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Journal of Natural Medicines

, Volume 72, Issue 2, pp 530–536 | Cite as

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

  • Shengli Gao
  • Hideo Satsu
  • Toshiaki MakinoEmail author
Original Paper

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 IC50 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 IC50 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.

Keywords

Glucose transporter 5 Fructose Bofutsushosan Zingiber officinale 6-gingerol 

References

  1. 1.
    Pharmaceutical and Medical Device Regulatory Science Society of Japan (2016) Japanese pharmacopoeia (JP XVII), 17th edn. Jiho, TokyoGoogle Scholar
  2. 2.
    Azushima K, Tamura K, Wakui H, Maeda A, Ohsawa M, Uneda K, Kobayashi R, Kanaoka T, Dejima T, Fujikawa T, Yamashita A, Toya Y, Umemura S (2013) Bofu-tsu-shosan, an oriental herbal medicine, exerts a combinatorial favorable metabolic modulation including antihypertensive effect on a mouse model of human metabolic disorders with visceral obesity. PLoS One 8:e75560CrossRefGoogle Scholar
  3. 3.
    Park J, Bose S, Hong SW, Lee DK, Yoo JW, Lim CY, Lee M, Kim H (2014) Impact of GNB3-C825T, ADRB3-Trp64Arg, UCP2-3′UTR 45 bp del/ins, and PPARγ-Pro12Ala polymorphisms on Bofutsushosan response in obese subjects: a randomized, double-blind, placebo-controlled trial. J Med Food 17:558–570CrossRefGoogle Scholar
  4. 4.
    Lin CH, Kuo YH, Shih CC (2014) Effects of Bofu–Tsusho–San on diabetes and hyperlipidemia associated with AMP-activated protein kinase and glucose transporter 4 in high-fat-fed mice. Int J Mol Sci 15:20022–20044CrossRefGoogle Scholar
  5. 5.
    Qian W, Hasegawa J, Tsuno S, Endo Y, Matsuda A, Miura N (2014) Effects of kampo formulas on the progression of hypercholesterolemia and fatty liver induced by high-cholesterol diet in rats. Yonago Acta Med 57:147–158PubMedPubMedCentralGoogle Scholar
  6. 6.
    Bray GA (2007) How bad is fructose? Am J Clin Nutr 86:895–896CrossRefGoogle Scholar
  7. 7.
    Tappy L, Mittendorfer B (2012) Fructose toxicity: is the science ready for public health actions? Curr Opin Clin Nutr Metab Care 15:357–361CrossRefGoogle Scholar
  8. 8.
    Hu FB, Malik VS (2010) Sugar-sweetened beverages and risk of obesity and type 2 diabetes: epidemiologic evidence. Physiol Behav 100:47–54CrossRefGoogle Scholar
  9. 9.
    Wright EM, Martin MG, Turk E (2003) Intestinal absorption in health and disease − sugars. Best Pract Res Clin Gastroenterol 17:943–956CrossRefGoogle Scholar
  10. 10.
    Douard V, Ferraris RP (2008) Regulation of the fructose transporter GLUT5 in health and disease. Am J Physiol Endocrinol Metab 295:E227–E237CrossRefGoogle Scholar
  11. 11.
    Barone S, Fussell SL, Singh AK, Lucas F, Xu J, Kim C, Wu X, Yu Y, Amlal H, Seidler U, Zuo J, Soleimani M (2009) Slc2a5 (Glut5) is essential for the absorption of fructose in the intestine and generation of fructose-induced hypertension. J Biol Chem 284:5056–5066CrossRefGoogle Scholar
  12. 12.
    Satsu H, Awara S, Unno T, Shimizu M (2018) Suppressive effect of nobiletin and epicatechin gallate on fructose uptake in human intestinal epithelial Caco-2 cells. Biosci Biotechnol Biochem.  https://doi.org/10.1080/09168451.09162017.01387515 CrossRefGoogle Scholar
  13. 13.
    Japan Kampo Medicines Manufacturers Association under the supervision of National Institute of Health Sciences, the affiliated institutions of the Ministry of Health, Labour and Welfare of Japan (2013) Handbook on OTC Medicinal Products in Kampo. JihoGoogle Scholar
  14. 14.
    Oji I, Yamamoto N, Totsuka M, Satsu H (2015) Development and analysis of evaluation system to search for food factors that modulate fructose transporter in intestinal epithelia. The 12th Asian Congress of Nutrition: ACN2015, May 14–18, Yokohama, Japan. OS19-13, p 151 (Abstract)Google Scholar
  15. 15.
    Semwal RB, Semwal DK, Combrinck S, Viljoen AM (2015) Gingerols and shogaols: important nutraceutical principles from ginger. Phytochemistry 117:554–568CrossRefGoogle Scholar
  16. 16.
    Villa-Rodriguez JA, Aydin E, Gauer JS, Pyner A, Williamson G, Kerimi A (2018) Green and chamomile teas, but not acarbose, attenuate glucose and fructose transport via inhibition of GLUT2 and GLUT5. Mol Nutr Food Res.  https://doi.org/10.1002/mnfr.201700566 CrossRefGoogle Scholar
  17. 17.
    McKay DL, Blumberg JB (2006) A review of the bioactivity and potential health benefits of chamomile tea (Matricaria recutita L.). Phytother Res 20:519–530CrossRefGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pharmacognosy, Graduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
  2. 2.Department of BiotechnologyMaebashi Institute of TechnologyMaebashiJapan

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