Molecular Mechanism of Inhibition of <i>α</i>-Glucosidase and HMG-CoA Reductase Activities by Steviol and Isosteviol

ZHANG Jun; WANG Fang; WANG Hang; YU Ningkang; YUE Xingwang; WANG Qingqing

doi:10.13386/j.issn1002-0306.2021060087

Volume 42 Issue 24

Dec. 2021

Turn off MathJax

Article Contents

Abstract

References

Science and Technology of Food Industry > 2021 > 42(24): 8-15. > DOI: 10.13386/j.issn1002-0306.2021060087

ZHANG Jun, WANG Fang, WANG Hang, et al. Molecular Mechanism of Inhibition of α-Glucosidase and HMG-CoA Reductase Activities by Steviol and Isosteviol[J]. Science and Technology of Food Industry, 2021, 42(24): 8−15. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2021060087.

Citation:

PDF (4179 KB)

Molecular Mechanism of Inhibition of α-Glucosidase and HMG-CoA Reductase Activities by Steviol and Isosteviol

School of Chemical Engineering & Food Science, Zhengzhou University of Technology, Zhengzhou 450000, China

More Information

Received Date: June 09, 2021
Available Online: October 11, 2021

Graphical Abstract

Abstract

Abstract

This study focused on the molecular mechanism of inhibition of activities of α-glucosidase and HMG-CoA reductase which were the key enzymes of hyperglycemia and hyperlipidemia by steviol and isosteviol. The inhibition rate of steviol and isosteviol to α-glucosidaseand HMG-CoA reductase was determined by spectrophotometry. The enzyme inhibition kinetics were studied by double reciprocal plot method, and the molecular binding mode was analysised by AutoDock software. The results showed that the IC₅₀ of steviol, isosteviol to α-glucosidase were 70.75 and 49.65 mg/L respectively. The activity of α-glucosidase was inhibited by competitive and non competitive methods. The IC₅₀ of steviol, isosteviol to HMG-CoA reductase were 46.29 and 36.66 mg/L, which competitively inhibited HMG-CoA reductase. The results of molecular docking showed that steviol and isosteviol were located in the hydrophobic pocket of α-glucosidase and HMG CoA reductase, they bind with multiple amino acid residues and have hydrophobic effect. This study would provide theoretical reference for the development of new type inhibitors of foodborne α-glucosidase and HMG-CoA reductase, and the promotion of the application of steviol and isosteviol in food and medicine.
- steviol,
- isosteviol,
- α-glucosidase,
- HMG-CoA reductase,
- AutoDock

FullText(HTML)

References (31)

References

[1]	DAILY S A T. The number of dyslipidemia has exceeded 400 million, Scientific lipid regulation should not be ignored in China [EB/OL]. http://www.xinhuanet.com/science/2019-08/16/c_138310843.htm.
[2]	REAVEN G M. Role of Insulin Resistance in Human[J]. Diabetes,1988(37):1595−1607.
[3]	王震宇, 禹同生, 王健, 等. 阿托伐他汀的药理作用及临床应用进展[J]. 中国新药杂志,2010,19(18):1684−1687,1698. [WANG Z, YU T, WANG J, et al. Advances in pharmacological effects and clinical application of atorvastatin[J]. Chinese Journal of New Drugs,2010,19(18):1684−1687,1698.
[4]	MAGANA-BARAJAS E, BUITIMEA-CANTUA G V, HERNANDEZ-MORALES A, et al. In vitro alpha-amylase and alpha-glucosidase enzyme inhibition and antioxidant activity by capsaicin and piperine from Capsicum chinense and Piper nigrum fruits[J]. J Environ Sci Health B,2021:1−10.
[5]	MAHDAVI A, BAGHERNIYA M, FAKHERAN O, et al. Medicinal plants and bioactive natural compounds as inhibitors of HMG-CoA reductase: A literature review[J]. BioFactors,2020,46(6):906−926. doi: 10.1002/biof.1684
[6]	GOYAL S K, SAMSHER, GOYAL R K. Stevia (Stevia rebaudiana) a bio-sweetener: A review[J]. International Journal of Food Sciences and Nutrition,2010,61(1):1−10. doi: 10.3109/09637480903193049
[7]	HOLTH T A D, WALTERS M A, HUTT O E, et al. Diversity-oriented library synthesis from steviol and isosteviol-derived scaffolds[J]. ACS Combinatorial Science,2020,22(3):150−155. doi: 10.1021/acscombsci.9b00186
[8]	MOSETTIG E, BEGLINGER U, DOLDER F, et al. The absolute configuration of steviol and isosteviol[J]. Journal of the American Chemical Society,1963,85(15):2305−2309. doi: 10.1021/ja00898a025
[9]	ULLAH A, MUNIR S, MABKHOT Y, et al. Bioactivity profile of the diterpene isosteviol and its derivatives[J]. Molecules,2019,24(4):678. doi: 10.3390/molecules24040678
[10]	GUPTA E, PURWAR S, SUNDARAM S, et al. Nutritional and therapeutic values of Stevia rebaudiana: A review[J]. Journal of Medicinal Plants Research,2013,7(46):3343−3353.
[11]	GREGERSEN S, JEPPESEN P B, HOLST J J, et al. Antihyperglycemic effects of stevioside in type 2 diabetic subjects[J]. Metabolism,2004,53(1):73−76. doi: 10.1016/j.metabol.2003.07.013
[12]	GU W, REBSDORF A, HERMANSEN K, et al. The dynamic effects of isosteviol on insulin secretion and its inability to counteract the impaired β-cell function during gluco-, lipo-, and aminoacidotoxicity: Studies in vitro[J]. Nutrients,2018,10(2):127. doi: 10.3390/nu10020127
[13]	XU D, XU M, LIN L, et al. The effect of isosteviol on hyperglycemia and dyslipidemia induced by lipotoxicity in rats fed with high-fat emulsion[J]. Life Sciences,2012,90(1):30−38.
[14]	PAGADALA N S, SYED K, TUSZYNSKI J. Software for molecular docking: a review[J]. Biophys Rev,2017,9(2):91−102. doi: 10.1007/s12551-016-0247-1
[15]	Sulimov V B, Kutov D C, Sulimov A V. Advances in Docking[J]. Current Medicinal Chemistry,2020,26(42):7555−7580. doi: 10.2174/0929867325666180904115000
[16]	马庆一, 陈春涛, 时国庆, 等. 天然α-葡萄糖苷酶抑制剂的研究[J]. 食品工业科技,2005(8):51−53. [MA Qingyi, CHEN Chuntao, SHI Guoqing, et al. Study on natural α-glucosidase inhibitors[J]. Science and Technology of Pood Industry,2005(8):51−53. doi: 10.3969/j.issn.1002-0306.2005.08.012
[17]	叶雅沁, 李泳宁, 李小芬, 等. 南非叶总黄酮的降血脂作用[J]. 食品工业科技,2020,41(16):304−307. [YE Yaqin, LI Yongning, LI Xiaofen, et al. Hypolipidemic activity of the total flavonoids from bitter leaf[J]. Science and Technology of Food Industry,2020,41(16):304−307.
