

  18. 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.

  19. 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."

  20. Characterization of the host–guest complex of a curcumin analog with β-cyclodextrin and β-cyclodextrin–gemini surfactant and evaluation of its anticancer activity

    PubMed Central

    Poorghorban, Masoomeh; Das, Umashankar; Alaidi, Osama; Chitanda, Jackson M; Michel, Deborah; Dimmock, Jonathan; Verrall, Ronald; Grochulski, Pawel; Badea, Ildiko

    2015-01-01

    Background Curcumin analogs, including the novel compound NC 2067, are potent cytotoxic agents that suffer from poor solubility, and hence, low bioavailability. Cyclodextrin-based carriers can be used to encapsulate such agents. In order to understand the interaction between the two molecules, the physicochemical properties of the host–guest complexes of NC 2067 with β-cyclodextrin (CD) or β-cyclodextrin–gemini surfactant (CDgemini surfactant) were investigated for the first time. Moreover, possible supramolecular structures were examined in order to aid the development of new drug delivery systems. Furthermore, the in vitro anticancer activity of the complex of NC 2067 with CDgemini surfactant nanoparticles was demonstrated in the A375 melanoma cell line. Methods Physicochemical properties of the complexes formed of NC 2067 with CD or CDgemini surfactant were investigated by synchrotron-based powder X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. Synchrotron-based small- and wide-angle X-ray scattering and size measurements were employed to assess the supramolecular morphology of the complex formed by NC 2067 with CDgemini surfactant. Lastly, the in vitro cell toxicity of the formulations toward A375 melanoma cells at various drug-to-carrier mole ratios were measured by cell viability assay. Results Physical mixtures of NC 2067 and CD or CDgemini surfactant showed characteristics of the individual components, whereas the complex of NC 2067 and CD or CDgemini surfactant presented new structural features, supporting the formation of the host–guest complexes. Complexes of NC 2067 with CDgemini surfactants formed nanoparticles having sizes of 100–200 nm. NC 2067 retained its anticancer activity in the complex with CDgemini surfactant for different drug-to-carrier mole ratios, with an IC50 (half-maximal inhibitory concentration) value comparable to that for NC 2067 without the carrier. Conclusion The formation of

  1. 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.

  2. 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.

  3. 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.

  4. An appraisal on recent medicinal perspective of curcumin degradant: Dehydrozingerone (DZG).

    PubMed

    Hampannavar, Girish A; Karpoormath, Rajshekhar; Palkar, Mahesh B; Shaikh, Mahamadhanif S

    2016-02-15

    Natural products serve as a key source for the design, discovery and development of potentially novel drug like candidates for life threatening diseases. Curcumin is one such medicinally important molecule reported for an array of biological activities. However, it has major drawbacks of very poor bioavailability and solubility. Alternatively, structural analogs and degradants of curcumin have been investigated, which have emerged as promising scaffolds with diverse biological activities. Dehydrozingerone (DZG) also known as feruloylmethane, is one such recognized degradant which is a half structural analog of curcumin. It exists as a natural phenolic compound obtained from rhizomes of Zingiber officinale, which has attracted much attention of medicinal chemists. DZG is known to have a broad range of biological activities like antioxidant, anticancer, anti-inflammatory, anti-depressant, anti-malarial, antifungal, anti-platelet and many others. DZG has also been studied in resolving issues pertaining to curcumin since it shares many structural similarities with curcumin. Considering this, in the present review we have put forward an effort to revise and systematically discuss the research involving DZG with its biological diversity. From literature, it is quite clear that DZG and its structural analogs have exhibited significant potential in facilitating design and development of novel medicinally active lead compounds with improved metabolic and pharmacokinetic profiles. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Processive Incorporation of Deoxynucleoside Triphosphate Analogs by Single-Molecule DNA Polymerase I (Klenow Fragment) Nanocircuits.

    PubMed

    Pugliese, Kaitlin M; Gul, O Tolga; Choi, Yongki; Olsen, Tivoli J; Sims, Patrick C; Collins, Philip G; Weiss, Gregory A

    2015-08-05

    DNA polymerases exhibit a surprising tolerance for analogs of deoxyribonucleoside triphosphates (dNTPs), despite the enzymes' highly evolved mechanisms for the specific recognition and discrimination of native dNTPs. Here, individual DNA polymerase I Klenow fragment (KF) molecules were tethered to a single-walled carbon nanotube field-effect transistor (SWCNT-FET) to investigate accommodation of dNTP analogs with single-molecule resolution. Each base incorporation accompanied a change in current with its duration defined by τclosed. Under Vmax conditions, the average time of τclosed was similar for all analog and native dNTPs (0.2 to 0.4 ms), indicating no kinetic impact on this step due to analog structure. Accordingly, the average rates of dNTP analog incorporation were largely determined by durations with no change in current defined by τopen, which includes molecular recognition of the incoming dNTP. All α-thio-dNTPs were incorporated more slowly, at 40 to 65% of the rate for the corresponding native dNTPs. During polymerization with 6-Cl-2APTP, 2-thio-dTTP, or 2-thio-dCTP, the nanocircuit uncovered an alternative conformation represented by positive current excursions that does not occur with native dNTPs. A model consistent with these results invokes rotations by the enzyme's O-helix; this motion can test the stability of nascent base pairs using nonhydrophilic interactions and is allosterically coupled to charged residues near the site of SWCNT attachment. This model with two opposing O-helix motions differs from the previous report in which all current excursions were solely attributed to global enzyme closure and covalent-bond formation. The results suggest the enzyme applies a dynamic stability-checking mechanism for each nascent base pair.

  6. A review of therapeutic effects of curcumin.

    PubMed

    Noorafshan, Ali; Ashkani-Esfahani, Soheil

    2013-01-01

    There is a growing interest in herbal medicine. Scientific studies have demonstrated the beneficial pharmacological effects of curcumin. Curcumin is a bright yellow spice, derived from the rhizome of Curcuma longa Linn. It has been proven that curcumin is a highly pleiotropic molecule which can be a modulator of intracellular signaling pathways that control cell growth, inflammation, and apoptosis. Curcumin might be a potential candidate for the prevention and/or treatment of some diseases due to its anti-oxidant, antiinflammatory activities and an excellent safety profile. We present an updated concise review of currently available animal and clinical studies demonstrating the therapeutic effect of curcumin.

  7. 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

  8. A liposomal formulation of the synthetic curcumin analog EF24 (Lipo-EF24) inhibits pancreatic cancer progression: towards future combination therapies.

    PubMed

    Bisht, Savita; Schlesinger, Martin; Rupp, Alexander; Schubert, Rolf; Nolting, Jens; Wenzel, Jörg; Holdenrieder, Stefan; Brossart, Peter; Bendas, Gerd; Feldmann, Georg

    2016-07-11

    Pancreatic cancer is one of the most lethal of human malignancies known to date and shows relative insensitivity towards most of the clinically available therapy regimens. 3,5-bis(2-fluorobenzylidene)-4-piperidone (EF24), a novel synthetic curcumin analog, has shown promising in vitro therapeutic efficacy in various human cancer cells, but insufficient water solubility and systemic bioavailability limit its clinical application. Here, we describe nano-encapsulation of EF24 into pegylated liposomes (Lipo-EF24) and evaluation of these particles in preclinical in vitro and in vivo model systems of pancreatic cancer. Transmission electron microscopy and size distribution studies by dynamic light scattering confirmed intact spherical morphology of the formed liposomes with an average diameter of less than 150 nm. In vitro, treatment with Lipo-EF24 induced growth inhibition and apoptosis in MIAPaCa and Pa03C pancreatic cancer cells as assessed by using cell viability and proliferation assays, replating and soft agar clonogenicity assays as well as western blot analyses. Lipo-EF24 potently suppressed NF-kappaB nuclear translocation by inhibiting phosphorylation and subsequent degradation of its inhibitor I-kappa-B-alpha. In vivo, synergistic tumor growth inhibition was observed in MIAPaCa xenografts when Lipo-EF24 was given in combination with the standard-of-care cytotoxic agent gemcitabine. In line with in vitro observations, western blot analysis revealed decreased phosphorylation of I-kappa-B-alpha in excised Lipo-EF24-treated xenograft tumor tissues. Due to its promising therapeutic efficacy and favorable toxicity profile Lipo-EF24 might be a promising starting point for development of future combinatorial therapeutic regimens against pancreatic cancer.

  9. The logic and design of analog-sensitive kinases and their small molecule inhibitors.

    PubMed

    Lopez, Michael S; Kliegman, Joseph I; Shokat, Kevan M

    2014-01-01

    Analog-sensitive AS Kinase technology allows for rapid, reversible, and highly specific inhibition of individual engineered kinases in cells and in mouse models of human diseases. The technique consists of two parts: a kinase containing a space-creating mutation in the ATP-binding pocket and a bulky ATP-competitive small molecule inhibitor that complements the shape of the mutant ATP pocket. This strategy enables dissection of phospho-signaling pathways, elucidation of the physiological function of individual kinases, and characterization of the pharmacology of clinical-kinase inhibitors. Here, we present an overview of AS technology and describe a stepwise approach for generating AS Kinase mutants and identifying appropriate small molecule inhibitors. We also describe commonly encountered technical obstacles and provide strategies to overcome them.

  10. 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

  11. Acenes, Heteroacenes and Analogous Molecules for Organic Photovoltaic and Field Effect Transistor Applications

    NASA Astrophysics Data System (ADS)

    Granger, Devin Benjamin

    Polycyclic aromatic hydrocarbons composed of benzenoid rings fused in a linear fashion comprise the class of compounds known as acenes. The structures containing three to six ring fusions are brightly colored and possess band gaps and charge transport efficiencies sufficient for semiconductor applications. These molecules have been investigated throughout the past several decades to assess their optoelectronic properties. The absorption, emission and charge transport properties of this series of molecules has been studied extensively to elucidate structure-property relationships. A wide variety of analogous molecules, incorporating heterocycles in place of benzenoid rings, demonstrate similar properties to the parent compounds and have likewise been investigated. Functionalization of acene compounds by placement of groups around the molecule affects the way in which molecules interact in the solid state, in addition to the energetics of the molecule. The use of electron donating or electron withdrawing groups affects the frontier molecular orbitals and thus affects the optical and electronic gaps of the molecules. The use of bulky side groups such as alkylsilylethynyl groups allows for crystal engineering of molecular aggregates, and changing the volume and dimensions of the alkylsilyl groups affects the intermolecular interactions and thus changes the packing motif. In chapter 2, a series of tetracene and pentacene molecules with strongly electron withdrawing groups is described. The investigation focuses on the change in energetics of the frontier molecular orbitals between the base acene and the nitrile and dicyanovinyl derivatives as well as the differences between the pentacene and tetracene molecules. The differences in close packing motifs through use of bulky alkylsilylethynyl groups is also discussed in relation to electron acceptor material design and bulk heterojunction organic photovoltaic characteristics. Chapter 3 focuses on molecular acceptor and

  12. Comparative Analysis of Small Molecules and Histone Substrate Analogs as LSD1 Lysine Demethylase Inhibitors

    PubMed Central

    Culhane, Jeffrey C.; Wang, Dongqing; Yen, Paul M.; Cole, Philip A.

    2010-01-01

    LSD1 is a flavin dependent histone demethylase that oxidatively removes methyl groups from Lys-4 of histone H3. LSD1 belongs to the amine oxidase enzyme superfamily which utilize molecular oxygen to transform amines to imines that are hydrolytically cleaved to formaldehyde. In prior studies, it has been shown that monoamine oxidase inhibitory scaffolds such as propargylamines and cyclopropylamines can serve as mechanism-based inactivators of LSD1. Propargylamine-histone H3 peptide analogs are potent LSD1 inhibitors whereas small molecule antidepressant MAO acetylenic inhibitors like pargyline do not inhibit LSD1. In contrast, the small molecule MAO cyclopropylamine inhibitor tranylcypromine is a time-dependent LSD1 inhibitor but exo-cyclopropylamine-peptide substrate analog is not. To provide further insight into small molecule versus peptide relationships in LSD1 inhibition, herein we further our analysis of warheads in peptide scaffolds to include the chlorovinyl, endo-cyclopropylamine, and hydrazine-functionalities as LSD1 inactivators. We find that chlorovinyl-H3 is a mechanism-based LSD1 inactivator whereas endo-cyclopropylamine-H3 does not show time-dependent inactivation. The hydrazine-H3 was shown to be the most potent LSD1 suicide inhibitor yet reported, more than 20-fold more efficient in inhibiting demethylation than propargylamine-H3 derivatives. We re-explored MAO antidepressant agent phenelzine (phenethylhydrazine), previously reported to be a weak LSD1 inhibitor, and found that it is far more potent than previously appreciated. We show that phenelzine can block histone H3K4Me demethylation in cells, validating it as a pharmacologic tool and potential lead structure for anti-cancer therapy. PMID:20148560

  13. 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.

  14. Curcumin, a component of golden spice: from bedside to bench and back.

    PubMed

    Prasad, Sahdeo; Gupta, Subash C; Tyagi, Amit K; Aggarwal, Bharat B

    2014-11-01

    Although the history of the golden spice turmeric (Curcuma longa) goes back thousands of years, it is only within the past century that we learned about the chemistry of its active component, curcumin. More than 6000 articles published within the past two decades have discussed the molecular basis for the antioxidant, anti-inflammatory, antibacterial, antiviral, antifungal, and anticancer activities assigned to this nutraceutical. Over sixty five clinical trials conducted on this molecules, have shed light on the role of curcumin in various chronic conditions, including autoimmune, cardiovascular, neurological, and psychological diseases, as well as diabetes and cancer. The current review provides an overview of the history, chemistry, analogs, and mechanism of action of curcumin. Published by Elsevier Inc.

  15. 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

  16. 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

  17. Recent Advances of Curcumin in the Prevention and Treatment of Renal Fibrosis.

    PubMed

    Sun, Xuejiao; Liu, Yi; Li, Cheng; Wang, Xiting; Zhu, Ruyuan; Liu, Chenyue; Liu, Haixia; Wang, Lili; Ma, Rufeng; Fu, Min; Zhang, Dongwei; Li, Yu

    2017-01-01

    Curcumin, a polyphenol derived from the turmeric, has received attention as a potential treatment for renal fibrosis primarily because it is a relatively safe and inexpensive compound that contributes to kidney health. Here, we review the literatures on the applications of curcumin in resolving renal fibrosis in animal models and summarize the mechanisms of curcumin and its analogs (C66 and (1E,4E)-1,5-bis(2-bromophenyl) penta-1,4-dien-3-one(B06)) in preventing inflammatory molecules release and reducing the deposition of extracellular matrix at the priming and activation stage of renal fibrosis in animal models by consulting PubMed and Cnki databases over the past 15 years. Curcumin exerts antifibrotic effect through reducing inflammation related factors (MCP-1, NF-κB, TNF-α, IL-1β, COX-2, and cav-1) and inducing the expression of anti-inflammation factors (HO-1, M6PRBP1, and NEDD4) as well as targeting TGF-β/Smads, MAPK/ERK, and PPAR-γ pathways in animal models. As a food derived compound, curcumin is becoming a promising drug candidate for improving renal health.

  18. Recent Advances of Curcumin in the Prevention and Treatment of Renal Fibrosis

    PubMed Central

    Sun, Xuejiao; Liu, Yi; Li, Cheng; Wang, Xiting; Zhu, Ruyuan; Liu, Chenyue; Liu, Haixia; Wang, Lili; Ma, Rufeng; Fu, Min

    2017-01-01

    Curcumin, a polyphenol derived from the turmeric, has received attention as a potential treatment for renal fibrosis primarily because it is a relatively safe and inexpensive compound that contributes to kidney health. Here, we review the literatures on the applications of curcumin in resolving renal fibrosis in animal models and summarize the mechanisms of curcumin and its analogs (C66 and (1E,4E)-1,5-bis(2-bromophenyl) penta-1,4-dien-3-one(B06)) in preventing inflammatory molecules release and reducing the deposition of extracellular matrix at the priming and activation stage of renal fibrosis in animal models by consulting PubMed and Cnki databases over the past 15 years. Curcumin exerts antifibrotic effect through reducing inflammation related factors (MCP-1, NF-κB, TNF-α, IL-1β, COX-2, and cav-1) and inducing the expression of anti-inflammation factors (HO-1, M6PRBP1, and NEDD4) as well as targeting TGF-β/Smads, MAPK/ERK, and PPAR-γ pathways in animal models. As a food derived compound, curcumin is becoming a promising drug candidate for improving renal health. PMID:28546962

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. Determining whether curcumin degradation/condensation is actually bioactivation (Review).

    PubMed

    Jankun, Jerzy; Wyganowska-Świątkowska, Marzena; Dettlaff, Katarzyna; Jelińska, Anna; Surdacka, Anna; Wątróbska-Świetlikowska, Dorota; Skrzypczak-Jankun, Ewa

    2016-05-01

    Curcumin has been shown to exert therapeutic or protective effects against a variety of diseases, such as cancer, pulmonary diseases, neurological, liver, metabolic, autoimmune, cardiovascular diseases and numerous other chronic ailments. Over 116 clinical studies on curcumin in humans were registered with the US National Institutes of Health in 2015. However, it is mystifying how curcumin can be so effective in the treatment of many diseases since it has very low water solubility and bioavailability. Furthermore, curcumin is not stable under various conditions; its degradation or condensation into different bioactive compounds may be responsible for its biological activities rather than curcumin itself. In this review, we provide evidence of curcumin degradation and condensation into different compounds which have or may have health benefits themselves. Literature reviews strongly suggest that these molecules contribute to the observed health benefits, rather than curcumin itself.

  7. 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".

  8. 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.

  9. 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.

  10. Small molecule functional analogs of peptides that inhibit lambda site-specific recombination and bind Holliday junctions.

    PubMed

    Ranjit, Dev K; Rideout, Marc C; Nefzi, Adel; Ostresh, John M; Pinilla, Clemencia; Segall, Anca M

    2010-08-01

    Our lab has isolated hexameric peptides that are structure-selective ligands of Holliday junctions (HJ), central intermediates of several DNA recombination reactions. One of the most potent of these inhibitors, WRWYCR, has shown antibacterial activity in part due to its inhibition of DNA repair proteins. To increase the therapeutic potential of these inhibitors, we searched for small molecule inhibitors with similar activities. We screened 11 small molecule libraries comprising over nine million individual compounds and identified a potent N-methyl aminocyclic thiourea inhibitor that also traps HJs formed during site-specific recombination reactions in vitro. This inhibitor binds specifically to protein-free HJs and can inhibit HJ resolution by RecG helicase, but only showed modest growth inhibition of bacterial with a hyperpermeable outer membrane; nonetheless, this is an important step in developing a functional analog of the peptide inhibitors. Copyright 2010 Elsevier Ltd. All rights reserved.

  11. Design, development and synthesis of mixed bioconjugates of piperic acid-glycine, curcumin-glycine/alanine and curcumin-glycine-piperic acid and their antibacterial and antifungal properties.

    PubMed

    Mishra, Satyendra; Narain, Upma; Mishra, Roli; Misra, Krishna

    2005-03-01

    In the present communication different curcumin bioconjugates viz. 4,4'-di-O-glycinoyl-curcumin, 4,4'-di-O-d-alaninoyl-curcumin, 4,4'-di-O-(glycinoyl-di-N-piperoyl)-curcumin, 4,4'-di-O-piperoyl curcumin, curcumin-4,4'-di-O-beta-d-glucopyranoside, 4,4'-di-O-acetyl-curcumin along with piperoyl glycine, have been synthesised and characterised by spectra UV, (1)H NMR and elemental analysis. All the covalent bonds used are biodegradable. This makes these derivatives as potent prodrugs, which can get hydrolysed at the target sites. These bioconjugates were tested in vitro against different bacteria and fungi. The 4,4'-di-O-(glycinoyl-di-N-piperoyl)-curcumin and 4,4'-di-O-acetyl-curcumin are more effective than Cefepime, an antibacterial drug available in market, at the same concentration. The 4,4'-di-O-(glycinoyl-di-N-piperoyl)-curcumin and 4,4'-di-O-piperoyl curcumin had antifungal activity in vitro almost comparable with fluconazole, the most popular antifungal drug. The enhanced activity of these bioconjugates vis-a-vis the parent molecule that is curcumin may be due to improved cellular uptake or reduced metabolism of these bioconjugates resulting in building up of enough concentration inside the infected cells. It opens a new era for exploring suitably designed curcumin bioconjugates as potential antibacterial/antifungal drugs.

  12. Therapeutic applications of curcumin for patients with pancreatic cancer

    PubMed Central

    Kanai, Masashi

    2014-01-01

    A number of preclinical studies have demonstrated anticancer effects for curcumin in various types of tumors, including pancreatic cancer. Curcumin has anticancer effects both alone and in combination with other anticancer drugs (e.g., gemcitabine, 5-fluorouracil, and oxaliplatin), and it has been shown to modulate a variety of molecular targets in preclinical models, with more than 30 molecular targets identified to date. Of these various molecules, NF-κB is thought to be one of the primary targets of curcumin activity. Based on these promising preclinical results, several research groups, including our own, have progressed to testing the anticancer effects of curcumin in clinical trials; however, the poor bioavailability of this agent has been the major challenge for its clinical application. Despite the ingestion of gram-level doses of curcumin, plasma curcumin levels remain at low (ng/mL) levels in patients, which is insufficient to yield the anticancer benefits of curcumin. This problem has been solved by the development of highly bioavailable forms of curcumin (THERACURMIN®), and higher plasma curcumin levels can now be achieved without increased toxicity in patients with pancreatic cancer. In this article, we review possible therapeutic applications of curcumin in patients with pancreatic cancer. PMID:25071333

  13. Therapeutic applications of curcumin for patients with pancreatic cancer.

    PubMed

    Kanai, Masashi

    2014-07-28

    A number of preclinical studies have demonstrated anticancer effects for curcumin in various types of tumors, including pancreatic cancer. Curcumin has anticancer effects both alone and in combination with other anticancer drugs (e.g., gemcitabine, 5-fluorouracil, and oxaliplatin), and it has been shown to modulate a variety of molecular targets in preclinical models, with more than 30 molecular targets identified to date. Of these various molecules, NF-κB is thought to be one of the primary targets of curcumin activity. Based on these promising preclinical results, several research groups, including our own, have progressed to testing the anticancer effects of curcumin in clinical trials; however, the poor bioavailability of this agent has been the major challenge for its clinical application. Despite the ingestion of gram-level doses of curcumin, plasma curcumin levels remain at low (ng/mL) levels in patients, which is insufficient to yield the anticancer benefits of curcumin. This problem has been solved by the development of highly bioavailable forms of curcumin (THERACURMIN), and higher plasma curcumin levels can now be achieved without increased toxicity in patients with pancreatic cancer. In this article, we review possible therapeutic applications of curcumin in patients with pancreatic cancer.

  14. Analytical Protocols for Analysis of Organic Molecules in Mars Analog Materials

    NASA Technical Reports Server (NTRS)

    Mahaffy, Paul R.; Brinkerhoff, W.; Buch, A.; Demick, J.; Glavin, D. P.

    2004-01-01

    A range of analytical techniques and protocols that might be applied b in situ investigations of martian fines, ices, and rock samples are evaluated by analysis of organic molecules m Mars analogues. These simulants 6om terrestrial (i.e. tephra from Hawaii) or extraterrestrial (meteoritic) samples are examined by pyrolysis gas chromatograph mass spectrometry (GCMS), organic extraction followed by chemical derivatization GCMS, and laser desorption mass spectrometry (LDMS). The combination of techniques imparts analysis breadth since each technique provides a unique analysis capability for Certain classes of organic molecules.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Curcumin and Its Role in Chronic Diseases.

    PubMed

    Kunwar, A; Priyadarsini, K I

    Curcumin, a yellow pigment from the spice turmeric, is used in Indian and Chinese medicine since ancient times for wide range of diseases. Extensive scientific research on this molecule performed over the last 3 to 4 decades has proved its potential as an important pharmacological agent. The antioxidant, anti-inflammatory, antimicrobial and chemopreventive activities of curcumin have been extended to explore this molecule against many chronic diseases with promising results. Further, its multitargeting ability and nontoxic nature to humans even up to 12 g/day have attracted scientists to explore this as an anticancer agent in the clinic, which is in different phases of trials. With much more scope to be investigated and understood, curcumin becomes one of the very few inexpensive botanical molecules with potent therapeutic abilities.

