Journal
BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volume 31, Issue 11, Pages 2154-2157Publisher
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.31.2154
Keywords
rhubarb; anthraquinone; diabetes; glucose transport
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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 mu M 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 mu M and unchanged Glut4 mRNA levels was observed following chrysophanol-8-O-beta-glucopyranoside treatment. Chrysophanol up to 100 mu M exerted mild glucose transport activity and elevated the tyrosine phosphorylation of IR via tyrosine phosphatase 1B inhibition (IC50=79.86 +/- 0.12 mu M); Glut4 mRNA expression was also significantly increased by 100 mu M. The ED50 values of the two compounds were 59.38 +/- 0.66 and 79.69 +/- 0.03 mu M, 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.
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