Curcumin 321668 225303924 2008-07-13T00:05:12Z WriterHound 266293 /* Risks and Side Effects */ copyedit {{Chembox new | Name = Curcumin | ImageFile = Curcumin structure (keto).svg | ImageSize = 300px | ImageName = Keto form | IUPACName = (1''E'',6''E'')-1,7-bis (4-hydroxy-<br />3-methoxyphenyl) -1,6-<br />heptadiene-3,5-dione | OtherNames = curcumin<br />diferuloylmethane<br />C.I. 75300<br />Natural Yellow 3 | Section1 = {{Chembox Identifiers | SMILES = Oc1ccc(cc1OC)/C<br />=C/C(=O)CC(=O)/C= C/c2ccc(O)c(OC)c2 | CASNo = 458-37-7 | RTECS = }} | Section2 = {{Chembox Properties | Formula = C<sub>21</sub>H<sub>20</sub>O<sub>6</sub> | MolarMass = 368.38 g/mol | Appearance = Bright Yellow<br />to Orange powder | Density = | Solubility = | MeltingPt = 183°C (361 K) | BoilingPt = | pKa = }} | Section7 = {{Chembox Hazards | ExternalMSDS = | MainHazards = | FlashPt = | RPhrases = | SPhrases = }} | Section8 = {{Chembox Related | OtherCpds = }} }} '''Curcumin''' is the principal curcuminoid of the Indian curry spice [[turmeric]], the other two [[curcuminoids]] being [[demethoxycurcumin]] and [[Bis-demethoxycurcumin]]. The curcuminoids are [[polyphenol]]s and are responsible for the yellow color of [[turmeric]]. Curcumin can exist in at least two [[tautomer]]ic forms, [[ketone|keto]] and [[enol]]. The enol form is more energetically stable in the solid phase and in solution.<ref>{{cite journal | last = Kolev | first = Tsonko M. | coauthors = et al. | title = DFT and Experimental Studies of the Structure and Vibrational Spectra of Curcumin | journal = International Journal of Quantum Chemistry | volume = 102 | issue = 6 |date = 2005 | pages = 1069&ndash;79 | publisher = Wiley Periodicals | doi = 10.1002/qua.20469}}</ref> It is also [[hepatoprotective]].<ref>{{cite journal | title = Hepatoprotective effect of a curcumin/absinthium compound in experimental severe liver injury | first = F. | last = Marotta | coauthors = et al. | journal = Chinese Journal of Digestive Diseases | volume = 4 | issue = 3 | date = October 2003 | pages = 122&ndash;7 | publisher = Blackwell Publishing | doi = 10.1046/j.1443-9573.2003.00133.x}}</ref> Curcumin can be used for boron quantification in the so-called curcumin method. It reacts with [[boric acid]] forming a red colored compound, known as [[rosocyanine]]. Since curcumin is brightly colored, it may be used as a [[food coloring]]. As a [[food additive]], its [[E number]] is [[E100]]. ==Chemistry== Curcumin incorporates several functional groups. The aromatic ring systems, which are [[polyphenol]]s are connected by two α,β-unsaturated [[carbonyl]] groups. The two carbonyl groups form a [[diketone]]. The diketone form stable [[enol]]s or are easily deprotonated and form enolates, while the α,β-unsaturated carbonyl is a good [[Michael acceptor]] and undergoes [[nucleophilic addition]]. ==Potential medical uses== Curcumin is known for its [[antitumor]],<ref>{{cite journal | title = Molecular targets of dietary agents for prevention and therapy of cancer | last = Aggarwal | first = BB. | coauthors = Shishodia S. | journal = Biochemical Pharmacology | date = May 2006 | volume = 71 | issue = 10 | pages = 1397&ndash;421 | publisher = Elsevier | doi = 10.1016/j.bcp.2006.02.009}}</ref><ref>{{cite journal | title = Curcumin Inhibits Hypoxia-Inducible Factor-1 by Degrading Aryl Hydrocarbon Receptor Nuclear Translocator: A Mechanism of Tumor Growth Inhibition | first = Hyunsung | last = Choi | coauthors = et al. | journal = Molecular Pharmacology | volume = 70 | date = July 2006 | pages = 1664&ndash;71 | publisher = American Society for Pharmacology and Experimental Therapeutics | doi = 10.1124/mol.106.025817 | pmid = 16880289}}</ref> [[antioxidant]], [[arthritis|antiarthritic]], [[amyloid|anti-amyloid]] and [[anti-inflammatory]] properties.<ref>{{cite journal | title = Spice Healer | url = http://sciam.com/article.cfm?chanID=sa006&articleID=131CED4F-E7F2-99DF-3C84BB412D1D3B51&pageNumber=1&catID=2 | journal = Scientific American | first = Gary | last = Stix |date=February 2007}}</ref> Anti-inflammatory properties may be due to inhibition of [[eicosanoid]] biosynthesis.