  20. Enantiomeric separation of complex organic molecules from irradiation of interstellar/circumstellar ice analogs

    NASA Astrophysics Data System (ADS)

    Nuevo, M.; Muñoz Caro, G.; Dartois, E.; D'Hendecourt, L.; Deboffle, D.; Meierhenrich, U.; Thiemann, W.; Bredehöft, J. H.; Nahon, L.

    Our laboratory group aims at studying the photo- and thermochemical evolution of dirty ice mixtures (containing H2O, CO, CH4, CH3OH, NH3, etc.) known to be present on the surface of interstellar grains observed in molecular clouds around protostars and also found in comets. The first step was to determine the chemical composition of these ices by comparison of interstellar ice infrared spectra from the European Infrared Space Observatory (ISO) with the spectra obtained in laboratory experiments. That work allowed us to identify and quantify the abundance of simple molecules such as H2O, CO, CO2 and CH4, as well as to understand the shapes of some infrared features (shifts, band widths, splittings) resulting from interactions within the ice structure due to molecular complexes. The irradiation of these ices with UV light at low temperatures down to 10 K leads to the formation of species such as H2CO, NH4+ and OCN-, which have been already identified in astrophysical sources. If the irradiation is continued, more complex molecules, stable at room temperature, are formed. The refractory residue obtained by warming up the sample to room temperature can be analyzed by chemical techniques such as gas chromatography coupled with mass spectrometry (GC-MS). A lot of complex molecules such as glycine, alanine or glycerol are detected, among them amino acids, known to play an important role in prebiotic chemistry. The extension of this experiment, called Chiral MICMOC (for Matière Interstellaire et Cométaire, Molécules Organiques Complexes, i.e. Interstellar and Cometary Matter, Complex Organic Molecules, repeating the same experiment using circularly polarized UV light has been performed with the synchrotron light of the SU5 beam in LURE. The purpose is to reveal and study the possible apparition of an enantiomeric excess on amino acids formed in such experiments. Our preliminary analyses results show that a possible enantiomeric excess would be small. A careful data

  1. Curcumin and aging

    USDA-ARS?s Scientific Manuscript database

    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...

  2. 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.

  3. 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.

  4. 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.

  5. Curcumin and genistein coloaded nanostructured lipid carriers: in vitro digestion and antiprostate cancer activity.

    PubMed

    Aditya, N P; Shim, Myeongkuk; Lee, Inae; Lee, YoungJoo; Im, Moo-Hyeog; Ko, Sanghoon

    2013-02-27

    To increase the oral bioavailability of curcumin and genistein, we fabricated nanostructured lipid carriers (NLCs), and the impact of these carriers on bioaccessibility of curcumin and genistein was studied. Entrapment efficiency was more than 75% for curcumin and/or genistein-loaded NLCs. Solubility of curcumin and/or genistein in simulated intestinal medium (SIM) was >75% after encapsulating within NLCs which otherwise was <20%. Both curcumin and genistein have shown good stability (≥85%) in SIM and simulated gastric medium (SGM) up to 6 h. Coloading of curcumin and genistein had no adverse effect on solubility and stability of each molecule. Instead, coloading increased loading efficiency and the cell growth inhibition in prostate cancer cells. Collectively, these results have shown that coloaded lipid based carriers are promising vehicles for oral delivery of poorly bioaccessible molecules like curcumin and genistein.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. Inhibition of anthrax lethal factor by curcumin and chemically modified curcumin derivatives

    PubMed Central

    Zhang, Yu; Golub, Lorne M.; Johnson, Francis; Simon, Sanford R.

    2014-01-01

    Curcuma longa Curcumin (diferuloylmethane), the active ingredient in the eastern spice turmeric (Curcuma longa), has been shown to inhibit the activities of numerous enzymes and signaling molecules involved in cancer, bacterial and viral infections and inflammatory diseases. We have investigated the inhibitory activities of curcumin and chemically modified curcumin (CMC) derivatives toward lethal factor (LF), the proteolytic component of anthrax toxin produced by the bacterium Bacillus anthracis. Curcumin (Compound 1) appears to inhibit the catalytic activity of LF through a mixture of inhibitory mechanisms, without significant compromise to the binding of oligopeptide substrates, and one CMC derivative in particular, Compound 3 (4-phenylaminocarbonylbis-demethoxycurcumin), is capable of inhibiting LF with potency comparable with the parent compound, while also showing improved solubility and stability. The quantitative reduction in catalytic activity achieved by the different CMC derivatives appears to be a function of the proportion of the multiple mechanisms through which they inhibit the enzyme. PMID:24102525

  11. 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.

  12. 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.

  13. Nanotechnology-applied curcumin for different diseases therapy.

    PubMed

    Ghalandarlaki, Negar; Alizadeh, Ali Mohammad; 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.

  14. 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.

  15. 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

  16. 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

  17. Curcumin nanomedicine: a road to cancer therapeutics.

    PubMed

    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, chemopreventive, 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.

  18. 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

  19. A comparative study of the spectral, fluorometric properties and photostability of natural curcumin, iron- and boron- complexed curcumin

    NASA Astrophysics Data System (ADS)

    Mohammed, Fatima; Rashid-Doubell, Fiza; Cassidy, Seamas; Henari, Fryad

    2017-08-01

    Curcumin is a yellow phenolic compound with a wide range of reported biological effects. However, two main obstacles hinder the use of curcumin therapeutically, namely its poor bioavailability and photostability. We have synthesized two curcumin complexes, the first a boron curcumin complex (B-Cur2) and the second an iron (Fe-Cur3) complex of curcumin. Both derivatives showed high fluorescence efficiency (quantum yield) and greater photostability in solution. The improved photostability could be attributed to the coordination structures and the removal of β-diketone group from curcumin. The fluorescence and ultra violet/visible absorption spectra of curcumin, B-Cur2 and Fe-Cur3 all have a similar spectral pattern when dissolved in the same organic solvent. However, a shift towards a lower wavelength was observed when moving from polar to non-polar solvents, possibly due to differences in solvent polarity. A plot of Stokes' shift vs the orientation polarity parameter (Δf) or vs the solvent polarity parameter (ET 30) showed an improved correlation between the solvent polarity parameter than with the orientation polarity parameter and indicating that the red shift observed could be due to hydrogen-bonding between the solvent molecules. A similar association was obtained when Stokes' shift was replaced by maximum synchronous fluorescence. Both B-Cur2 and Fe-Cur3 had larger quantum yields than curcumin, suggesting they may be good candidates for medical imaging and in vitro studies.

  20. Photokilling of bacteria by curcumin in selected polyethylene glycol 400 (PEG 400) preparations. Studies on curcumin and curcuminoids, XLI.

    PubMed

    Haukvik, T; Bruzell, E; Kristensen, S; Tønnesen, H H

    2010-08-01

    Curcumin, bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, is a yellow-orange pigment which can be synthesised chemically or isolated from the plant Curcuma longa L. Curcumin has a rather broad absorption peak in the range 300-500 nm (maximum approximately 430 nm) and has potential as a photosensitiser for treatment of localised superficial infections in e.g., the mouth or skin. Previously, we have demonstrated phototoxic effects of curcumin in selected aqueous preparations against both gram-positive Enterococcus faecalis and Streptococcus intermedius and gram-negative Escherichia coil bacteria in vitro. One of the most efficient preparations was curcumin in polyethylene glycol (PEG 400) dissolved in phosphate buffered saline (PBS), pH 6.1. In this study the solubilising effect of PEG 400 on curcumin molecules and the in vitro phototoxic effects of these preparations were further evaluated. The effect of varying the curcumin concentration (2.50 microM -25.00 microM), the radiant exposure (0.5-30 J/cm2) and the physical state of curcumin against the survival of E. coli was investigated. PEG 400 showed an increasing physically stabilising effect towards crystallisation of curcumin in aqueous preparation with increasing concentrations (2.5%-10.0% v/v). Despite a higher solubility of curcumin with increasing PEG 400 concentrations, the surfactant reduced the phototoxicity of curcumin against E. coil. The highest phototoxic effect was obtained when curcumin was present in the least physically stable preparation, a stock solution in ethanol added to PBS with or without the lowest test concentration of PEG 400 (2.5% v/v). The obtained phototoxic effect can be increased by increasing the irradiation dose or by choosing an optimal curcumin concentration. E. faecalis was efficiently killed by the lowest concentration of curcumin in combination with the lowest radiant exposure when curcumin was dissolved in certain PEG solutions (< 0.02% survival), but showed no

  1. 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

  2. A comprehensive review on SAR of curcumin.

    PubMed

    Reddy, A Rajasekhar; Dinesh, P; Prabhakar, A S; Umasankar, K; Shireesha, B; Raju, M Bhagavan

    2013-10-01

    Curcumin, a natural diaryl heptanoid continues to be used as an alternative medicinal agent in many parts of South East Asia for treatment of many ailments. It can be usually obtained from substituted aryl aldehydes and acetylacetone and this route enables synthesis of a diverse set of curcumin analogues. Numerous analogues have been synthesized and tested by several researchers to investigate their activity against known biological targets and to improve upon the pharmacological and ADME profile by modifying substitutions on aromatic rings, β-diketone moiety and two flanking double bonds conjugated to the β-diketone moiety. Successful synthesis of such derivatives with modifications has resulted in the development of potential anticancer candidates that target various stages in cancer cell growth and development. Based on the evidences in modifications of these three functional elements, we have attempted to summarize the structure activity relationship of molecules which can be further utilized by researchers in medicinal chemistry in exploring the structure of curcumin.

  3. Therapeutic potential of curcumin in digestive diseases

    PubMed Central

    Dulbecco, Pietro; Savarino, Vincenzo

    2013-01-01

    Curcumin is a low-molecular-weight hydrophobic polyphenol that is extracted from turmeric, which possesses a wide range of biological properties including anti-inflammatory, anti-oxidant, anti-proliferative and anti-microbial activities. Despite its diverse targets and substantial safety, clinical applications of this molecule for digestive disorders have been largely limited to case series or small clinical trials. The poor bioavailability of curcumin is likely the major hurdle for its more widespread use in humans. However, complexation of curcumin into phytosomes has recently helped to bypass this problem, as it has been demonstrated that this new lecithin formulation enables increased absorption to a level 29-fold higher than that of traditional curcuminoid products. This allows us to achieve much greater tissue substance delivery using significantly lower doses of curcumin than have been used in past clinical studies. As curcumin has already been shown to provide good therapeutic results in some small studies of both inflammatory and neoplastic bowel disorders, it is reasonable to anticipate an even greater efficacy with the advent of this new technology, which remarkably improves its bioavailability. These features are very promising and may represent a novel and effective therapeutic approach to both functional and organic digestive diseases. PMID:24409053

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Energy levels of a polarizable linear polar molecule in a dc electric field obtained by analogy with the nonrelativistic hydrogen atom

    SciTech Connect

    Sekatskii, S. K.

    2007-05-15

    We note that an equation governing the dynamics of a polarizable linear polar molecule in a dc electric field coincides with one of two equations describing a hydrogen atom in the prolate spheroidal coordinate system. Using this analogy, as well as the known algebra of the angular momentum and Runge-Lenz-Pauli operators for the case of a hydrogen atom, the energy levels of a polarizable linear polar molecule in a dc electric field are calculated. For some cases, these energy values are exact.

  9. Curcumin and neurodegenerative diseases

    PubMed Central

    Monroy, Adriana; Lithgow, Gordon J.; Alavez, Silvestre

    2013-01-01

    Over the last ten years curcumin has been reported to be effective against a wide variety of diseases and is characterized as having anti-carcinogenic, hepatoprotective, thrombosuppressive, cardioprotective, anti-arthritic, and anti-infectious properties. Recent studies performed in both vertebrate and invertebrate models have been conducted to determine whether curcumin was also neuroprotective. The efficacy of curcumin in several pre-clinical trials for neurodegenerative diseases has created considerable excitement mainly due to its lack of toxicity and low cost. This suggests that curcumin could be a worthy candidate for nutraceutical intervention. Since aging is a common risk factor for neurodegenerative diseases, it is possible that some compounds that target aging mechanisms could also prevent these kinds of diseases. One potential mechanism to explain several of the general health benefits associated with curcumin is that it may prevent aging-associated changes in cellular proteins that lead to protein insolubility and aggregation. This loss in protein homeostasis is associated with several age-related diseases. Recently, curcumin has been found to help maintain protein homeostasis and extend lifespan in the model invertebrate Caenorhabditis elegans. Here, we review the evidence from several animal models that curcumin improves healthspan by preventing or delaying the onset of various neurodegenerative diseases. PMID:23303664

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Design and development of novel mitochondrial targeted nanocarriers, DQAsomes for curcumin inhalation.

    PubMed

    Zupančič, Špela; Kocbek, Petra; Zariwala, M Gulrez; Renshaw, Derek; Gul, Mine Orlu; Elsaid, Zeeneh; Taylor, Kevin M G; Somavarapu, Satyanarayana

    2014-07-07

    Curcumin has potent antioxidant and anti-inflammatory properties but poor absorption following oral administration owing to its low aqueous solubility. Development of novel formulations to improve its in vivo efficacy is therefore challenging. In this study, formulation of curcumin-loaded DQAsomes (vesicles formed from the amphiphile, dequalinium) for pulmonary delivery is presented for the first time. The vesicles demonstrated mean hydrodynamic diameters between 170 and 200 nm, with a ζ potential of approximately +50 mV, high drug loading (up to 61%) and encapsulation efficiency (90%), resulting in enhanced curcumin aqueous solubility. Curcumin encapsulation in DQAsomes in the amorphous state was confirmed by X-ray diffraction and differential scanning calorimetry analysis. The existence of hydrogen bonds and cation-π interaction between curcumin and vesicle building blocks, namely dequalinium molecules, were shown in lyophilized DQAsomes using FT-IR analysis. Encapsulation of curcumin in DQAsomes enhanced the antioxidant activity of curcumin compared to free curcumin. DQAsome dispersion was successfully nebulized with the majority of the delivered dose deposited in the second stage of the twin-stage impinger. The vesicles showed potential for mitochondrial targeting. Curcumin-loaded DQAsomes thus represent a promising inhalation formulation with improved stability characteristics and mitochondrial targeting ability, indicating a novel approach for efficient curcumin delivery for effective treatment of acute lung injury and the rationale for future in vivo studies.

  15. Role of microRNAs in the Therapeutic Effects of Curcumin in Non-Cancer Diseases.

    PubMed

    Momtazi, Amir Abbas; Derosa, Giuseppe; Maffioli, Pamela; Banach, Maciej; Sahebkar, Amirhossein

    2016-08-01

    Curcumin is a bioactive polyphenol occurring in the rhizomes of Curcuma longa. It is well-reputed for its chemopreventive and anticancer properties; however, recent evidence has revealed numerous biological and pharmacological effects of curcumin that are relevant to the treatment of non-cancer diseases. Mechanistically, curcumin exerts its pharmacological effects through anti-inflammatory and antioxidant mechanisms via interaction with different signaling molecules and transcription factors. In addition, epigenetic modulators such as microRNAs (miRs) have emerged as novel targets of curcumin. Curcumin was found to modulate the expression of several pathogenic miRs in brain, ocular, renal, and liver diseases. The present systematic review was conducted to identify miRs that are regulated by curcumin in non-cancer diseases.

  16. Recent progress on curcumin-based therapeutics: a patent review (2012-2016). Part I: Curcumin.

    PubMed

    Di Martino, Rita Maria Concetta; Luppi, Barbara; Bisi, Alessandra; Gobbi, Silvia; Rampa, Angela; Abruzzo, Angela; Belluti, Federica

    2017-05-01

    curcumin is the main bioactive component contained in Curcuma Longa, largely employed in traditional medicine. Recently, beneficial properties, useful for prevention and treatment of several disorders, have been discovered for this compound. Peculiar structural feature is an α,β-unsaturated carbonyl system essential for establishing contacts with critical cysteine residues of several targets. This distinctive mechanism of action imparts to the molecule the ability to affect a large number of targets, accounting for its pleiotropic behaviour and definition of "privileged structure". Areas covered: The objective of the review is an examination of the recent developments in the field of the anti-cancer applications of curcumin, together with formulation issues, considering the patent literature in the years 2012-2016. Expert opinion: The wide therapeutic efficacy of curcumin is related to synergistic interactions with several biological targets, along with the modulation of several signaling pathways. This peculiar behaviour could be useful in the treatment of multifactorial diseases such as cancer. Combination of curcumin with a first line antineoplastic drug proved to be a valuable strategy to obtain an amplified response with minimized side effects. Innovative curcumin formulations based on the nanotechnology approach allowed improving both bioavailability and therapeutic efficacy.

  17. 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.

  18. Curcumin nanodisks: formulation and characterization

    PubMed Central

    Ghosh, Mistuni; Singh, Amareshwar T. K.; Xu, Wenwei; Sulchek, Todd; Gordon, Leo I.; Ryan, Robert O.

    2010-01-01

    Nanodisks (ND) are nanoscale, disk-shaped phospholipid bilayers whose edge is stabilized by apolipoproteins. In the present study, ND were formulated with the bioactive polyphenol, curcumin, at a 6:1 phospholipid:curcumin molar ratio. Atomic force microscopy revealed that curcumin-ND are particles with diameters <50 nm and thickness of a phospholipid bilayer. When formulated in ND, curcumin is water-soluble and gives rise to a characteristic absorbance spectrum with a peak centered at 420 nm. Fluorescence spectroscopy of curcumin-ND provided evidence of self-quenching. Incubation of curcumin-ND with empty-ND relieved the self-quenching, indicating redistribution of curcumin between curcumin loaded- and empty-ND. In HepG2 cells, curcumin-ND mediated enhanced cell growth inhibition compared to free curcumin. In a cell culture model of mantle cell lymphoma, curcumin-ND were a more potent inducer of apoptosis than free curcumin. The nanoscale size of the complexes, combined with their ability to solubilize curcumin, indicates ND may have in vivo therapeutic applications. PMID:20817125

  19. Effect of curcumin on nasal symptoms and airflow in patients with perennial allergic rhinitis.

    PubMed

    Wu, Sihai; Xiao, Dajiang

    2016-12-01

    Allergic rhinitis (AR) is a common disorder that can significantly affect patient quality of life. Previous studies have found that curcumin had anti-inflammatory and antioxidant effects and clinical benefits in cancer and asthma. To determine the efficacy of curcumin in the treatment of AR and to explore the molecular mechanisms involved. In a randomized, double-blind study, 241 patients with AR received either placebo or oral curcumin for 2 months. The therapeutic effects of curcumin were evaluated by nasal symptoms and nasal airflow resistance. In addition, the production of interferon γ, interleukin (IL) 4, IL-10, and tumor necrosis factor α from mononuclear cells and IL-8, soluble intercellular adhesion molecule, polyethylene glycol 2, and leukotriene C4 from polymorphonuclear neutrophils were compared before and after curcumin treatment. Curcumin alleviated nasal symptoms (sneezing and rhinorrhea) and nasal congestion through reduction of nasal airflow resistance. Curcumin was found to exert diverse immunomodulatory effects, including suppression of IL-4, IL-8, and tumor necrosis factor α and increased production of IL-10 and soluble intercellular adhesion molecule. However, curcumin did not affect the release of prostaglandin E2 and leukotriene C4 from polymorphonuclear neutrophils. This pilot study provides the first evidence of the capability of curcumin of improving nasal airflow and modulating immune response in patients with AR. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  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. Multitargeting by curcumin as revealed by molecular interaction studies

    PubMed Central

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

    2012-01-01

    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 Ca2+ 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

  3. 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

  4. Effect of interfacial composition on uptake of curcumin-piperine mixtures in oil in water emulsions by Caco-2 cells.

    PubMed

    Gülseren, İbrahim; Guri, Anilda; Corredig, Milena

    2014-06-01

    Encapsulation in lipid particles is often proposed as a solution to improve curcumin bioavailability. This bioactive molecule has low water solubility and rapidly degrades during digestion. In the present study, the uptake of curcumin from oil in water emulsions, prepared with two different emulsifiers, Tween 20 and Poloxamer 407, was investigated to determine the effect of interfacial composition on absorption. Piperine was added to the curcumin to limit the degradation of curcumin because it is known to inhibit β-glucuronidase activity. The emulsions were administered to Caco-2 cell cultures, which is used as a model for intestinal uptake, and the recovery of curcumin was measured. The curcumin uptake was significantly affected by the type of interface, and the extent of curcumin uptake improved significantly by piperine addition only in the case of oil-in-water emulsions stabilized by Poloxamer 407. This work provides further evidence of the importance of interfacial composition on the delivery of bioactives.

  5. Targets of curcumin

    PubMed Central

    Zhou, Hongyu; Beevers, Christopher S.; Huang, Shile

    2010-01-01

    Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-κB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer’s disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here. PMID:20955148

  6. Identification of a melampomagnolide B analog as a potential lead molecule for treatment of acute myelogenous leukemia.

    PubMed

    Albayati, Zaineb A F; Janganati, Venumadhav; Chen, Zheng; Ponder, Jessica; Breen, Philip J; Jordan, Craig T; Crooks, Peter A

    2017-02-01

    A series of carbamate derivatives of the antileukemic sesquiterpene melampomagnolide B (MMB) has been synthesized utilizing a 1,2,4-triazole carbamate conjugate of MMB as an intermediate synthon. Five imidazole- and benzimidazole-carbamate analogs of MMB (8a-8e) were prepared and evaluated for anti-leukemic activity against cultured M9 ENL1 AML cells. All the analogs exhibited improved anti-leukemic activity (EC50=0.90-3.93μM) when compared to parthenolide and the parent sesquiterpene, MMB (EC50=7.0μM and 15.5μM, respectively). The imidazole carbamate analog, 8a (EC50=0.9μM), was 16 times more potent than MMB. The comparative bioavailabilities of 8a and MMB were determined in BALB/c mice following oral dosing of these compounds. It has been demonstrated that the absolute plasma bioavailabilities of MMB and 8a were 6.7±0.8%, and 45.5±2%, respectively. These results indicate that, compared to MMB, the PK parameters for 8a display significantly improved bioavailability and exposure after oral administration. Analog 8a is considered to be a potential clinical candidate for treatment of acute myelogenous leukemia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. 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

  8. 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.

  9. 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

  10. Curcumin attenuates angiogenesis in liver fibrosis and inhibits angiogenic properties of hepatic stellate cells

    PubMed Central

    Zhang, Feng; Zhang, Zili; Chen, Li; Kong, Desong; Zhang, Xiaoping; Lu, Chunfeng; Lu, Yin; Zheng, Shizhong

    2014-01-01

    Hepatic fibrosis is concomitant with sinusoidal pathological angiogenesis, which has been highlighted as novel therapeutic targets for the treatment of chronic liver disease. Our prior studies have demonstrated that curcumin has potent antifibrotic activity, but the mechanisms remain to be elucidated. The current work demonstrated that curcumin ameliorated fibrotic injury and sinusoidal angiogenesis in rat liver with fibrosis caused by carbon tetrachloride. Curcumin reduced the expression of a number of angiogenic markers in fibrotic liver. Experiments in vitro showed that the viability and vascularization of rat liver sinusoidal endothelial cells and rat aortic ring angiogenesis were not impaired by curcumin. These results indicated that hepatic stellate cells (HSCs) that are characterized as liver-specific pericytes could be potential target cells for curcumin. Further investigations showed that curcumin inhibited VEGF expression in HSCs associated with disrupting platelet-derived growth factor-β receptor (PDGF-βR)/ERK and mTOR pathways. HSC motility and vascularization were also suppressed by curcumin associated with blocking PDGF-βR/focal adhesion kinase/RhoA cascade. Gain- or loss-of-function analyses revealed that activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) was required for curcumin to inhibit angiogenic properties of HSCs. We concluded that curcumin attenuated sinusoidal angiogenesis in liver fibrosis possibly by targeting HSCs via a PPAR-γ activation-dependent mechanism. PPAR-γ could be a target molecule for reducing pathological angiogenesis during liver fibrosis. PMID:24779927

  11. 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.

