The role of metabolites of steviol glycosides and their glucosylated derivatives against diabetes-related metabolic disorders

Food and Function

Volumn 12, Issue 18, 2021, Pages 8248-8259

  Li, Yuqi ^a   Zhu, Wanfang ^a   Cai, Jing ^a   Liu, Wenyuan ^a   Akihisa, Toshihiro ^a,b   Li, Wei ^c   Kikuchi, Takashi ^c   Xu, Jian ^a   Feng, Feng ^a,d   Zhang, Jie ^a,d  

^a CHINA PHARMACEUTICAL UNIVERSITY   (China)

^b TOKYO UNIVERSITY OF SCIENCE   (Japan)

^c TOHO UNIVERSITY   (Japan)

^d Jiangsu Food and Pharmaceutical Science College   (China)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCOSE; INSULIN; METABOLISM; METABOLITES; SUGAR (SUCROSE); SUGAR SUBSTITUTES;

CARBOHYDRATE METABOLISM; DIABETES MELLITUS; GLUCURONIDES; INSULIN SECRETION; LIPID METABOLISMS; METABOLIC DISORDERS; PROTEIN METABOLISM; STEVIOL; STEVIOL GLYCOSIDES; TARGET CELLS;

BIOMOLECULES;

GLUCOSIDE; GLYCOSIDE; KAURANE DERIVATIVE; STEVIOSIDE;

ANIMAL; DIABETES MELLITUS; DIABETIC COMPLICATION; HUMAN; METABOLISM;

ANIMALS; DIABETES COMPLICATIONS; DIABETES MELLITUS; DITERPENES, KAURANE; GLUCOSIDES; GLYCOSIDES; HUMANS;

EID: 85115640243     PISSN: 20426496     EISSN: 2042650X     Source Type: Journal    
DOI: 10.1039/d1fo01370j     Document Type: Review

References (107)