<ref>{{cite journal | last = Srivastava | first = KC | coauthors = Bordia A; Verma SK | title = Curcumin, a major component of the food spice turmeric (Curcuma longa), inhibits aggregation and alters eicosanoid metabolism in human blood platelets | journal = Prostaglandins Leukot Essent Fatty Acids | date = April 1995 | volume = 52 | issue = 4 | pages = 223&ndash;7 | pmid = 7784468 | doi = 10.1016/0952-3278(95)90040-3}}</ref> In addition it may be effective in treating [[malaria]], prevention of [[cervical cancer]], and may interefere with the replication of the [[HIV]] virus.<ref>{{cite news | title = Turmeric can combat malaria, cancer virus and HIV | url = http://www.scidev.net/News/index.cfm?fuseaction=readNews&itemid=1987&language=1 | date = 2005-03-11 | author = Padma, TV | work = SciDev.net}}</ref> In HIV, it appears to act by interfering with [[P300/CBP|P300/CREB-binding protein (CBP)]]. A 2008 study at [[Michigan State University]] showed that low concentrations of curcumin interfere with [[Herpesviridae|Herpes simplex virus-1 (HSV-1)]] replication.<ref name="PMID18191976">{{cite journal |title=Curcumin inhibits herpes simplex virus immediate-early gene expression by a mechanism independent of p300/CBP histone acetyltransferase activity |journal=Virology |date=January 2008 |author = Kutluay SB, Doroghazi J, Roemer ME, Triezenberg SJ <!-- volume = *unknown* --> <!-- issue = *unknown* --> <!-- pages = *unknown* --> |pmid=18191976 |doi=10.1016/j.virol.2007.11.028 |pages=239 |volume=373}}</ref> The same study showed that curcumin inhibited the recruitment of [[RNA polymerase II]] to viral DNA, thus inhibiting the [[transcription (genetics)|transcription]] of the viral DNA.<ref name="PMID18191976"/> This effect was shown to be independent of effect on histone acetyltransferase activities of p300/CBP.<ref name="PMID18191976"/> A previous (1999) study performed at [[University of Cincinnati]] indicated that curcumin is significantly associated with protection from infection by HSV-2 in animal models of intravaginal infections.<ref name="PMID10443534">{{cite journal |title=Plant products as topical microbicide candidates: assessment of in vitro and in vivo activity against herpes simplex virus type 2 |journal=Antiviral research |date=1999 Jul |author = Bourne KZ, Bourne N, Reising SF, Stanberry LR |volume=42 |issue=3 |pages=219–26 |pmid=10443534 |doi=10.1016/S0166-3542(99)00020-0}}</ref> Curcumin acts as a free radical scavenger and antioxidant, inhibiting [[lipid peroxidation]] and oxidative DNA damage. Curcuminoids induce [[glutathione S-transferase]] and are potent inhibitors of [[cytochrome P450]]. For the last few decades, extensive work has been done to establish the biological activities and pharmacological actions of curcumin. Its anticancer effects stem from its ability to induce [[apoptosis]] in cancer cells without cytotoxic effects on healthy cells. Curcumin can interfere with the activity of the transcription factor [[NF-κB]], which has been linked to a number of inflammatory diseases such as [[cancer]].<ref>Aggarwal BB, Shishodia S. Suppression of the nuclear factor-kappaB activation pathway by spice-derived phytochemicals: reasoning for seasoning. Ann N Y Acad Sci. 2004 Dec;1030:434-41. PMID 15659827.</ref> Indeed, when 0.2% curcumin is added to diet given to rats or mice previously given a carcinogen, it significantly reduces colon carcinogenesis (Data from sixteen scientific articles reported in the [http://www.inra.fr/reseau-nacre/sci-memb/corpet/indexan.html Chemoprevention Database]). A 2007 report indicates that curcumin may suppress [[MDM2]], an [[oncogene]] involved in mechanisms of [[malignant]] [[tumor]] formation.<ref>{{cite news | title = Curcumin's anti-cancer mechanism proposed | date = 2007-04-13 | url = http://www.nutraingredients-usa.com/news/ng.asp?n=75745&m=1NIU413&c=zondoewvtjilvpr | work = nutraingredients-usa.com}}</ref> A 2004 UCLA-Veterans Affairs study involving genetically altered mice suggests that curcumin might inhibit the accumulation of destructive beta-amyloid in the brains of [[Alzheimer's disease]] patients and also break up existing plaques associated with the disease.<ref>{{cite journal | last = Yang | first = F | coauthors = Lim GP; Begum AN; Ubeda OJ; Simmons MR; Ambegaokar SS; Chen PP; Kayed R; Glabe CG; Frautschy SA; Cole GM | title = Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo | journal = Journal of Biological Chemistry | date = February 2005 | volume = 280 | issue = 7 | pages = 5892&ndash;901 | pmid = 15590663 | publisher = American Society for Biochemistry and Molecular Biology | doi = 10.1074/jbc.M404751200}}</ref> There is also circumstantial evidence that curcumin improves mental functions; a survey of 1010 Asian people who ate [[yellow curry]] and were between the ages of 60 and 93 showed that those who ate the sauce "once every six months" or more had higher [[Mini-mental state examination|MMSE]] results than those who did not.<ref>{{cite journal | author = Ng TP; Chiam PC; Lee T; Chua HC; Lim L; Kua EH | title = Curry consumption and cognitive function in the elderly | journal = American Journal of Epidemiology | date = November 2006 | volume = 164 | issue = 9 | pages = 898&ndash;906 | pmid = 16870699 | publisher = Oxford University Press | doi = 10.1093/aje/kwj267}}</ref> From a scientific standpoint, though, this does not show whether the curry caused it, or people who had healthy habits also tended to eat the curry, or some completely different relationship. Numerous studies have demonstrated that curcumin, amongst only a few other things such as high impact exercise, learning, bright light, and antidepressant usage, has a positive affect on neurogenesis in the [[hippocampus]] and concentrations of [[Brain-derived neurotrophic factor]] (BDNF), reductions in both of which are associated with stress, depression, and anxiety. <ref name="xu">{{cite journal | author = Xu Y, Ku B, Cui L, Li X, Barish PA, Foster TC, Ogle WO. | title = Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats | journal = Brain Res | date = August 2007 | pmid = 17617388 | volume = 1162 | pages = 9 | doi = 10.1016/j.brainres.2007.05.071}}</ref> <ref name="wu">{{cite journal | author = Wu A, Ying Z, Gomez-Pinilla F. | title = Dietary curcumin counteracts the outcome of traumatic brain injury on oxidative stress, synaptic plasticity, and cognition | journal = Experimental Neurology | date = February 2006 | pmid = 16364299 | volume = 197 | pages = 309 | doi = 10.1016/j.expneurol.2005.09.004}}</ref> <ref name="Bala">{{cite journal | author = Bala K, Tripathy BC, Sharma D. | title = Neuroprotective and anti-ageing effects of curcumin in aged rat brain regions | journal = Biogerontology | date = April 2006 | pmid = 16802111 | volume = 7 | pages = 81 | doi = 10.1007/s10522-006-6495-x}}</ref> et al. Little curcumin, when eaten, is absorbed{{ndash}} 2 to 10 grams of curcumin alone resulted in undetectable to very low serum levels.<ref name="Shoba">{{cite journal | author = Shoba G; Joy D; Joseph T; Majeed M; Rajendran R; Srinivas PS | title = Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers | journal = Planta Med | date = May 1998 | volume = 64 | issue = 4 | pages = 353&ndash;6 | pmid = 9619120 | doi = 10.1055/s-2006-957450}}</ref> Curcumin is unstable in the gut, and the traces that pass through the GI tract rapidly degrades or is conjugated through [[glucuronidation]]. Co-supplementation with 20 mg of [[piperine]] (extracted from black pepper) significantly increased the absorption of curcumin by 2000% in a study funded by a prominent manufacturer of piperine<ref name="Shoba"/>. However, due to its effects on drug metabolism, piperine should be taken cautiously (if at all) by individuals taking other medications. Some benefits of curcumin, such as the potential protection from colon cancer, may not require systemic absorption. Alternatively, dissolving curcumin in hot water prior to ingestion, or in warm oily liquids, appears to increase bioavailability, however no published studies to date have documented this. Cooking with curcumin and oil may