title: An updated systematic review of the pharmacology of silymarin.
abstract: BACKGROUND
  Recent years have seen an explosion of scientific papers that deal with drugs from the fruits of milk thistle and its active substances silymarin (standardized mixture of flavonolignanes), thus justifying an updated systematic review.
  
  
  METHODS
  Electronic databases identified silymarin, silibinin, silicristin or milk thistle as descriptors in >700 papers (34% published in last 5 years; 92% dealt with animal pharmacological). Only papers adequately reporting on experimental conditions, dosing, variables tested and statistics were analysed.
  
  
  RESULTS
  Silymarin was found to modify specifically the functions related to various transporters and receptors located in the cell membranes; that is, organic anion uptake transporter peptides (OATP), ABC transporters (P-gp), bile salt export pump, as well as TNF-alpha-dependent and possibly selectin-dependent phenomena. In the cytoplasm, some antioxidant properties and the inhibition of the lipoxygenase pathway seem quite selective and could concur to the antitoxic effects. Some effects like the inhibition of inducible nitric-oxide synthase, of nuclear factor kappa B, and reduction of collagen synthesis are indicative of DNA/RNA-mediated effects. Several studies using 'in vitro' and 'in vivo' cancer models suggest a potential of silymarin in such diseases. Topical and systemic silymarin has skin protective properties against UV-induced damage in epidermis and causes an up-regulation of tumour-suppressor genes p53- and p21CIP1. There were no data on hepatic viral replication, viremia or spontaneous tumours in the data examined.
  
  
  CONCLUSIONS
  Data presented here do not solve the question about the complex mechanism(s) of action of the medicinal herbal drug silymarin. Silymarin may be a natural multi-functional and multi-target drug.
authors.affiliation: Institute of Complementary Medicine, Department of Internal Medicine, University Hospital Zurich, Zurich, Switzerland. reinhard.saller@usz.ch
authors.forename: Reinhard
authors.initials: R
authors.lastname: Saller
authors.forename: Jörg
authors.initials: J
authors.lastname: Melzer
authors.forename: Jürgen
authors.initials: J
authors.lastname: Reichling
authors.forename: Reto
authors.initials: R
authors.lastname: Brignoli
authors.forename: Remy
authors.initials: R
authors.lastname: Meier
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects; D020944:Silybum marianum / Q000737:chemistry; D008517:Phytotherapy; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D012838:Silymarin / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D020011:Protective Agents; D012838:Silymarin