1. M. Jaiswal J. Divers D. Dabelea S. Isom R. A. Bell C. L. Martin D. J. Pettitt S. Saydah C. Pihoker D. A. Standiford L. M. Dolan S. Marcovina B. Linder A. D. Liese R. Pop-Busui E. L. Feldman Prevalence of and risk factors for diabetic peripheral neuropathy in youth with type 1 and type 2 diabetes: Search for diabetes in youth study Diabetes Care 2017 40 1226 1232
2. S. F. Farsani M. P. van der Aa M. M. J. van der Vorst C. A. J. Knibbe A. de Boer Global trends in the incidence and prevalence of type 2 diabetes in children and adolescents: a systematic review and evaluation of methodological approaches Diabetologia 2013 56 1471 1488
3. N. H. Cho J. E. Shaw S. Karuranga Y. Huang J. D. D. Rocha Fernandes A. W. Ohlrogge B. Malanda IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045 Diabetes Res. Clin. Pract. 2018 138 271 281
4. D. B. Savage K. F. Petersen G. I. Shulman Disordered lipid metabolism and the pathogenesis of insulin resistance Physiol. Rev. 2007 87 507 520
5. P. E. Scherer J. A. Hill Obesity, diabetes, and cardiovascular diseases: A compendium Circ. Res. 2016 118 1703 1705
6. American Diabetes Association Standards of medical care in diabetes-2017: summary of revisions Diabetes Care 2017 40 S4 S5
7. Guideline: Sugars intake for adults and children, World Health Organization, Geneva, https://www.who.int/publications/i/item/9789241549028, (accessed 4 March 2015)
8. E. Mejia M. Pearlman Natural alternative sweeteners and diabetes management Curr. Diabetes Rep. 2019 19 142
9. R. Lemus-Mondaca A. Vega-Galvez L. Zura-Bravo K. Ah-Hen Stevia rebaudiana Bertoni, source of a high-potency natural sweetener: A comprehensive review on the biochemical, nutritional and functional aspects Food Chem. 2012 132 1121 1132
10. D. D. Soejarto, in Stevia, the Geuns of Stevia, Medicinal and Aromatic Plants - mdash;Industrial Profiles, ed., A. D. Kinghorn, Taylor and Francis, London, 2002, pp. 18-39
11. J. C. Ruiz-Ruiz Y. B. Moguel-Ordoñez M. R. Segura-Campos Biological activity of Stevia rebaudiana Bertoni and their relationship to health Crit. Rev. Food Sci. Nutr. 2017 57 2680 2690
12. A. Momtazi-Borojeni S. A. Esmaeili E. Abdollahi A. Sahebkar A review on the pharmacology and toxicology of steviol glycosides extracted from Stevia rebaudiana Curr. Pharm. Des. 2017 23 1616 1622
13. Evaluation of certain food additives, Eighty-second report of the Joint FAO/WHO Expert Committee on Food Additives, JECFA (Joint FAO/WHO Expert Committee on Food Additives), https://apps.who.int/iris/bitstream/handle/10665/250277/9789241210003-eng.pdf?sequence=1
14. K. Yadav S. Singh D. Dhyani P. S. Ahuja A review on the improvement of Stevia [Stevia rebaudiana (Bertoni)] Can. J. Plant Sci. 2011 91 1 27
15. C. Hellfritsch A. Brockhoff F. Stähler W. Meyerhof T. Hofmann Human psychometric and taste receptor responses to steviol glycosides J. Agric. Food Chem. 2012 60 6782 6793
16. G. J. Gerwig E. M. Te Poele L. Dijkhuizen J. P. Kamerling Stevia glycosides: chemical and enzymatic modifications of their carbohydrate moieties to improve the sweet-tasting quality Adv. Carbohydr. Chem. Biochem. 2016 73 1 72
17. R. Adari S. Alavala S. A. George H. M. Meshram A. K. Tiwari A. V. Sarma Synthesis of rebaudioside-A by enzymatic transglycosylation of stevioside present in the leaves of Stevia rebaudian a, Bertoni Food Chem. 2016 200 154 158
18. I. Prakash A. Markosyan C. Bunders Development of next generation Stevia sweetener: rebaudioside M Foods 2014 3 162 175
19. L. Allen J. E. McGeary J. E. Hayes Rebaudioside A and rebaudioside D bitterness do not covary with acesulfame K bitterness or polymorphisms in TAS2R9 and TAS2R31 Chemosens. Percept. 2013 6 109 117
