Curcumin

Curcumin

Curcumin
Skeletal formula
Enol form
Skeletal formula
Keto form
Ball-and-stick model
Ball-and-stick model
Names
IUPAC name
(1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione
Other names
Diferuloylmethane; curcumin I; C.I. 75300; Natural Yellow 3
Identifiers
 Y
ChEBI  Y
ChEMBL  N
ChemSpider  Y
Jmol-3D images Image
PubChem
UNII  Y
Properties
C21H20O6
Molar mass 368.39 g·mol−1
Appearance Bright yellow-orange powder
Melting point 183 °C (361 °F; 456 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
 N  (: Y/N?)

Curcumin () is a keto domitates.[2]

Curcumin can be used for boron quantification in the curcumin method. It reacts with boric acid to form a red-color compound, rosocyanine.

Curcumin is a bright-yellow color and may be used as a food coloring. As a food additive, its E number is E100.[3]

Curcumin

Contents

  • Adverse effects 1
  • Chemistry 2
    • Biosynthesis 2.1
  • Pharmacodynamics 3
  • Pharmacokinetics 4
  • Research 5
  • References 6
  • External links 7

Adverse effects

Clinical studies in humans with high doses (2–12 grams) of curcumin have shown few side-effects,[4] with some subjects reporting mild nausea or diarrhea.[5] More recently, curcumin was found to alter iron metabolism by chelating iron and suppressing the protein hepcidin, potentially causing iron deficiency in susceptible patients.[6]

Chemistry

Curcumin incorporates several functional groups. The aromatic ring systems, which are phenols, are connected by two α,β-unsaturated carbonyl groups. The diketones form stable enols and are readily deprotonated to form enolates; the α,β-unsaturated carbonyl group is a good Michael acceptor and undergoes nucleophilic addition. The structure was first identified in 1910 by J. Miłobędzka, Stanisław Kostanecki and Wiktor Lampe.[7]

Curcumin is used as an indicator for boron.[8]

Biosynthesis

The biosynthetic route of curcumin has proven to be very difficult for researchers to determine. In 1973, Roughly and Whiting proposed two mechanisms for curcumin biosynthesis. The first mechanism involved a chain extension reaction by cinnamic acid and 5 malonyl-CoA molecules that eventually arylized into a curcuminoid. The second mechanism involved two cinnamate units coupled together by malonyl-CoA. Both mechanisms use cinnamic acid as their starting point, which is derived from the amino acid phenylalanine. This is noteworthy because plant biosyntheses employing cinnamic acid as a starting point are rare compared to the more common use of p-coumaric acid.[9] Only a few identified compounds, such as anigorufone and pinosylvin, use cinnamic acid as their starting molecule.[10][11] An experimentally backed route was not presented until 2008. This proposed biosynthetic route follows both the first and second mechanisms suggested by Roughley and Whiting. However, the labeling data supported the first mechanism model in which 5 malonyl-CoA molecules react with cinnamic acid to form curcumin. However, the sequencing in which the functional groups, the alcohol and the methoxy, introduce themselves onto the curcuminoid seems to support more strongly the second proposed mechanism.[9] Therefore, it was concluded the second pathway proposed by Roughly and Whiting was correct.

malonyl-CoA (5)
Biosynthetic pathway of curcumin in Curcuma longa.[9]

Pharmacodynamics

In vitro, curcumin has been shown to inhibit certain epigenetic enzymes (the histone deacetylases: HDAC1, HDAC3, and HDAC8) and transcriptional co-activator proteins (the p300 histone acetyltransferase).[12][13][14] Curcumin also inhibits the arachidonate 5-lipoxygenase enzyme in vitro,[15] as well as the enzyme cyclooxygenase.

Pharmacokinetics

In Phase I clinical trials, dietary curcumin was shown to exhibit poor bioavailability, exhibited by rapid metabolism, low levels in plasma and tissues, and extensive rapid excretion.[16] Potential factors that limit the bioavailability of curcumin include insolubility in water (more soluble in alkaline solutions) and poor absorption.[16] Numerous approaches to increase curcumin bioavailability have been explored, including the use of absorption factors (such as piperine), liposomes, nanoparticles or a structural analogue.[16]

Research

A survey of the literature shows a number of potential effects under study and that daily consumption over a 3-month period of up to 12 grams were safe.[17] However, several studies of curcumin efficacy and safety revealed poor absorption and low bioavailability.[18]

As of June 2015, there were 116 clinical trials evaluating the possible anti-disease effect of curcumin in humans, as registered with the US National Institutes of Health, including studies on cancer, gastrointestinal diseases, cognitive disorders, and psychiatric conditions.[18]

References

  1. ^ H. Vogel, J. Pelletier, Curcumin-biological and medicinal properties, Journal de Pharmacie. 1815;I:289.
  2. ^ Manolova, Yana; Deneva, Vera; Antonov, Liudmil; at al; Momekova, Denitsa; Lambov, Nikolay (2014). "The effect of the water on the curcumin tautomerism: A quantitative approach". Spectrochimica Acta 132A (1): 815–820.  
  3. ^  
  4. ^ Cheng, A. L.; Hsu, C. H.; Lin, J. K.; Hsu, M. M.; Ho, Y. F.; Shen, T. S.; Ko, J. Y.; Lin, J. T.; Lin, B. R.; Ming-Shiang, W; Yu, H. S.; Jee, S. H.; Chen, G. S.; Chen, T. M.; Chen, C. A.; Lai, M. K.; Pu, Y. S.; Pan, M. H.; Wang, Y. J.; Tsai, C. C.; Hsieh, C. Y. (2001). "Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions". Anticancer research 21 (4B): 2895–900.  
  5. ^ Hsu, C. H.; Cheng, A. L. (2007). "Clinical studies with curcumin". Advances in Experimental Medicine and Biology. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 595: 471–480.  
  6. ^ Jiao Y; et al. (January 2009). "Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator". Blood 113 (2): 462–469.  
  7. ^ Miłobȩdzka, J.; v. Kostanecki, St.; Lampe, V. (1910). "Zur Kenntnis des Curcumins". Berichte der deutschen chemischen Gesellschaft 43 (2): 2163–70.  
  8. ^ "EPA Method 212.3: Boron (Colorimetric, Curcumin)" (PDF). 
  9. ^ a b c Kita, Tomoko; Imai, Shinsuke; Sawada, Hiroshi; Kumagai, Hidehiko; Seto, Haruo (2008). "The Biosynthetic Pathway of Curcuminoid in Turmeric (Curcuma longa) as Revealed by 13C-Labeled Precursors". Bioscience, Biotechnology, and Biochemistry 72 (7): 1789.  
  10. ^ Schmitt, Bettina; Hölscher, Dirk; Schneider, Bernd (2000). "Variability of phenylpropanoid precursors in the biosynthesis of phenylphenalenones in Anigozanthos preissii". Phytochemistry 53 (3): 331–7.  
  11. ^ Gehlert, R.; Schoeppner, A.; Kindl, H. (1990). : Purification and Induction in Response to Fungal Infection"Pinus sylvestris"Stilbene Synthase from Seedlings of (pdf). Molecular Plant-Microbe Interactions 3 (6): 444–449.  
  12. ^ Reuter S, Gupta SC, Park B, Goel A, Aggarwal BB (May 2011). "Epigenetic changes induced by curcumin and other natural compounds". Genes Nutr 6 (2): 93–108.  
    Figure 2
  13. ^ Vahid F, Zand H, Nosrat-Mirshekarlou E, Najafi R, Hekmatdoost A (May 2015). "The role dietary of bioactive compounds on the regulation of histone acetylases and deacetylases: a review". Gene 562 (1): 8–15.  
  14. ^ "Curcumin". IUPHAR. IUPHAR/BPS Guide to PHARMACOLOGY. Retrieved 22 May 2015. 
  15. ^ Bishayee K, Khuda-Bukhsh AR (September 2013). "5-lipoxygenase antagonist therapy: a new approach towards targeted cancer chemotherapy". Acta Biochim. Biophys. Sin. (Shanghai) 45 (9): 709–719.  
  16. ^ a b c Anand, P.; Kunnumakkara, A. B.; Newman, R. A.; Aggarwal, B. B. (2007). "Bioavailability of curcumin: problems and promises". Molecular Pharmaceutics 4 (6): 807–818.  
  17. ^ Goel, Ajay; Kunnumakkara, Ajaikumar B.; Aggarwal, Bharat B. (2008). "Curcumin as "Curecumin": From kitchen to clinic". Biochemical Pharmacology 75 (4): 787–809.  
  18. ^ a b "ClinicalTrials.gov: Current clinical trials on curcumin". US National Institutes of Health, Clinical Trial Registry. June 2015. 

External links