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Differential solubility of curcuminoids in serum and albumin solutions: implications for analytical and therapeutic applications.

Quitschke WW - BMC Biotechnol. (2008)

Bottom Line: Either method of solubilization was equally effective in inhibiting dose-dependent HeLa cell proliferation in culture.These results suggest the possibility of alternative therapeutic approaches by injection or infusion of relatively small amounts of curcuminoid-enriched serum.The differential solubility of curcuminoids achieved by different methods of solubilization offers convenient alternatives to assess the diverse biological effects contributed by curcumin and its derivatives.

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Affiliation: Department of Psychiatry and Behavioral Science, State University of New York at Stony Brook, Stony Brook, NY 11794-8101, USA. wquitschke@notes.cc.sunysb.edu

ABSTRACT

Background: Commercially available curcumin preparations contain a mixture of related polyphenols, collectively referred to as curcuminoids. These encompass the primary component curcumin along with its co-purified derivatives demethoxycurcumin and bisdemethoxycurcumin. Curcuminoids have numerous biological activities, including inhibition of cancer related cell proliferation and reduction of amyloid plaque formation associated with Alzheimer disease. Unfortunately, the solubility of curcuminoids in aqueous solutions is exceedingly low. This restricts their systemic availability in orally administered formulations and limits their therapeutic potential.

Results: Methods are described that achieve high concentrations of soluble curcuminoids in serum. Solid curcuminoids were either mixed directly with serum, or they were predissolved in dimethyl sulfoxide and added as aliquots to serum. Both methods resulted in high levels of curcuminoid-solubility in mammalian sera from different species. However, adding aliquots of dimethyl sulfoxide-dissolved curcuminoids to serum proved to be more efficient, producing soluble curcuminoid concentrations of at least 3 mM in human serum. The methods also resulted in the differential solubility of individual curcuminoids in serum. The addition of dimethyl sulfoxide-dissolved curcuminoids to serum preferentially solubilized curcumin, whereas adding solid curcuminoids predominantly solubilized bisdemethoxycurcumin. Either method of solubilization was equally effective in inhibiting dose-dependent HeLa cell proliferation in culture. The maximum concentration of curcuminoids achieved in serum was at least 100-fold higher than that required for inhibiting cell proliferation in culture and 1000-fold higher than the concentration that has been reported to prevent amyloid plaque formation associated with Alzheimer disease. Curcuminoids were also highly soluble in solutions of purified albumin, a major component of serum.

Conclusion: These results suggest the possibility of alternative therapeutic approaches by injection or infusion of relatively small amounts of curcuminoid-enriched serum. They also provide tools to reproducibly solubilize curcuminoids for analysis in cell culture applications. The differential solubility of curcuminoids achieved by different methods of solubilization offers convenient alternatives to assess the diverse biological effects contributed by curcumin and its derivatives.

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Elution profiles of curcuminoids separated by reversed phase chromatography. A) 30 mg of solid (left profile) curcuminoids or 10 μl of 500 mM DMSO-dissolved (right profile) curcuminoids solubilized in 1 ml of FCS. B) 30 mg of solid (left profile) curcuminoids or 10 μl of 500 mM DMSO-dissolved (right profile) curcuminoids solubilized in 1 ml of 5% BSA. C) 30 mg of solid curcuminoids solubilized in 1 ml of 1% BSA (left profile) or 20% BSA (right profile). Vertical bars represent mAUs and individual curcuminoids are designated as described in Fig. 1C.
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Figure 4: Elution profiles of curcuminoids separated by reversed phase chromatography. A) 30 mg of solid (left profile) curcuminoids or 10 μl of 500 mM DMSO-dissolved (right profile) curcuminoids solubilized in 1 ml of FCS. B) 30 mg of solid (left profile) curcuminoids or 10 μl of 500 mM DMSO-dissolved (right profile) curcuminoids solubilized in 1 ml of 5% BSA. C) 30 mg of solid curcuminoids solubilized in 1 ml of 1% BSA (left profile) or 20% BSA (right profile). Vertical bars represent mAUs and individual curcuminoids are designated as described in Fig. 1C.

Mentions: The differential solubility of curcuminoids in FCS and BSA solutions was also analyzed by reversed phase chromatography (Fig 4). When DMSO-dissolved curcuminoids were solubilized in either FCS or 5% BSA, their relative concentrations declined in the order: curcumin (72%) > demethoxycurcumin (23%) > bisdemethoxycurcumin (5%) [Fig. 4A,B]. These soluble curcuminoid ratios were largely a reflection of the ratios in the DMSO stock solution (Fig. 1C). In contrast, when 5% BSA or FCS was incubated with solid curcuminoids, the elution profile of the solubilized curcuminoids was effectively reversed. Here, the major solubilized curcuminoid was bisdemethoxycurcumin (71%) followed by demethoxycurcumin (26%) and curcumin (3%) [Fig. 4A,B]. The effect of solubilizing 30 mg of solid curcuminoids on elution profiles was also examined when the BSA concentrations were increased from 1% to 20%. However, this increase in BSA concentration produced only modest changes in the curcuminoid ratios. The relative amount of bisdemethoxycurcumin declined from 76% with 1% BSA to 64% with 20% BSA, which was reflected in a concomitant increase in the relative amount of demethoxycurcumin from 23% to 32%, and of curcumin from 1% to 4% (Fig 4C). These results show that the different methods of solubilizing curcuminoids not only produced quantitative differences in the total amounts solubilized, but they also resulted in profound changes in the relative concentrations of the individual curcuminoids.


