Development of a multi-component drug from turmeric using central composite design

Abstract

A methodology to develop multi-component drugs based on traditional Chinese medicines has been developed using central composite design. Several active components from the traditional Chinese medicine turmeric were chosen for use in a multi-component antitumor drug. Response surface methodology based on a central composite design was applied to determine the quantitative composition-activity relationships in order to optimize the amount of each component in the drug. An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to measure the pharmacological activity as the response value. The experimental antitumor activity of the optimum combination was 92.85% in the MTT assay and superior to the activities of each single component. These results demonstrate that response surface methodology based on a central composite design is suitable for the design of multi-component drugs.

Keywords

multi-component drug development / central composite design / turmeric / curcuminoids

References

[1] Wang Y, Fan X, Qu H, Gao X, Cheng Y Y. Strategies and techniques for multi-component drug design from medicinal herbs and traditional Chinese medicine. Current Topics in Medicinal Chemistry, 2012, 129(12): 1356–1362

[2] Ruffolo R R. Why has R&D productivity declined in the pharmaceutical industry? Expert Opinion Drug Discovery, 2006, 1(2): 99–102

[3] Hiroaki K. A robustness-based approach to systems-oriented drug design. Nature Reviews. Drug Discovery, 2007, 6(3): 202–210

[4] Keith C T, Borisy A A, Stockwell B R. Multicomponent therapeutics for networked systems. Nature Reviews. Drug Discovery, 2005, 4(1): 71–78

[5] Ke L, Wei J. An integrated metabolomics and pharmacokinetics strategy for multi-component drugs evaluation. Current Drug Metabolism, 2010, 11(1): 105–114

[6] Tian X Y, Liu L. Drug discovery enters a new era with multi-target intervention strategy. Chinese Journal of Integrative Medicine, 2012, 18(7): 539–542

[7] Li J, Lu C, Jiang M, Niu X Y, Guo H T, Li L, Bian Z X, Lin N, Lu A P. Traditional Chinese medicine-based network pharmacology could lead to new multicompound drug discovery. Evidence-Based Complementary and Alternative Medicine, 2012, 149762:1–149762:11

[8] Borisy A A, Elliott P J, Hurst N W, Lee M S, Lehar J, Price E R, Serbedzija G, Zimmermann G R, Foley M A, Stockwell B R, Keith C T. Systematic discovery of multicomponent therapeutics. Proceedings of the National Academy of Sciences of the United States of America, 2003, 100(13): 7977–7982

[9] Kvalheim O M, Chan H, Benzie I F F, Szeto Y T, Tzang A H C, Mok D K W, Chau F T. Chromatographic profiling and multivariate analysis for screening and quantifying the contributions from individual components to the bioactive signature in natural products. Chemometrics and Intelligent Laboratory Systems, 2011, 107(1): 98–105

[10] Roldan C, Torre A, Mota S, Morales S A, Menendez J, Segura Carretero A. Identification of active compounds in vegetal extracts based on correlation between activity and HPLC-MS data. Food Chemistry, 2013, 136(2): 392–399

[11] Süntar I, Küpeli Akkol E, Keles H, Yesilada E, Sarker S D, Arroo R, Baykal T. Efficacy of Daphne oleoides subsp. kurdica used for wound healing: Identification of active compounds through bioassay guided isolation techniqueSarker S D. Journal of Ethnopharmacology, 2012, 141(3): 1058–1070

[12] Jiang J L, Jin X L, Zhang H, Su X, Qiao B, Yuan Y J. Identification of antitumor constituents in curcuminoids from Curcuma longa L. based on the composition-activity relationship. Journal of Pharmaceutical and Biomedical Analysis, 2012, 70: 664–670

[13] Jiang J L, Su X, Zhang H, Zhang X H, Yuan Y J. A novel approach to active compounds identification based on support vector regression model and mean impact value. Chemical Biology & Drug Design, 2013, 81(5): 650–657

[14] Jiang J L, Zhang H, Zhou P P, Han S N, Han Y D, Yuan Y J. Composition-activity relationship modeling to predict the antitumor activity for quality control of curcuminoids from Curcuma longa L. (turmeric). Analytical Methods, 2013, 5(3): 641–647

[15] Goel A, Aggarwal B B. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutrition and Cancer, 2010, 62(7): 919–930

[16] Shehzad A, Wahid F, Lee Y S. Curcumin in cancer chemoprevention: Molecular targets, pharmacokinetics, bioavailability, and clinical trials. Archivder Pharmazie Chemistry in Life Sciences, 2010, 343(9): 489–499

[17] Zhang L J, Wu C F, Meng X L, Yuan D, Cai X D, Wang Q L, Yang J Y. Comparison of inhibitory potency of three different curcuminoid pigments on nitric oxide and tumor necrosis factor production of rat primary microglia induced by lipopolysaccharide. Neuroscience Letters, 2008, 447(1): 48–53

[18] Luthra P M, Kumar R, Prakash A. Demethoxycurcumin induces Bcl-2 mediated G2/M arrest and apoptosis in human glioma U87 cells. Biochemical and Biophysical Research Communications, 2009, 384(4): 420–425

[19] Yodkeeree S, Chaiwangyen W, Garbisa S, Limtrakul P. Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit cancer cell invasion through the down-regulation of MMPs and uPA. Journal of Nutritional Biochemistry, 2009, 20(2): 87–95

Acknowledgments

This work was supported by Natural Science Foundation of China (Grant No.81102900).

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg