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Gelidium amansii Extract, a Potent α-glucosidase and α-amylase Inhibitor, Alleviates Postprandial Hyperglycemia in Diabetic Mice

당뇨 마우스에서 우뭇가사리(Gelidium amansii)의 식후 고혈당 완화 효과

  • Park, Jae-Eun (Department of Food Science and Nutrition, Pusan National University) ;
  • Kim, Jung-Min (Department of Food Science and Nutrition, Pusan National University) ;
  • Han, Ji-Sook (Department of Food Science and Nutrition, Pusan National University)
  • 박재은 (부산대학교 식품영양학과) ;
  • 김정민 (부산대학교 식품영양학과) ;
  • 한지숙 (부산대학교 식품영양학과)
  • Received : 2017.06.26
  • Accepted : 2017.08.17
  • Published : 2017.09.30

Abstract

Gelidium amansii shows antioxidant and anti-obesity effects; however, the effect on postprandial blood glucose levels is not known. The objective of the present study was to investigate the inhibitory effect of Gelidium amansii extract (GAE) on carbohydrate-digesting enzymes and its ability to alleviate postprandial hyperglycemia in streptozotocin (STZ)-induced diabetic mice. Gelidium amansii was extracted with 80% ethanol and concentrated for use in this study. The ${\alpha}-glucosidase$ and ${\alpha}-amylase$ inhibition assays were performed using the colorimetric method. ICR normal and STZ-induced diabetic mice were orally administered GAE (300 mg/kg body weight) or acarbose (100 mg/kg body weight) alone or soluble starch (2 g/kg body weight). Blood samples were taken from the tail vein at 0, 30, 60 and 120 min. Our results indicated that GAE markedly inhibited ${\alpha}-glucosidase$ and ${\alpha}-amylase$ activities with $IC_{50}$ values of $0.099{\pm}0.009mg/ml$ and $0.178{\pm}0.038mg/ml$, respectively, and was a more effective inhibitor than acarbose, the positive control. Further, the postprandial blood glucose levels of STZ-induced diabetic mice in the GAE-administered group were significantly lower than those of control group mice (p<0.05). Moreover, the area under the curves (AUC) significantly decreased with GAE administration in STZ-induced diabetic mice (p<0.05). These results indicate that GAE may be effective in decreasing postprandial blood glucose levels by inhibiting carbohydrate-digesting enzymes such as ${\alpha}-amylase$ and ${\alpha}-glucosidase$. Therefore, GAE could be used as a potential functional food for alleviating postprandial hyperglycemia.

우뭇가사리(Gelidium amansi)는 홍조류로서 우뭇가사리과(Gelidiaceae)에 속한다. 현재까지 우뭇가사리의 항산화 및 항비만 효과 등의 기능들이 연구되었으나 식후 혈당 수치에 미치는 영향에 관한 연구는 부족한 실정이다. 이에 본 연구에서는 Gelidium amansii extract (GAE)가 탄수화물 가수분해 효소(${\alpha}-glucosidase$, ${\alpha}-amylase$)에 미치는 억제 효과 및 streptozotocin (STZ)으로 유도된 당뇨병 마우스의 식후고혈당에 미치는 완화효과를 조사하였다. 정상군과 STZ으로 유도된 당뇨병 마우스에 수용성 전분(2 g/kg body weight)을 경구투여한 후 GAE (300 mg/kg body weight) 또는 acarbose (100 mg/kg body weight)를 단독 또는 함께 투여하였다. 혈당은 꼬리채혈을 통해 0, 30, 60, 120분 간격으로 측정하였다. ${\alpha}-glucosidase$${\alpha}-amylase$에 대한 GAE의 $IC_{50}$ 값은 각각 $0.099{\pm}0.009mg/ml$$0.178{\pm}0.038mg/ml$의 결과값을 나타내어, 양성대조군인 acarbose보다 더 효과적이었다. STZ으로 유발된 당뇨병 마우스의 식후 혈당 수치는 대조군에 비해 GAE 투여 시 유의적으로 더 낮았다(p<0.05). 또한 GAE 투여는 당뇨병 마우스에서 포도당 반응에 대한 곡선하면적 감소와 관련이 있었다(p<0.05). 이러한 결과는 GAE가 ${\alpha}-glucosidase$, ${\alpha}-amylas$와 같은 탄수화물 가수분해 효소를 억제함으로써 식후 고혈당을 완화시키는 유용한 천연기능성 식품이 될 것으로 사료된다.