increase absorption, however peer-reviewed scientific literature has not documented this, while the literature has documented concerns regarding the heat stability and degradation of curcumin in the gut. Recently, a polymeric nanoparticle encapsulated formulation of curcumin ("nanocurcumin"<ref name="PMID17439648">{{cite journal | irst = Savita | last = Bisht | coauthors = et al. | doi = 10.1186/1477-3155-5-3 | title = Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): a novel strategy for human cancer therapy | journal = Journal of Nanobiotechnology | date = 2007 | volume = 5 | issue = 3 | publisher = BioMed Central | pmid = 17439648 | pages = 3}}</ref>) has been synthesized which has the potential to bypass many of the shortcomings associated with free curcumin, such as poor solubility and poor systemic bioavailability. Nanocurcumin particles have a size of less than 100 nanometers on average, and demonstrate comparable to superior efficacy compared to free curcumin in human cancer cell line models.<ref name="PMID17439648"/> However, actual in vivo absorption has not been demonstrated with this nanoparticle. Other researchers have developed a number of other curcumin analogs that appear to have greater bioavailability, but these analogs have not been tested broadly, either in vitro or in vivo, for medicinal purposes. Another method to increase the bioavailability of curcumin has recently been patented that involves a simple procedure creating a complex with soy phospholipids. <ref>European patent EP20060004820 </ref> At this point no supplements are available on the market in this form. ==Risks and side effects== Kawanishi et al. (2005) of NCBI remarked that curcumin, like many antioxidants, can be a "double-edged sword" where in the test tube, anti-cancer and antioxidant effects may be seen in addition to pro-oxidant effects.<ref>{{cite journal | author = Kawanishi, S; Oikawa, S; Murata, M; | title = Evaluation for safety of antioxidant chemopreventive agents | date = 2005 | journal = Antioxidants & Redox Signaling | volume = 7 | issue = 11-12 | pages = 1728&ndash;39 | pmid = 16356133 | doi = 10.1089/ars.2005.7.1728}}</ref> Carcinogenic effects are inferred from interference with the [[p53]] [[tumor suppressor]] pathway, an important factor in human [[colon cancer]].<ref>{{cite journal | author = Moos PJ; Edes K; Mullally JE; Fitzpatrick FA | date = 2004 | title = Curcumin impairs tumor suppressor p53 function in colon cancer cells | journal = Carcinogenesis | volume = 25 | issue = 9 | pages = 1611&ndash;7 | pmid = 15090465 | doi = 10.1093/carcin/bgh163}}</ref> Carcinogenic and [[LD50|LD<sub>50</sub>]] tests in mice and rats, however, have failed to establish a relationship between tumorogenesis and administration of curcumin in turmeric [[oleoresin]] at >98% concentrations.<ref>Lois Swirsky Gold. Turmeric (>98% curcurmin). Carcinogenic Potency Database Project. Last updated 3 Apr 2006. Last accessed 4 Jan 2007. [http://potency.berkeley.edu/chempages/TURMERIC%20(%3E98%25%20CURCUMIN).html]</ref> This may prove curcumin medicinally useful as it helps activate [[p53]]{{Fact|date=April 2007}}. When a cell is inhibited by cancer the concentrations of p53 increase, helping cells defend against cancer mechanisms{{Fact|date=April 2007}}. But it may also suppress p53 levels, preventing cells from initiating defensive mechanisms, a response seen only in certain diseases {{Fact|date=April 2007}}. Clinical studies in humans with high doses (>2-12 grams) curcumin supplementation have shown some subjects reporting diarrhea and nausea, however curcumin has also been indicated for these conditions as well. <ref>{{cite journal | author = Hsu CH; Cheng AL.| title = Adv Exp Med Biol | date = 2007 | pmid = 17569225}}</ref> ==References== {{Cleanup-section|date=May 2008}} {{reflist|2}} {{refbegin|2}} * Aggarwal, Bharat B.; Kumar, Anushree; Aggarwal, Manoj S.; Shishodia, Shishir. 