Anti-diabetic Properties of Chrysophanol and Its Glucoside from Rhubarb Rhizome

• Published in: Biological & Pharmaceutical Bulletin 2008/11/01, Vol.31(11), pp.2154-2157
• Main Authors: Lee, Myung Sun, Sohn, Cheon Bae
• Format: Article
• Language: English
• Subjects: Animals; anthraquinone; Anthraquinones - isolation & purification; Anthraquinones - pharmacology; Biological Transport; Cell Differentiation; Cell Line; Cell Survival - drug effects; diabetes; Dose-Response Relationship, Drug; Glucose - metabolism; glucose transport; Glucose Transporter Type 4 - biosynthesis; Glucosides - isolation & purification; Glucosides - pharmacology; Hypoglycemic Agents - isolation & purification; Hypoglycemic Agents - pharmacology; Insulin - pharmacology; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; Myoblasts - drug effects; Myoblasts - metabolism; Phosphorylation; Rats; Receptor, Insulin - metabolism; Rheum - chemistry; Rhizome - chemistry; rhubarb; Tyrosine - metabolism
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.31.2154

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-β-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-β-D-glucopyranoside up to 25 μM 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 μM and unchanged Glut4 mRNA levels was observed following chrysophanol-8-O-β-D-glucopyranoside treatment. Chrysophanol up to 100 μM exerted mild glucose transport activity and elevated the tyrosine phosphorylation of IR via tyrosine phosphatase 1B inhibition (IC50=79.86±0.12 μM); Glut4 mRNA expression was also significantly increased by 100 μM. The ED50 values of the two compounds were 59.38±0.66 and 79.69±0.03 μM, respectively. Therefore, these two anthraquinones from rhubarb rhizome, chrysophanol-8-O-β-D-glucopyranoside and chrysophanol, have mild cytotoxicity and anti-diabetic properties and could play metabolic roles in the insulin-stimulated glucose transport pathway.