Curcumin

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Curcumin
Keto form
IUPAC name (1E,6E)-1,7-bis (4-hydroxy-
3-methoxyphenyl) -1,6-
heptadiene-3,5-dione
Other names curcumin
diferuloylmethane
C.I. 75300
Natural Yellow 3
Identifiers
CAS number [458-37-7]
SMILES Oc1ccc(cc1OC)/C
=C/C(=O)CC(=O)/C= C/c2ccc(O)c(OC)c2
Properties
Molecular formula C21H20O6
Molar mass 368.38 g/mol
Appearance Bright Yellow
to Orange powder
Melting point

183°C (361 K)
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)
Infobox disclaimer and references

Curcumin is the principal curcuminoid of the Indian curry spice turmeric, the other two curcuminoids being demethoxycurcumin and Bis-demethoxycurcumin. The curcuminoids are polyphenols and are responsible for the yellow color of turmeric. Curcumin can exist in at least two tautomeric forms, keto and enol. The enol form is more energetically stable in the solid phase and in solution.[1] It is also hepatoprotective.[2]

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.

Contents

[edit] Chemistry

Curcumin incorporates several functional groups. The aromatic ring systems, which are polyphenols are connected by two α,β-unsaturated carbonyl groups. The two carbonyl groups form a diketone. The diketone form stable enols or are easily deprotonated and form enolates, while the α,β-unsaturated carbonyl is a good Michael acceptor and undergoes nucleophilic addition.

[edit] Potential medical uses

Curcumin is known for its antitumor,[3][4] antioxidant, antiarthritic, anti-amyloid and anti-inflammatory properties.[5] Anti-inflammatory properties may be due to inhibition of eicosanoid biosynthesis.[6] In addition it may be effective in treating malaria, prevention of cervical cancer, and may interefere with the replication of the HIV virus.[7] In HIV, it appears to act by interfering with P300/CREB-binding protein (CBP). A 2008 study at Michigan State University showed that low concentrations of curcumin interfere with Herpes simplex virus-1 (HSV-1) replication.[8] The same study showed that curcumin inhibited the recruitment of RNA polymerase II to viral DNA, thus inhibiting the transcription of the viral DNA.[8] This effect was shown to be independent of effect on histone acetyltransferase activities of p300/CBP.[8] 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.[9]

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.[10] 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 Chemoprevention Database). A 2007 report indicates that curcumin may suppress MDM2, an oncogene involved in mechanisms of malignant tumor formation.[11]

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.[12]

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 MMSE results than those who did not.[13] 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), both of which reductions in are associated with stress, depression, and anxiety. [14] [15] [16] et al.

Little curcumin, when eaten, is absorbed – 2 to 10 grams of curcumin alone resulted in undetectable to very low serum levels.[17] 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[17]. 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"[18]) 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.[18] 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. [19] At this point no supplements are available on the market in this form.

[edit] 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.[20] Carcinogenic effects are inferred from interference with the p53 tumor suppressor pathway, an important factor in human colon cancer.[21] Carcinogenic and LD50 tests in mice and rats, however, have failed to establish a relationship between tumorogenesis and administration of curcumin in turmeric oleoresin at >98% concentrations.[22] This may prove curcumin medicinally useful as it helps activate p53[citation needed]. When a cell is inhibited by cancer the concentrations of p53 increase, helping cells defend against cancer mechanisms[citation needed]. But it may also suppress p53 levels, preventing cells from initiating defensive mechanisms, a response seen only in certain diseases[citation needed].

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. [23]

Curcumin Analogs:

S. Mishra et al. have synthesized various conjugates of curcumin. And it was found that curcumin bioconjugates containing glycine, alanine, and/or piperic acid were found to show improved antimicrobial[24] properties over curcumin, suggesting increased cellular uptake or reduced metabolism of these bioconjugates resulting in increased concentration inside the infected cells.[25] Study of pro- and anti-oxidant properties of different bioconjugates of curcumin and testing their apoptotic potential on tumor cells. [26] Various curcumin based natural antimalarial agent’s viz. pyrazole, isoxazole, substituted pyrazole and Knoevenagel condensates of curcumin have been designed and synthesized. It was found that some of the curcumin analogs showed better activity (in nanomolar range) as compared to the parent molecule against malarial parasite; P. falciparum. [27]

