Inhibition of sodium glucose cotransporter-1 expressed inXenopus laevisoocytes by 4-acetoxyscirpendiol from Cordyceps takaomantana (anamorph = Paecilomyces tenuipes)

Abstract

Cordyceps contains many health-promoting constituents. Recent studies revealed that the fruiting body of cordyceps significantly alleviates hyperglycemia which usually accompanies diabetes mellitus. The mechanism of the anti-hyperglycemic effect by cordyceps, however, is not fully understood. In this study, methanolic extracts were prepared from fruiting bodies of Paecilomyces tenuipes, and 4-beta acetoxyscirpendiol (ASD) was eventually purified from the extracts. The Na+/ glucose transporter-1 (SGLT-1) was expressed in Xenopus oocytes, and the effect of ASD on it was analyzed using voltage clamp and 2-deoxy-D-glucose (2-DOG) uptake studies. Fluorescence microscopy was performed to monitor the effect of ASD on glucose uptake using HEK293 cells expressing recombinant SGLT-1. ASD inhibited SGLT-1 activity, and its two derivatives (2-acetoxyscirpenol and 15-acetoxyscirpendiol), were also effective; 15-acetoxyscirepenol was as inhibitory as ASD while diacetoxyscirpenol had less effect. Thus, the ASD in P. tenuipes may play an important role in lowering blood sugar in the circulatory system along with its derivatives as specific inhibitors of SGLT-1.

Secondary metabolites from entomopathogenic Hypocrealean fungi

“…4-Acetoxyscirpenediol (69) showed low micromolar cytotoxic activity against the SNU-1, SNU-C4, SNU-354 and sarcoma-180 cell lines, 278 and inhibited the SGLT-1 Na (+) /glucose cotransporter. 279 Paecilomycines A, B, and C (70), 280 tenuipesine A (71), 281 and the spirocyclic trichothecanes spirotenuipesines A and B (72) 281 were isolated from cultivated fruiting bodies of P. tenuipes. Paecilomycine A and the spirotenuipesines promote neurotrophic factor biosynthesis in glial cells in vitro.…”

Functional characterization of SGLT1 using SSM-based electrophysiology: Kinetics of sugar binding and translocation

“…One discrepancy is the high K M value obtained for OMG of 241 ± 18 mM. In the literature we found values between 3.3 mM and 22 mM ( Hirayama et al, 1996 ; Díez-Sampedro et al, 2001 ; Yoo and Lee, 2006 ; Tyagi et al, 2007 ). On the other hand, the K M value of 305 ± 167 mM we determined for D-xylose is closer to the values of 50–100 mM reported in the literature ( Hager et al, 1995 ; Díez-Sampedro et al, 2001 ).…”