Ligustilide Suppresses the Biological Properties of Danggui Buxue Tang: A Chinese Herbal Decoction Composed of Radix Astragali and Radix Angelica sinensis

Abstract

Danggui Buxue Tang (DBT), a herbal decoction composed of Radix Astragali (RA) and Radix Angelica sinensis (RAS), has been used for treating menopausal irregularity in women for more than 800 years in China. According to the old tradition, RAS had to be processed with yellow wine before DBT preparation, which markedly reduced the amount of ligustilide in RAS and DBT, as well as enhanced the bioactivities of DBT. Here, we hypothesized that ligustilide would be an ingredient that possessed suppressive effects on DBT's functions. In the presence of ligustilide, the amount of astragaloside IV, calycosin, formononetin, and total polysaccharides extracted from RA were decreased. An increase of ligustilide caused a decrease of DBT's osteogenic activity in stimulating proliferation and differentiation of cultured bone cells. In addition, in the presence of a high level of ligustilide, DBT caused a side effect inducing the proliferation of breast MCF-7 cells. The current results strongly suggest that ligustilide is a negative regulator that hinders DBT to achieve its biological efficacy, which supports the traditional practice of preparing DBT using the ethanol-treated RAS.

Key words

Angelica sinensis - Umbelliferae - Astragalus membranaceus var. mongholicus - Leguminosae - ligustilide

References

• 1 Zheng X Y. Pharmacopoeia of the People's Republic of China. Beijing; Chemistry Industry Press 2005
• 2 Song Z H, Ji Z H, Lo C K, Dong T T X, Zhao K J, Li O T W, Haines C J, Kung S D, Tsim K W K. Chemical and biological assessment of a traditional Chinese herbal decoction prepared from Radix Astragali and Radix Angelicae sinensis: orthogonal array design to optimize the extraction of chemical constituents.  Planta Med. 2004;  70 1222-1227
• 3 Dong T T X, Zhao K J, Gao Q T, Ji Z N, Zhu T T, Li J, Duan R, Cheung A W, Tsim K W K. Chemical and biological assessment of a Chinese herbal decoction containing Radix Astragali and Radix Angelicae sinensis: determination of drug ratio in having optimized properties.  J Agric Food Chem. 2006;  54 2767-2774
• 4 Wagner H, Bauer R, Xiao P G, Chen J M, Michler G. Chinese monographs and analysis: Angelica sinensis, Vol. 3. Rimbach; Verlag im Wald 2001
• 5 Zhao K J, Dong T T X, Tu P F, Song Z H, Lo C K, Tsim K W K. Molecular genetic and chemical assessment of Radix Angelica (Danggui) in China.  J Agric Food Chem. 2003;  51 2576-2583
• 6 Li S P, Zhao K J, Ji Z N, Song Z H, Dong T T X, Lo C K, Cheung J K H, Zhu S Q, Tsim K W K. A polysaccharide isolated from Cordyceps sinensis, a traditional Chinese medicine, protects PC12 cells against hydrogen peroxide induced injury.  Life Sci. 2003;  73 2503-2513
• 7 Dong T T X, Cui X M, Song Z H, Zhao K J, Ji Z N, Lo C K, Tsim K W K. Chemical assessment of roots of Panax notoginseng in China: regional and seasonal variations in its active constituents.  J Agric Food Chem. 2003;  51 4617-4623
• 8 Zhu T T, Choi R C Y, Chu G K Y, Cheung A W H, Gao Q T, Li J, Jiang Z Y, Dong T T X, Tsim K W K. Flavonoids possess neuroprotective effects on cultured pheochromocytoma PC12 cells: a comparison of different flavonoids in activating estrogenic effect and in preventing beta-amyloid-induced cell death.  J Agric Food Chem. 2007;  55 2438-2445
• 9 Lbbotson K J, Harrod J, Gowen M, D'Souza S, Smith D D, Winkler M E, Derynck R, Mundy G R. Human recombinant transforming growth factor alpha stimulates bone resorption and inhibits formation in vitro.  Proc Natl Acad Sci USA. 1986;  83 2228-2232
• 10 Choi R C Y, Gao Q T, Cheung A W H, Zhu T T, Lau F T C, Li J, Li Z M, Chu G K Y, Duan R, Cheung J K H, Ding A W, Zhao K J, Dong T T X, Tsim K W K. A Chinese herbal decoction, Danggui Buxue Tang, stimulates proliferation, differentiation and gene expression of cultured osteosarcoma cells: genomic approach to reveal specific gene activation.  eCAM. 2009;  DOI: 10.1093/ecam/nen085 , advance online publication
  
• 11 Gao Q T, Choi R C Y, Cheung A W H, Zhu T T, Li J, Lau F T C, Chu G K Y, Duan R, Cheung J K H, Jiang Z Y, Dong X B, Zhao K J, Dong T T X, Tsim K W K. Danggui Buxue Tang – a Chinese herbal decoction activates the phosphorylations of extracellular signal-regulated kinase and estrogen receptor alpha in cultured MCF-7 cells.  FEBS Lett. 2007;  581 233-240
• 12 Zhang E Q. The Chinese Materia Medica. Shanghai; Publishing House of Shanghai University of Traditional Chinese Medicine 1988
• 13 Ye Y N, Liu E S, Li Y, So H L, Cho C C, Sheng H P, Lee S S, Cho C H. Protective effect of polysaccharides enriched fraction from Angelica sinensis on hepatic injury.  Life Sci. 2001;  69 637-646
• 14 Xie M. Modern study of the medical formulae in traditional Chinese medicine, Vol. 1. Beijing; Xueyuan Press 1997: 603-604
• 15 Ozaki Y, Sekita S, Harada M. Centrally acting muscle relaxant effect of phthalides (ligustilide, cnidilide and senkyunolide) obtained from Cnidium officinale Makino.  Yakugaku Zasshi. 1989;  109 402-406
• 16 Huang W H, Song C Q. Advances of Angelica sinensis chemical and pharmacology.  China J Chin Mater Med. 2001;  26 147-151
• 17 Yan S, Qiao G F. Effect of the oil of Angelica sinensis on contractial function of isolated uterine smooth muscle of mice.  Chin Tradit Herb Drugs. 2000;  31 604-606
• 18 Kan W L T, Cho C H, Rudd J A, Lin G. Study of the anti-proliferative effects and synergy of phthalides from Angelica sinensis on colon cancer cells.  J Ethnopharmacol. 2008;  120 36-43