4-acetoxyscirpendiol of Paecilomyces tenuipes inhibits Na(+)/D-glucose cotransporter expressed in Xenopus laevis oocytes.
Cordyceps, an entomopathogenic fungus, contains many health-promoting ingredients. Recent reports indicate that the consumption of cordyceps helps reduce blood-sugar content in diabetics. However, the mechanism underlying this reduction in circulatory sugar content is not fully understood. Methanolic extracts were prepared from the fruiting bodies of Paecilomyces tenuipes, and 4-beta acetoxyscirpendiol (4-ASD) was eventually isolated and purified. Na(+)/Glucose transporter-1 (SGLT-1) was expressed in Xenopus oocytes, and the effect of 4-ASD on SGLT-1 was analyzed utilizing a voltage clamp and by performing 2-deoxy-D-glucose (2-DOG) uptake studies. 4-ASD was shown to significantly inhibit SGLT-1 activity compared to the non-treated control in a dose-dependent manner. In the presence of the derivatives of 4-ASD (diacetoxyscirpenol or 15-acetoxyscirpendiol), SGLT-1 activity was greatly inhibited in an 4-ASD-like manner. Of these derivatives, 15-acetoxyscirepenol inhibited SGLT-1 as well as 4-ASD, whereas diacetoxyscirpenol was slightly less effective. Taken together, these results strongly indicate that 4-ASD in P. tenuipes may lower blood sugar levels in the circulatory system. We conclude that 4-ASD and its derivatives are effective SGLT-1 inhibitors.
Yoo
Ocki
O
Department of Life Sciences, University of Seoul, Seoul 130-743, Korea.
Son
Joo-Hiuk
JH
Lee
Dong-Hee
DH
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D010143:Paecilomyces / Q000737:chemistry; D018408:Patch-Clamp Techniques; D051269:Sodium-Glucose Transporter 1; D013605:T-2 Toxin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014255:Trichothecenes / Q000737:chemistry / Q000494:pharmacology; D014982:Xenopus laevis
C482282:4beta-acetoxyscirpendiol; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; C495674:SLC5A1 protein, human; D051269:Sodium-Glucose Transporter 1; D014255:Trichothecenes; D003847:Deoxyglucose; D013605:T-2 Toxin; C001809:diacetoxyscirpenol