  12. 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

  13. 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

  14. Curcumin reduces the antimicrobial activity of ciprofloxacin against Salmonella typhimurium and Salmonella typhi.

    PubMed

    Marathe, Sandhya A; Kumar, Rupesh; Ajitkumar, Parthasarathi; Nagaraja, Valakunja; Chakravortty, Dipshikha

    2013-01-01

    Typhoidal and non-typhoidal infection by Salmonella is a serious threat to human health. Ciprofloxacin is the last drug of choice to clear the infection. Ciprofloxacin, a gyrase inhibitor, kills bacteria by inducing chromosome fragmentation, SOS response and reactive oxygen species (ROS) in the bacterial cell. Curcumin, an active ingredient from turmeric, is a major dietary molecule among Asians and possesses medicinal properties. Our research aimed at investigating whether curcumin modulates the action of ciprofloxacin. We investigated the role of curcumin in interfering with the antibacterial action of ciprofloxacin in vitro and in vivo. RT-PCR, DNA fragmentation and confocal microscopy were used to investigate the modulation of ciprofloxacin-induced SOS response, DNA damage and subsequent filamentation by curcumin. Chemiluminescence and nitroblue tetrazolium reduction assays were performed to assess the interference of curcumin with ciprofloxacin-induced ROS. DNA binding and cleavage assays were done to understand the rescue of ciprofloxacin-mediated gyrase inhibition by curcumin. Curcumin interferes with the action of ciprofloxacin thereby increasing the proliferation of Salmonella Typhi and Salmonella Typhimurium in macrophages. In a murine model of typhoid fever, mice fed with curcumin had an increased bacterial burden in the reticuloendothelial system and succumbed to death faster. This was brought about by the inhibition of ciprofloxacin-mediated downstream signalling by curcumin. The antioxidant property of curcumin is crucial in protecting Salmonella against the oxidative burst induced by ciprofloxacin or interferon γ (IFNγ), a pro-inflammatory cytokine. However, curcumin is unable to rescue ciprofloxacin-induced gyrase inhibition. Curcumin's ability to hinder the bactericidal action of ciprofloxacin and IFNγ might significantly augment Salmonella pathogenesis.

  15. 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.

  16. 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.

  17. Curcumin Modulates Pancreatic Adenocarcinoma Cell-Derived Exosomal Function

    PubMed Central

    Osterman, Carlos J. Diaz; Lynch, James C.; Leaf, Patrick; Gonda, Amber; Ferguson Bennit, Heather R.; Griffiths, Duncan; Wall, Nathan R.

    2015-01-01

    Pancreatic cancer has the highest mortality rates of all cancer types. One potential explanation for the aggressiveness of this disease is that cancer cells have been found to communicate with one another using membrane-bound vesicles known as exosomes. These exosomes carry pro-survival molecules and increase the proliferation, survival, and metastatic potential of recipient cells, suggesting that tumor-derived exosomes are powerful drivers of tumor progression. Thus, to successfully address and eradicate pancreatic cancer, it is imperative to develop therapeutic strategies that neutralize cancer cells and exosomes simultaneously. Curcumin, a turmeric root derivative, has been shown to have potent anti-cancer and anti-inflammatory effects in vitro and in vivo. Recent studies have suggested that exosomal curcumin exerts anti-inflammatory properties on recipient cells. However, curcumin’s effects on exosomal pro-tumor function have yet to be determined. We hypothesize that curcumin will alter the pro-survival role of exosomes from pancreatic cancer cells toward a pro-death role, resulting in reduced cell viability of recipient pancreatic cancer cells. The main objective of this study was to determine the functional alterations of exosomes released by pancreatic cancer cells exposed to curcumin compared to exosomes from untreated pancreatic cancer cells. We demonstrate, using an in vitro cell culture model involving pancreatic adenocarcinoma cell lines PANC-1 and MIA PaCa-2, that curcumin is incorporated into exosomes isolated from curcumin-treated pancreatic cancer cells as observed by spectral studies and fluorescence microscopy. Furthermore, curcumin is delivered to recipient pancreatic cancer cells via exosomes, promoting cytotoxicity as demonstrated by Hoffman modulation contrast microscopy as well as AlamarBlue and Trypan blue exclusion assays. Collectively, these data suggest that the efficacy of curcumin may be enhanced in pancreatic cancer cells through

  18. 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.

  19. 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.

  20. 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

  1. Curcumin Protects Membranes through a Carpet or Insertion Model Depending on Hydration.

    PubMed

    Alsop, Richard J; Dhaliwal, Alexander; Rheinstädter, Maikel C

    2017-08-29

    Curcumin is the main ingredient in turmeric, a common Indian spice. Curcumin shows a broad spectrum of effects, including anti-Alzheimer's and antioxidant properties. An interaction between curcumin and lipid membranes has been speculated as the root cause of this activity, and the molecule is often proposed to protect the bilayer. However, the detailed molecular mechanism of this protection is disputed. There is evidence that curcumin either (a) lies flat on the bilayer and provides a "carpet" for protection by forming a steric barrier, or (b) inserts into the membrane and stiffens tails, thereby protecting against peptide insertion. We studied the interaction between curcumin and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers at different concentrations using high-resolution X-ray diffraction and molecular dynamics (MD) computer simulations. We observed curcumin molecules forming a carpet in dehydrated bilayers, whereas in hydrated membranes the curcumin molecules were found to insert into the bilayers. From calculations of the potential of mean force (PMF), we find two minima, a metastable state in the headgroup region, at |z| ≈ 22 Å, and a global minimum in the hydrophobic membrane core, at |z| ≈ 9 Å. The population of the two states depends on membrane hydration. Experiments may thus observe curcumin in a carpet or inserted position, depending on the osmotic pressure conditions created, for instance, by salts, buffer solutions, substrates, or macromolecular solutes. In the carpet model, curcumin dehydrates lipid bilayers and decreases fluidity. When inserted, curcumin leads to a further fluidification of the membranes and an increase in tail fluctuations, contrary to cholesterol's condensing effect.

  2. 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

  3. Evaluation of in vitro antileishmanial activity of curcumin and its derivatives "gallium curcumin, indium curcumin and diacethyle curcumin".

    PubMed

    Fouladvand, M; Barazesh, A; Tahmasebi, R

    2013-12-01

    Leishmania parasites are intracellular haemoflagellates that infect macrophages of the skin and viscera to produce diseases in their vertebrates hosts. Antileishmania therapy is based on pentavalent antimony compounds which toxicity of these agents and the persistence of side effects are severe. Curcumin was identified to be responsible for most of the biological effects of turmeric. Turmeric plant extracts (curcumin and other derivatives) have anti-inflammatory, anti-arthritic, antioxidant, anti-microbial, antileishmanial, hepato protective, anti-cancer, anti-ulcer and anti diabetic activity. Stock solutions of curcumin, indium curcumin, diacetylcurcumin and Gallium curcumin were made up in DMSO. From the each stock solution serial dilutions were made with phosphate buffered saline and 100 µl of each prepared concentration was added to each well of 96-well micro plate. All tests were performed in triplicate. Negative control only received RPMI-1640 medium with a parasite density of 106 parasites /ml and the positive control contained varying concentrations of standard antileishmania compound, Amphotericine B. MTT solution was prepared as 5 mg/ml in RPMI-1640 and 20 µl of this concentration was added to each well. Antileishmania effects of test agents and control were evaluated by using the MTT assay. Mean growth inhibition of triplicate for each concentration of test agents and control were measured. The IC50 values for curcumin, gallium curcumin [ga (CUR) 3], indium curcumin [in (CUR)3], Diacethyle Curcumin (DAC ) and Amphotericine B were 38 µg/ml, 32 µg/ml, 26 µg/ml, 52 µg/ml and 20 µg/ml respectively. Indium curcumin [in (CUR) 3] with IC50 values of 26 µg/ml was more effective than other three test agents against Leishmania. Mean growth inhibition of triplicate for Amphotericine B as control drug, was 20 µg/ml. Indium curcumin and Gallium curcumin complex showed more antileishmanial activity than curcumin and diacetylcurcumin and could be suitable

  4. 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.

  5. Curcumin (Turmeric) and cancer.

    PubMed

    Unlu, Ahmet; Nayir, Erdinc; Dogukan Kalenderoglu, Muhammed; Kirca, Onder; Ozdogan, Mustafa

    2016-01-01

    Curcumin is a substance obtained from the root of the turmeric plant, which has the feature of being a yellow or orange pigment. It is also the main component of curry powder commonly used in Asian cuisine. Curcumin, a substance that has had an important place in traditional Indian and Chinese medicines for thousands of years, has been the center of interest for scientific studies especially in the field of cancer treatment for several years. Laboratory studies have presented some favorable results in terms of curcumin's antioxidant, antiinflammatory and anticancer properties in particular. However, since such findings have yet to be confirmed in clinical studies, its effect on humans is not clearly known. Therefore, when its advantages in terms of toxicity, cost and availability as well as the favorable results achieved in laboratory studies are considered, it would not be wrong to say that curcumin is a substance worth being studied. However, for now the most correct approach is to abstain from its use for medical purposes due to lack of adequate reliable evidence obtained from clinical studies, and because of its potential to interfere with other drugs.

  6. 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

  7. Curcumin and Endothelial Function: Evidence and Mechanisms of Protective Effects.

    PubMed

    Karimian, Maryam S; Pirro, Matteo; Johnston, Thomas P; Majeed, Muhammed; Sahebkar, Amirhossein

    2017-01-01

    The endothelium is a large paracrine organ regulating cell growth, vascular tone and thrombogenicity as well as platelet and leukocyte interactions. Endothelial function can be assessed by noninvasive techniques [e.g. flow-mediated vasodilation, nitroglycerin-mediated dilation and pulse wave velocity] and measuring specific circulating biomarkers [cell adhesion molecules, endothelial microparticles and endothelial progenitor cells]. Impaired endothelial function plays a key role in the development of atherosclerosis, arterial hypertension, heart failure, ischemia-reperfusion injury, Alzheimer's disease and other conditions. Endothelial function is also involved in growth and proliferation of tumor cells. We performed a literature review and assessed the role of the natural polyphenol, curcumin, as a potential inexpensive, well-tolerated, and safe agent for improving endothelial function. Curcumin exerts several positive pharmacological effects; these include anti-inflammatory, antioxidant, anti-hypertensive, anti-cancer, antiviral, anti-infective and wound-healing properties. Specifically, curcumin's anti-inflammatory effects are thought to be caused by reducing trans-endothelial monocyte migration by reduction of mRNA and protein expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and P-selectin and by modulating NFκB, JNK, p38 and STAT-3 in endothelial cells. Dietary curcumin supplementation can also increase antioxidant activity through the induction of heme oxygenase-1, a scavenger of free radicals, and by reduction of reactive oxygen species and Nox-2. Curcumin appears to improve endothelial function but additional research is needed to determine the precise mechanism(s) and biomarkers involved in curcumin's therapeutic effects on endothelial dysfunction. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. 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.

  9. An experimental study of the organic molecules produced in cometary and interstellar ice analogs by thermal formaldehyde reactions

    NASA Technical Reports Server (NTRS)

    Schutte, W. A.; Allamandola, L. J.; Sandford, S. A.

    1993-01-01

    Results of an experimental study tracing thermal formaldehyde reactions in astrophysically relevant ices in dense molecular clouds are reported. The formaldehyde chemistry during warm-up of ices containing H2CO and one or more of the molecules H2O, CH3OH, CO, O2, and NH3 were monitored using IR spectroscopy. Conversion of H2CO into residues was observed to start at about 40 K for NH3:H2CO ices and at about 80 K in H2O-rich ices. A total of five different organic products of these reactions were distinguished: POM and reaction products of H2CO and H2O, CH3OH, and NH3. Given the measured reaction paths and efficiencies, it is estimated that on the order of 1 percent of the organics found in the coma of Comet P/Halley could have been produced by thermal formaldehyde reactions taking place in the nucleus.

  10. Therapeutic Applications of Curcumin Nanoformulations.

    PubMed

    Yallapu, Murali M; Nagesh, Prashanth K Bhusetty; Jaggi, Meena; Chauhan, Subhash C

    2015-11-01

    Curcumin (diferuloylmethane) is a bioactive and major phenolic component of turmeric derived from the rhizomes of curcuma longa linn. For centuries, curcumin has exhibited excellent therapeutic benefits in various diseases. Owing to its anti-oxidant and anti-inflammatory properties, curcumin plays a significant beneficial and pleiotropic regulatory role in various pathological conditions including cancer, cardiovascular disease, Alzheimer's disease, inflammatory disorders, neurological disorders, and so on. Despite such phenomenal advances in medicinal applications, the clinical implication of native curcumin is hindered due to low solubility, physico-chemical instability, poor bioavailability, rapid metabolism, and poor pharmacokinetics. However, these issues can be overcome by utilizing an efficient delivery system. Active scientific research was initiated in 2005 to improve curcumin's pharmacokinetics, systemic bioavailability, and biological activity by encapsulating or by loading curcumin into nanoform(s) (nanoformulations). A significant number of nanoformulations exist that can be translated toward medicinal use upon successful completion of pre-clinical and human clinical trials. Considering this perspective, current review provides an overview of an efficient curcumin nanoformulation for a targeted therapeutic option for various human diseases. In this review article, we discuss the clinical evidence, current status, and future opportunities of curcumin nanoformulation(s) in the field of medicine. In addition, this review presents a concise summary of the actions required to develop curcumin nanoformulations as pharmaceutical or nutraceutical candidates.

  11. 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.

  12. 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.

  13. Curcumin and cancer: barriers to obtaining a health claim.

    PubMed

    Devassy, Jessay G; Nwachukwu, Ifeanyi D; Jones, Peter J H

    2015-03-01

    Curcumin is a highly pleiotropic molecule found in the rhizomes of Curcuma longa (turmeric). It is responsible for the yellow color of turmeric and has been shown to inhibit the proliferation of cancer cells and to be of use in preventing or treating a number of diseases. Curcumin has been shown to modulate multiple cell-signaling pathways simultaneously, thereby mitigating or preventing many different types of cancers, including multiple myeloma and colorectal, pancreatic, breast, prostate, lung, head, and neck cancers, in both animal models and humans. Current therapeutic approaches using a single cancer drug for a single target can be expensive, have serious side effects, or both. Consequently, new approaches to the treatment and prevention of cancer, including the integration of curcumin as a viable treatment strategy where dysregulation of many pathways is involved, are warranted. A methodical review of the evidence was performed to evaluate the effects of curcumin in support of a health claim, as established through the regulatory framework of Health Canada, for a relationship between the consumption of curcumin and the prevention and treatment of cancer. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Impact of curcumin supersaturation in antibacterial photodynamic therapy--effect of cyclodextrin type and amount: studies on curcumin and curcuminoides XLV.

    PubMed

    Hegge, Anne B E E; Nielsen, Thorbjørn T; Larsen, Kim L; Bruzell, Ellen; Tønnesen, Hanne H

    2012-04-01

    Curcumin has been investigated as a potential photosensitizer (PS) in antimicrobial photodynamic therapy (aPDT). The phototoxic effect of curcumin is dependent on proper formulations of the compound because of the lipophilic nature of the molecule and the extremely low water solubility at physiological conditions. In the present study, the combination of curcumin with either a methylated β-cyclodextrin (CD) or polyethylene glycol-based β-CD or γ-CD polymers was investigated in aPDT using Escherichia coli (E. coli) and Enterococcus faecalis as model bacteria. Solutions with various supersaturation ratios of curcumin were prepared with the selected CD or CD polymers. The concept of supersaturation was then investigated as a mean to enhance the phototoxic effect of curcumin, especially toward the gram-negative bacteria E. coli. A high supersaturation ratio corresponded with high phototoxicity of E. coli. Depending on the curcumin preparation, the bacterial survival ranged from 0.01% to no significant effect after irradiation with blue light (29 J/cm(2) ). Temporal stabilization of the supersaturated state is necessary in order to retain high and predictable photoreactivity of the PS. Further studies will be needed in order to formulate curcumin preparations with acceptable hydrolytic and photolytic stability and a temporal stabilization of a supersaturated state. Copyright © 2012 Wiley Periodicals, Inc.

  15. Synthesis, antibacterial and antiviral properties of curcumin bioconjugates bearing dipeptide, fatty acids and folic acid.

    PubMed

    Singh, Ramendra K; Rai, Diwakar; Yadav, Dipti; Bhargava, A; Balzarini, J; De Clercq, E

    2010-03-01

    Curcumin bioconjugates, viz. di-O-tryptophanylphenylalanine curcumin (2), di-O-decanoyl curcumin (3), di-O-pamitoyl curcumin (4), di-O-bis-(gamma,gamma)folyl curcumin (6), C(4)-ethyl-O-gamma-folyl curcumin (8) and 4-O-ethyl-O-gamma-folyl curcumin (10) have been synthesized and tested for their antibacterial and antiviral activities. The conjugates 2, 3, 4, 6 and 8 have shown very promising antibacterial activity with MIC ranging between 0.09 and 0.67 microM against Gram-positive cocci and Gram-negative bacilli. Further, the conjugates 2, 3, 6, 8 and 10 have been screened for their antiviral activities against HSV, VSV, FIPV, PIV-3, RSV and FHV and the molecules 2 and 3 have shown good results with EC(50) 0.011 microM and 0.029 microM against VSV and FIPV/FHV, respectively. However, the molecules did not show expected results against HIV-1 III(B) and ROD strains in MTT assay. Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

  16. 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.

  17. 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.

  18. Comparative absorption of curcumin formulations.

    PubMed

    Jäger, Ralf; Lowery, Ryan P; Calvanese, Allison V; Joy, Jordan M; Purpura, Martin; Wilson, Jacob M

    2014-01-24

    The potential health benefits of curcumin are limited by its poor solubility, low absorption from the gut, rapid metabolism and rapid systemic elimination. The purpose of this study was the comparative measurement of the increases in levels of curcuminoids (curcumin, demethoxycurcumin, bisdemethoxycurcumin) and the metabolite tetrahydrocurcumin after oral administration of three different curcumin formulations in comparison to unformulated standard. The relative absorption of a curcumin phytosome formulation (CP), a formulation with volatile oils of turmeric rhizome (CTR) and a formulation of curcumin with a combination of hydrophilic carrier, cellulosic derivatives and natural antioxidants (CHC) in comparison to a standardized curcumin mixture (CS) was investigated in a randomized, double-blind, crossover human study in healthy volunteers. Samples were analyzed by HPLC-MS/MS. Total curcuminoids appearance in the blood was 1.3-fold higher for CTR and 7.9-fold higher for CP in comparison to unformulated CS. CHC showed a 45.9-fold higher absorption over CS and significantly improved absorption over CP (5.8-fold) and CTR (34.9-fold, all p < 0.001). A formulation of curcumin with a combination of hydrophilic carrier, cellulosic derivatives and natural antioxidants significantly increases curcuminoid appearance in the blood in comparison to unformulated standard curcumin CS, CTR and CP.

  19. Comparative absorption of curcumin formulations

    PubMed Central

    2014-01-01

    Background The potential health benefits of curcumin are limited by its poor solubility, low absorption from the gut, rapid metabolism and rapid systemic elimination. The purpose of this study was the comparative measurement of the increases in levels of curcuminoids (curcumin, demethoxycurcumin, bisdemethoxycurcumin) and the metabolite tetrahydrocurcumin after oral administration of three different curcumin formulations in comparison to unformulated standard. Methods The relative absorption of a curcumin phytosome formulation (CP), a formulation with volatile oils of turmeric rhizome (CTR) and a formulation of curcumin with a combination of hydrophilic carrier, cellulosic derivatives and natural antioxidants (CHC) in comparison to a standardized curcumin mixture (CS) was investigated in a randomized, double-blind, crossover human study in healthy volunteers. Samples were analyzed by HPLC-MS/MS. Results Total curcuminoids appearance in the blood was 1.3-fold higher for CTR and 7.9-fold higher for CP in comparison to unformulated CS. CHC showed a 45.9-fold higher absorption over CS and significantly improved absorption over CP (5.8-fold) and CTR (34.9-fold, all p < 0.001). Conclusion A formulation of curcumin with a combination of hydrophilic carrier, cellulosic derivatives and natural antioxidants significantly increases curcuminoid appearance in the blood in comparison to unformulated standard curcumin CS, CTR and CP. PMID:24461029

  20. Curcumin and its analogues: a potential natural compound against HIV infection and AIDS.

    PubMed

    Prasad, Sahdeo; Tyagi, Amit K

    2015-11-01

    No safe and effective cure currently exists for human immunodeficiency virus (HIV). However, antiretroviral therapy can prolong the lives of HIV patients and lowers the secondary infections. Natural compounds, which are considered to be pleiotropic molecules, could be useful against HIV. Curcumin, a yellow pigment present in the spice turmeric (Curcuma longa), can be used for the treatment of several diseases including HIV-AIDS because of its antioxidant, anti-inflammatory, anticancer, antiviral, and antibacterial nature. In this review we have summarized that how curcumin and its analogues inhibit the infection and replication of viral genes and prevent multiplicity of HIV. They are inhibitors of HIV protease and integrase. Curcumin also inhibits Tat transactivation of the HIV1-LTR genome, inflammatory molecules (interleukins, TNF-α, NF-κB, COX-2) and HIV associated various kinases including tyrosine kinase, PAK1, MAPK, PKC, cdk and others. In addition, curcumin enhances the effect of conventional therapeutic drugs and minimizes their side effects.

  1. Structure and gelation properties of casein micelles doped with curcumin under acidic conditions.

    PubMed

    Khanji, Aya N; Michaux, Florentin; Jasniewski, Jordane; Petit, Jeremy; Lahimer, Emna; Cherif, Mohamed; Salameh, Dominique; Rizk, Toufic; Banon, Sylvie

    2015-12-01

    In this study, the ability of micellar casein (MC) to interact with curcumin during acidification and to produce acid gel was investigated. Steady-state fluorescence spectroscopy of curcumin variation and fluorescence quenching of caseins upon binding with curcumin molecules were evidenced. Increasing the temperature from 20 to 35 °C enhanced MC-curcumin interactions as reflected by the increase in the binding constant from 0.6 ± 0.3 × 10(4) to 6.6 ± 0.6 × 10(4) M(-1). From changes in entropy, enthalpy and Gibbs free energy, hydrophobic interactions were proposed as major binding forces. Static fluorescence MC quenching was demonstrated for the MC-curcumin complex during acidification. From pH 7.4 to pH 5.0, the binding site numbers varied in the range from 1.25 ± 0.05 to 1.49 ± 0.05 and the binding constant kb varied from 3.9 ± 0.4 × 10(4) to 7.5 ± 0.7 × 10(4) M(-1). Small angle X-ray scattering profiles demonstrated that the MC internal structure was unchanged upon curcumin binding. The ζ-potential value of curcumin-doped MC indicated that curcumin did not modify the global charge of MC particles. Acid gelation studied by oscillation rheology and static multiple light scattering at 20 and 35 °C led to a similar behavior for native and curcumin-doped MC suspensions. For the first time, it was demonstrated that the colloidal and functional properties of MC were unchanged when doped with curcumin during acidification.

  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. Discovery of curcumin, a component of golden spice, and its miraculous biological activities.

    PubMed

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

    2012-03-01

    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 signalling 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 signalling molecules, it has been reported to possess pleiotropic activities. First demonstrated to have antibacterial activity in 1949, curcumin has since been shown to have anti-inflammatory, anti-oxidant, pro-apoptotic, chemopreventive, chemotherapeutic, antiproliferative, wound healing, antinociceptive, antiparasitic and antimalarial properties as well. Animal studies have suggested that curcumin may be active against a wide range of human diseases, including diabetes, obesity, neurological 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 the safety and efficacy of curcumin 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 US, Thailand, China, Korea, Turkey, South Africa, Nepal and Pakistan. Although inexpensive, apparently well tolerated and potentially active, curcumin has not been approved for the treatment of any human disease. 4. In the present article, we discuss the discovery and key biological activities of curcumin, with a particular emphasis on its activities at the molecular and cellular levels, as well as in animals and humans. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell

  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. 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

  9. The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: A recent update.

    PubMed

    Ghosh, Shatadal; Banerjee, Sharmistha; Sil, Parames C

    2015-09-01

    The concept of using phytochemicals has ushered in a new revolution in pharmaceuticals. Naturally occurring polyphenols (like curcumin, morin, resveratrol, etc.) have gained importance because of their minimal side effects, low cost and abundance. Curcumin (diferuloylmethane) is a component of turmeric isolated from the rhizome of Curcuma longa. Research for more than two decades has revealed the pleiotropic nature of the biological effects of this molecule. More than 7000 published articles have shed light on the various aspects of curcumin including its antioxidant, hypoglycemic, anti-inflammatory and anti-cancer activities. Apart from these well-known activities, this natural polyphenolic compound also exerts its beneficial effects by modulating different signalling molecules including transcription factors, chemokines, cytokines, tumour suppressor genes, adhesion molecules, microRNAs, etc. Oxidative stress and inflammation play a pivotal role in various diseases like diabetes, cancer, arthritis, Alzheimer's disease and cardiovascular diseases. Curcumin, therefore, could be a therapeutic option for the treatment of these diseases, provided limitations in its oral bioavailability can be overcome. The current review provides an updated overview of the metabolism and mechanism of action of curcumin in various organ pathophysiologies. The review also discusses the potential for multifunctional therapeutic application of curcumin and its recent progress in clinical biology. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. Protective effects of curcumin on acute gentamicin-induced nephrotoxicity in rats.