Keywords

References

  1. Abid, S., Lekchiri, A., Mekhfi, H., Ziyyat, A., Legssyer, A., Aziz, M. and Bnouham, M. 2014. Inhibition of ${\alpha}$-glucosidase and glucose intestinal absorption by Thymelaea hirsuta fractions. J. Diabetes 6, 351-359. https://doi.org/10.1111/1753-0407.12106
  2. Baron, A. D. 1998. Postprandial hyperglycaemia and alpha-glucosidase inhibitors. Diabetes Res. Clin. Pract. 40, S51-S55. https://doi.org/10.1016/S0168-8227(98)00043-6
  3. Carroll, M. F., Gutierrez, A., Castro, M., Tsewang, D. and Schade, D. S. 2003. Targeting postprandial hyperglycemia: a comparative study of insulinotropic agents in type 2 diabetes. J. Clin. Endocrin. Metab. 88, 5248-5254. https://doi.org/10.1210/jc.2003-030649
  4. Ceriello, A., Davidson, J., Hanefeld, M., Leiter, L., Monnier, L., Owens, D., Tajima, N. and Tuomilehto, J. 2006. International prandial glucose regulation study group. Postprandial hyperglycaemia and cardiovascular complications of diabetes: an update. Nutr. Metab. Cardiovasc. Dis. 16, 453-456. https://doi.org/10.1016/j.numecd.2006.05.006
  5. Choi, K. H., Kang, J. H. and Han, J. S. 2016. Alleviating effects of mulberry fruit extract on postprandial hyperglycemia in streptozotocin-induced diabetic mice. J. Life Sci. 8, 921-927
  6. Derosa, G. and Maffioli, P. 2012. ${\alpha}$-Glucosidase inhibitors and their use in clinical practice. Arch. Med. Sci. 8, 899-906.
  7. Firdaus, M. and Prihanto, A. 2014. ${\alpha}$-Amylase and ${\alpha}$-glucosidase inhibition by brown seaweed (Sargassum sp.) extracts. Res. J. Life Sci. 1, 6-11. https://doi.org/10.21776/ub.rjls.2014.001.01.2
  8. Fonseca, V. 2003. Clinical significance of targeting postprandial and fasting hyperglycemia in managing type 2 diabetes mellitus. Curr. Med. Res. Opin. 19, 635-641. https://doi.org/10.1185/030079903125002351
  9. Fu, Y. W., Hou, W. Y., Yeh, S. T., Li, C. H. and Chen, J. C. 2007. The immunostimulatory effects of hot-water extract of Gelidium amansii via immersion, injection and dietary administrations on white shrimp Litopenaeus vannamei and its resistance against Vibrio alginolyticus. Fish Shellfish Immunol. 22, 673-685. https://doi.org/10.1016/j.fsi.2006.08.014
  10. Hadrich, F., Bouallagui, Z., Junkyu, H., Isoda, H. and Sayadi, S. 2015. The ${\alpha}$-glucosidase and ${\alpha}$-amylase enzyme inhibitory of hydroxytyrosol and oleuropein. J. Oleo. Sci. 64, 835-843. https://doi.org/10.5650/jos.ess15026
  11. Hanefeld, M. 1998. The role of acarbose in the treatment of non-insulin-dependent diabetes mellitus. J. Diabetes Complicat. 12, 228-237. https://doi.org/10.1016/S1056-8727(97)00123-2
  12. Hanhineva, K., Torronen, R., Isabel, B. P., Pekkinen, J., Kolehmainen, M., Mykkanen, H. and Poutanen, K. 2010. Impact of dietary polyphenols on carbohydrate metabolism. Int. J. Mol. Sci. 11, 1365-1402. https://doi.org/10.3390/ijms11041365
