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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.

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.

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Cell culture media preparation and curcuminoid solubilization in FCS produced by different mixing techniques. A) Solutions for cell culture media were prepared by adding either solid (white bars) or DMSO-dissolved (500 mM) curcuminoids (gray bars) to FCS. The FCS was subsequently added to DMEM at a final concentration of 5%. The total curcuminoid concentrations in the media were then determined by butanol extraction. The measured (meas.) values were compared to the calculated (calc.) values (brackets) for both media prepared with solid (white bars) and DMSO-dissolved (gray bars) curcuminoids. On the right side of the panel DMSO-dissolved (gray bars) or solid curcuminoids (white bars) were mixed with FCS either by stirring or by rotation. The total amount of total curcuminoids solubilized by either method was determined spectrophotometrically. B) Elution profiles after separation by reversed phase chromatography of DMSO-dissolved curcuminoids solubilized in FCS, mixed either by stirring (right) or rotation (left). C) Elution profiles of solid curcuminoids solubilized in FCS, mixed either by stirring (right) or rotation (left).
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Figure 8: Cell culture media preparation and curcuminoid solubilization in FCS produced by different mixing techniques. A) Solutions for cell culture media were prepared by adding either solid (white bars) or DMSO-dissolved (500 mM) curcuminoids (gray bars) to FCS. The FCS was subsequently added to DMEM at a final concentration of 5%. The total curcuminoid concentrations in the media were then determined by butanol extraction. The measured (meas.) values were compared to the calculated (calc.) values (brackets) for both media prepared with solid (white bars) and DMSO-dissolved (gray bars) curcuminoids. On the right side of the panel DMSO-dissolved (gray bars) or solid curcuminoids (white bars) were mixed with FCS either by stirring or by rotation. The total amount of total curcuminoids solubilized by either method was determined spectrophotometrically. B) Elution profiles after separation by reversed phase chromatography of DMSO-dissolved curcuminoids solubilized in FCS, mixed either by stirring (right) or rotation (left). C) Elution profiles of solid curcuminoids solubilized in FCS, mixed either by stirring (right) or rotation (left).

Mentions: Curcuminoids were solubilized in FCS for use in tissue culture medium to explore their effect on biological activity. Specifically, 29 ml of FCS were mixed either with 870 mg of solid or 145 μl of 500 mM DMSO-dissolved curcuminoids for 16–24 h with a magnetic stirrer. The final concentration of soluble curcuminoids was 966 μM for the preparation with solid curcuminoids and 850 μM for the preparation with DMSO-dissolved curcuminoids (Fig. 8A). Tissue culture medium was prepared by adding 25 ml of FCS-solubilized curcumin to 500 ml DMEM. Final curcuminoid concentrations were about 55 μM in the medium prepared with solid curcumin and 51 μM in the medium prepared with DMSO-dissolved curcumin. These measured values were within 10% of the calculated values expected from the dilution of FCS-solubilized curcumin (Fig. 8A).


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

Quitschke WW - BMC Biotechnol. (2008)

Cell culture media preparation and curcuminoid solubilization in FCS produced by different mixing techniques. A) Solutions for cell culture media were prepared by adding either solid (white bars) or DMSO-dissolved (500 mM) curcuminoids (gray bars) to FCS. The FCS was subsequently added to DMEM at a final concentration of 5%. The total curcuminoid concentrations in the media were then determined by butanol extraction. The measured (meas.) values were compared to the calculated (calc.) values (brackets) for both media prepared with solid (white bars) and DMSO-dissolved (gray bars) curcuminoids. On the right side of the panel DMSO-dissolved (gray bars) or solid curcuminoids (white bars) were mixed with FCS either by stirring or by rotation. The total amount of total curcuminoids solubilized by either method was determined spectrophotometrically. B) Elution profiles after separation by reversed phase chromatography of DMSO-dissolved curcuminoids solubilized in FCS, mixed either by stirring (right) or rotation (left). C) Elution profiles of solid curcuminoids solubilized in FCS, mixed either by stirring (right) or rotation (left).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 8: Cell culture media preparation and curcuminoid solubilization in FCS produced by different mixing techniques. A) Solutions for cell culture media were prepared by adding either solid (white bars) or DMSO-dissolved (500 mM) curcuminoids (gray bars) to FCS. The FCS was subsequently added to DMEM at a final concentration of 5%. The total curcuminoid concentrations in the media were then determined by butanol extraction. The measured (meas.) values were compared to the calculated (calc.) values (brackets) for both media prepared with solid (white bars) and DMSO-dissolved (gray bars) curcuminoids. On the right side of the panel DMSO-dissolved (gray bars) or solid curcuminoids (white bars) were mixed with FCS either by stirring or by rotation. The total amount of total curcuminoids solubilized by either method was determined spectrophotometrically. B) Elution profiles after separation by reversed phase chromatography of DMSO-dissolved curcuminoids solubilized in FCS, mixed either by stirring (right) or rotation (left). C) Elution profiles of solid curcuminoids solubilized in FCS, mixed either by stirring (right) or rotation (left).
Mentions: Curcuminoids were solubilized in FCS for use in tissue culture medium to explore their effect on biological activity. Specifically, 29 ml of FCS were mixed either with 870 mg of solid or 145 μl of 500 mM DMSO-dissolved curcuminoids for 16–24 h with a magnetic stirrer. The final concentration of soluble curcuminoids was 966 μM for the preparation with solid curcuminoids and 850 μM for the preparation with DMSO-dissolved curcuminoids (Fig. 8A). Tissue culture medium was prepared by adding 25 ml of FCS-solubilized curcumin to 500 ml DMEM. Final curcuminoid concentrations were about 55 μM in the medium prepared with solid curcumin and 51 μM in the medium prepared with DMSO-dissolved curcumin. These measured values were within 10% of the calculated values expected from the dilution of FCS-solubilized curcumin (Fig. 8A).

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