    PubMed

    He, Liyu; Peng, Xiaofei; Zhu, Jiefu; Liu, Guoyong; Chen, Xian; Tang, Chengyuan; Liu, Hong; Liu, Fuyou; Peng, Youming

    2015-04-01

    Gentamicin-induced nephrotoxicity is one of the most common causes of acute kidney injury (AKI). The phenotypic alterations that contribute to acute kidney injury include inflammatory response and oxidative stress. Curcumin has a wide range biological functions, especially as an antioxidant. This study was designed to evaluate the renoprotective effects of curcumin treatment in gentamicin-induced AKI. Gentamicin-induced AKI was established in female Sprague-Dawley rats. Rats were treated with curcumin (100 mg/kg body mass) by intragastric administration, once daily, followed with an intraperitoneal injection of gentamicin sulfate solution at a dose of 80 mg/kg body mass for 8 consecutive days. At days 3 and 8, the rats were sacrificed, and the kidneys and blood samples were collected for further analysis. The animals treated with gentamicin showed marked deterioration of renal function, together with higher levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) in the plasma as compared with the controls. Animals that underwent intermittent treatment with curcumin exhibited significant improvements in renal functional parameters. We also observed that treatment with curcumin significantly attenuated renal tubular damage, apoptosis, and oxidative stress. Curcumin treatment exerted anti-apoptosis and anti-oxidative effects by up-regulating Nrf2/HO-1 and Sirt1 expression. Our data clearly demonstrate that curcumin protects kidney from gentamicin-induced AKI via the amelioration of oxidative stress and apoptosis of renal tubular cells, thus providing hope for the amelioration of gentamicin-induced nephrotoxicity.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. Curcumin as a putative antidepressant.

    PubMed

    Seo, Ho-Jun; Wang, Sheng-Min; Han, Changsu; Lee, Soo-Jung; Patkar, Ashwin A; Masand, Prakash S; Pae, Chi-Un

    2015-03-01

    Due to inadequate efficacy of antidepressants, various new chemical entities and agents of natural origin have been tested for therapeutic efficacy both alone and to augment existing antidepressants, producing varied clinical results. This article summarizes the basic properties of curcumin and its mechanisms of action, with specific emphasis on the etiopathogenesis of depression, preclinical and current clinical evidence, and future research directions, to better understand the possible role of curcumin in treating depression. Curcumin may have antidepressant activities with diverse mechanisms of action involving primarily neurotransmitters, transcription pathways, neurogenesis, the hypothalamic-pituitary-adrenal axis and inflammatory and immune pathways, as demonstrated in various animal and human studies. Current published randomized clinical trials suggest a small, non-significant benefit of curcumin for major depression. More adequately-powered and methodologically improved studies are mandatory.

  20. 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.

  1. 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.

  2. 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.

  3. Curcumin and chronic kidney disease (CKD): major mode of action through stimulating endogenous intestinal alkaline phosphatase.

    PubMed

    Ghosh, Siddhartha S; Gehr, Todd W B; Ghosh, Shobha

    2014-12-02

    Curcumin, an active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa), has significant anti-inflammatory properties. Chronic kidney disease (CKD), an inflammatory disease, can lead to end stage renal disease resulting in dialysis and transplant. Furthermore, it is frequently associated with other inflammatory disease such as diabetes and cardiovascular disorders. This review will focus on the clinically relevant inflammatory molecules that play a role in CKD and associated diseases. Various enzymes, transcription factors, growth factors modulate production and action of inflammatory molecules; curcumin can blunt the generation and action of these inflammatory molecules and ameliorate CKD as well as associated inflammatory disorders. Recent studies have shown that increased intestinal permeability results in the leakage of pro-inflammatory molecules (cytokines and lipopolysaccharides) from gut into the circulation in diseases such as CKD, diabetes and atherosclerosis. This change in intestinal permeability is due to decreased expression of tight junction proteins and intestinal alkaline phosphatase (IAP). Curcumin increases the expression of IAP and tight junction proteins and corrects gut permeability. This action reduces the levels of circulatory inflammatory biomolecules. This effect of curcumin on intestine can explain why, despite poor bioavailability, curcumin has potential anti-inflammatory effects in vivo and beneficial effects on CKD.

  4. 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).

  5. 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.

  6. 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

  7. Inhibition of IL-6 Signaling Pathway by Curcumin in Uterine Decidual Cells

    PubMed Central

    Devi, Y. Sangeeta; DeVine, Majesta; DeKuiper, Justin; Ferguson, Susan; Fazleabas, Asgerally T.

    2015-01-01

    IL-6 is a multifunctional pro-inflammatory cytokine and has been implicated in many gestational disorders including preterm birth. Currently, there are no appropriate therapeutic interventions available to circumvent inflammatory-mediated gestational disorders. Therefore, the goal of this study was to identify a safe and effective pharmacological compound to counterbalance inflammatory responses in the uterus. Curcumin, a naturally-occuring polyphenolic compound, has been widely used in alternative medicine to treat inflammatory diseases. However, the anti-inflammatory effect of curcumin has not been explored in uterine decidual cells, a major source of IL-6. Therefore, we examined the effect of curcumin on IL-6 expression using two types of uterine decidual cells 1) HuF cells, primary human fibroblast cells obtained from the decidua parietalis; 2) UIII cells, a rodent non-transformed decidual cell line. Curcumin treatment completely abrogated the expression of IL-1β-induced IL-6 in these cells. Curcumin also strongly inhibited the expression of gp130, a critical molecule in IL-6 signaling, whereas expression of IL-6R and sIL-6R was not affected. Curcumin also inhibited phosphorylation and nuclear localization of STAT3, a well-known downstream mediator of IL-6 signaling. Furthermore, curcumin attenuated IL-1β-induced IL-6 promoter reporter activity suggesting transcriptional regulation. To further understand whether NF-ҡB is involved in this inhibition, we examined the effect of curcumin on the expression of p50 and p65 subunits of NF-ҡB in decidual cells. Expression of IL-1β-induced p50 mRNA was repressed by curcumin while p65 mRNA was not affected. However, curcumin treatment dramatically inhibited both p50 and p65 protein levels and prevented its nuclear localization. This effect is at least partly mediated through the deactivation of IKK, since IL-1β-induced IKKα/β phosphorylation is decreased upon curcumin treatment. Our results not only revealed

  8. 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.

  9. Antibacterial Activity of Curcumin Against Periodontopathic Bacteria.

    PubMed

    Izui, Shusuke; Sekine, Shinichi; Maeda, Kazuhiko; Kuboniwa, Masae; Takada, Akihiko; Amano, Atsuo; Nagata, Hideki

    2016-01-01

    Curcumin is a polyphenol extracted from root of turmeric and known to possess multifunctional properties, including antibacterial activity. Although previous studies have investigated the effects of curcumin on microorganisms, available knowledge on the effects of curcumin on periodontopathic bacteria is still limited. In this study, the antibacterial effect of curcumin on periodontopathic bacteria is investigated, particularly Porphyromonas gingivalis. Representative periodontopathic bacteria were cultured in media with and without various curcumin concentrations, and the optical density at 600 nm was measured for 60 hours. The inhibitory effect of curcumin on P. gingivalis Arg- and Lys-specific proteinase (RGP and KGP, respectively) activities were assessed using spectrofluorophotometric assay. Analysis of biofilm formation by P. gingivalis with or without Streptococcus gordonii was conducted using confocal laser-scanning microscopy (CLSM). Curcumin inhibited the growth of P. gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Treponema denticola in a dose-dependent manner. Bacterial growth was suppressed almost completely at very low concentrations of curcumin. Conversely, 100 μg/mL curcumin did not suppress the growth of Aggregatibacter actinomycetemcomitans. It also demonstrated inhibitory effects against RGP and KGP activities in a dose-dependent manner. CLSM revealed that curcumin suppressed P. gingivalis homotypic and P. gingivalis-S. gordonii heterotypic biofilm formation in a dose-dependent manner. A concentration of 20 μg/mL curcumin inhibited these P. gingivalis biofilm formations by >80%. Curcumin possesses antibacterial activity against periodontopathic bacteria and may be a potent agent for preventing periodontal diseases.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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".

  15. 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

  16. Curcumin ameliorates insulin signalling pathway in brain of Alzheimer's disease transgenic mice.

    PubMed

    Feng, Hui-Li; Dang, Hui-Zi; Fan, Hui; Chen, Xiao-Pei; Rao, Ying-Xue; Ren, Ying; Yang, Jin-Duo; Shi, Jing; Wang, Peng-Wen; Tian, Jin-Zhou

    2016-12-01

    Deficits in glucose, impaired insulin signalling and brain insulin resistance are common in the pathogenesis of Alzheimer's disease (AD); therefore, some scholars even called AD type 3 diabetes mellitus. Curcumin can reduce the amyloid pathology in AD. Moreover, it is a well-known fact that curcumin has anti-oxidant and anti-inflammatory properties. However, whether or not curcumin could regulate the insulin signal transduction pathway in AD remains unclear. In this study, we used APPswe/PS1dE9 double transgenic mice as the AD model to investigate the mechanisms and the effects of curcumin on AD. Immunohistochemical (IHC) staining and a western blot analysis were used to test the major proteins in the insulin signal transduction pathway. After the administration of curcumin for 6 months, the results showed that the expression of an insulin receptor (InR) and insulin receptor substrate (IRS)-1 decreased in the hippocampal CA1 area of the APPswe/PS1dE9 double transgenic mice, while the expression of phosphatidylinositol-3 kinase (PI3K), phosphorylated PI3K (p-PI3K), serine-threonine kinase (AKT) and phosphorylated AKT (p-AKT) increased. Among the curcumin groups, the medium-dose group was the most effective one. Thus, we believe that curcumin may be a potential therapeutic agent that can regulate the critical molecules in brain insulin signalling pathways. Furthermore, curcumin could be adopted as one of the AD treatments to improve a patient's learning and memory ability.

  17. Research on curcumin: A meta-analysis of potentially malignant disorders.

    PubMed

    Ara, Syeda Arshiya; Mudda, Jayashree A; Lingappa, Ashok; Rao, Purushottam

    2016-01-01

    Turmeric has been described in ayurveda, and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, 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. Various preclinical, clinical, and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic, as a mediator of chemoresistance, chemopreventive, and as a therapeutic agent. Thus, curcumin a spice once relegated to the kitchen shelf has moved into the clinic and may prove to be "Curecumin." Methodology and Objectives: The focus of this publication is to provide research on curcumin with scientific publications on curcumin indexed in PubMed, Google J-Gate including systematic reviews, randomized controlled trials (RCT's), observational studies, or case series reports for various potentially malignant disorders (PMD's) with special attention to studies on oral submucous fibrosis. This research will be valuable in terms of identifying opportunities to provide recommendations for future research, in terms of the populations to research, the types of interventions needed, the types of outcomes to be measured, the study designs needed, to initiate a pathway for a low-cost research plan for future clinical trials in this field with an emphasis on conducting studies in regions of the world where PMD's are prevalent. There is a lacunae for scientific review of curcumin for PMDs specially on OSMF. Appropriate therapeutic interventions are needed for the initial, intermediate, and advanced stages of the disease. High-quality RCTs should be initiated.

  18. 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.

  19. 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

  20. 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.

  1. Effects of curcumin and curcumin analogues on TRP channels.

    PubMed

    Nalli, Marianna; Ortar, Giorgio; Schiano Moriello, Aniello; Di Marzo, Vincenzo; De Petrocellis, Luciano

    2017-10-01

    A series of 33 curcumin analogues was synthesized and tested on TRPA1, TRPM8, and TRPV1 channels. Twenty of them acted as good modulators of TRPA1 channels. None was able to significantly activate TRPM8 channels, while curcumin itself and six curcuminoids belonging to the 1,3-dicarbonyl and acyclic series behaved as 'true' antagonists with IC50 values<5μM. Only few curcuminoids were able to modulate TRPV1 channels with EC50 and IC50 values ranging from 3.4 and 6.0μM. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Investigating the use of curcumin-loaded electrospun filaments for soft tissue repair applications.

    PubMed

    Mouthuy, Pierre-Alexis; Somogyi Škoc, Maja; Čipak Gašparović, Ana; Milković, Lidija; Carr, Andrew J; Žarković, Neven

    2017-01-01

    Electrospun filaments represent a new generation of medical textiles with promising applications in soft tissue repair. A potential strategy to improve their design is to combine them with bioactive molecules. Curcumin, a natural compound found in turmeric, is particularly attractive for its antioxidant, anti-inflammatory, and antimicrobial properties. However, investigating the range of relevant doses of curcumin in materials designed for tissue regeneration has remained limited. In this paper, a wide range of curcumin concentrations was explored and the potential of the resulting materials for soft tissue repair applications was assessed. Polydioxanone (PDO) filaments were prepared with various amounts of curcumin: 0%, 0.001%, 0.01%, 0.1%, 1%, and 10% (weight to weight ratio). The results from the present study showed that, at low doses (≤0.1%), the addition of curcumin has no influence on the spinning process or on the physicochemical properties of the filaments, whereas higher doses lead to smaller fiber diameters and improved mechanical properties. Moreover, filaments with 0.001% and 0.01% curcumin stimulate the metabolic activity and proliferation of normal human dermal fibroblasts (NHDFs) compared with the no-filament control. However, this stimulation is not significant when compared to the control filaments (0%). Highly dosed filaments induce either the inhibition of proliferation (with 1%) or cell apoptosis (with 10%) as a result of the concentrations of curcumin found in the medium (9 and 32 μM, respectively), which are near or above the known toxicity threshold of curcumin (~10 μM). Moreover, filaments with 10% curcumin increase the catalase activity and glutathione content in NHDFs, indicating an increased production of reactive oxygen species resulting from the large concentration of curcumin. Overall, this study suggested that PDO electrospun filaments loaded with low amounts of curcumin are more promising compared with higher concentrations for

  3. Investigating the use of curcumin-loaded electrospun filaments for soft tissue repair applications

    PubMed Central

    Mouthuy, Pierre-Alexis; Somogyi Škoc, Maja; Čipak Gašparović, Ana; Milković, Lidija; Carr, Andrew J; Žarković, Neven

    2017-01-01

    Electrospun filaments represent a new generation of medical textiles with promising applications in soft tissue repair. A potential strategy to improve their design is to combine them with bioactive molecules. Curcumin, a natural compound found in turmeric, is particularly attractive for its antioxidant, anti-inflammatory, and antimicrobial properties. However, investigating the range of relevant doses of curcumin in materials designed for tissue regeneration has remained limited. In this paper, a wide range of curcumin concentrations was explored and the potential of the resulting materials for soft tissue repair applications was assessed. Polydioxanone (PDO) filaments were prepared with various amounts of curcumin: 0%, 0.001%, 0.01%, 0.1%, 1%, and 10% (weight to weight ratio). The results from the present study showed that, at low doses (≤0.1%), the addition of curcumin has no influence on the spinning process or on the physicochemical properties of the filaments, whereas higher doses lead to smaller fiber diameters and improved mechanical properties. Moreover, filaments with 0.001% and 0.01% curcumin stimulate the metabolic activity and proliferation of normal human dermal fibroblasts (NHDFs) compared with the no-filament control. However, this stimulation is not significant when compared to the control filaments (0%). Highly dosed filaments induce either the inhibition of proliferation (with 1%) or cell apoptosis (with 10%) as a result of the concentrations of curcumin found in the medium (9 and 32 μM, respectively), which are near or above the known toxicity threshold of curcumin (~10 μM). Moreover, filaments with 10% curcumin increase the catalase activity and glutathione content in NHDFs, indicating an increased production of reactive oxygen species resulting from the large concentration of curcumin. Overall, this study suggested that PDO electrospun filaments loaded with low amounts of curcumin are more promising compared with higher concentrations for

  4. Curcumin-ER Prolonged Subcutaneous Delivery for the Treatment of Non-Small Cell Lung Cancer.

    PubMed

    Ranjan, Amalendu P; Mukerjee, Anindita; Gdowski, Andrew; Helson, Lawrence; Bouchard, Annie; Majeed, Muhammed; Vishwanatha, Jamboor K

    2016-04-01

    Non-small-cell lung cancer therapy is a challenge due to poor prognosis and low survival rate. There is an acute need for advanced therapies having higher drug efficacy, low immunogenicity and fewer side effects which will markedly improve patient compliance and quality of life of cancer patients. The purpose of this study was to develop a novel hybrid curcumin nanoformulation (Curcumin-ER) and evaluate the therapeutic efficacy of this formulation on a non-small cell lung cancer xenograft model. Use of curcumin, a natural anticancer agent, is majorly limited due to its poor aqueous solubility and hence it's low systemic bioavailability. In this paper, we carried out the nanoformulation of Curcumin-ER, optimized the formulation process and determined the anticancer effects of Curcumin-ER against human A549 non-small cell lung cancer using in vitro and in vivo studies. Xenograft tumors in nude mice were treated with 20 mg/kg subcutaneous injection of Curcumin-ER and liposomal curcumin (Lipocurc) twice a week for seven weeks. Results showed that tumor growth was suppressed by 52.1% by Curcumin-ER treatment and only 32.2% by Lipocurc compared to controls. Tumor sections were isolated from murine xenografts and histology and immunohistochemistry was performed. A decrease in expression of NFκB-p65 subunit and proliferation marker, Ki-67 was observed in treated tumors. In addition, a potent anti-angiogenic effect, characterized by reduced expression of annexin A2 protein, was observed in treated tumors. These results establish the effectiveness of Curcumin-ER in regressing human non-small cell lung cancer growth in the xenograft model using subcutaneous route of administration. The therapeutic efficacy of Curcumin-ER highlights the potential of this hybrid nanoformulation in treating patients with non-small cell lung cancer.

  5. Curcumin blocks brain tumor formation.

    PubMed

    Purkayastha, Sudarshana; Berliner, Alexandra; Fernando, Suraj Shawn; Ranasinghe, Buddima; Ray, Indrani; Tariq, Hussnain; Banerjee, Probal

    2009-04-17

    Turmeric, an essential ingredient of culinary preparations of Southeast Asia, contains a major polyphenolic compound, named curcumin or diferuloylmethane, which eliminates cancer cells derived from a variety of peripheral tissues. Although in vitro experiments have addressed its anti-tumor property, no in vivo studies have explored its anti-cancer activity in the brain. Oral delivery of this food component has been less effective because of its low solubility in water.We show that a soluble formulation of curcumin crosses the blood–brain barrier but does not suppress normal brain cell viability. Furthermore, tail vein injection, or more effectively, intracerebral injection through a cannula, blocks brain tumor formation in mice that had already received an intracerebral bolus of mouse melanoma cells (B16F10).While exploring the mechanism of its action in vitro we observed that the solubilized curcumin causes activation of proapoptotic enzymes caspase 3/7 in human oligodendroglioma (HOG) and lung carcinoma (A549) cells, and mouse tumor cells N18(neuroblastoma), GL261 (glioma), and B16F10. A simultaneous decrease in cell viability is also revealed by MTT [3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide]assays. Further examination of the B16F10 cells showed that curcumin effectively suppresses Cyclin D1, P-NF-kB, BclXL, P-Akt, and VEGF, which explains its efficacy in blocking proliferation, survival, and invasion of the B16F10 cells in the brain. Taken together,solubilized curcumin effectively blocks brain tumor formation and also eliminates brain tumor cells. Therefore, judicious application of such injectable formulations of curcumin could be developed into a safe therapeutic strategy for treating brain tumors.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Epigenetic impact of curcumin on stroke prevention.

    PubMed

    Kalani, Anuradha; Kamat, Pradip K; Kalani, Komal; Tyagi, Neetu

    2015-04-01

    The epigenetic impact of curcumin in stroke and neurodegenerative disorders is curiosity-arousing. It is derived from Curcuma longa (spice), possesses anti-oxidative, anti-inflammatory, anti-lipidemic, neuro-protective and recently shown to exhibit epigenetic modulatory properties. Epigenetic studies include DNA methylation, histone modifications and RNA-based mechanisms which regulate gene expression without altering nucleotide sequences. Curcumin has been shown to affect cancer by altering epigenetic changes but its role as an epigenetic agent in cerebral stroke has not been much explored. Although curcumin possesses remarkable medicinal properties, the bioavailability of curcumin has limited its success in epigenetic studies and clinical trials. The present review is therefore designed to look into epigenetic mechanisms that could be induced with curcumin during stroke, along with its molecular designing with different moieties that may increase its bioavailability. Curcumin has been shown to be encapsulated in exosomes, nano-vesicles (<200 nm), thereby showing its therapeutic effects in brain diseases. Curcumin delivered through nanoparticles has been shown to be neuroregenerative but the use of nanoparticles in brain has limitations. Hence, curcumin-encapsulated exosomes along with curcumin-primed exosomes (exosomes released by curcumin-treated cells) are much needed to be explored to broadly look into their use as a novel therapy for stroke.

  12. Inhibition of Enveloped Viruses Infectivity by Curcumin

    PubMed Central

    Wen, Hsiao-Wei; Ou, Jun-Lin; Chiou, Shyan-Song; Chen, Jo-Mei; Wong, Min-Liang; Hsu, Wei-Li

    2013-01-01

    Curcumin, a natural compound and ingredient in curry, has antiinflammatory, antioxidant, and anticarcinogenic properties. Previously, we reported that curcumin abrogated influenza virus infectivity by inhibiting hemagglutination (HA) activity. This study demonstrates a novel mechanism by which curcumin inhibits the infectivity of enveloped viruses. In all analyzed enveloped viruses, including the influenza virus, curcumin inhibited plaque formation. In contrast, the nonenveloped enterovirus 71 remained unaffected by curcumin treatment. We evaluated the effects of curcumin on the membrane structure using fluorescent dye (sulforhodamine B; SRB)-containing liposomes that mimic the viral envelope. Curcumin treatment induced the leakage of SRB from these liposomes and the addition of the influenza virus reduced the leakage, indicating that curcumin disrupts the integrity of the membranes of viral envelopes and of liposomes. When testing liposomes of various diameters, we detected higher levels of SRB leakage from the smaller-sized liposomes than from the larger liposomes. Interestingly, the curcumin concentration required to reduce plaque formation was lower for the influenza virus (approximately 100 nm in diameter) than for the pseudorabies virus (approximately 180 nm) and the vaccinia virus (roughly 335 × 200 × 200 nm). These data provide insights on the molecular antiviral mechanisms of curcumin and its potential use as an antiviral agent for enveloped viruses. PMID:23658730

  13. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. 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.

  15. 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

  16. 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).

  17. 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.

  18. A Comprehensive Review on Pharmacotherapeutics of Three Phytochemicals, Curcumin, Quercetin, and Allicin, in the Treatment of Gastric Cancer.

    PubMed

    Haghi, Atousa; Azimi, Haniye; Rahimi, Roja

    2017-08-22

    Gastric cancer is one of the most common causes of cancer-related death worldwide. Medicinal plants are one of the main sources for discovery of new pharmacological agents especially for treatment of cancers. The aim of the present study is to review pharmacotherapeutic aspects of three mostly studied phytochemicals including curcumin, quercetin, and allicin for management of gastric cancer. Scopus, PubMed, Web of Science, and Google Scholar were searched for the effects of curcumin, quercetin, allicin, and their analogs in gastric cancer. Data were collected up to November 2015. The search terms were "curcumin," "quercetin," "allicin," and "gastric cancer" or "cancer." Curcumin demonstrated anti-angiogenic, anti-proliferative, anti-metastatic, pro-apoptotic, and anti-helicobacter activities. Quercetin inhibited cell growth and induced apoptosis, necrosis, and autophagy as well as anti-Helicobacter activity. Allicin showed apoptotic and anti-Helicobacter properties. All three natural compounds had low bioavailability. Although preclinical studies demonstrated the activity of curcumin, quercetin, and allicin in gastric cancer, clinical trials are needed to confirm their effectiveness. Applying their possible synergistic action and suitable drug delivery system in clinical studies can be also an attractive approach with the purpose of finding new extremely efficient anti-gastric cancer agents. Curcumin, quercetin, and allicin seem to be good candidates for management of gastric cancer through their pro-apoptotic, anti-proliferative, and anti-helicobacter activities.