  13. Hara, Y. and Honda, M. 1990. The inhibition of ${\alpha}$-amylase by tea polyphenols. Agric. Biol. Chem. 54, 1939-1945.
  14. Heo S. J., Park, E. J., Lee, K. W. and Jeon, Y. J. 2005. Antioxidant activities of enzymatic extracts from brown seaweeds. Bioresour. Technol. 96, 1613-1623. https://doi.org/10.1016/j.biortech.2004.07.013
  15. Inoue, I., Takahashi, K., Noji, S., Awata, T., Negishi, K. and Katayama, S. 1997. Acarbose controls postprandial hyper-proinsulinemia in non-insulin-dependent diabetes mellitus. Diabetes Res. Clin. Pract. 36, 143-151. https://doi.org/10.1016/S0168-8227(97)00045-4
  16. Kang, J. H., Lee, H. A., Kim, H. J. and Han, J. S. 2017. Gelidium amansii extract ameliorates obesity by down-regulating adipogenic transcription factors in diet-induced obese mice. Nutr. Res. Pract. 11, 17-24. https://doi.org/10.4162/nrp.2017.11.1.17
  17. Kim, K. Y., Nam, K. A., Kurihara, H. and Kim, S. M. 2008. Potent ${\alpha}$-glucosidase inhibitors purified from the red alga. Phytochemistry 69, 2820-2825. https://doi.org/10.1016/j.phytochem.2008.09.007
  18. Kim, S. Y., Kim, S. J., Kim, J. A., Kim, D. H., Kwak, S. H., Chung, C. H. and Jeong, S. I. 2014. Anti-oxidant and ${\alpha}$ -glucosidase inhibition activity of extracts or fractions from Diospyros lotus L. leaves and quantitative analysis of their flavonoid compounds. J. Life Sci. 24, 935-945. https://doi.org/10.5352/JLS.2014.24.9.935
  19. Korean diabetes association. 1968. www.diabetes.or.kr
  20. Lebovitz, H. E. 2002. Treating hyperglycemia in type 2 diabetes: new goals and strategies. Cleve. Clin. J. Med. 69, 809-820. https://doi.org/10.3949/ccjm.69.10.809
  21. Lee, B. H., Eskandari, R., Jones, K., Reddy, K. R., Quezada, C. R., Rose, D. R., Hamaker, B. R. and Ponto, B. M. 2012. Modulation of starch digestion for slow glucose release through "toggling" of activities of mucosal ${\alpha}$-glucosidases. J. Biol. Chem. 287, 31929-31938. https://doi.org/10.1074/jbc.M112.351858
  22. Marles, R. J. and Farnsworth, N. R. 1995. Antidiabetic plants and their active constituents. Phytomedicine 2, 137-189. https://doi.org/10.1016/S0944-7113(11)80059-0
  23. Martinello, F., Soares, S. M., Franco, J. J., Santos, A. C., Sugohara, A., Garcia, S. B., Curti, C. and Uyemura, S. A. 2006. Hypolipidemic and antioxidant activities from Tamar indus indica L. pulp fruit extract in hypercholesterolemic hamsters. Food Chem. Toxicol. 44, 810-818. https://doi.org/10.1016/j.fct.2005.10.011
  24. Matsui, T., Tanaka, T., Tamura, S., Toshima, A., Tamaya, K., Miyata, Y., Tanaka, K. and Matsumoto, K. 2007. ${\alpha}$-Glucosidase inhibitory profile of catechins and theaflavins. J. Agric. Food Chem. 55, 99-105. https://doi.org/10.1021/jf0627672