2005. "Curcumin derived from turmeric (Curcuma longa): A spice for all seasons." ''Phytopharmaceuticals in Cancer Chemoprevention'', 349-387. * Aggarwal, Bharat et al; December 2006; "Curcumin: The Indian Solid Gold" [http://www.curcumin.co.nz/pdf/Curcumin_The_Indian_Solid_Gold.pdf] * Aggarwal BB, Kumar A, Bharti AC; "Anticancer potential of curcumin: preclinical and clinical studies." ''Anticancer Res.' 2003 Jan-Feb;23(1A):363-98. (PMID 12680238) * Ahmed M. Zahran. Influence of Curcumin on the Redox ‎System and Lipid Peroxidation in Gamma Irradiated Rats. ''‎Egypt. J. Rad. Sci. Applic.'', 20(2): 385-404 (2007).‎ * Campbell, Frederick C.; Collett, Gavin P. 2005. "Chemopreventive properties of curcumin." ''Future Oncology'', 1(3), 405-414. (PMID 16556014) * Chattopadhyay, Ishita; Biswas, Kaushik; Bandyopadhyay, Uday; Banerjee, Ranajit K. 2004. "Turmeric and curcumin: biological actions and medicinal applications." ''Current Science', 87(1), 44-53. * Goel A, Kunnumakkara AB, Aggarwal BB; "Curcumin as 'Curecumin': From kitchen to clinic." ''Biochem Pharmacol', 2007 Aug 19; (PMID 17900536) * Ringman, John M.; Frautschy, Sally A.; Cole, Gregory M.; Masterman, Donna L.; Cummings, Jeffrey L. "A potential role of the curry spice curcumin in Alzheimer's disease." ''Current Alzheimer Research'', 2(2), 131-136. (PMID 15974909) {{refend}} ==External links== {{external links}} *[http://www.mskcc.org/mskcc/html/11571.cfm?RecordID=429&tab=HC Sloan-Kettering Herbal Guide] * [http://www.mdanderson.org/departments/cimer/dindex.cfm?pn=915cd45e-7c37-4305-8e778e10de640e0c Curcumin at M.D. Anderson] * [http://www2.mdanderson.org/depts/oncolog/articles/07/9-sep/9-07-2.html Can a Common Spice Be Used to Treat Cancer?], Dianne C. Witter, OncoLog, September 2007, Vol. 52, No. 9 * [http://www.umm.edu/altmed/articles/turmeric-000277.htm Turmeric], (University of Maryland info on complementary and alternative medicines) * [http://www.herbmed.org/herbs/herb9.htm#Category1Herb9 Clinical trials info on Curcuma Longa at HerbMed] * [http://lpi.oregonstate.edu/infocenter/phytochemicals/curcumin/ Curcumin (metabolism, effects, bioavailability,...], Linus Pauling Institute, Oregon State U. * [http://sciam.com/article.cfm?chanID=sa006&articleID=131CED4F-E7F2-99DF-3C84BB412D1D3B51&pageNumber=1&catID=2 Spice Healer--An ingredient in curry shows promise for treating Alzheimer's, cancer and other diseases], Gary Stix, Scientific American, Feb 2007 *[http://alzheimer.neurology.ucla.edu/Curcumin.html Curcumin & Alzheimer's and Cancer], ongoing studies at Alzheimer's research lab, UCLA, plus human drug trial [http://alzheimer.neurology.ucla.edu/trials.html] * [http://www.technologyreview.com/Nanotech/18849/ Nanocurry vs. cancer] Technology Review, June 12, 2007 * [http://pubs.acs.org/cgi-bin/abstract.cgi/mpohbp/2007/4/i06/abs/mp700113r.html Bioavailability of Curcumin: Problems and Promises], Preetha Anand, Ajaikumar B. Kunnumakkara, Robert A. Newman, and Bharat B. Aggarwal * [http://www.telegraphindia.com/1070611/asp/knowhow/story_7904021.asp Tumour tripper -- Turmeric can boost the immune system in cancer..], The Telegraph, June 11, 2007 * [http://www.patentstorm.us/patents/7196105.html Treatment of human multiple myeloma by curcumin]; US Patent Issued on March 27, 2007 * [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1891180 Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer—Part 2], Curr Oncol. 2006 June; 13(3): 99–107. * [http://www.sciencedaily.com/releases/2007/11/071105083732.htm Curry-derived Molecules Might Be Too Spicy For Colorectal Cancers], ScienceDaily (Nov. 6, 2007) * [http://www.mdanderson.org/pdf/cimer_im_curcumin.pdf Anti-cancer Potential of Curcumin - Presentation] by Bharat Aggarwal Ph.D. [[Category:Natural dyes]] [[Category:Food colorings]] [[Category:Phenols]] [[Category:Phytochemicals]] [[Category:Anti-inflammatory agents]] [[Category:Antioxidants]] [[Category:Dietary antioxidants]] [[Category:Biologically based therapies]] [[bg:Куркумин]] [[cs:Kurkumin]] [[de:Curcumin]] [[es:Curcumina]] [[fr:curcumine]] [[hr:Kurkumin]] [[id:Kurkumin]] [[it:Curcumina]] [[hu:Kurkumin]] [[nl:Curcumine]] [[ja:クルクミン]] [[pl:Kurkumina]] [[pt:Curcumina]] [[ru:Куркумин]] [[sv:Kurkumin]] [[th:ไพล]] [[tr:Kurkumin]]