  19. 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.

  20. 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

  1. The Essential Medicinal Chemistry of Curcumin.

    PubMed

    Nelson, Kathryn M; Dahlin, Jayme L; Bisson, Jonathan; Graham, James; Pauli, Guido F; Walters, Michael A

    2017-03-09

    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.

  2. 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

  3. Small molecule tolfenamic acid and dietary spice curcumin treatment enhances antiproliferative effect in pancreatic cancer cells via suppressing Sp1, disrupting NF-kB translocation to nucleus and cell cycle phase distribution.

    PubMed

    Basha, Riyaz; Connelly, Sarah F; Sankpal, Umesh T; Nagaraju, Ganji Purnachandra; Patel, Hassaan; Vishwanatha, Jamboor K; Shelake, Sagar; Tabor-Simecka, Leslie; Shoji, Mamoru; Simecka, Jerry W; El-Rayes, Bassel

    2016-05-01

    Combination of dietary/herbal spice curcumin (Cur) and COX inhibitors has been tested for improving therapeutic efficacy in pancreatic cancer (PC). The objective of this study was to identify agent with low toxicity and COX-independent mechanism to induce PC cell growth inhibition when used along with Cur. Anticancer NSAID, tolfenamic acid (TA) and Cur combination were evaluated using PC cell lines. L3.6pl and MIA PaCa-2 cells were treated with Cur (5-25μM) or TA (25-100μM) or combination of Cur (7.5μM) and TA (50μM). Cell viability was measured at 24-72h posttreatment using CellTiter-Glo kit. While both agents showed a steady/consistent effect, Cur+TA caused higher growth inhibition. Antiproliferative effect was compared with COX inhibitors, Ibuprofen and Celebrex. Cardiotoxicity was assessed using cordiomyocytes (H9C2). The expression of Sp proteins, survivin and apoptotic markers (western blot), caspase 3/7 (caspase-Glo kit), Annexin-V staining (flow cytometry), reactive oxygen species (ROS) and cell cycle phase distribution (flow cytometry) was measured. Cells were treated with TNF-α, and NF-kB translocation from cytoplasm to nucleus was evaluated (immunofluorescence). When compared to individual agents, combination of Cur+TA caused significant increase in apoptotic markers, ROS levels and inhibited NF-kB translocation to nucleus. TA caused cell cycle arrest in G0/G1, and the combination treatment showed mostly DNA synthesis phase arrest. These results suggest that combination of Cur+TA is less toxic and effectively enhance the therapeutic efficacy in PC cells via COX-independent mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Small molecule tolfenamic acid and dietary spice curcumin treatment enhances anti-proliferative effect in pancreatic cancer cells via suppressing Sp1, disrupting NF-kB translocation to nucleus and cell cycle phase distribution

    PubMed Central

    Basha, Riyaz; Connelly, Sarah F.; Sankpal, Umesh T.; Nagaraju, Ganji Purnachandra; Patel, Hassaan; Vishwanatha, Jamboor K.; Shelake, Sagar; Tabor-Simecka, Leslie; Shoji, Mamoru; Simecka, Jerry W.; El-Rayes, Bassel

    2016-01-01

    Combination of dietary/herbal spice curcumin (Cur) and COX inhibitors has been tested for improving therapeutic efficacy in pancreatic cancer (PC). The objective of this study was to identify agent with low toxicity and COX-independent mechanism to induce PC cell growth inhibition when used along with Cur. Anti-cancer NSAID, Tolfenamic acid (TA) and Cur combination was evaluated using PC cell lines. L3.6pl and MIA PaCa-2 cells were treated with Cur (5–25 μM) or TA (25–100 μM) or combination of Cur (7.5 μM) and TA (50 μM). Cell viability was measured at 24–72 h post-treatment using CellTiter-Glo kit. While both agents showed a steady/consistent effect, Cur+TA caused higher growth inhibition. Anti-proliferative effect was compared with COX inhibitors, Ibuprofen and Celebrex. Cardiotoxicity was assessed using cordiomyocytes (H9C2). The expression of Sp proteins, survivin, and apoptotic markers (Western blot), caspase 3/7 (caspase-Glo kit), Annexin-V staining (flow cytometry), reactive oxygen species (ROS) and cell cycle phase distribution (flow cytometry) were measured. Cells were treated with TNF-α and NF-kB translocation from cytoplasm to nucleus was evaluated (immunofluorescence). When compared to individual agents, combination of Cur+TA caused significant increase in apoptotic markers, ROS levels and augmented NF-kB translocation to nucleus. TA caused cell cycle arrest in G0/G1 and the combination treatment showed mostly DNA synthesis phase arrest. These results suggest that combination of Cur+TA is less toxic and effectively enhance the therapeutic efficacy in PC cells via COX-independent mechanisms. PMID:27133426

  5. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26644941

  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. Curcumin suppresses ovalbumin-induced allergic conjunctivitis

    PubMed Central

    Chung, So-Hyang; Choi, Seong Hyun; Choi, Jin A.; Chuck, Roy S.

    2012-01-01

    Purpose Allergic conjunctivitis (AC) from an allergen-driven T helper 2 (Th2) response is characterized by conjunctival eosinophilic infiltration. Because curcumin has shown anti-allergic activity in an asthma and contact dermatitis laboratory models, we examined whether administration of curcumin could affect the severity of AC and modify the immune response to ovalbumin (OVA) allergen in an experimental AC model. Methods Mice were challenged with two doses of topical OVA via the conjunctival sac after systemic sensitization with OVA in aluminum hydroxide (ALUM). Curcumin was administered 1 h before OVA challenge. Several indicators for allergy such as serum immunoglubulin E (IgE) antibodies production, eosinophil infiltration into the conjunctiva and Th2 cytokine production were evaluated in mice with or without curcumin treatment. Results Mice challenged with OVA via the conjunctival sac following systemic sensitization with OVA in ALUM had severe AC. Curcumin administration markedly suppressed IgE-mediated and eosinophil-dependent conjunctival inflammation. In addition, mice administered curcumin had less interleukin-4 (IL-4) and interleukin-5 (IL-5) (Th2 type cytokine) production in conjunctiva, spleen, and cervical lymph nodes than mice in the non-curcumin-administered group. OVA challenge resulted in activation of the production of inducible nitric oxide (iNOS), and curcumin treatment inhibited iNOS production in the conjunctiva. Conclusions We believe our findings are the first to demonstrate that curcumin treatment suppresses allergic conjunctival inflammation in an experimental AC model. PMID:22876123

  10. 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.

  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. 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.

  13. 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.

  14. Curcumin bioconjugates: studies on structure-activity relationship and antibacterial properties against clinically isolated strains.

    PubMed

    Rai, Diwakar; Kumari, Garima; Singh, Anuradha; Singh, Ramendra K

    2013-11-01

    Curcumin bioconjugates, with folic acid, fatty acids and dipeptide, have shown much lower MIC than curcumin against clinically isolated Gram-positive, S.viridians, and Gram-negative bacterial strains, E. coli, P. mirabilis and K. pneumoniae. Polynomial regression analysis was performed to establish a correlation between lipophilicity (logP) and antibacterial activity (pMIC), which showed the efficacy of these molecules against the bacterial strains in the following order: E. coli > S viridans = K. pneumoniae > P. mirabilis. The regression coefficients (R(2) = 0.62 to 0.91) derived for each strain were correlated significantly and led to a conclusion that it was the amphiphilic nature that governed the antibacterial activity. Thus, the bioconjugate 2, having folic acid attached at active methylene site of curcumin with free phenolic hydroxyls, showed the best result.

  15. 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

  16. 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.

  17. Interaction of curcumin with phosphocasein micelles processed or not by dynamic high-pressure.

    PubMed

    Benzaria, Amal; Maresca, Marc; Taieb, Nadira; Dumay, Eliane

    2013-06-15

    The binding of curcumin to native-like phosphocaseins (PC) dispersed in simulated milk ultrafiltrate at pH 6.6 was assessed by fluorescence spectrophotometry. Curcumin binds to native-like PC micelles with ∼1 binding site per casein molecule, and a binding constant of 0.6-5.6 × 10(4)M(-1). Dynamic high pressure (or ultra-high pressure homogenisation, UHPH) at 200 MPa did not affect the binding parameters of curcumin to processed PC. UHPH-processing of PC dispersions at 300 MPa was followed by a slight but significant (p=0.05) increase in the binding constant of curcumin to processed PC, which may result from the significant UHPH-induced dissociation of initial PC micelles into neo-micelles of smaller sizes, and from the corresponding 1.5-2-fold increase in micelle surface area. PC-curcumin complexes were resistant to pepsin but were degraded by pancreatin, providing the possibility of a spatiotemporally controlled release and protection of bound biomolecules. UHPH-processed PC did not induce TC7-cell damage or major inflammation as assessed by LDH release or IL-8 secretion, respectively, compared with native-like PC. PC micelles could provide a valuable submicron system to vectorise drugs and nutrients. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. 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.

  19. Curcumin: A new candidate for melanoma therapy?

    PubMed

    Mirzaei, Hamed; Naseri, Gholamreza; Rezaee, Ramin; Mohammadi, Mohsen; Banikazemi, Zarrin; Mirzaei, Hamid Reza; Salehi, Hossein; Peyvandi, Mostafa; Pawelek, John M; Sahebkar, Amirhossein

    2016-10-15

    Melanoma remains among the most lethal cancers and, in spite of great attempts that have been made to increase the life span of patients with metastatic disease, durable and complete remissions are rare. Plants and plant extracts have long been used to treat a variety of human conditions; however, in many cases, effective doses of herbal remedies are associated with serious adverse effects. Curcumin is a natural polyphenol that shows a variety of pharmacological activities including anti-cancer effects, and only minimal adverse effects have been reported for this phytochemical. The anti-cancer effects of curcumin are the result of its anti-angiogenic, pro-apoptotic and immunomodulatory properties. At the molecular and cellular level, curcumin can blunt epithelial-to-mesenchymal transition and affect many targets that are involved in melanoma initiation and progression (e.g., BCl2, MAPKS, p21 and some microRNAs). However, curcumin has a low oral bioavailability that may limit its maximal benefits. The emergence of tailored formulations of curcumin and new delivery systems such as nanoparticles, liposomes, micelles and phospholipid complexes has led to the enhancement of curcumin bioavailability. Although in vitro and in vivo studies have demonstrated that curcumin and its analogues can be used as novel therapeutic agents in melanoma, curcumin has not yet been tested against melanoma in clinical practice. In this review, we summarized reported anti-melanoma effects of curcumin as well as studies on new curcumin formulations and delivery systems that show increased bioavailability. Such tailored delivery systems could pave the way for enhancement of the anti-melanoma effects of curcumin. © 2016 UICC.

  20. 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.

  1. New Difluoro Knoevenagel Condensates of Curcumin, Their Schiff Bases and Copper Complexes as Proteasome Inhibitors and Apoptosis Inducers in Cancer Cells

    PubMed Central

    Padhye, Subhash; Yang, Huanjie; Jamadar, Abeda; Cui, Qiuzhi Cindy; Chavan, Deepak; Dominiak, Kristin; McKinney, Jaclyn; Banerjee, Sanjeev; Dou, Q. Ping; Sarkar, Fazlul H.

    2013-01-01

    Purpose Emerging evidence clearly suggests the potential chemopreventive and anti-tumor activity of a well known “natural agent” curcumin. However, studies have shown that curcumin is not readily bioavailable, and thus the tissue bioavailability of curcumin is also poor except for gastrointestinal track. Because of the potential biological activity of curcumin, many studies have attempted for making a better analog of cucumin that is equally effective or better with increased bioavailability, which was the purpose of our current study. Methods We have designed and synthesized new difluoro Knoevenagel condensates of curcumin and Schiff bases along with their copper (II) complexes and evaluated their biological activities with respect to the inhibitory effects on purified rabbit 26S proteasome, and growth inhibition and induction of apoptosis in colon and pancreatic cancer cell lines. Results All copper complexes possess distorted square planar geometries with 1:1 metal to ligand stoichiometry with reversible copper redox couple. The difluoro compound CDF exhibited inhibitory effects on purified rabbit 20S proteasome or cellular 26S proteasome, and caused both growth inhibition of cancer cell lines and induced apoptotic cell death in our preliminary assessment. Conclusion Our results suggest that our newly synthesized classes of curcumin analogs could be useful as chemopreventive and/or therapeutic agents against cancers. PMID:19421843

  2. The assignment of the normal modes of the BEDT-TTF electron-donor molecule using the infrared and Raman spectra of several isotopic analogs

    NASA Astrophysics Data System (ADS)

    Eldridge, J. E.; Homes, C. C.; Williams, Jack M.; Kini, A. M.; Wang, H. Hau

    1995-06-01

    Room-temperature infrared and Raman measurements on neutral bis(ethylenedithio) tetrathiafulvalene, abbreviated to BEDT-TTF, and four of its isotopic analogs are reported. The analogs are 13C(6) in which the central six carbon atoms are substituted with 13C; 13C(2) in which only the two central atoms are substituted and 34S(8) and d(8) in which all of the sulphur or all of the hydrogen atoms are substituted; respectively. The frequencies and frequency shifts of the Raman features and the infrared powder absorption features are measured. The polarized infrared reflectivity of a single crystal, and the intensities of the Raman features, help in assigning symmetries to certain resonances. By comparing these shifts to those calculated using a realistic valence force model the assigment of most of the in-plane fundamental intermolecular vibrational modes, and a few of the out-of-plane ethylene modes is achieved. The force constants are refined to produce excellent overall agreement between the measured and calculated frequencies and isotope shifts.

  3. 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.

  4. Turmeric (curcumin) remedies gastroprotective action.

    PubMed

    Yadav, Santosh Kumar; Sah, Ajit Kumar; Jha, Rajesh Kumar; Sah, Phoolgen; Shah, Dev Kumar

    2013-01-01

    The purpose of this review is to summarize the pertinent literature published in the present era regarding the antiulcerogenic property of curcumin against the pathological changes in response to ulcer effectors (Helicobacter pylori infection, chronic ingestion of non-steroidal anti-inflammatory drugs, and exogenous substances). The gastrointestinal problems caused by different etiologies was observed to be associated with the alterations of various physiologic parameters such as reactive oxygen species, nitric oxide synthase, lipid peroxidation, and secretion of excessive gastric acid. Gastrointestinal ulcer results probably due to imbalance between the aggressive and the defensive factors. In 80% of the cases, gastric ulcer is caused primarily due to the use of non-steroidal anti-inflammatory category of drug, 10% by H. pylori, and about 8-10% by the intake of very spicy and fast food. Although a number of antiulcer drugs and cytoprotectants are available, all these drugs have side effects and limitations. In the recent years a widespread search has been launched to identify new antiulcer drugs from synthetic and natural resources. An Indian dietary derivative (curcumin), a yellow pigment found in the rhizome of Curcuma longa, has been widely used for the treatment of several diseases. Epidemiologically, it was suggested that curcumin might reduce the risk of inflammatory disorders, such as cancer and ulcer. These biological effects are attributed to its anti-inflammatory and antioxidant activities. It can, therefore, be reported from the literature that curcumin PRevents gastrointestinal-induced ulcer and can be recommended as a novel drug for ulcer treatment.

  5. Simple analytical strategy for MALDI-TOF-MS and nanoUPLC-MS/MS: quantitating curcumin in food condiments and dietary supplements and screening of acrylamide-induced ROS protein indicators reduced by curcumin.

    PubMed

    Huang, Yu-Shu; Hsieh, Tusty-Jiuan; Lu, Chi-Yu

    2015-05-01

    Curcumin is the major active ingredient of turmeric and is widely used as a preservative, flavouring and colouring agent. Curcumin is a potent substance with several functions, including antioxidant, antitumor, anti-inflammatory, antimicrobial, antiparasitic, antimutagenic, chemopreventive and chemotherapeutic activities. Matrix-assisted laser desorption/ionisation coupled with time-of-flight mass spectrometry (MALDI-TOF-MS) has been used to analyse various molecules (including natural antioxidants). This study established an expeditious method that couples MALDI-TOF-MS with a simple dilution method to quantify curcumin in food condiments and dietary supplements. The linear range of curcumin detection ranged from 1 to 100 μg/mL. In further experiments, liver cells were treated with curcumin after exposure to acrylamide. Nano ultra performance liquid chromatographic system (nanoUPLC) coupled with tandem mass spectrometry (MS/MS) was used to evaluate the potential proteins and protein modifications induced by acrylamide. The results indicate that curcumin reduces the effects of reactive oxygen species induced by acrylamide. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. 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.

  7. Effects of curcumin on HDL functionality.

    PubMed

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

    2017-05-01

    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. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Curcumin as a wound healing agent.

    PubMed

    Akbik, Dania; Ghadiri, Maliheh; Chrzanowski, Wojciech; Rohanizadeh, Ramin

    2014-10-22

    Turmeric (Curcuma longa) is a popular Indian spice that has been used for centuries in herbal medicines for the treatment of a variety of ailments such as rheumatism, diabetic ulcers, anorexia, cough and sinusitis. Curcumin (diferuloylmethane) is the main curcuminoid present in turmeric and responsible for its yellow color. Curcumin has been shown to possess significant anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-mutagenic, anti-coagulant and anti-infective effects. Curcumin has also been shown to have significant wound healing properties. It acts on various stages of the natural wound healing process to hasten healing. This review summarizes and discusses recently published papers on the effects of curcumin on skin wound healing. The highlighted studies in the review provide evidence of the ability of curcumin to reduce the body's natural response to cutaneous wounds such as inflammation and oxidation. The recent literature on the wound healing properties of curcumin also provides evidence for its ability to enhance granulation tissue formation, collagen deposition, tissue remodeling and wound contraction. It has become evident that optimizing the topical application of curcumin through altering its formulation is essential to ensure the maximum therapeutical effects of curcumin on skin wounds. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Curcumin Alleviates Neuropathic Pain by Inhibiting p300/CBP Histone Acetyltransferase Activity-Regulated Expression of BDNF and Cox-2 in a Rat Model

    PubMed Central

    Zhu, Xiaoyan; Li, Qian; Chang, Ruimin; Yang, Dong; Song, Zongbing; Guo, Qulian; Huang, Changsheng

    2014-01-01

    The management of neuropathic pain is still a major challenge because of its unresponsiveness to most common treatments. Curcumin has been reported to play an active role in the treatment of various neurological disorders, such as neuropathic pain. Curcumin has long been recognized as a p300/CREB-binding protein (CBP) inhibitor of histone acetyltransferase (HAT) activity. However, this mechanism has never been investigated for the treatment of neuropathic pain with curcumin. The aim of the present study was to investigate the anti-nociceptive role of curcumin in the chronic constriction injury (CCI) rat model of neuropathic pain. Furthermore, with this model we investigated the effect of curcumin on P300/CBP HAT activity-regulated release of the pro-nociceptive molecules, brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (Cox-2). Treatment with 40 and 60 mg/kg body weight curcumin for 7 consecutive days significantly attenuated CCI-induced thermal hyperalgesia and mechanical allodynia, whereas 20 mg/kg curcumin showed no significant analgesic effect. Chromatin immunoprecipitation analysis revealed that curcumin dose-dependently reduced the recruitment of p300/CBP and acetyl-Histone H3/acetyl-Histone H4 to the promoter of BDNF and Cox-2 genes. A similar dose-dependent decrease of BDNF and Cox-2 in the spinal cord was also observed after curcumin treatment. These results indicated that curcumin exerted a therapeutic role in neuropathic pain by down-regulating p300/CBP HAT activity-mediated gene expression of BDNF and Cox-2. PMID:24603592

  10. 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.

  11. Curcumin: a pleiotropic phytonutrient in diabetic complications.

    PubMed

    Jeenger, Manish Kumar; Shrivastava, Shweta; Yerra, Veera Ganesh; Naidu, V G M; Ramakrishna, Sistla; Kumar, Ashutosh

    2015-02-01

    Curcumin is the major polyphenolic constituent of an indigenous herb, Curcuma longa, found to have a wide range of applications right from its kitchen use as a spicy ingredient to therapeutic and medicinal applications in various diseases. Curcumin has been identified to have a plethora of biologic and pharmacologic properties owing to its antioxidant and anti-inflammatory activities. This pleiotropic regulation of redox balance of cell and inflammation might be the basis of curcumin's beneficial activities in various pathologic conditions including diabetic complications. This review summarizes various in vitro, in vivo studies done on curcumin and its therapeutic utility in diabetic micro-vascular complications. This review also emphasizes the importance of curcumin in addition to the existing therapeutic modalities in diabetic complications. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. New perspectives of curcumin in cancer prevention

    PubMed Central

    Park, Wungki; Amin, A.R.M Ruhul; Chen, Zhuo Georgia; Shin, Dong M.

    2013-01-01

    Numerous natural compounds have been extensively investigated for their potential for cancer prevention over decades. Curcumin, from Curcuma longa, is a highly promising natural compound that can be potentially used for chemoprevention of multiple cancers. Curcumin modulates multiple molecular pathways involved in the lengthy carcinogenesis process to exert its chemopreventive effects through several mechanisms: promoting apoptosis, inhibiting survival signals, scavenging reactive oxidative species (ROS), and reducing the inflammatory cancer microenvironment. Curcumin fulfills the characteristics for an ideal chemopreventive agent with its low toxicity, affordability, and easy accessibility. Nevertheless, the clinical application of curcumin is currently compromised by its poor bioavailability. Here we review the potential of curcumin in cancer prevention, its molecular targets, and action mechanisms. Finally, we suggest specific recommendations to improve its efficacy and bioavailability for clinical applications. PMID:23466484

  13. Investigation on Curcumin nanocomposite for wound dressing.

    PubMed

    Venkatasubbu, G Devanand; Anusuya, T

    2017-05-01

    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. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. 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.

  15. Curcumin Prevents Formation of Polyglutamine Aggregates by Inhibiting Vps36, a Component of the ESCRT-II Complex

    PubMed Central

    Verma, Meenakshi; Sharma, Abhishek; Naidu, Swarna; Bhadra, Ankan Kumar; Kukreti, Ritushree; Taneja, Vibha

    2012-01-01

    Small molecules with antioxidative properties have been implicated in amyloid disorders. Curcumin is the active ingredient present in turmeric and known for several biological and medicinal effects. Adequate evidence substantiates the importance of curcumin in Alzheimer's disease and recent evidence suggests its role in Prion and Parkinson's disease. However, contradictory effects have been suggested for Huntington's disease. This difference provided a compelling reason to investigate the effect of curcumin on glutamine-rich (Q-rich) and non-glutamine-rich (non Q-rich) amyloid aggregates in the well established yeast model system. Curcumin significantly inhibited the formation of htt72Q-GFP (a Q-rich) and Het-s-GFP (a non Q-rich) aggregates in yeast. We show that curcumin prevents htt72Q-GFP aggregation by down regulating Vps36, a component of the ESCRT-II (Endosomal sorting complex required for transport). Moreover, curcumin disrupted the htt72Q-GFP aggregates that were pre-formed in yeast and cured the yeast prion, [PSI+]. PMID:22880132

  16. Cooking enhances curcumin anti-cancerogenic activity through pyrolytic formation of "deketene curcumin".

    PubMed

    Dahmke, Indra N; Boettcher, Stefan P; Groh, Matthias; Mahlknecht, Ulrich

    2014-05-15

    Curcumin is widely used in traditional Asian kitchen as a cooking ingredient. Despite its low bioavailability, epidemiological data, on low cancer incidence in Asia, suggest beneficial health effects of this compound. Therefore, the question arose whether cooking modifies the anti-cancerogenic effects of curcumin. To evaluate this, we pyrolysed curcumin with and without coconut fat or olive oil, and analysed the products by high-performance liquid chromatography (HPLC). A number of more hydrophilic curcumin isoforms and decomposition products, including a compound later identified by nuclear magnetic resonance spectroscopy (NMR) as "deketene curcumin" (1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one), formerly described as a synthetic curcumin derivative, were detected. Additionally, we proved that deketene curcumin, compared to curcumin, exhibits higher toxicity on B78H1 melanoma cells resulting in G2 arrest. In conclusion, deketene curcumin is formed as a consequence of pyrolysis during common household cooking, showing stronger anti-cancer effects than curcumin. Moreover, we propose a chemical reaction-pathway for this process. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. 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

  18. beta-Cyclodextrin-curcumin self-assembly enhances curcumin delivery in prostate cancer cells.

