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Evidence-Based Complementary and Alternative Medicine
Volume 2013 (2013), Article ID 541436, 10 pages
Research Article

Optimizing Combinations of Flavonoids Deriving from Astragali Radix in Activating the Regulatory Element of Erythropoietin by a Feedback System Control Scheme

1State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, Jiangsu, China
2Department of Mechanical Engineering, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong
3Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong
4School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China
5Center for Cell Control, Mechanical and Aerospace Engineering Department, Biomedical Engineering Department, University of California, Los Angeles, CA 90095-1597, USA

Received 4 February 2013; Accepted 22 March 2013

Academic Editor: Shao Li

Copyright © 2013 Hui Yu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Identifying potent drug combination from a herbal mixture is usually quite challenging, due to a large number of possible trials. Using an engineering approach of the feedback system control (FSC) scheme, we identified the potential best combinations of four flavonoids, including formononetin, ononin, calycosin, and calycosin-7-O-β-D-glucoside deriving from Astragali Radix (AR; Huangqi), which provided the best biological action at minimal doses. Out of more than one thousand possible combinations, only tens of trials were required to optimize the flavonoid combinations that stimulated a maximal transcriptional activity of hypoxia response element (HRE), a critical regulator for erythropoietin (EPO) transcription, in cultured human embryonic kidney fibroblast (HEK293T). By using FSC scheme, 90% of the work and time can be saved, and the optimized flavonoid combinations increased the HRE mediated transcriptional activity by ~3-fold as compared with individual flavonoid, while the amount of flavonoids was reduced by ~10-fold. Our study suggests that the optimized combination of flavonoids may have strong effect in activating the regulatory element of erythropoietin at very low dosage, which may be used as new source of natural hematopoietic agent. The present work also indicates that the FSC scheme is able to serve as an efficient and model-free approach to optimize the drug combination of different ingredients within a herbal decoction.