[18]	CHEWCHINDA S, SURIYAPHAN O, KANCHANADUMKERNG P, et al. Comparison of antioxidant and α-glucosidase inhibitory activities in different cultivars of five mango (Mangifera Indica L.) leaf extracts[J]. Chiang Mai University Journal of Natural Sciences,2021,20(1):1−16.
[19]	赵光耀, 赵坤, 蒋文雯, 等. 基于网络药理学对蒲公英抑制α-葡萄糖苷酶活性成分及作用机制的研究[J]. 天然产物研究与开发,2020,32(3):403−413. [ZHAO Guangyao, ZHAO Kun, JIANG Wenwen, et al. Study on active components and mechanism of inhibition of α-glucosidase by Taraxacum mongolicum based on network pharmacology[J]. Natural Product Research and Development,2020,32(3):403−413.
[20]	汪晖, 郭喻, 平洁, 等. 一种检测HMG-CoA还原酶活性的改良分光光度法及应用: 中国, 102221531A[P]. 2011-10-19. WANG Hui, GUO Yu, PING Jie, et al. An improved spectrophotometric method for detecting HMG CoA reductase activity and its application: CN, 102221531A[P]. 2011-10-19.
[21]	李鹏, 陈兰英. 血脂康抑制猪肝HMG-CoA还原酶的活力[J]. 基础医学与临床,2003(5):531−534. [LI Peng, CHEN Lanying. Xuezhikang inhibits the activity of HMG-CoA reductase in pig liver[J]. Basic Medical Sciences and Clinics,2003(5):531−534. doi: 10.3969/j.issn.1001-6325.2003.05.014
[22]	朱庆亚. α-葡萄糖苷酶抑制剂的筛选及其对糖尿病大鼠糖吸收抑制作用的研究[D]. 成都: 西南交通大学, 2009. ZHU Qingya. Screening of α-glucosidase inhibitors and their inhibitory effects on glucose absorption in diabetic rats[D]. Chengdu: Southwest Jiaotong University, 2009.
[23]	吴学强. 类黄酮物质对精氨酸激酶和α-葡萄糖苷酶抑制机理及分子对接研究[D]. 泰安: 山东农业大学, 2009. WU Xueqiang. The inhibition mechanism of flavonoids on argininekinase and α-glucosidase merging with molecular docking[D]. Taian: Shandong Agricultural University, 2009.
[24]	韩芬霞, 范新景, 耿升, 等. 异甘草素抑制α-葡萄糖苷酶的分子机制[J]. 食品科学,2019,40(15):37−42. [HAN Fenxia, FAN Xinjing, GENG Sheng, et al. Inhibitory mechanism of isoliquiritigenin against α-glucosidase[J]. Food Science,2019,40(15):37−42. doi: 10.7506/spkx1002-6630-20180830-337
[25]	COSCONATI S, FORLI S, PERRYMAN A L, et al. Virtual screening with AutoDock: Theory and practice[J]. Expert Opinion On Drug Discovery,2010,5(6):597−607. doi: 10.1517/17460441.2010.484460
[26]	SEVCIK J, HOSTINOVA E, SOLOVICOVA A, et al. Structure of the complex of a yeast glucoamylase with acarbose reveals the presence of a raw starch binding site on the catalytic domain[J]. Febs J,2006,273(10):2161−2171. doi: 10.1111/j.1742-4658.2006.05230.x
[27]	MALHOTRA H S, GOA K L. Atorvastatin: An updated review of its pharmacological properties and use in dyslipidaemia[J]. Drugs,2001,61(12):1835−1881. doi: 10.2165/00003495-200161120-00012
[28]	LIÑARES-BLANCO J, MUNTEANU C R, PAZOS A, et al. Molecular docking and machine learning analysis of Abemaciclib in colon cancer[J]. BMC Molecular and Cell Biology,2020,21(1):1−18. doi: 10.1186/s12860-020-0246-8
[29]	JOSEPH NAGUIB M, MOUSTAFA KAMEL A, THABET NEGMELDIN A, et al. Molecular docking and statistical optimization of taurocholate-stabilized galactose anchored bilosomes for the enhancement of sofosbuvir absorption and hepatic relative targeting efficiency[J]. Drug Delivery,2020,27(1):996−1009. doi: 10.1080/10717544.2020.1787557
[30]	DYDUCH-SIEMIŃSKA M, NAJDA A, GAWROŃSKI J, et al. Stevia rebaudiana bertoni, a source of high-potency natural sweetener-biochemical and genetic characterization[J]. Molecules,2020,25(4):767. doi: 10.3390/molecules25040767
[31]	TAO X, HUANG Y, WANG C, et al. Recent developments in molecular docking technology applied in food science: A review[J]. International Journal of Food Science & Technology,2019,55(1):33−45.

Supplements (0)

Cited By

Cited by

Periodical cited type(2)

1.	陈吉圣，卢雪旎，王兴强，曹梅，李永，秦传新. 基于sRNA的脊尾白虾对低温胁迫的响应研究. 海洋渔业. 2024(05): 616-627 .
2.	高程海，夏家朗，梁考云，刘永宏，易湘茜. 北部湾海洋植物及其共附生微生物次级代谢产物研究进展. 广西植物. 2022(08): 1259-1272 .