    PubMed

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

    2010-08-01

    Curcumin, a hydrophobic polyphenolic compound derived from the rhizome of the herb Curcuma longa, possesses a wide range of biological applications including cancer therapy. However, its prominent application in cancer treatment is limited due to sub-optimal pharmacokinetics and poor bioavailability at the tumor site. In order to improve its hydrophilic and drug delivery characteristics, we have developed a beta-cyclodextrin (CD) mediated curcumin drug delivery system via encapsulation technique. Curcumin encapsulation into the CD cavity was achieved by inclusion complex mechanism. Curcumin encapsulation efficiency was improved by increasing the ratio of curcumin to CD. The formations of CD-curcumin complexes were characterized by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), thermo-gravimetric analysis (TGA), scanning electron microscope (SEM), and transmission electron microscope (TEM) analyses. An optimized CD-curcumin complex (CD30) was evaluated for intracellular uptake and anti-cancer activity. Cell proliferation and clonogenic assays demonstrated that beta-cyclodextrin-curcumin self-assembly enhanced curcumin delivery and improved its therapeutic efficacy in prostate cancer cells compared to free curcumin. Copyright 2010 Elsevier B.V. All rights reserved.

  19. Comparison of the Effects of Curcumin and RG108 on NGF-Induced PC-12 Adh Cell Differentiation and Neurite Outgrowth.

    PubMed

    Dikmen, Miriş

    2017-04-01

    DNA methyltransferases (DNMTs) are promising epigenetic targets for the development of novel drugs, especially for neurodegenerative disorders. In recent years, there has been increased interest in small molecules that can cross the blood-brain barrier for the treatment of neurodegenerative diseases. Therefore, comparing the neuronal differentiative effects of a natural compound curcumin and a synthetic small molecule RG108 was the aim of this study. The effects of curcumin and RG108 on neuronal differentiation and neurite outgrowth were investigated in the PC-12 Adh cell line. First, a nontoxic concentration was determined to be 100 nM with WST-1 assay. Subsequently, cells were treated with 100 nM curcumin and RG108 alone or in combination with 50 nM nerve growth factor (NGF). Cell differentiations were evaluated by a real-time cell analyzer system. Neurite outgrowth was determined and morphologically shown by immunofluorescence staining with anti-beta III tubulin antibody on PC-12 Adh cells. Also, growth-associated protein-43 (GAP-43) and β-tubulin III mRNA expression levels, associated with neurite outgrowth promotion, were determined with real-time polymerase chain reaction (RT-PCR). According to our results, 100 nM curcumin and RG108 significantly induced neurite outgrowth of PC-12 Adh cells with 50 nM NGF. Curcumin + NGF combination further increased cell differentiations and total neurite lengths more than curcumin alone and RG108 + NGF combination groups. Strikingly, curcumin and NGF combination upregulated GAP-43 and β-tubulin mRNA expression levels excessively. In conclusion, curcumin was found to be more effective than RG108 on neuronal differentiation and neurite outgrowth of PC-12 Adh cells in a combination with NGF. Therefore, natural DNMT1 inhibitors, such as curcumin, can be a novel approach for the neurodegenerative disorders treatment.

  20. Recent progress on curcumin-based therapeutics: a patent review (2012-2016). Part II: curcumin derivatives in cancer and neurodegeneration.

    PubMed

    Di Martino, Rita Maria Concetta; Bisi, Alessandra; Rampa, Angela; Gobbi, Silvia; Belluti, Federica

    2017-08-01

    Curcumin, the main bioactive compound found in the rhizome of Curcuma longa L., is considered a 'privileged structure', due to its ability to modulate different signaling pathways involved in the pathogenesis of several diseases. Unfortunately, its poor pharmacodynamic and pharmacokinetic properties, mainly related to chemical instability, low solubility and rapid metabolism, greatly reduce its therapeutic potential. In the last years a number of derivatives were developed and patented, aimed both at improving its multifaceted biological profile and overcoming its undesired effects. Areas covered: This review summarizes the patent literature of the last five years dealing with synthetic curcumin-related compounds in cancer and neurodegeneration, properly designed in order to avoid the so-called 'dark side of curcumin', and to take advantage of the beneficial properties of this molecule, worth to be further exploited to obtain effective therapeutics. Expert opinion: Due to the synergistic binding to several networked targets, curcumin turned out to be suitable for polypharmacological approaches, and its 'privileged structure' could also provide the key scaffold to develop novel multipotent drugs useful for treating multifactiorial pathologic conditions such as cancer and neurodegeneration.

  1. A curcumin activated carboxymethyl cellulose-montmorillonite clay nanocomposite having enhanced curcumin release in aqueous media.

    PubMed

    Madusanka, Nadeesh; de Silva, K M Nalin; Amaratunga, Gehan

    2015-12-10

    A novel curcumin activated carboxymethylcellulose-montmorillonite nanocomposite is reported. A superabsorbent biopolymer; carboxymethyl cellulose (CMC) was used as an emulsifier for curcumin which is a turmeric derived water insoluble polyphenolic compound with antibacterial/anti-cancer properties. Montmorillonite (MMT) nanoclay was incorporated in the formulation as a matrix material which also plays a role in release kinetics. It was observed that water solubility of curcumin in the nanocomposite has significantly increased (60% release within 2h and 30 min in distilled water at pH 5.4) compared to pure curcumin. The prepared curcumin activated carboxymethylcellulose-montmorillonite nanocomposite is suitable as a curcumin carrier having enhanced release and structural properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Curcumin (diferuloylmethane) delivery methods: a review.

    PubMed

    Helson, Lawrence

    2013-01-01

    Curcumin interacts with a large number of extra- and intracellular targets in a biphasic dose-dependent manner. It controls inflammation, oxidative stress, cell survival, cell secretion, homeostasis, and proliferation. Its mechanisms of action are generally directed toward cells that exhibit disordered physiology or blatant mutation-based abnormal states. Optimizing preventative or therapeutic applications require delivering appropriate quantities of curcumin to lesioned cellular targets. Since diseased conditions anatomically are located from topical to systemic sites, efficient application of curcumin requires specific lesion-oriented delivery methods, representatives of which are here reviewed. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

  8. 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).

  9. Excretion of NaCl and KCl loads in mosquitoes. 2. Effects of the small molecule Kir channel modulator VU573 and its inactive analog VU342

    PubMed Central

    Rouhier, Matthew F.; Hine, Rebecca M.; Park, Seokhwan Terry; Raphemot, Rene; Denton, Jerod; Piermarini, Peter M.

    2014-01-01

    The effect of two small molecules VU342 and VU573 on renal functions in the yellow fever mosquito Aedes aegypti was investigated in vitro and in vivo. In isolated Malpighian tubules, VU342 (10 μM) had no effect on the transepithelial secretion of Na+, K+, Cl−, and water. In contrast, 10 μM VU573 first stimulated and then inhibited the transepithelial secretion of fluid when the tubules were bathed in Na+-rich or K+-rich Ringer solution. The early stimulation was blocked by bumetanide, suggesting the transient stimulation of Na-K-2Cl cotransport, and the late inhibition of fluid secretion was consistent with the known block of AeKir1, an Aedes inward rectifier K+ channel, by VU573. VU342 and VU573 at a hemolymph concentration of about 11 μM had no effect on the diuresis triggered by hemolymph Na+ or K+ loads. VU342 at a hemolymph concentration of 420 μM had no effect on the diuresis elicited by hemolymph Na+ or K+ loads. In contrast, the same concentration of VU573 significantly diminished the Na+ diuresis by inhibiting the urinary excretion of Na+, Cl−, and water. In K+-loaded mosquitoes, 420 μM VU573 significantly diminished the K+ diuresis by inhibiting the urinary excretion of K+, Na+, Cl−, and water. We conclude that 1) the effects of VU573 observed in isolated Malpighian tubules are overwhelmed in vivo by the diuresis triggered with the coinjection of Na+ and K+ loads, and 2) at a hemolymph concentration of 420 μM VU573 affects Kir channels systemically, including those that might be involved in the release of diuretic hormones. PMID:25056106

  10. Curcumin Implants, not Curcumin Diet Inhibits Estrogen-Induced Mammary Carcinogenesis in ACI Rats

    PubMed Central

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

    2014-01-01

    Curcumin is widely known for its anti-oxidant, anti-inflammatory and anti-proliferative activities in cell culture studies. However, poor oral bioavailability limited its efficacy in animal and clinical studies. Recently, we developed polymeric curcumin implants that circumvents oral bioavailability issues, and tested their potential against 17β-estradiol (E2)-mediated mammary tumorigenesis. Female 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 prior to grafting a subcutaneous E2 silastic implant (1.2 cm, 9 mg E2). Implants were changed after 4½ 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 mm3 vs 280±141 mm3; 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 presence of E2. Since CYP1A and 3A4 metabolize most of the E2 to its non-carcinogenic 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 HPLC showed substantially higher curcumin levels via implants versus the dietary route despite substantially higher dose administered. PMID:24501322

  11. 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.

  12. Curcumin in Treating Breast Cancer: A Review.

    PubMed

    Wang, Yiwei; Yu, Jiayi; Cui, Ran; Lin, Jinjin; Ding, Xianting

    2016-12-01

    Breast cancer is among the most common malignant tumors. It is the second leading cause of cancer mortality among women in the United States. Curcumin, an active derivative from turmeric, has been reported to have anticancer and chemoprevention effects on breast cancer. Curcumin exerts its anticancer effect through a complicated molecular signaling network, involving proliferation, estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2) pathways. Experimental evidence has shown that curcumin also regulates apoptosis and cell phase-related genes and microRNA in breast cancer cells. Herein, we review the recent research efforts in understanding the molecular targets and anticancer mechanisms of curcumin in breast cancer. © 2016 Society for Laboratory Automation and Screening.

  13. 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

  14. Photodynamic effect of curcumin on Vibrio parahaemolyticus.

    PubMed

    Wu, Juan; Mou, Haijin; Xue, Changhu; Leung, Albert Wingnang; Xu, Chuanshan; Tang, Qing-Juan

    2016-09-01

    Vibrio parahaemolyticus (V. parahaemolyticus) is currently a major cause of bacterial diarrhoea associated with seafood consumption. The objective of this study was to determine the inactivation effect of curcumin-mediated photodynamic action on V. parahaemolyticus. First of all, V. parahaemolyticus suspended in PBS buffer was irradiated by a visible light from a LED light source with an energy density of 3.6J/cm(2). Colony forming units (CFU) were counted and the viability of V. parahaemolyticus cells was calculated after treatment. Singlet oxygen ((1)O2) production after photodynamic action of curcumin was evaluated using 9,10-Anthracenediyl-bis (methylene) dimalonic acid (ADMA). Bacterial outer membrane protein was extracted and analyzed using electrophoresis SDS-PAGE. DNA and RNA of V. parahaemolyticus were also extracted and analyzed using agarose gel electrophoresis after photodynamic treatment. Finally, the efficacy of photodynamic action of curcumin was preliminarily evaluated in the decontamination of V. parahaemolyticus in oyster. Results showed that the viability of V. parahaemolyticus was significantly decreased to non-detectable levels over 6.5-log reductions with the curcumin concentration of 10 and 20μM. Photodynamic action of curcumin significantly increased the singlet oxygen level with the curcumin concentration of 10μM. Notable damage was found to bacterial outer membrane proteins and genetic materials after photodynamic treatment. Photodynamic action of curcumin reduced the number of V. parahaemolyticus contaminating in oyster to non-detectable level. Our findings demonstrated that photodynamic action of curcumin could be a potentially good method to inactivate Vibrio parahaemolyticus contaminating in oyster.

  15. 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.

  16. 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.

  17. Curcumin and lung cancer--a review.

    PubMed

    Mehta, Hiren J; Patel, Vipul; Sadikot, Ruxana T

    2014-12-01

    Curcumin (diferuloylmethane) is the most important component of the spice turmeric and is derived from the rhizome of the East Indian plant Curcuma longa. Curcumin has been used extensively in Ayurvedic medicine for centuries, as it is nontoxic and has a variety of therapeutic properties including antioxidant, analgesic, anti-inflammatory, and antiseptic activities. Recently, curcumin has been widely studied for its anticancer properties via its effects on a variety of biological pathways involved in apoptosis, tumor proliferation, chemo- and radiotherapy sensitization, tumor invasion, and metastases. Curcumin can be an effective adjunct in treating solid organ tumors due to its properties of regulating oncogenes like p53, egr-1, c-myc, bcl-XL, etc.; transcription factors like NF-kB, STAT-3, and AP-1; protein kinases like MAPK; and enzymes like COX and LOX. Lung cancer is the most common malignancy worldwide and a leading cause of cancer-related deaths. Seventy-five percent of lung cancer presents at an advanced stage where the existing treatment is not very effective and may result in tremendous patient morbidity. As a result, there is a significant interest in developing adjunctive chemotherapies to augment currently available treatment protocols, which may allow decreased side effects and toxicity without compromising therapeutic efficacy. Curcumin is one such potential candidate, and this review presents an overview of the current in vitro and in vivo studies of curcumin in lung cancer.

  18. 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.

  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. 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

  1. Acid-induced release of curcumin from calcium containing nanotheranostic excipient.

    PubMed

    Wang, Aifei; Muhammad, Faheem; Qi, Wenxiu; Wang, Nan; Chen, Liang; Zhu, Guangshan

    2014-08-27

    Poor water solubility is believed one of the most critical problems of numerous promising pharmaceutical ingredients in their successful clinical utilization. Nanomedicine holds considerable promise to address this challenge, because it extends the therapeutic window of hydrophobic drugs through nanonization approach. Recently, the integration of diagnostic agents with smart therapeutic nanocarriers is also an emerging research arena to simultaneously visualize diseased tissues, achieve site specific drug release and track the impact of therapy. In this study, we have developed a biocompatible smart theranostic nanosystem which transports a highly promising hydrophobic drug (curcumin) in response to mildly acidic environment. As calcium is a main constituent of human body, hence we exploited the reversible calcium chelate formation tendency of divalent calcium to load and unload curcumin molecules. Moreover, an emerging T1 contrast agent is also tethered onto the surface of nanocarrier to realize MRI diagnosis application. In-vitro cell experiments revealed a significantly high chemotherapeutic efficiency of curcumin nanoformulation (IC50; 1.67 μg/mL), whereas free curcumin was found ineffective at the corresponding concentration (IC50; 29.72 μg/mL). MR imaging test also validated the performance of resulting system. Our strategy can be extended for the targeted delivery of other hydrophobic pharmaceutical ingredients.

  2. 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).

  3. 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.

  4. 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. Copyright © 2016. Published by Elsevier B.V.

  5. Structure based comprehensive modelling, spatial fingerprints mapping and ADME screening of curcumin analogues as novel ALR2 inhibitors

    PubMed Central

    Verma, Sant Kumar

    2017-01-01

    Aldose reductase (ALR2) inhibition is the most legitimate approach for the management of diabetic complications. The limited triumph in the drug development against ALR2 is mainly because of its close structural similarity with the other members of aldo-keto reductase (AKR) superfamily viz. ALR1, AKR1B10; and lipophilicity problem i.e. poor diffusion of synthetic aldose reductase inhibitors (ARIs) to target tissues. The literature evidenced that naturally occurring curcumin demonstrates relatively specific and non-competitive inhibition towards human recombinant ALR2 over ALR1 and AKR1B10; however β-diketone moiety of curcumin is a specific substrate for liver AKRs and accountable for it’s rapid in vivo metabolism. In the present study, structure based comprehensive modelling studies were used to map the pharmacophoric features/spatial fingerprints of curcumin analogues responsible for their ALR2 specificity along with potency on a data set of synthetic curcumin analogues and naturally occurring curcuminoids. The data set molecules were also screened for drug-likeness or ADME parameters, and the screening data strongly support that curcumin analogues could be proposed as a good drug candidate for the development of ALR2 inhibitors with improved pharmacokinetic profile compared to curcuminoids due to the absence of β-diketone moiety in their structural framework. PMID:28399135

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. [Preparation and drug releasing property of curcumin nanoparticles].

    PubMed

    Liu, Zhan-jun; Han, Gang; Yu, Jiu-gao; Dai, Hong-guang

    2009-02-01

    To prepare curcumin nanoparticles and evaluate the in vitro release of curcumin. The chitosan-graft-vinyl acetate copolymers were synthesized by free radical polymerization. Curcumin nanoparticles were synthesized by ultrasonic irradiation. The encapsulation efficiency of the nanoparticles and the in vitro release of curcumin were studied. The nanoparticles were discrete and uniform spheres, covered with positive charges. The encapsulation efficiency of nanoparticles was up to 91.6%. The in vitro release profile showed the slower release rate of curcumin. The methods is simple. The nanoparticles possess good physical performance and sustained release character in vitro.

  11. 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.

  12. [Pharmacological researches of curcumin solid dispersions in treatment of cancer].

    PubMed

    Mei, Xue-Ting; Xu, Dong-Hui; He, Xue-Ni; Lu, Yong-Chang

    2012-10-01

    To investigate the anticancer effect of curcumin Solid Dispersions (SDs). Curcumin SDs were prepared by patent technology. The anticancer effect of curcumin SDs were investigated by vivo and vitro tests of SCG-7901, BEL-7402, S-180 and Ehrlich ascites tumor models. The results showed that Curcumin SDs had markedly anticancer effect and could improve the anticancer effect of cisplatin. Curcumin SDs could be developed into one kind of adjuvant drug for anticancer, as it has markedly anticancer effect, and could improve the anticancer effects of cisplatin.

  13. Curcumin delivery from poly(acrylic acid-co-methyl methacrylate) hollow microparticles prevents dopamine-induced toxicity in rat brain synaptosomes.

    PubMed

    Yoncheva, Krassimira; Kondeva-Burdina, Magdalena; Tzankova, Virginia; Petrov, Petar; Laouani, Mohamed; Halacheva, Silvia S

    2015-01-01

    The potential of poly(methyl methacrylate-co-acrylic acid) (PMMA-AA) copolymers to form hollow particles and their further formulation as curcumin delivery system have been explored. The particles were functionalized by crosslinking the acrylic acid groups via bis-amide formation with either cystamine (CYS) or 3,3'-dithiodipropionic acid dihydrazide (DTP) which simultaneously incorporated reversibility due to the presence of disulfide bonds within the crosslinker. Optical micrographs showed the formation of spherical hollow microparticles with a size ranging from 1 to 7 μm. Curcumin was loaded by incubation of its ethanol solution with aqueous dispersions of the cross-linked particles and subsequent evaporation of the ethanol. Higher loading was observed in the microparticles with higher content of hydrophobic PMMA units indicating its influence upon the loading of hydrophobic molecules such as curcumin. The in vitro release studies in a phosphate buffer showed no initial burst effect and sustained release of curcumin that correlated with the swelling of the particles under these conditions. The capacity of encapsulated and free curcumin to protect rat brain synaptosomes against dopamine-induced neurotoxicity was examined. The encapsulated curcumin showed greater protective effects in rat brain synaptosomes as measured by synaptosomal viability and increased intracellular levels of glutathione. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. 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.

  15. 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.

  16. Recent advances in curcumin nanoformulation for cancer therapy.

    PubMed

    Lee, Wing-Hin; Loo, Ching-Yee; Young, Paul M; Traini, Daniela; Mason, Rebecca S; Rohanizadeh, Ramin

    2014-08-01

    Natural compounds are emerging as effective agents for the treatment of malignant diseases. Curcumin (diferuloylmethane), the active constituent of turmeric extract, has gained significant interest as a plant-based compound with anti-cancer properties. Curcumin is physiologically very well tolerated, with negligible systemic toxicity observed even after high oral doses administration. Despite curcumin's superior properties as an anti-cancer agent its applications are limited due to its low solubility and physico-chemical stability, rapid systemic clearance and low cellular uptake. This review focuses on the development of curcumin nano-particle formulation to improve its therapeutic index through enhanced cellular uptake, localization to targeted areas and improved bioavailability. The feasibility of nano-formulation in delivering curcumin and the limitations and challenges in designing and administrating the nano-sized curcumin particles are also covered in this review. Nanotechnology is a promising tool to enhance efficacy and delivery of drugs. In this context, formulation of curcumin as nano-sized particles could reduce the required therapeutic dosages and subsequently reduced its cell toxicity. These nanoparticles are capable to provide local delivery of curcumin targeted to specific areas and thereby preventing systemic clearance. In addition, using specific coating, better pharmacokinetic and internalization of nano-curcumin could be achieved. However, the potential toxicity of nano-carriers for curcumin delivery is an important issue, which should be taken into account in curcumin nano-formulation.

  17. 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.

  18. Protective mechanism of curcumin against Vibrio vulnificus infection.

    PubMed

    Na, Hee Sam; Cha, Mi Hye; Oh, Dool-Ri; Cho, Cheong-Weon; Rhee, Joon Haeng; Kim, Young Ran

    2011-12-01

    Curcumin, a natural polyphenolic flavonoid extracted from the rhizome of Curcuma longa L., has many beneficial biological activities. However, there are relatively few reports of the effects of curcumin on pathogen infections. This study examined the effect of curcumin on a Vibrio vulnificus infection. The cytotoxicity of V. vulnificus to HeLa cells was significantly inhibited by curcumin (at 10 or 30 μM). To further examine the inhibitory mechanism of curcumin against V. vulnificus-mediated cytotoxicity, the level of bacterial growth, bacterial motility, cell adhesion, RTX toxin expression and host cell reactions were evaluated. Curcumin inhibited V. vulnificus growth in HI broth. Curcumin inhibited both bacterial adhesion and RTX toxin binding to the host cells, which can be considered the major protective mechanisms for the decrease in V. vulnificus cytotoxicity. Curcumin also inhibited host cell rounding and actin aggregation, which are the early features of cell death caused by V. vulnificus. In addition, curcumin decreased the V. vulnificus-induced NF-κB translocation in HeLa cells. Finally, curcumin protected mice from V. vulnificus-induced septicemia. In conclusion, curcumin may be an alternative antimicrobial agent against fatal bacterial infections. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  19. 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

  20. 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.

  1. Bioavailability of a Sustained Release Formulation of Curcumin.

    PubMed

    Madhavi, Doddabele; Kagan, Daniel

    2014-06-01

    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. 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. 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. The study was done in MAZE Laboratories (Purchase, NY, USA). 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. 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 washout period of 14 d, the protocol was repeated with Micro

  2. Curcumin and anthocyanin inhibit pepsin-mediated cell damage and carcinogenic changes in airway epithelial cells.

    PubMed

    Samuels, Tina L; Pearson, Amy C S; Wells, Clive W; Stoner, Gary D; Johnston, Nikki

    2013-10-01

    Laryngopharyngeal reflux (LPR) is associated with inflammatory and neoplastic airway diseases. Gastric pepsin internalized by airway epithelial cells during reflux contributes to oxidative stress, inflammation, and carcinogenesis. Several plant extracts and compounds inhibit digestive enzymes and inflammatory or neoplastic changes to the esophagus in models of gastroesophageal reflux. This study examined the potential of chemoprotective phytochemicals to inhibit peptic activity and mitigate pepsin-mediated damage of airway epithelial cells. Cultured human laryngeal and hypopharyngeal epithelial cells were pretreated with curcumin (10 micromol/L), ecabet sodium (125 microg/mL), and anthocyanin-enriched black-raspberry extract (100 microg/mL) 30 minutes before treatment with pepsin (0.1 mg/mL; 1 hour; pH 7). Controls were treated with media pH 7 or pepsin pH 7 without phytochemicals. Cell damage and proliferative changes were assessed by electron microscopy, cell count, thymidine analog incorporation, and real-time polymerase chain reaction array. Pepsin inhibition was determined by in vitro kinetic assay. Micromolar concentrations of curcumin, ecabet sodium, and black-raspberry extract inhibited peptic activity and pepsin-induced mitochondrial damage and hyperproliferation. Curcumin abrogated pepsin-mediated depression of tumor suppressor gene expression and altered the subcellular localization of pepsin following endocytosis. Several phytochemicals inhibit the pepsin-mediated cell damage underlying inflammatory or neoplastic manifestations of LPR. Dietary supplementation or adjunctive therapy with phytochemicals may represent novel preventive or therapeutic strategies for LPR-attributed disease.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

    PubMed

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

    2014-11-14

    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

  10. 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

  11. 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.

