Curcuminoid

Curcumin[1]
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 Y
Jmol-3D images	Image 1
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, 456 K, 361 °F
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Demethoxycurcumin[1]
IUPAC name (1E,6E)-1,6-Heptadiene-3,5-dione, 1-(4-hydroxy-3-methoxyphenyl) -7-(4-hydroxyphenyl)
Other names 4-hydroxycinnamoyl(feroyl) methane, curcumin II, BHCFM
Identifiers
CAS number	24939-17-1
Jmol-3D images	Image 1
SMILES C(=C\C(CC(\C=C\c1ccc(cc1)O)=O)=O)\c1cc(c(cc1)O)OC
Properties
Molecular formula	C20H18O5
Molar mass	338.35 g/mol
Appearance	Yellow powder
Melting point	172 °C, 445 K, 342 °F
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Bisdemethoxycurcumin[1]
IUPAC name (1E,6E)-1,7-bis (4-hydroxyphenyl) hepta-1,6-diene- 3,5-dione
Other names Bis(4-hydroxycinnamoyl)methane, BHCMT
Identifiers
CAS number	24939-16-0
Jmol-3D images	Image 1
SMILES C(=C\C(CC(\C=C\c1ccc(cc1)O)=O)=O)\c1ccc(cc1)O
Properties
Molecular formula	C19H16O4
Molar mass	308.33 g/mol
Appearance	Yellow powder
Melting point	222 °C, 495 K, 432 °F
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

A curcuminoid is a curcumin or a derivative of a curcumin with different chemical groups that have been formed to increase solubility of curcumins and make them suitable for drug formulation. These compounds are polyphenols and produce a pronounced yellow color. Many curcumin characters are unsuitable for use as drugs by themselves. They have poor solubility in water at acidic and physiological pH, and also hydrolyze rapidly in alkaline solutions. Therefore, curcumin derivatives are synthezised to increase their solubility and hence bioavailability.^[2] Curcuminoids are soluble in dimethyl sulfoxide (DMSO), acetone and ethanol,^[3] but are poorly soluble in lipids. It is possible to increase curcuminoid solubility in aqueous phase with surfactants or co-surfactants.^[4] Curcumin derivatives have been synthesized that could possibly be more potent than curcumin itself. Most common derivatives have different substituents on the phenyl groups.^[3] There is an increasing demand of late for demethoxycurcumin and (curcuminoids) because of their recently discovered biological activity.^[4]

Cyclodextrins

Curcuminoids form a more stable complex with solutions which contain cyclodextrin towards hydrolytic degradations.^[5] The stability differs between size and characterzation of the cyclodextrins that are used.^[2] Dissolution of demethoxycurcumin, bisdemethoxycurcumin and curcumin are greatest in the hydroxypropyl-γ-cyclodextrin (HPγCD) cavity. The curcuminoids which have a substituent connected to the phenyl groups show more affinity for the HPγCD compound. Degradation rate is depended on pH of the solution and how much protection the cyclodextrins provide the curcuminoids. The derivatives are usually more stable than curcumin against hydrolysis in cyclodextrin solution. No covalent bonds are present between the cyclodextrins and the curcuminoids so they are easily released from the complex by simple solvent effects.^[3]

Micelles and nanoparticles

A drug design with curcuminoids in complex with micelles could be one solution of the insolubility of the curcuminoids. The curcuminoids would be in complex with the core of the micelles similar to the complex inside the cyclodextrins. The micelles are dissolved in a suitable solvent where the headgroups of the micelles interact with the solvent. Curcuminoids as loaded solid lipid nanoparticles (SLN) have been developed with great success by using microemulsion technique. The loading capacity, the mean particle size and size distribution are all factors that have to be considered when the effects of curcuminoids in different strength are observed because it could variate.^[3] The advantages of SLN are the possibilities of controlled drug release and drug targeting, protection of incorporated compound against chemical degradation, no biotoxicity of the carrier, avoidance of organic solvent and no problems with respect to large scale production.^[3] In vitro studies show a prolonged release of curcuminoids from the nanoparticle preparate up to 12 hours and the curcuminoids maintained their physical and chemical stability after 6 months of storage in the absence of light at room temperature. The sensitivity of curcuminoids to light and oxygen is greatly reduced by formulation of curcuminoids in SLN.^[3]

SLN for cosmetics

SLN preparate has been developed for cosmetics where the curcuminoids are used in cream base. But there are some stability issues which have not been overcome yet, further studies need to be done to find a suitable formulation which can be carried out in order to prolong the stability of the curcuminoids. Nevertheless there have been improvements in formulation of some stable model cream preparations with SLN curcuminoids.^[3] It is suggested that most of the curcuminoids are incorporated at the SLN surface where they are diffused into the cream matrix until a steady state is reached. At this state the curcuminoids go from the cream to the dissolution medium. A possible burst release in creams containing curcuminoids have been reported where the curcuminoids are rapidly released in a sufficient amount from the cream into the skin and is followed by a controlled release.^[3] When SLN are prepared by microemulsion at a temperature with the range of 70-75 °C an oil-in-water microemulsion is spontaneously formed. The SLN are obtained immediately when they are dispersed in the warm microemulsion into cold water, with the help of a homogenizer. The cold water facilitates a rapid crystallization of the lipids and therefore prevents aggregation of the lipids. After freeze drying the yellow curcuminoids containing SLN were obtained and could easily be redispersed in water and the model cream. The SLN have uniform distribution and according to electron micrograph scan they had a spherical shape and smooth surface.^[3] It has been reported that increasing the lipid content over 5-10%(w/w) increased the mean particle size and broader size distribution in most common cases. That range should there for be ideal concentration for formulation of the SLN.^[3]

