title: Indole-3-Carbinol (I3C) and its Major Derivatives: Their Pharmacokinetics and Important Roles in Hepatic Protection.
abstract: BACKGROUND
  Indoles, including indole-3-carbinol (I3C) and its derivatives, are the products of glucosinolate hydrolysis catalyzed by the enzyme myrosinase. Under acidic conditions, I3C polymerizes into 3, 3- diindolylmethane (DIM), [2-(indol-3-ylmethyl)-indol-3-yl]indol-3-ylmethane (LTr1), 1-(3-hydroxymethyl)- indolyl-3-indolylmethane (HI-IM) and indolo[3,2b]carbazole (ICZ). Recently, I3C and its dimer DIM have shown pleiotropic protective effects on chronic liver injuries, including viral hepatitis, hepatic steatosis, hepatic cirrhosis, hepatocellular carcinoma, and so on.
  
  
  METHODS
  We reviewed the published papers about the pharmacokinetics of I3C and its derivatives in vitro and in vivo, and summarized their multiple protective roles in the processes of chronic liver diseases.
  
  
  RESULTS
  Indoles not only regulate transcriptional factors and their respective signaling pathways, but also relieve oxidative stress and inhibit the synthesis of DNA to influence the activation, proliferation and apoptosis of target cells. Moreover, indoles modulate the enzymes that are relevant to hepatitis viral replication, lipogenesis, and the metabolism of ethanol and some hepatotoxic substances to protect the liver. Currently, the immunomodulatory biofunction of indoles contributes to improving non-alcoholic steatohepatitis. In addition, indoles also function as the inhibitors of pro-inflammatory cytokines and chemokines to reduce microbial-induced liver injures.
  
  
  CONCLUSIONS
  Indoles, especially I3C and DIM as phytochemicals, exert anti-fibrosis, anti-tumor, anti-oxidant, immunomodulatory, detoxification and anti-inflammation effects on hepatic protection through pleiotropic mechanism.
authors.forename: Si-qi
authors.initials: SQ
authors.lastname: Wang
authors.forename: Li-sha
authors.initials: LS
authors.lastname: Cheng
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Ji-yao
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China. jiang.wei@zs-hospital.sh.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D002908:Chronic Disease; D006026:Glycoside Hydrolases / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000187:drug effects; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008107:Liver Diseases / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D064209:Phytochemicals / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D018925:Chemokines; D007211:Indoles; D064209:Phytochemicals; D014157:Transcription Factors; C016517:indole-3-carbinol; D006026:Glycoside Hydrolases; C022739:thioglucosidase; C016392:3,3'-diindolylmethane