  12. Characterization of Toxoplasma gondii glyoxalase 1 and evaluation of inhibitory effects of curcumin on the enzyme and parasite cultures.

    PubMed

    Goo, Youn-Kyoung; Yamagishi, Junya; Ueno, Akio; Terkawi, Mohamad Alaa; Aboge, Gabriel Oluga; Kwak, Dongmi; Hong, Yeonchul; Chung, Dong-Il; Igarashi, Makoto; Nishikawa, Yoshifumi; Xuan, Xuenan

    2015-12-23

    The glyoxalase pathway, which includes two enzymes, glyoxalase 1 and 2 (Glo1 and Glo2), is a ubiquitous cellular system responsible for the removal of cytotoxic methylglyoxal produced during glycolysis. Protozoan parasites, including Toxoplasma gondii (T. gondii) tachyzoites, produce methylglyoxal because of increased glycolytic fluxes. A Glo1 inhibitor such as curcumin could be considered a drug candidate for anti-protozoan, anti-inflammatory, and anti-cancer therapy. The T. gondii Glo1 gene (TgGlo1) was cloned and the recombinant protein was produced. Enzyme kinetics of TgGlo1 and five mutants were evaluated by adding methylglyoxal and glutathione to a reaction mixture. Finally, the inhibitory effects of various concentrations of curcumin on recombinant TgGlo1 were evaluated using in vitro cultures of T. gondii. Active recombinant TgGlo1 was successfully produced and the active sites (E166 and E251) of TgGlo1 were verified by point mutagenesis. Curcumin at the tested doses inhibited the enzymatic activity of recombinant TgGlo1 as well as the parasitic propagation of in vitro-cultured T. gondii. The Ki and IC50 were 12.9 ± 0.5 μM and 38.3 ± 0.9 μM, respectively. The inhibitory effect of curcumin on the enzymatic activity of TgGlo1 and parasitic propagation of T. gondii could be explored in the potential development of a potent drug for the treatment of toxoplasmosis. However, considering the fact that curcumin is known to have many effects on other molecules in the micromolar range, further elucidation of curcumin's direct inhibition of the glyoxalase system of T. gondii will be needed.

  13. Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma

    PubMed Central

    2011-01-01

    Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. Curcumin has been used extensively in Ayurvedic medicine for centuries, as it is nontoxic and has a variety of therapeutic properties including anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer activities via its effect on a variety of biological pathways involved in mutagenesis, oncogene expression, cell cycle regulation, apoptosis, tumorigenesis and metastasis. Curcumin has shown anti-proliferative effect in multiple cancers, and is an inhibitor of the transcription factor NF-κB and downstream gene products (including c-myc, Bcl-2, COX-2, NOS, Cyclin D1, TNF-α, interleukins and MMP-9). In addition, curcumin affects a variety of growth factor receptors and cell adhesion molecules involved in tumor growth, angiogenesis and metastasis. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and treatment protocols include disfiguring surgery, platinum-based chemotherapy and radiation, all of which may result in tremendous patient morbidity. As a result, there is significant interest in developing adjuvant chemotherapies to augment currently available treatment protocols, which may allow decreased side effects and toxicity without compromising therapeutic efficacy. Curcumin is one such potential candidate, and this review presents an overview of the current in vitro and in vivo data supporting its therapeutic activity in head and neck cancer as well as some of the challenges concerning its development as an adjuvant chemotherapeutic agent. PMID:21299897

  14. Recent developments in curcumin and curcumin based polymeric materials for biomedical applications: A review.

    PubMed

    Mahmood, Kashif; Zia, Khalid Mahmood; Zuber, Mohammad; Salman, Mahwish; Anjum, Muhammad Naveed

    2015-11-01

    Turmeric (Curcuma longa) is a popular Indian spice that has been used for centuries in herbal medicines for the treatment of a variety of ailments such as rheumatism, diabetic ulcers, anorexia, cough and sinusitis. Curcumin (diferuloylmethane) is the main curcuminoid present in turmeric and responsible for its yellow color. Curcumin has been shown to possess significant anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-mutagenic, anticoagulant and anti-infective effects. This review summarizes and discusses recently published papers on the key biomedical applications of curcumin based materials. The highlighted studies in the review provide evidence of the ability of curcumin to show the significant vitro antioxidant, diabetic complication, antimicrobial, neuroprotective, anti-cancer activities and detection of hypochlorous acid, wound healing, treatment of major depression, healing of paracentesis, and treatment of carcinoma and optical detection of pyrrole properties. Hydrophobic nature of this polyphenolic compound along with its rapid metabolism, physicochemical and biological instability contribute to its poor bioavailability. To redress these problems several approaches have been proposed like encapsulation of curcumin in liposomes and polymeric micelles, inclusion complex formation with cyclodextrin, formation of polymer-curcumin conjugates, etc. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Curcumin as potential therapeutic natural product: a nanobiotechnological perspective.

    PubMed

    Shome, Soumitra; Talukdar, Anupam Das; Choudhury, Manabendra Dutta; Bhattacharya, Mrinal Kanti; Upadhyaya, Hrishikesh

    2016-12-01

    Nanotechnology-based drug delivery systems can resolve the poor bioavailability issue allied with curcumin. The therapeutic potential of curcumin can be enhanced by making nanocomposite preparation of curcumin with metal oxide nanoparticles, poly lactic-co-glycolic acid (PLGA) nanoparticles and solid lipid nanoparticles that increases its bioavailability in the tissue. Curcumin has manifold therapeutic effects which include antidiabetic, antihypertensive, anticancer, anti-inflammatory and antimicrobial properties. Curcumin can inhibit diabetes, heavy metal and stress-induced hypertension with its antioxidant, chelating and inhibitory effects on the pathways that lead to hypertension. Curcumin is an anticancer agent that can prevent abnormal cell proliferation. Nanocurcumin is an improved form of curcumin with enhanced therapeutic properties due to improved delivery to the diseased tissue, better internalization and reduced systemic elimination. Curcumin has multiple pharmacologic effects, but its poor bioavailability reduces its therapeutic effects. By conjugating curcumin to metal oxide nanoparticles or encapsulation in lipid nanoparticles, dendrimers, nanogels and polymeric nanoparticles, the water solubility and bioavailability of curcumin can be improved and thus increase its pharmacological effectiveness. © 2016 Royal Pharmaceutical Society.

  16. Preparation of curcumin nanoparticle by using reinforcement ionic gelation technique

    NASA Astrophysics Data System (ADS)

    Suryani, Halid, Nur Hatidjah Awaliyah; Akib, Nur Illiyyin; Rahmanpiu, Mutmainnah, Nina

    2017-05-01

    Curcumin, a polyphenolic compound present in curcuma longa has a wide range of activities including anti-inflammatory properties. The potency of curcumin is limited by its poor oral bioavailability because of its poor solubility in aqueous. Various methods have been tried to solve the problem including its encapsulation into nanoparticle. The aim of this study is to develop curcumin nanoparticle by using reinforcement ionic gelation technique and to evaluate the stability of curcumin nanoparticles in gastrointestinal fluid. Curcumin nanoparticles were prepared by using reinforcement ionic gelation technique with different concentrations of chitosan, trypolyphosphate, natrium alginate and calcium chloride. Curcumin nanoparticles were then characterized including particle size and zeta potential by using particle size analyzer and morphology using a transmission electron microscope, entrapment efficiency using UV-Vis Spectrophotometer and chemical structure analysis by Infra Red Spectrophotometer (FTIR). Furthermore, the stability of curcumin nanoparticles were evaluated on artificial gastric fluid and artificial intestinal fluids by measuring the amount of curcumin released in the medium at a time interval. The result revealed that curcumin nanoparticles can be prepared by reinforcement ionic gelation technique, the entrapment efficiency of curcumin nanoparticles were from 86.08 to 91.41%. The average of particle size was 272.9 nm and zeta potential was 12.05 mV. The morphology examination showed that the curcumin nanoparticles have spherical shape. The stability evaluation of curcumin nanoparticles showed that the nanoparticles were stable on artificial gastric fluid and artificial intestinal fluid. This result indicates that curcumin nanoparticles have the potential to be developed for oral delivery.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. Biological and therapeutic activities, and anticancer properties of curcumin

    PubMed Central

    PERRONE, DONATELLA; ARDITO, FATIMA; GIANNATEMPO, GIOVANNI; DIOGUARDI, MARIO; TROIANO, GIUSEPPE; LO RUSSO, LUCIO; DE LILLO, ALFREDO; LAINO, LUIGI; LO MUZIO, LORENZO

    2015-01-01

    Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant. Curcumin has been used extensively in Ayurvedic medicine, as it is nontoxic and exhibits a variety of therapeutic properties, including antioxidant, analgesic, anti-inflammatory and antiseptic activities. Recently, certain studies have indicated that curcumin may exert anticancer effects in a variety of biological pathways involved in mutagenesis, apoptosis, tumorigenesis, cell cycle regulation and metastasis. The present study reviewed previous studies in the literature, which support the therapeutic activity of curcumin in cancer. In addition, the present study elucidated a number of the challenges concerning the use of curcumin as an adjuvant chemotherapeutic agent. All the studies reviewed herein suggest that curcumin is able to exert anti-inflammatory, antiplatelet, antioxidative, hepatoprotective and antitumor activities, particularly against cancers of the liver, skin, pancreas, prostate, ovary, lung and head neck, as well as having a positive effect in the treatment of arthritis. PMID:26640527

  2. 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.

  3. 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.

  4. 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.

  5. A Review on Antibacterial, Antiviral, and Antifungal Activity of Curcumin

    PubMed Central

    Zorofchian Moghadamtousi, Soheil; Abdul Kadir, Habsah; Hassandarvish, Pouya; Tajik, Hassan; Abubakar, Sazaly; Zandi, Keivan

    2014-01-01

    Curcuma longa L. (Zingiberaceae family) and its polyphenolic compound curcumin have been subjected to a variety of antimicrobial investigations due to extensive traditional uses and low side effects. Antimicrobial activities for curcumin and rhizome extract of C. longa against different bacteria, viruses, fungi, and parasites have been reported. The promising results for antimicrobial activity of curcumin made it a good candidate to enhance the inhibitory effect of existing antimicrobial agents through synergism. Indeed, different investigations have been done to increase the antimicrobial activity of curcumin, including synthesis of different chemical derivatives to increase its water solubility as well ass cell up take of curcumin. This review aims to summarize previous antimicrobial studies of curcumin towards its application in the future studies as a natural antimicrobial agent. PMID:24877064

  6. 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

  7. 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.

  8. Plasma Proteins Interaction with Curcumin Nanoparticles: Implications in Cancer Therapeutics

    PubMed Central

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

    2014-01-01

    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. PMID:23566382

  9. 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.

  10. A review on antibacterial, antiviral, and antifungal activity of curcumin.

    PubMed

    Moghadamtousi, Soheil Zorofchian; Kadir, Habsah Abdul; Hassandarvish, Pouya; Tajik, Hassan; Abubakar, Sazaly; Zandi, Keivan

    2014-01-01

    Curcuma longa L. (Zingiberaceae family) and its polyphenolic compound curcumin have been subjected to a variety of antimicrobial investigations due to extensive traditional uses and low side effects. Antimicrobial activities for curcumin and rhizome extract of C. longa against different bacteria, viruses, fungi, and parasites have been reported. The promising results for antimicrobial activity of curcumin made it a good candidate to enhance the inhibitory effect of existing antimicrobial agents through synergism. Indeed, different investigations have been done to increase the antimicrobial activity of curcumin, including synthesis of different chemical derivatives to increase its water solubility as well ass cell up take of curcumin. This review aims to summarize previous antimicrobial studies of curcumin towards its application in the future studies as a natural antimicrobial agent.

  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. ApoE enhances nanodisk-mediated curcumin delivery to glioblastoma multiforme cells

    PubMed Central

    Ghosh, Mistuni; Ryan, Robert O

    2013-01-01

    Aim To evaluate the effect of incorporating the polyphenol, curcumin, into nanodisk (ND) particles on its biological activity. Materials & methods Curcumin-NDs formulated with different scaffold proteins were incubated with cultured glioblastoma multiforme cells. Results When ApoE was employed as the ND scaffold protein, enhanced curcumin uptake was observed. Furthermore, ApoE curcumin-NDs induced greater cell death than either free curcumin or ApoAI curcumin-NDs. A total of 1 h after exposure of glioblastoma multiforme cells to ApoE curcumin-NDs, significant curcumin uptake was detected while ApoE was localized at the cell surface. After 2 h, a portion of the curcumin had migrated to the nucleus, giving rise to enhanced fluorescence intensity in discrete intranuclear sites. Conclusion ApoE-mediated interaction of curcumin-NDs with glioblastoma multiforme cells leads to enhanced curcumin uptake and increased biological activity. PMID:23879635

  13. 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.

  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. Targeting cancer stem cells by curcumin and clinical applications.

    PubMed

    Li, Yanyan; Zhang, Tao

    2014-05-01

    Curcumin is a well-known dietary polyphenol derived from the rhizomes of turmeric, an Indian spice. The anticancer effect of curcumin has been demonstrated in many cell and animal studies, and recent research has shown that curcumin can target cancer stem cells (CSCs). CSCs are proposed to be responsible for initiating and maintaining cancer, and contribute to recurrence and drug resistance. A number of studies have suggested that curcumin has the potential to target CSCs through regulation of CSC self-renewal pathways (Wnt/β-catenin, Notch, sonic hedgehog) and specific microRNAs involved in acquisition of epithelial-mesenchymal transition (EMT). The potential impact of curcumin, alone or in combination with other anticancer agents, on CSCs was evaluated as well. Furthermore, the safety and tolerability of curcumin have been well-established by numerous clinical studies. Importantly, the low bioavailability of curcumin has been dramatically improved through the use of structural analogues or special formulations. More clinical trials are underway to investigate the efficacy of this promising agent in cancer chemoprevention and therapy. In this article, we review the effects of curcumin on CSC self-renewal pathways and specific microRNAs, as well as its safety and efficacy in recent human studies. In conclusion, curcumin could be a very promising adjunct to traditional cancer treatments. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Cytoprotective mechanism of action of curcumin against cataract.

    PubMed

    Raman, Thiagarajan; Ramar, Manikandan; Arumugam, Munusamy; Nabavi, Seyed Mohammad; Varsha, Mosur Kumaraswamy Nagarajan Sai

    2016-06-01

    This review discusses the relationship between oxidative stress and cataract formation, molecular mechanism of curcumin action and potential benefits of treatment with the antioxidant curcumin. The first section deals with curcumin and endogenous antioxidants. The second section focuses on the action of curcumin on lipid peroxidation. Calcium homeostasis and curcumin will be discussed in the third section. The fourth section discusses the role of crystallin proteins that are responsible for maintaining lens transparency and the role of curcumin in regulating crystallin expression. The interaction of curcumin with transcription factors will be dealt in the fifth section. The final section will focus on the effect of curcumin on aldose reductase, which is associated with hyperglycemia and cataract. One of the strongest antioxidants is curcumin which has been shown to be very effective against cataract. This compound is better than other antioxidants in preventing cataract but its limited bioavailability can be addressed by employing nanotechnology. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  18. Curcumin: A Natural Lead for Potential New Drug Candidates.

    PubMed

    Oliveira, Ana Sofia; Sousa, Emília; Vasconcelos, Maria Helena; Pinto, Madalena

    2015-01-01

    Curcumin (1) is a secondary metabolite of turmeric, derived from Curcuma longa L. and was shown to have many biological activities. One of the most interesting properties of curcumin (1) is the antitumour activity allied with the ability to act as a multidrug resistance (MDR) modulator. Several curcumin derivatives have been synthesized with the purpose of discovering more information about the mechanisms of action, to establish structure-activity relationships (SAR), and to overcome pharmacokinetic problems. Over the past few decades, more potent and more stable curcumin derivatives have emerged with potential as drug candidates. Some important SAR studies pointed out that the unstable α,β-unsaturated diketone linker present in curcumin (1) may not be necessary for the antitumour activity; generally, shorter linkers result in more potent compounds than curcumin (1); the type of substituents and their substitution pattern are crucial regarding the biological activities of interest. Overall, the structure of curcumin (1) may represent an important basis for the development of more effective therapeutic agents, particularly in chemotherapy, as reflected by ongoing clinical trials. This article aims to review the synthesis and biological activities of curcumin (1) and derivatives, highlighting the MDR modulation properties of curcumin (1), since these effects makes this natural product a promising lead compound for the development of new anticancer drugs.

  19. Highly loaded, sustained-release microparticles of curcumin for chemoprevention.

    PubMed

    Shahani, Komal; Panyam, Jayanth

    2011-07-01

    Curcumin, a dietary polyphenol, has preventive and therapeutic potential against several diseases. Because of the chronic nature of many of these diseases, sustained-release dosage forms of curcumin could be of significant clinical value. However, extreme lipophilicity and instability of curcumin are significant challenges in its formulation development. The objectives of this study were to fabricate an injectable microparticle formulation that can sustain curcumin release over a 1-month period and to determine its chemopreventive activity in a mouse model. Microparticles were fabricated using poly(D, L-lactide-co-glycolide) polymer. Conventional emulsion solvent evaporation method of preparing microparticles resulted in crystallization of curcumin outside of microparticles and poor entrapment (∼1%, w/w loading). Rapid solvent removal using vacuum dramatically increased drug entrapment (∼38%, w/w loading; 76% encapsulation efficiency). Microparticles sustained curcumin release over 4 weeks in vitro, and drug release rate could be modulated by varying the polymer molecular weight and/or composition. A single subcutaneous dose of microparticles sustained curcumin liver concentration for nearly a month in mice. Hepatic glutathione-s-transferase and cyclooxygenase-2 activities, biomarkers for chemoprevention, were altered following treatment with curcumin microparticles. The results of these studies suggest that sustained-release microparticles of curcumin could be a novel and effective approach for cancer chemoprevention. Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

  20. Highly Loaded, Sustained-Release Microparticles of Curcumin for Chemoprevention

    PubMed Central

    SHAHANI, KOMAL; PANYAM, JAYANTH

    2014-01-01

    Curcumin, a dietary polyphenol, has preventive and therapeutic potential against several diseases. Because of the chronic nature of many of these diseases, sustained-release dosage forms of curcumin could be of significant clinical value. However, extreme lipophilicity and instability of curcumin are significant challenges in its formulation development. The objectives of this study were to fabricate an injectable microparticle formulation that can sustain curcumin release over a 1-month period and to determine its chemopreventive activity in a mouse model. Microparticles were fabricated using poly(D, L-lactide-co-glycolide) polymer. Conventional emulsion solvent evaporation method of preparing microparticles resulted in crystallization of curcumin outside of microparticles and poor entrapment (~1%, w/w loading). Rapid solvent removal using vacuum dramatically increased drug entrapment (~38%, w/w loading; 76% encapsulation efficiency). Microparticles sustained curcumin release over 4 weeks in vitro, and drug release rate could be modulated by varying the polymer molecular weight and/or composition. A single subcutaneous dose of microparticles sustained curcumin liver concentration for nearly a month in mice. Hepatic glutathione-s-transferase and cyclooxygenase-2 activities, biomarkers for chemoprevention, were altered following treatment with curcumin microparticles. The results of these studies suggest that sustained-release microparticles of curcumin could be a novel and effective approach for cancer chemoprevention. PMID:21547911

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. 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.

  12. 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.

  13. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. 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.

  15. Curcumin inhibits superoxide anion-induced pain-like behavior and leukocyte recruitment by increasing Nrf2 expression and reducing NF-κB activation.

    PubMed

    Fattori, Victor; Pinho-Ribeiro, Felipe A; Borghi, Sergio M; Alves-Filho, José C; Cunha, Thiago M; Cunha, Fernando Q; Casagrande, Rubia; Verri, Waldiceu A

    2015-12-01

    This study aimed at evaluating the activity of curcumin in superoxide anion-induced pain-like behavior and leukocyte recruitment in mice. Administration of curcumin 10 mg/kg subcutaneously 1 h before stimulus. KO2 was used as superoxide anion donor. Overt pain-like behaviors were determined by the number of abdominal writhings, paw flinches and time spent licking the paw. Mechanical and thermal hyperalgesia were determined using an electronic anesthesiometer and hot plate, respectively. Cytokine concentration and NF-κB activity were determined by ELISA, antioxidant effect by nitrobluetretrazolium assay and ABTS radical scavenging ability. Myeloperoxidase activity was measured by colorimetric assay. The Nrf2, heme oxygenase-1 (HO-1) and gp91phox mRNA expression was determined by quantitative PCR. Data were analyzed by ANOVA followed by Tukey's post hoc and considered significant when p<0.05. Curcumin inhibited superoxide anion-induced overt pain-like behaviors as well as mechanical and thermal hyperalgesia. Curcumin also inhibited superoxide anion-induced leukocyte recruitment in the peritoneal cavity and in the paw skin inhibited myeloperoxidase activity, oxidative stress, IL-1β and TNF-α production and NF-κB activation as well as enhanced IL-10 production, and HO-1 and Nrf2 mRNA expression. Curcumin inhibits superoxide anion-induced inflammatory pain-like behaviors and leukocyte recruitment by targeting inflammatory molecules and oxidative stress; and inducing antioxidant and anti-inflammatory pathways.

  16. One pot synthesis, structural and spectral analysis of some symmetrical curcumin analogues catalyzed by calcium oxide under microwave irradiation.

    PubMed

    Elavarasan, S; Bhakiaraj, D; Chellakili, B; Elavarasan, T; Gopalakrishnan, M

    2012-11-01

    A series of sixteen number of curcumin analogues have been synthesized under microwave irradiation using calcium oxide as a catalyst. The synthesized compounds have been characterized using FT-IR, MS, elemental analysis, (1)H and (13)C NMR spectroscopic techniques. The UV-Vis absorption studies for these compounds have been studied in order to provide the electronic transitions taking place in the molecule. When compared to the curcumin ((1E,4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one), the absorption maxima, λ(max) for all the synthesized curcumin analogues with a variety of substituents gets blue shifted i.e., hypsochromic shift was observed. This shift may be assigned to the change of dipole moment within the solvated molecule. Theoretical calculations regarding the optimization of the synthesized molecules, electronic properties like highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) and mapped electron density surface diagrams were done. The geometrical energy, dipole moments and heat of formation values have also been calculated using the ArgusLab package by AM1 semi-empirical method. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. When Gesture Becomes Analogy.

    PubMed

    Cooperrider, Kensy; Goldin-Meadow, Susan

    2017-07-01

    Analogy researchers do not often examine gesture, and gesture researchers do not often borrow ideas from the study of analogy. One borrowable idea from the world of analogy is the importance of distinguishing between attributes and relations. Gentner (, ) observed that some metaphors highlight attributes and others highlight relations, and called the latter analogies. Mirroring this logic, we observe that some metaphoric gestures represent attributes and others represent relations, and propose to call the latter analogical gestures. We provide examples of such analogical gestures and show how they relate to the categories of iconic and metaphoric gestures described previously. Analogical gestures represent different types of relations and different degrees of relational complexity, and sometimes cohere into larger analogical models. Treating analogical gestures as a distinct phenomenon prompts new questions and predictions, and illustrates one way that the study of gesture and the study of analogy can be mutually informative. Copyright © 2017 Cognitive Science Society, Inc.

  18. 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.

  19. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Curcumin for the Treatment of Glioblastoma.

    PubMed

    Sordillo, Laura A; Sordillo, Peter P; Helson, Lawrence

    2015-12-01

    Glioblastoma multiforme is a highly aggressive primary cancer of the brain associated with a poor prognosis. Modest increases in survival can sometimes be achieved with the use of temozolomide and radiation therapy after surgery, but second-line therapy after recurrence has a limited efficacy. Curcumin has demonstrated promising results against this form of cancer in experimental models. The reported activity of curcumin against cancer stem cells, a major cause of glioblastoma resistance to therapy, and its ability to augment the apoptotic effects of ceramides, suggest it would have a synergistic effect with cytotoxic chemotherapy agents currently used in second-line therapy, such as lomustine. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. 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

  2. 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.

  3. 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.

  4. 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.

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

    PubMed

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

    2014-01-01

    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. 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. 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. Nanotized curcumin holds a considerable promise in therapeutics as demonstrated here for treating malaria as a test system.

