Received: 23 October, 2008. Accepted: 7 March, 2009. Review Medicinal and Aromatic Plant Science and Biotechnology ©2009 Global Science Books Progress in Research and Application of Silymarin Yong-ping Pei • Jian Chen • Wei-lin Li * Institute of Botany, Jiangsu Province and the Chinese Academy of Sciences, Nanjing 210014, China Corresponding author: * lwlcnbg@mail.cnbg.net ABSTRACT Silymarin (SL), a mixture of flavonolignans mainly including silybin A and B, isosilybin A and B, silidianin, and silychristine from the seeds of Silybum marianum L., has been widely used to treat acute and chronic viral hepatitis, toxin/drug-induced hepatitis, cirrhosis, alcoholic fatty liver diseases and other ailments because of its excellent hepatoprotective effect. Silybin is the most active component of SL, which is administered orally in most cases of clinical use. However, its bioavailability is low due to poor water solubility. The present paper reviews the research results on isolation methods, pharmacological activities, action mechanisms, preparation techniques, quality control and market state of SL in the hope that it would be helpful to better understand and use this traditional Chinese medicine. _____________________________________________________________________________________________________________ Keywords: action mechanism, isolation methods, pharmacological activity, preparation techniques, quality control CONTENTS INTRODUCTION.......................................................................................................................................................................................... 1 EXTRACTION AND SEPARATION ............................................................................................................................................................ 1 PHARMACOLOGICAL ACTIVITIES ......................................................................................................................................................... 2 Hepatoprotective effect .............................................................................................................................................................................. 2 Anti-inflammatory effect ........................................................................................................................................................................... 2 Antitumor effect ........................................................................................................................................................................................ 2 Anti-diabetes effect.................................................................................................................................................................................... 3 MECHANISMS FOR THE PROTECTIVE EFFECT AGAINST LIVER DISEASE.................................................................................... 3 Antioxidation ............................................................................................................................................................................................. 3 Inhibit the production of NO ..................................................................................................................................................................... 3 Decrease the activity of phospholipase ...................................................................................................................................................... 3 Protection of the cell membrane ................................................................................................................................................................ 4 Steady cell membrane and facilitate energy metabolism ........................................................................................................................... 4 Promote hepatic cytothesis ........................................................................................................................................................................ 4 Cytokine and immunomodulatory function ............................................................................................................................................... 4 Inhibition of the synthesis of extracellular matrix (ECM) ......................................................................................................................... 4 ACHIEVEMENTS OF RESEARCH IN SILYMARIN PREPARATION ...................................................................................................... 4 Tablets ....................................................................................................................................................................................................... 4 Capsules .................................................................................................................................................................................................... 5 Granules .................................................................................................................................................................................................... 5 Injections ................................................................................................................................................................................................... 5 Other preparations ..................................................................................................................................................................................... 5 QUALITY CONTROL .................................................................................................................................................................................. 6 MARKET TRADE......................................................................................................................................................................................... 6 PROSPECTS.................................................................................................................................................................................................. 7 REFERENCES............................................................................................................................................................................................... 7 _____________________________________________________________________________________________________________ INTRODUCTION Silybum marianum L. was originally planted in India and the Kashmir area of Pakistan, then introduced and cul- tivated in Europe, America and Australia. The plant was introduced into China from Germany in 1927, mainly grown in Jiangsu, Shaanxi and Beijing. Silymarin (SL) is a mixture of flavonolignans isolated from the seeds of S. marianum, including many isomers with poor water solu- bility. The main chemical constituents of SL are silybin A and B, isosilybin A and B, silidianin, and silychristin, among which, silybins are the most active components with the highest content. SL has an excellent clinical effect to treat acute and chronic viral hepatitis, cirrhosis and meta- bolic toxin-induced liver injury by improving the hepatic function, and enhancing activity of the cell membrane. This article reviews research advances in the isolation methods, pharmacological activities, clinical uses, action mechanisms, preparation techniques, quality control and market state of SL. EXTRACTION AND SEPARATION Early in 1974, Wagner et al. (1974) extracted silybin, iso- silybin, silychristine and silidianin from seeds of S. mari- anum. In 2003, Lee et al. (2003) extracted two isomers of silybin and isosilybin, silybin A and B, isosilybin A and B for the first time. Chinese scientists (Chang and Wu 1985) ®