  25. Nakai, M., Kageyama, N., Nakahara, K. and Miki, W. 2006. Phlorotannins as radical scavengers from the extract of Sargassum ringgoldianum. Mar. Biotech. 8, 409-414. https://doi.org/10.1007/s10126-005-6168-9
  26. Pierpoint, W. S. 1969. o-Quinones formed in plant extracts. Their reactions with amino acids and peptides. J. Biochem. 112, 609-616. https://doi.org/10.1042/bj1120609
  27. Prospective Diabetes Study Group. 1998. Intensive blood glucose control with sulphony lureas or insulin compared with conventional treatment and risk of complications in patients with patients with type 2 diabetes. Lancet 352, 837-853. https://doi.org/10.1016/S0140-6736(98)07019-6
  28. Stern, J. L., Hagerman, A. E., Steinberg, P. D. and Mason, P. K. 1996. Phlorotannin-protein interactions. J. Chem. Ecol. 22, 1877-1899. https://doi.org/10.1007/BF02028510
  29. Wang, M. L., Hou, Y. Y., Chiu, Y. S. and Chen, Y. H. 2013. Immunomodulatory activities of Gelidium amansii gel extracts on murine RAW 264.7 macrophages. J. Food Drug Anal. 21, 397-403. https://doi.org/10.1016/j.jfda.2013.09.002
  30. Watanabe, J, J., Kawabata, H., Kurihara, H. and Niki, R. 1997. Isolation and identification of ${\alpha}$-glucosidase inhibitors from tochu-cha (Eucommia ulmoides). Biosci. Biotechnol. Bio chem. 61, 177-178. https://doi.org/10.1271/bbb.61.177
  31. Yan, X. J., Li, X. C., Zhou, C. X. and Fan, X. 1996. Prevention of fish oil rancidity by phlorotannins from Sagassum kjellmanianum. J. Appl. Phycol. 8, 201-203. https://doi.org/10.1007/BF02184972
  32. Yan, X., Nagata, T. and Fan, X. 1998. Antioxidative activities in some common seaweeds. Plant Foods Hum. Nutr. 52, 253-262. https://doi.org/10.1023/A:1008007014659
  33. Yan, X., Chuda, Y., Suzuki, M. and Nagata, T. 1999. Fucoxanthin as the major antioxidant in Hijikia fusiformis, a common edible seaweed. Biosci. Biotechnol. Biochem. 63, 605-607. https://doi.org/10.1271/bbb.63.605
  34. Yang, T. H., Yao, H. T. and Chiang, M. T. 2015. Red algae (Gelidium amansii) reduces adiposity via activation of lipolysis in rats with diabetes induced by streptozotocinnicotinamide. J. Food Drug Anal. 23, 758-765 https://doi.org/10.1016/j.jfda.2015.06.003
  35. Yasuji, O. and Kiyoka, H. O. 1994. identification of antimutagenic activities in the extract of an edible brown algae. Hijikia fusiformis, (Hijiki) by ume gene expression system in Salmonella typhimurium (TA 1535/pSK 1002). J. Sci. Food Agric. 66, 103-109. https://doi.org/10.1002/jsfa.2740660115
  36. Yuan, H., Song, J., Li, X., Li, N. and Dai, J. 2006. Immunomodulation and antitumor activity of kappa-carrageenan oligosaccharides. Cancer Lett. 243, 228-34. https://doi.org/10.1016/j.canlet.2005.11.032
  37. Zhang, Q., Li, N., Liu, X., Zhao, Z., Li, Z. and Xu, Z. 2004. The structure of a sulfated galactan from Porphyra haitanesis and its in vivo antioxidant activity. Carbohydr. Res. 339, 105-111. https://doi.org/10.1016/j.carres.2003.09.015