  6. Curcumin: a novel treatment for skin-related disorders.

    PubMed

    Nguyen, Tuyet A; Friedman, Adam J

    2013-10-01

    Curcumin, or diferuloylmethane, is a crystalline compound which gives the East Asian spice turmeric its bright yellow color. The medicinal properties of this spice have been referenced in numerous countries and cultures throughout the world. Today, there is growing scientific evidence suggesting curcumin's utility in the treatment of chronic pain, inflammatory dermatoses, acceleration of wound closure, skin infections, as well as cosmetic ailments such as dyspigmentation. In addition, curcumin may have a protective role against various pollutants and cytotoxic agents, indicating that it may be beneficial in a mitigational or prophylaxis role. Although turmeric has been used for thousands of years in alternative medicine, curcumin has yet to emerge as a component of our mainstream dermatologic therapeutic armamentarium. Interestingly, curcumin provides an ideal alternative to current therapies because of its relative safety profile even at high doses. Although the advantageous properties of curcumin in medicine are well established, its therapeutic potential thus far has been limited because of its poor oral bioavailablity. Topical administration of curcumin can directly deliver it to the affected tissue making it useful in treating skin-related disorders. However, limitations still exist such as the cosmetically unpleasing bright yellow-orange color, its poor solubility, and its poor stability at a high pH. Here the current literature detailing the potential and current use of curcumin in dermatology is reviewed.

  7. Oxidative Metabolites of Curcumin Poison Human Type II Topoisomerases†

    PubMed Central

    Ketron, Adam C.; Gordon, Odaine N.; Schneider, Claus; Osheroff, Neil

    2013-01-01

    The polyphenol curcumin is the principal flavor and color component of the spice turmeric. Beyond its culinary uses, curcumin is believed to positively impact human health and displays antioxidant, anti-inflammatory, antibacterial, and chemopreventive properties. It also is in clinical trials as an anticancer agent. In aqueous solution at physiological pH, curcumin undergoes spontaneous autoxidation that is enhanced by oxidizing agents. The reaction proceeds through a series of quinone methide and other reactive intermediates to form a final dioxygenated bicyclopentadione product. Several naturally occurring polyphenols that can form quinones have been shown to act as topoisomerase II poisons (i.e., increase levels of topoisomerase II-mediated DNA cleavage). Because several of these compounds have chemopreventive properties, we determined the effects of curcumin, its oxidative metabolites, and structurally related degradation products (vanillin, ferulic acid, and feruloylmethane), on the DNA cleavage activities of human topoisomerase IIα and IIβ. Intermediates in the curcumin oxidation pathway increased DNA scission mediated by both enzymes ~4-5–fold. In contrast, curcumin and the bicyclopentadione, as well as vanillin, ferulic acid, and feruloylmethane, had no effect on DNA cleavage. As found for other quinone-based compounds, curcumin oxidation intermediates acted as redox-dependent (as opposed to interfacial) topoisomerase II poisons. Finally, under conditions that promote oxidation, the dietary spice turmeric enhanced topoisomerase II-mediated DNA cleavage. Thus, even within the more complex spice formulation, oxidized curcumin intermediates appear to function as topoisomerase II poisons. PMID:23253398

  8. 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

  9. 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

  10. 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

  11. 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

  12. Synergy of bone marrow transplantation and curcumin ensue protective effects at early onset of diabetes in mice.

    PubMed

    Arivazhagan, Arivarasan; Krishna, Soni; Yadav, Shivangi; Shah, Harshit Rajesh; Kumar, Pravir; Ambasta, Rashmi Kumar

    2015-07-01

    The aim of this study was to investigate the early onset effects of diabetes on pro-angiogenic signaling pathway, total number of bone marrow cells, organs (pancreas and kidney) damage and the reversal effect of diabetes by combinatorial treatment of curcumin and bone marrow transplantation in streptozotocin (STZ) induced diabetic mice. In the present study, Streptozotocin induced diabetic mice were transplanted with bone marrow cells (2 × 10(6) ) followed by the administration of curcumin (80 mg/kg bodyweight). Effect of diabetes on the different organs was studied by H&E, Western blotting and immunofluorescence using vascular endothelial growth factor (VEGF), platelet/endothelial cell adhesion molecule (PECAM), insulin, Caspase-9 and Caspase-3 antibodies. The effect of diabetes results in the reduction of the total cell number and viability of the bone marrow cells, organ degeneration and lower VEGF/PECAM expression. However, transplantation with normal bone marrow cells significantly reduced the blood glucose levels (above normal range) and initiated the organ regeneration via the VEGF/PECAM mediated manner. Curcumin treatment further reduced the blood glucose level (near normal); and accelerated the organ regeneration, enhanced VEGF/PECAM expression and decreased caspase expression level in the organs. Curcumin also had a protective role against the glucotoxicity test performed on the bone marrow cells. This study suggests that bone marrow transplantation and curcumin administration is an effective treatment in reversing the early onset effects of diabetes via the VEGF/PECAM signaling pathway. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

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

    PubMed

    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.

  14. 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

  15. Degradation of Curcumin: From Mechanism to Biological Implications.

    PubMed

    Schneider, Claus; Gordon, Odaine N; Edwards, Rebecca L; Luis, Paula B

    2015-09-09

    Curcumin is the main bioactive ingredient in turmeric extract and widely consumed as part of the spice mix curry or as a dietary supplement. Turmeric has a long history of therapeutic application in traditional Asian medicine. Biomedical studies conducted in the past two decades have identified a large number of cellular targets and effects of curcumin. In vitro curcumin rapidly degrades in an autoxidative transformation to diverse chemical species, the formation of which has only recently been appreciated. This paper discusses how the degradation and metabolism of curcumin, through products and their mechanism of formation, provide a basis for the interpretation of preclinical data and clinical studies. It is suggested that the previously unrecognized diversity of its degradation products could be an important factor in explaining the polypharmacology of curcumin.

  16. 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

  17. Degradation of curcumin: From mechanism to biological implications

    PubMed Central

    Schneider, Claus; Gordon, Odaine N.; Edwards, Rebecca L.; Luis, Paula B.

    2016-01-01

    Curcumin is the main bioactive ingredient in turmeric extract and widely consumed as part of the spice mix curry or as dietary supplement. Turmeric has a long history of therapeutic application in traditional Asian medicine. Biomedical studies conducted in the past two decades have identified a large number of cellular targets and effects of curcumin. In vitro curcumin rapidly degrades in an autoxidative transformation to diverse chemical species, formation of which has only recently been appreciated. We discuss how degradation and metabolism of curcumin, through products and their mechanism of formation, provide a basis for the interpretation of preclinical data and clinical studies. We suggest that the previously unrecognized diversity of its degradation products could be an important factor in explaining the polypharmacology of curcumin. PMID:25817068

  18. Heterocyclic Curcumin Derivatives of Pharmacological Interest: Recent Progress.

    PubMed

    Martinez-Cifuentes, Maximiliano; Weiss-Lopez, Boris; Santos, Leonardo S; Araya-Maturana, Ramiro

    2015-01-01

    Curcumin, a natural yellow polyphenol, is isolated from the herb Curcuma longa L. (turmeric), a member of the ginger family. It has been extensively studied due to their multiple pharmacological properties. Nevertheless, curcumin has disadvantages such as poor water solubility, poor bioavailability and rapid metabolism, which has prompted the search for analogues that overcome these shortcomings while maintaining or improving their good pharmacological properties. Among the main curcumin analogues that have been developed, the heterocyclic curcuminoids show a high interest. In this review, we describe recent progress in the synthesis and pharmacological properties of new heterocyclic curcumin derivatives. The most recent developments in anti-cancer, anti-Alzheimer, anti-bacterial and anti-oxidants heterocyclic curcumin derivatives are covered.

  19. Synergistic antibacterial activity of Curcumin with antibiotics against Staphylococcus aureus.

    PubMed

    Teow, Sin-Yeang; Ali, Syed Atif

    2015-11-01

    This study evaluated the synergistic antibacterial activity of Curcumin with 8 different antibiotic groups. Two reference, one clinical and ten environmental strains of Staphylococcus aureus (S. aureus) were tested. Disc diffusion assay with 25 μg/mL Curcumin demonstrated synergism in combination with a majority of tested antibiotics against S. aureus. However, checkerboard micro dilution assay only showed synergism, fractional inhibitory concentration index (FICI) <0.5 in three antibiotics i.e. Gentamicin, Amikacin, and Ciprofloxacin. Other antibiotics showed indifferent interactions but no antagonism was observed. In time-kill curve, appreciable reduction of bacterial cells was also observed in combination therapy (Curcumin + antibiotics) compared to monotherapy (Curcumin or antibiotic(s) alone). The antibiotics with higher synergistic interaction with Curcumin are arranged in a decreasing order: Amikacin > Gentamicin > Ciprofloxacin.

  20. Polymeric Curcumin Nanoparticle Pharmacokinetics and Metabolism in Bile Duct Cannulated Rats

    PubMed Central

    Zou, Peng; Helson, Lawrence; Maitra, Anirban; Stern, Stephan T.; McNeil, Scott E.

    2013-01-01

    The objective of this study was to compare the pharmacokinetics and metabolism of polymeric nanoparticle encapsulated (nanocurcumin), and solvent solubilized curcumin formulations in Sprague Dawley (SD) rats. Nanocurcumin is currently under development for cancer therapy. Since free, unencapsulated curcumin is rapidly metabolized and excreted in rats, upon i.v. administration of nanocurcumin only nanoparticle encapsulated curcumin can be detected in plasma samples. Hence, the second objective of this study was to utilize the metabolic instability of curcumin to assess in vivo drug release from nanocurcumin. Nanocurcumin and solvent solubilized curcumin were administered at 10 mg curcumin/kg by jugular vein to bile duct-cannulated male SD rats (n = 5). Nanocurcumin increased the plasma Cmax of curcumin 1749 fold relative to the solvent solubilized curcumin. Nanocurcumin also increased the relative abundance of curcumin and glucuronides in bile, but did not dramatically alter urine and tissue metabolite profiles. The observed increase in biliary and urinary excretion of both curcumin and metabolites for the nanocurcumin formulation suggested rapid, “burst” release of curcumin. Although the burst release observed in this study is a limitation for targeted tumor delivery, nanocurcumin still exhibits major advantages over solvent solubilized curcumin, as the nanoformulation does not result in the lung accumulation observed for the solvent solubilized curcumin and increases overall systemic curcumin exposure. Additionally, the remaining encapsulated curcumin fraction following burst release is available for tumor delivery via the enhanced permeation and retention effect commonly observed for nanoparticle formulations. PMID:23534919

  1. 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.

  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. Cyclodextrin-complexed curcumin exhibits anti-inflammatory and antiproliferative activities superior to those of curcumin through higher cellular uptake.

    PubMed

    Yadav, Vivek R; Prasad, Sahdeo; Kannappan, Ramaswamy; Ravindran, Jayaraj; Chaturvedi, Madan M; Vaahtera, Lauri; Parkkinen, Jaakko; Aggarwal, Bharat B

    2010-10-01

    Curcumin, a yellow pigment present in the spice turmeric (Curcuma longa), has been linked with multiple beneficial activities, but its optimum potential is limited by poor bioavailability, in part due to the lack of solubility in aqueous solvents. To overcome the solubility problem, we have recently developed a novel cyclodextrin complex of curcumin (CDC) and examined here this compound for anti-inflammatory and antiproliferative effects. Using the electrophoretic mobility shift assay, we found that CDC was more active than free curcumin in inhibiting TNF-induced activation of the inflammatory transcription factor NF-kappaB and in suppressing gene products regulated by NF-kappaB, including those involved in cell proliferation (cyclin D1), invasion (MMP-9), and angiogenesis (VEGF). CDC was also more active than free curcumin in inducing the death receptors DR4 and DR5. Annexin V staining, cleavage of caspase-3 and PARP, and DNA fragmentation showed that CDC was more potent than free curcumin in inducing apoptosis of leukemic cells. Antiproliferative assays also demonstrated that CDC was more active than free curcumin in suppressing proliferation of various cancer cell lines. The cyclodextrin vehicle had no effect in these assays. Compared with free curcumin, CDC had a greater cellular uptake and longer half-life in the cells. Overall we demonstrated that CDC had superior attributes compared with free curcumin for cellular uptake and for antiproliferative and anti-inflammatory activities. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  4. Cyclodextrin-Complexed Curcumin Exhibits Anti-inflammatory and Antiproliferative Activities Superior to Those of Curcumin Through Higher Cellular Uptake

    PubMed Central

    Yadav, Vivek R.; Prasad, Sahdeo; Kannappan, Ramaswamy; Ravindran, Jayaraj; Chaturvedi, Madan M; Vaahtera, Lauri; Parkkinen, Jaakko; Aggarwal, Bharat B.

    2010-01-01

    Curcumin, a yellow pigment present in the spice turmeric (Curcuma longa), has been linked with multiple beneficial activities, but its optimum potential is limited by poor bioavailability, in part due to lack of solubility in aqueous solvents. To overcome the solubility problem, we have recently developed a novel cyclodextrin complex of curcumin (CDC) and examined here this compound for anti-inflammatory and antiproliferative effects. Using the electrophoretic gel shift mobility assay, we found that CDC was more active than free curcumin in inhibiting TNF-induced activation of the inflammatory transcription factor NF-κB and in suppressing gene products regulated by NF-κB, including those involved in cell proliferation (cyclin D1), invasion (MMP-9), and angiogenesis (VEGF). CDC was also more active than free curcumin in inducing the death receptors DR4 and DR5. Annexin V staining, cleavage of caspase-3 and PARP, and DNA fragmentation showed that CDC was more potent than free curcumin in inducing apoptosis of leukemic cells. Antiproliferative assays also demonstrated that CDC was more active than free curcumin in suppressing proliferation of various cancer cell lines. The cyclodextrin vehicle had no effect in these assays. Compared with free curcumin, CDC had a greater cellular uptake and longer half-life in the cells. Overall we demonstrated that CDC had superior attributes compared with free curcumin for cellular uptake and for antiproliferative and anti-inflammatory activities. PMID:20599780

  5. 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…

  6. 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

  7. 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.

  8. 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.

  9. In vitro biocompatibility and release of curcumin from curcumin microcomplex-loaded chitosan scaffold.

    PubMed

    Amirthalingam, Muthukumar; Kasinathan, Narayanan; Mutalik, Srinivas; Udupa, Nayanabhirama

    2015-01-01

    Scaffold if suitably modified could be used as a drug delivery system. To develop chitosan scaffold as a delivery system for delivering curcumin in wound-healing application. Chitosan-curcumin microcomplex particles were prepared, and the effect of drug-polymer ratio (DPR) and homogenisation speed (HS) was studied using a two-level full-factorial design. Chitosan scaffold was prepared and incorporated with curcumin microcomplexes to obtain a chitosan scaffold-containing chitosan-curcumin microcomplex (CS-CCM). Antimicrobial property of the CS-CCM against Escherichia coli was studied. The cytotoxicity of CS-CCM was studied by assessing the cell viability by MTT assay. DPR had a significant effect (p ≤ 0.05) on the drug content. CS-CCM was able to inhibit the growth of E. coli considerably. The MTT results showed that CS-CCM is non-cytotoxic and supports cell proliferation. CS-CCM due to its biocompatibility and antimicrobial property could be further evaluated for potential application in wound healing.

  10. 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.

  11. Dimethoxycurcumin, a metabolically stable analogue of curcumin enhances the radiosensitivity of cancer cells: Possible involvement of ROS and thioredoxin reductase

    SciTech Connect

    Jayakumar, Sundarraj; Patwardhan, R.S.; Pal, Debojyoti; Sharma, Deepak; Sandur, Santosh K.

    2016-09-09

    Dimethoxycurcumin (DIMC), a structural analogue of curcumin, has been shown to have more stability, bioavailability, and effectiveness than its parent molecule curcumin. In this paper the radiosensitizing effect of DIMC has been investigated in A549 lung cancer cells. As compared to its parent molecule curcumin, DIMC showed a very potent radiosensitizing effect as seen by clonogenic survival assay. DIMC in combination with radiation significantly increased the apoptosis and mitotic death in A549 cells. This combinatorial treatment also lead to effective elimination of cancer stem cells. Further, there was a significant increase in cellular ROS, decrease in GSH to GSSG ratio and also significant slowdown in DNA repair when DIMC was combined with radiation. In silico docking studies and in vitro studies showed inhibition of thioredoxin reductase enzyme by DIMC. Overexpression of thioredoxin lead to the abrogation of radiosensitizing effect of DIMC underscoring the role of thioredoxin reductase in radiosensitization. Our results clearly demonstrate that DIMC can synergistically enhance the cancer cell killing when combined with radiation by targeting thioredoxin system. - Highlights: • DIMC enhances radiosensitivity of cancer cells by inducing cell death. • DIMC with radiation disrupted the cellular redox and targeted cancer stem cells. • DNA repair is hampered when cells are treated with DIMC. • DIMC inhibited thioredoxin reductase in cancer cells.

  12. Submicron complex lipid carriers for curcumin delivery to intestinal epithelial cells: Effect of different emulsifiers on bioaccessibility and cell uptake.

    PubMed

    Yucel, Cigdem; Quagliariello, Vincenzo; Iaffaioli, Rosario Vincenzo; Ferrari, Giovanna; Donsì, Francesco

    2015-10-15

    Submicrometric lipid-based carriers were developed to encapsulate curcumin and deliver it to intestinal epithelial cells. A lipid matrix comprising monoolein, sunflower oil and water at weight ratio 1:1:1 was selected, upon screening of different combinations of amphiphilic molecules, vegetable oils and water, because of its high encapsulations efficiency of curcumin, retained over time and relatively lower content of amphiphilic molecules. Upon dispersion in aqueous phase, the carriers were stabilized by: (a) whey protein isolates (WPI), alone and (b) in combination with modified starch (WPI-MS), or by (c) polysorbate 20 (T20). Whereas T20-stabilized systems exhibited extremely fine particles (120 nm), WPI and WPI-MS stabilized carriers were characterized by a significantly larger mean particle size (270 nm). The thicker macromolecular layer of WPI and WPI-MS enabled better (a) physical stability, (b) controlled shell degradation during simulated digestion, and (c) curcumin bioaccessibility targeted at the intestinal digestion phase than T20-systems. However, uptake studies in HT29 cell lines, simulating intestinal epithelial cells, showed that WPI and WPI-MS carriers exhibited after 24h a lower relative uptake than T20-stabilized systems (about 60% and 80%, respectively), as a consequence of smaller size and higher cell adherence of T20 carriers to the cell membrane. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. 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.

  14. 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.

  15. 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)

  16. 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)

  17. 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)

  18. 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

  19. 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

  20. 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.

  1. 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.

  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. 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

  4. 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.

  5. 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.

  6. Mucoadhesive liposomes as new formulation for vaginal delivery of curcumin.

    PubMed

    Berginc, Katja; Suljaković, Sabina; Škalko-Basnet, Nataša; Kristl, Albin

    2014-05-01

    Local delivery to the affected area represents the optimal means by which advantageous pharmacological properties of curcumin may be fully exploited as currently, due to the biopharmaceutical limitations associated with this polyphenol, its full beneficial effects remain limited. Curcumin-containing liposomes coated with bioadhesive polymers of natural and synthetic origin (chitosan and Carbopol) were evaluated in vitro. For these purposes, an in vitro model of vaginal mucus was developed allowing the monitoring of curcumin permeability in the conditions mimicking vaginal environment. The model was optimized by varying the amounts of glycoproteins, as compared to the permeabilities determined through isolated bovine mucus. The strength of bioadhesion was evaluated using the isolated bovine mucosa. Both curcumin solution and non-coated curcumin liposomes served as controls. Bioadhesive polymers enabled significantly higher (p<0.05) curcumin permeability through the artificial and isolated bovine mucus compared to the controls. Polymer coating of liposomes resulted in an increase in their bioadhesiveness. Mucoadhesive liposomes can be considered as potential novel drug delivery systems intended for vaginal administration of curcumin. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. Curcumin mediates anticancer effects by modulating multiple cell signaling pathways.

    PubMed

    Kunnumakkara, Ajaikumar B; Bordoloi, Devivasha; Harsha, Choudhary; Banik, Kishore; Gupta, Subash C; Aggarwal, Bharat B

    2017-08-01

    Curcumin, a component of a spice native to India, was first isolated in 1815 by Vogel and Pelletier from the rhizomes of Curcuma longa (turmeric) and, subsequently, the chemical structure of curcumin as diferuloylmethane was reported by Milobedzka et al. [(1910) 43., 2163-2170]. Since then, this polyphenol has been shown to exhibit antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antifungal activities. The current review primarily focuses on the anticancer potential of curcumin through the modulation of multiple cell signaling pathways. Curcumin modulates diverse transcription factors, inflammatory cytokines, enzymes, kinases, growth factors, receptors, and various other proteins with an affinity ranging from the pM to the mM range. Furthermore, curcumin effectively regulates tumor cell growth via modulation of numerous cell signaling pathways and potentiates the effect of chemotherapeutic agents and radiation against cancer. Curcumin can interact with most of the targets that are modulated by FDA-approved drugs for cancer therapy. The focus of this review is to discuss the molecular basis for the anticancer activities of curcumin based on preclinical and clinical findings. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  12. 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.

  13. 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.

  14. 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.

  15. Curcumin-based anti-prostate cancer agents.

    PubMed

    Chen, Qiao-Hong

    2015-01-01

    Prostate cancer possesses the highest occurrence rate and is the second-paramount disease that causes cancer-affiliated death among men in the United States. Approximately 30,000 men die each year of castration-resistant prostate cancer due to the inevitable progression of resistance to first-line treatment with docetaxel. The safety profile of dietary curcumin in humans has been well-documented, and its therapeutic prospect in treating prostate cancer, especially for castration-resistant prostate cancer, has been evidenced in several cell culture systems and human xenograft mouse models. The critical disadvantage of curcumin as a drug candidate is its low bioavailability caused by poor water solubility and rapid in vivo metabolism. Curcumin is characteristic of regulating multiple targets, representing a good example for the philosophy to search for multitargeted drugs in the realm of drug design and drug development. This feature, together with its potential in treating castration-resistant prostate cancer and its safety profile, enables curcumin to serve as an ideal lead compound for the design and syntheses of curcumin-based agents with improved potential for the clinical therapies of prostate cancer. Several researches aiming to improve its bioavailability and potency resulted in the discovery and development of a wealth of curcumin-based compounds with an enhanced anticancer potential and/or an improved pharmacokinetic profile. This review starts with a brief summarization of the prospect of curcumin in treating prostate cancer and its mechanisms of action, then provides an in-depth overview of current development of curcumin-based anti-prostate cancer agents and their structure-activity relationships, and ends with the syntheses and pharmacokinetic studies of curcumin.

  16. Potential anticancer properties and mechanisms of action of curcumin.

    PubMed

    Vallianou, Natalia G; Evangelopoulos, Angelos; Schizas, Nikos; Kazazis, Christos

    2015-02-01

    Curcumin, a yellow substance belonging to the polyphenols superfamily, is the active component of turmeric, a common Indian spice, which is derived from the dried rhizome of the Curcuma longa plant. Numerous studies have demonstrated that curcumin possesses anti-oxidant, anti-inflammatory and anticancerous properties. The purpose of this review is to focus on the anti-tumor effects of curcumin. Curcumin inhibits the STAT3 and NF-κB signaling pathways, which play key-roles in cancer development and progression. Also, inhibition of Sp-1 and its housekeeping gene expressions may serve as an important hypothesis to prevent cancer formation, migration, and invasion. Recent data have suggested that curcumin may act by suppressing the Sp-1 activation and its downstream genes, including ADEM10, calmodulin, EPHB2, HDAC4, and SEPP1 in a concentration-dependent manner in colorectal cancer cell lines; these results are consistent with other studies, which have reported that curcumin could suppress the Sp-1 activity in bladder cancer and could decrease DNA binding activity of Sp-1 in non-small cell lung carcinoma cells. Recent data advocate that ER stress and autophagy may as well play a role in the apoptosis process, which is induced by the curcumin analogue B19 in an epithelial ovarian tumor cell line and that autophagy inhibition could increase curcumin analogue-induced apoptosis by inducing severe ER stress. The ability of curcumin to induce apoptosis in tumor cells and its anti-angiogenic potential will be discussed in this review. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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 washo