Differential solubility of curcuminoids in serum and albumin solutions: implications for analytical and therapeutic applications.

Quitschke WW - BMC Biotechnol. (2008)

Elution profiles of curcuminoids separated by reversed phase chromatography. A) 30 mg of solid (left profile) curcuminoids or 10 μl of 500 mM DMSO-dissolved (right profile) curcuminoids solubilized in 1 ml of FCS. B) 30 mg of solid (left profile) curcuminoids or 10 μl of 500 mM DMSO-dissolved (right profile) curcuminoids solubilized in 1 ml of 5% BSA. C) 30 mg of solid curcuminoids solubilized in 1 ml of 1% BSA (left profile) or 20% BSA (right profile). Vertical bars represent mAUs and individual curcuminoids are designated as described in Fig. 1C.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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Figure 4: Elution profiles of curcuminoids separated by reversed phase chromatography. A) 30 mg of solid (left profile) curcuminoids or 10 μl of 500 mM DMSO-dissolved (right profile) curcuminoids solubilized in 1 ml of FCS. B) 30 mg of solid (left profile) curcuminoids or 10 μl of 500 mM DMSO-dissolved (right profile) curcuminoids solubilized in 1 ml of 5% BSA. C) 30 mg of solid curcuminoids solubilized in 1 ml of 1% BSA (left profile) or 20% BSA (right profile). Vertical bars represent mAUs and individual curcuminoids are designated as described in Fig. 1C.
Mentions: The differential solubility of curcuminoids in FCS and BSA solutions was also analyzed by reversed phase chromatography (Fig 4). When DMSO-dissolved curcuminoids were solubilized in either FCS or 5% BSA, their relative concentrations declined in the order: curcumin (72%) > demethoxycurcumin (23%) > bisdemethoxycurcumin (5%) [Fig. 4A,B]. These soluble curcuminoid ratios were largely a reflection of the ratios in the DMSO stock solution (Fig. 1C). In contrast, when 5% BSA or FCS was incubated with solid curcuminoids, the elution profile of the solubilized curcuminoids was effectively reversed. Here, the major solubilized curcuminoid was bisdemethoxycurcumin (71%) followed by demethoxycurcumin (26%) and curcumin (3%) [Fig. 4A,B]. The effect of solubilizing 30 mg of solid curcuminoids on elution profiles was also examined when the BSA concentrations were increased from 1% to 20%. However, this increase in BSA concentration produced only modest changes in the curcuminoid ratios. The relative amount of bisdemethoxycurcumin declined from 76% with 1% BSA to 64% with 20% BSA, which was reflected in a concomitant increase in the relative amount of demethoxycurcumin from 23% to 32%, and of curcumin from 1% to 4% (Fig 4C). These results show that the different methods of solubilizing curcuminoids not only produced quantitative differences in the total amounts solubilized, but they also resulted in profound changes in the relative concentrations of the individual curcuminoids.

Bottom Line: Either method of solubilization was equally effective in inhibiting dose-dependent HeLa cell proliferation in culture.These results suggest the possibility of alternative therapeutic approaches by injection or infusion of relatively small amounts of curcuminoid-enriched serum.The differential solubility of curcuminoids achieved by different methods of solubilization offers convenient alternatives to assess the diverse biological effects contributed by curcumin and its derivatives.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Psychiatry and Behavioral Science, State University of New York at Stony Brook, Stony Brook, NY 11794-8101, USA. wquitschke@notes.cc.sunysb.edu

ABSTRACT

Background: Commercially available curcumin preparations contain a mixture of related polyphenols, collectively referred to as curcuminoids. These encompass the primary component curcumin along with its co-purified derivatives demethoxycurcumin and bisdemethoxycurcumin. Curcuminoids have numerous biological activities, including inhibition of cancer related cell proliferation and reduction of amyloid plaque formation associated with Alzheimer disease. Unfortunately, the solubility of curcuminoids in aqueous solutions is exceedingly low. This restricts their systemic availability in orally administered formulations and limits their therapeutic potential.

Results: Methods are described that achieve high concentrations of soluble curcuminoids in serum. Solid curcuminoids were either mixed directly with serum, or they were predissolved in dimethyl sulfoxide and added as aliquots to serum. Both methods resulted in high levels of curcuminoid-solubility in mammalian sera from different species. However, adding aliquots of dimethyl sulfoxide-dissolved curcuminoids to serum proved to be more efficient, producing soluble curcuminoid concentrations of at least 3 mM in human serum. The methods also resulted in the differential solubility of individual curcuminoids in serum. The addition of dimethyl sulfoxide-dissolved curcuminoids to serum preferentially solubilized curcumin, whereas adding solid curcuminoids predominantly solubilized bisdemethoxycurcumin. Either method of solubilization was equally effective in inhibiting dose-dependent HeLa cell proliferation in culture. The maximum concentration of curcuminoids achieved in serum was at least 100-fold higher than that required for inhibiting cell proliferation in culture and 1000-fold higher than the concentration that has been reported to prevent amyloid plaque formation associated with Alzheimer disease. Curcuminoids were also highly soluble in solutions of purified albumin, a major component of serum.

Conclusion: These results suggest the possibility of alternative therapeutic approaches by injection or infusion of relatively small amounts of curcuminoid-enriched serum. They also provide tools to reproducibly solubilize curcuminoids for analysis in cell culture applications. The differential solubility of curcuminoids achieved by different methods of solubilization offers convenient alternatives to assess the diverse biological effects contributed by curcumin and its derivatives.

Show MeSH
Related in: MedlinePlus