title: Anti-diabetic properties of chrysophanol and its glucoside from rhubarb rhizome.
abstract: An ethanol extract of rhubarb rhizome exhibited marked glucose transport activity in differentiated L6 rat myotubes. Activity-guided fractionation resulted in the isolation of two anthraquinones, chrysophanol-8-O-beta-D-glucopyranoside (1) and chrysophanol (2). The anti-diabetic effect was examined by glucose transport activity, glucose transporter 4 (Glut4) expression in myotubes, and the level of insulin receptor (IR) tyrosine phosphorylation as influenced by tyrosine phosphatase 1B, each of which is a major target of diabetes treatment. Chrysophanol-8-O-beta-D-glucopyranoside up to 25 microM dose-dependently activated glucose transport in insulin-stimulated myotubes. Increased tyrosine phosphorylation of IR due to tyrosine phosphatase 1B inhibitory activity with an IC50 value of 18.34+/-0.29 microM and unchanged Glut4 mRNA levels was observed following chrysophanol-8-O-beta-D-glucopyranoside treatment. Chrysophanol up to 100 microM exerted mild glucose transport activity and elevated the tyrosine phosphorylation of IR via tyrosine phosphatase 1B inhibition (IC50=79.86+/-0.12 microM); Glut4 mRNA expression was also significantly increased by 100 microM. The ED50 values of the two compounds were 59.38+/-0.66 and 79.69+/-0.03 microM, respectively. Therefore, these two anthraquinones from rhubarb rhizome, chrysophanol-8-O-beta-D-glucopyranoside and chrysophanol, have mild cytotoxicity and anti-diabetic properties and could play metabolic roles in the insulin-stimulated glucose transport pathway.
authors.affiliation: Department of Food and Nutrition, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Myung Sun
authors.initials: MS
authors.lastname: Lee
authors.forename: Cheon Bae
authors.initials: CB
authors.lastname: Sohn
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000302:isolation & purification / Q000494:pharmacology*; D001692:Biological Transport; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D012250:Rheum / Q000737:chemistry*; D027343:Rhizome / Q000737:chemistry; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D051275:Glucose Transporter Type 4; D005960:Glucosides; D007004:Hypoglycemic Agents; D007328:Insulin; C495694:Slc2a4 protein, rat; C533998:chrysophanol-8-O-glycopyranoside; D014443:Tyrosine; D011972:Receptor, Insulin; D005947:Glucose; C027113:chrysophanic acid