Inhibitory effect of bofutsushosan (fang feng tong sheng san) on glucose transporter 5 function in vitro

Abstract

Bofutsushosan (BTS; fang feng tong sheng san in Chinese) is a formula in traditional Japanese Kampo medicine and Chinese medicine comprising eighteen crude drugs, and is used to treat obesity and metabolic syndrome. Fructose is contained in refreshing beverages as high-fructose corn syrup, and is associated with obesity. Fructose is absorbed via glucose transporter 5 (GLUT5) in the intestine. Therefore, the inhibition of GLUT5 is considered to be a target of obesity drugs. We evaluated the inhibitory effects of BTS extract and its constituents on fructose uptake using Chinese hamster ovary K1 cells, i.e., cells stably expressing GLUT5. Boiled water extract of BTS significantly suppressed GLUT5 function in a concentration-dependent manner without cytotoxicities. Among 18 components of BTS, the boiled water extracts of the rhizome of Zingiber officinale, the root and rhizome of Saposhnikovia divaricata, and the root of Platycodon grandiflorum exhibited significant inhibitory effects on fructose uptake with IC values of 314, 119 and 475 µg/ml, respectively. Among the constituents of the rhizome of Z. officinale extract, 6-gingerol significantly inhibited GLUT5 with an IC value of 39 µM, while 6-shogaol exhibited a significant but weak inhibition on GLUT5 at 100 µM. One of the mechanisms of action of BTS may be the inhibition of fructose absorption in the intestine, and one of the active components of BTS is the rhizome of Z. officinale and 6-gingerol.

Inhibitory effect of Bofutsushosan (Fangfengtongshengsan) extract on the absorption of fructose in rats and mice

“…In a previous in vitro study [ 9 ], we revealed that the extract of BTS significantly inhibited GLUT5, which transports fructose from the intestinal lumen into epithelial cells and plays a role in the absorption of fructose in the intestine. The present in vivo study reproduced these in vitro results.…”

“…The present in vivo study reproduced these in vitro results. However, although the extract of RR exhibited a significant inhibitory effect of GLUT5 in a previous in vitro study, the effect was not strong, and other crude drug extracts of ZR, SaR, PlR, MH, GaF, and CR exhibited stronger effects than the RR extract [ 9 ]. The mechanisms of fructose absorption may not be fully explained by the function of GLUT5 in vivo, and mechanisms other than GLUT5 could contribute to the absorption of fructose.…”

“…It has been shown that BTS extract has a preventive effect against hyperglycemia and body fat accumulation caused by fructose loading in in vivo study [ 8 ]. In our previous study, BTS boiling water extract inhibited the uptake of fructose absorbed via glucose transporter 5 (GLUT5) in cultured cells [ 9 ].…”

Oenothein B in Eucalyptus Leaf Extract Suppresses Fructose Absorption in Caco-2 Cells

“…At this dose, ELE-treated cells did not show different morphological features, as confirmed by transepithelial/endothelial electrical resistance (TEER) and microscopic analyses; before and after fructose permeation, the TEER values of the blank and ELE (1 mg/mL) were retained by 91% and 81%, respectively. Many studies have reported various polyphenols derived from edible plants with inhibitory activity against fructose absorption [ 32 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. We examined the effects of the ELE with reduced polyphenolic substances.…”

Bofutsushosan Significantly Ameliorated Betamethasone-Induced Cushing’s Syndrome

“…Fructose is absorbed via glucose transporter 5 (GLUT5) in the intestine. Inhibitory effect of BTS on GLUT5 function in vitro was observed [ 2 ]. BTS increased mRNA expression levels of leptin, adiponectin, and UCP1 in brown adipose tissues (BAT), and improved insulin resistance, and subsequently reduced serum levels of leptin and triglyceride in parallel with decreased visceral white adipose tissue (WAT) volume and adipocyte size in high-fat diet-fed obese mice [ 3 ].…”