Incorporation and formulation

Incorporation is one thing that needs to be considered in formulation of SLN. Concentration of the lipid, emulsifier and co-emulsifier solution is a key factor on this conversion of the SLN. If the amount of emulsifier and co-emulsifier are increased but the lipid amount is constant the surface of the SLN which is formed will be too small to adsorb all the surfactant and co-surfactant molecules, and a formation of curcuminoids solution micelles will be created. This will then increase the water solubility of the curcuminoids and they could partition from the SLN into the micelles that were formed during a wash procedure. This will reduce the final incorporation efficacy on the surface of the SLN.^[3]

Anti-oxidant activity

The curcumin derivatives demethoxycurcumin and bisdemethoxycurcumin have, like curcumin itself been tested for their antioxidant activities in vitro.^[4] Antioxidants can be used to extend the shelf life for food and maintain their safety, nutritional quality, functionality and palatability.^[4] Pure chemicals of curcumin and its derivatives are not available in the open market. Commercially available curcumin contains 77% curcumin, 17% demethoxycurcumin and 3% bisdemethoxycurcumin from the herb Curcuma longa. Curcumin is mainly produced in industry as pigment by using turmeric oleoresin as the starting material which curcuminoids can be isolated from. After the isolation of the curcuminoids, the extract which is about 75% liquor mainly contains oil, resin and more curcuminoids which can be isolated further. This isolation method was used to demonstrate the antioxidant activities of curcuminoids, where they isolated pure curcuminoids from the main liquor.^[4] One research reported that curcumin was the strongest antioxidant, demethoxycurcumin the second strongest and bisdemethoxycurcumin the least effective. Curcuminoids nevertheless showed activity against oxidation. Curcuminoids act as a superoxide radical scavenger as well as singlet oxygen quencher and gives the antioxidant its effectiveness.^[4] Tetrahydrocurcumin, one of the main metabolites of curcumin, is the most potent antioxidant among the naturally occurring curcuminoids.^[4] The curcuminoids are capable of inhibiting damage to super coiled plasmid DNA by hydroxyl radicals. It was concluded that the derivatives of curcumin are good in trapping the 2,2-diphenyl-1-picrylhydrazyl(DPPH) radical as efficiently as curcumin which is a well known antioxidant.^[4]

Anti-inflammatory activity

Anti-inflammatory effects of curcumin and its derivatives are because of the hydroxyl and phenol groups in the molecules. These groups are essential for inhibition of prostaglandin synthetase and leukotrienes synthesis. A system with conjugated double bonds or dienes is also believed to be responsible for the anti-inflammatory effect as well as antiparasitic activity. The diene system seems to make the compounds more lipophilic and therefore provide a better skin penetration which could be good for that kind of drug preparation.^[4]

Chemotherapeutic activity

Studies suggest that the bioavailability of curcumin and possibly its derivatives is greatest in the colon. The tissue in the gastrointestinal tract seems to be more exposed predominantly to unmetabolised curcumin than other tissues hence they could support clinical studies of curcumin as a colorectal cancer preventive agent.^[4] Demethoxycurcumin has recently been tested in colon cancer and it showed more effective inhibitation of cell division and apoptosis than curcumin. It is possible that the difference in apoptosis in vitro is connected to the degradation of the two chemicals and/or their stability.^[3]

References

1. ^ ^{a b c} Péret-Almeida L, Cherubino APF, Alves RJ, Dufossé L, Glória MBA (October-November 2005). "Separation and determination of the physico-chemical characteristics of curcumin, demethoxycurcumin and bisdemethoxycurcumin". Food Research International 38 (8–9): 1039–44. doi:10.1016/j.foodres.2005.02.021. 
2. ^ ^{a b} Tomren MA, Másson M, Loftsson T, Tønnesen HH (June 2007). "Studies on curcumin and curcuminoids XXXI. Symmetric and asymmetric curcuminoids: stability, activity and complexation with cyclodextrin". Int J Pharm 338 (1–2): 27–34. doi:10.1016/j.ijpharm.2007.01.013. PMID 17298869. 
3. ^ ^{a b c d e f g h i j k l} Tiyaboonchai W, Tungpradit W, Plianbangchang P (June 2007). "Formulation and characterization of curcuminoids loaded solid lipid nanoparticles". Int J Pharm 337 (1–2): 299–306. doi:10.1016/j.ijpharm.2006.12.043. PMID 17287099. 
4. ^ ^{a b c d e f g h i j} Jayaprakasha GK, Rao LJ, Sakariah KK (2006). "Antioxidant activities of curcumin, demethoxycurcumin and bisdemethoxycurcumin". Food Chemistry 98 (4): 720–4. doi:10.1016/j.foodchem.2005.06.037. 
5. ^ Tønnesen, H, Mássonb, M, Loftsson, T (September 2002). Studies of curcumin and curcuminoids. XXVII. Cyclodextrin complexation: solubility, chemical and photochemical stabilit. 244. pp. 127–135. doi:10.1016/S0378-5173(02)00323-X.