[edit] References

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Please improve this article if you can (May 2008).
  1. ^ Kolev, Tsonko M.; et al. (2005). "DFT and Experimental Studies of the Structure and Vibrational Spectra of Curcumin". International Journal of Quantum Chemistry 102 (6): 1069–79. Wiley Periodicals. 
  2. ^ Marotta, F.; et al. (October 2003). "Hepatoprotective effect of a curcumin/absinthium compound in experimental severe liver injury". Chinese Journal of Digestive Diseases 4 (3): 122–7. Blackwell Publishing. 
  3. ^ Aggarwal, BB.; Shishodia S. (May 2006). "Molecular targets of dietary agents for prevention and therapy of cancer". Biochemical Pharmacology 71 (10): 1397–421. Elsevier. 
  4. ^ Choi, Hyunsung; et al. (July 2006). "Curcumin Inhibits Hypoxia-Inducible Factor-1 by Degrading Aryl Hydrocarbon Receptor Nuclear Translocator: A Mechanism of Tumor Growth Inhibition". Molecular Pharmacology 70: 1664–71. American Society for Pharmacology and Experimental Therapeutics. 
  5. ^ Stix, Gary (February 2007). "Spice Healer". Scientific American. 
  6. ^ Srivastava, KC; Bordia A; Verma SK (April 1995). "Curcumin, a major component of the food spice turmeric (Curcuma longa), inhibits aggregation and alters eicosanoid metabolism in human blood platelets". Prostaglandins Leukot Essent Fatty Acids 52 (4): 223–7. PMID 7784468. 
  7. ^ Padma, TV. "Turmeric can combat malaria, cancer virus and HIV", SciDev.net, 2005-03-11. 
  8. ^ a b c Kutluay SB, Doroghazi J, Roemer ME, Triezenberg SJ (January 2008). "Curcumin inhibits herpes simplex virus immediate-early gene expression by a mechanism independent of p300/CBP histone acetyltransferase activity". Virology: 239. doi:10.1016/j.virol.2007.11.028. PMID 18191976. 
  9. ^ Bourne KZ, Bourne N, Reising SF, Stanberry LR (1999 Jul). "Plant products as topical microbicide candidates: assessment of in vitro and in vivo activity against herpes simplex virus type 2". Antiviral research 42 (3): 219-26. doi:10.1016/S0166-3542(99)00020-0. PMID 10443534. 
  10. ^ 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.
  11. ^ "Curcumin's anti-cancer mechanism proposed", nutraingredients-usa.com, 2007-04-13. 
  12. ^ Yang, F; Lim GP; Begum AN; Ubeda OJ; Simmons MR; Ambegaokar SS; Chen PP; Kayed R; Glabe CG; Frautschy SA; Cole GM (February 2005). "Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo". Journal of Biological Chemistry 280 (7): 5892–901. American Society for Biochemistry and Molecular Biology. PMID 15590663. 
  13. ^ Ng TP; Chiam PC; Lee T; Chua HC; Lim L; Kua EH (November 2006). "Curry consumption and cognitive function in the elderly". American Journal of Epidemiology 164 (9): 898–906. Oxford University Press. doi:10.1093/aje/kwj267. PMID 16870699. 
  14. ^ Xu Y, Ku B, Cui L, Li X, Barish PA, Foster TC, Ogle WO. (August 2007). "Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats.". Brain Res 1162: 9. doi:10.1016/j.brainres.2007.05.071. PMID 17617388. 
  15. ^ Wu A, Ying Z, Gomez-Pinilla F. (February 2006). "Dietary curcumin counteracts the outcome of traumatic brain injury on oxidative stress, synaptic plasticity, and cognition.". Experimental Neurology 197: 309. doi:10.1016/j.expneurol.2005.09.004. PMID 16364299. 
  16. ^ Bala K, Tripathy BC, Sharma D. (April 2006). "Neuroprotective and anti-ageing effects of curcumin in aged rat brain regions.". Biogerontology 7: 81. doi:10.1007/s10522-006-6495-x. PMID 16802111. 
  17. ^ a b Shoba G; Joy D; Joseph T; Majeed M; Rajendran R; Srinivas PS (May 1998). "Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers". Planta Med 64 (4): 353–6. doi:10.1055/s-2006-957450. PMID 9619120. 
  18. ^ a b Bisht; et al. (2007). "Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): a novel strategy for human cancer therapy". Journal of Nanobiotechnology 5 (3). BioMed Central. doi:10.1186/1477-3155-5-3. PMID 17439648. 
  19. ^ European patent EP20060004820
  20. ^ Kawanishi, S; Oikawa, S; Murata, M; (2005). "Evaluation for safety of antioxidant chemopreventive agents". Antioxidants & Redox Signaling 7 (11-12): 1728–39. PMID 16356133. 
  21. ^ Moos PJ; Edes K; Mullally JE; Fitzpatrick FA (2004). "Curcumin impairs tumor suppressor p53 function in colon cancer cells". Carcinogenesis 25 (9): 1611–7. doi:10.1093/carcin/bgh163. PMID 15090465. 
  22. ^ Lois Swirsky Gold. Turmeric (>98% curcurmin). Carcinogenic Potency Database Project. Last updated 3 Apr 2006. Last accessed 4 Jan 2007. [1]
  23. ^ Hsu CH; Cheng AL. (2007). "Adv Exp Med Biol.". PMID 17569225. 
  24. ^ Satyendra Mishra, Snehlata Tripathi, Roli Mishra and Krishna Misra. Design, synthesis and characterisation of a novel anticancer prodrug having antiproliferative activity against prostrate tumour, Ind. J. Chem., 2005,44B, (10),
  25. ^ Satyendra Mishra, Snehlata Tripathi, Roli Mishra and Krishna Misra. Design, synthesis and characterisation of a novel anticancer prodrug having antiproliferative activity against prostrate tumour, Ind. J. Chem., 2005,44B, (10),
  26. ^ Satyendra Mishra, Neha Kapoor, A. Mubarak Ali, B. V. V. Pardhasaradhi, A. Leela Kumari, Ashok Khar, Krishna Misra Differential apoptotic and redox regulatory activities of curcumin and its derivatives. Free Radic. Biol. Med. 2005, 38 1353– 1360.PMID: 15855053
  27. ^ Satyendra Mishra, Krishanpal Karmodiya, Namita Surolia; Avadhesha Surolia. Synthesis and exploration of novel curcumin analogues as antimalarial agents. Bioorg. Med. Chem., 2008, 16(6), .
* 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.
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