20. M. Younes G. Aquilina K.-H. Engel P. Fowler M. J. F. Fernandez P. Furst R. Gurtler U. Gundert-Remy T. Husoy W. Mennes P. Moldeus A. Oskarsson R. Shah I. Waalkens-Berendsen D. Wolfle G. Degen D. Gott J.-C. Leblanc L. Herman J. Aguilera A. Giarola A. M. Rincon L. Castle E. P. F. A. Flavouri Safety of the proposed amendment of the specifications for steviol glycosides (E 960) as a food additive: Rebaudioside M produced via enzyme-catalysed bioconversion of purified stevia leaf extract EFSA J. 2019 17 5867
21. T. Devlamynck E. M. Te Poele K. Quataert G. J. Gerwig D. Van de Walle K. Dewettinck J. P. Kamerling W. Soetaert L. Dijkhuizen Trans-a-glucosylation of stevioside by the mutant glucansucrase enzyme Gtf180-?N-Q1140E improves its taste profile Food Chem. 2019 272 653 662
22. V. Bhardwaj R. Singh P. Singh R. Purohit S. Kumar Elimination of bitter-off taste of stevioside through structure modification and computational interventions J. Theor. Biol. 2020 486 110094
23. W. Acevedo F. González-Nilo E. Agosin Docking and molecular dynamics of steviol glycoside-human bitter receptor interactions J. Agric. Food Chem. 2016 64 7585 7596
24. R. N. Philippe M. De Mey J. Anderson P. K. Ajikumar Biotechnological production of natural zero-calorie sweeteners Curr. Opin. Biotechnol. 2014 26 155 161
25. A. Modi N. Litoriya V. Prajapati R. Rafalia S. Narayanan Transcriptional profiling of genes involved in steviol glycoside biosynthesis in Stevia rebaudiana Bertoni during plant hardening Dev. Dyn. 2014 243 1067 1073
26. E. J. Kennelly, in Stevia: the Genus of Stevia, Medicinal and Aromatic Plants - mdash;Industrial Profiles, ed., A. D. Kinghorn, Taylor and Francis, London, 2002, pp. 68-85
27. N. Starratt C. W. Kirby R. Pocs J. E. Brandle Rebaudioside F, a diterpene glycoside from Stevia rebaudiana Phytochemistry 2002 59 367 370
28. C. Diaz-Gutierrez A. Hurtado A. Ortiz C. Poschenrieder C. Arroyave C. Pelaez Increase in steviol glycosides production from Stevia rebaudian a, Bertoni under organo-mineral fertilization Ind. Crops Prod. 2020 147 112220
29. N. R. Abdelsalam W. A. Botros A. E. Khaled M. A. Ghonema S. G. Hussein H. M. Ali M. S. Elshikh Comparison of uridine diphosphate-glycosyltransferase UGT76G1 genes from some varieties of Stevia rebaudiana, Bertoni Sci. Rep. 2019 9 8559
30. E. Petit A. Jacques J. Daydé V. Vallejo M. Berger UGT76G1 polymorphism in Stevia rebaudiana: new variants for steviol glycosides conjugation Plant Physiol. Biochem. 2019 135 563 569
31. L. Tedone C. Ruta F. De Cillis G. De Mastro Effects of Septoglomus viscosum inoculation on biomass yield and steviol glycoside concentration of some Stevia rebaudiana chemotypes Sci. Hortic. 2020 262 109026
32. P. Guleria S. K. Yadav Agrobacterium mediated transient gene silencing (AMTS) in Stevia rebaudiana: insights into steviol glycoside biosynthesis pathway PLoS One 2013 8 e74731
33. M. Saifi S. Yogindran N. Nasrullah U. Nissar I. Gul M. Z. Abdin Co-expression of anti-miR319 g and miRStv_11 lead to enhanced steviol glycosides content in Stevia rebaudiana BMC Plant Biol. 2019 19 274
34. C. Vazquez-Hernandez A. A. Feregrino-Perez I. Perez-Ramirez R. V. Ocampo-Velazquez E. Rico-Garcia I. Torres-Pacheco R. G. Guevara-Gonzalez Controlled elicitation increases steviol glycosides (SGs) content and gene expression-associated to biosynthesis of SGs in Stevia rebaudiana B. cv. Morita II Ind. Crops Prod. 2019 139 111479
35. A. Ko S. H. Nam J. Y. Park Y. Wee D. Kim W. S. Lee Y. B. Ryu Y. M. Kim Synthesis and characterization of glucosyl stevioside using Leuconosto c, dextransucrase Food Chem. 2016 211 577 582
36. S. H. Lee J. A. Ko H. S. Kim M. H. Jo J. S. Kim D. Kim J. Y. Cho Y. J. Wee Y. M. Kim Enzymatic synthesis of glucosyl rebaudioside A and its characterization as a sweetener J. Food Sci. 2019 84 3186 3193
37. A. Ko Y. B. Ryu J. Y. Park C. Y. Kim J. S. Kim S. H. Nam W. S. Lee Y. M. Kim Glucosyl rubusosides by dextransucrases improve thequality of taste and sweetness J. Microbiol. Biotechnol. 2016 26 493 497
38. J. Gerwig E. M. te Poele L. Dijkhuizen J. P. Kamerling Structural analysis of rebaudioside A derivatives obtained by Lactobacillus reuter i, 180 glucansucrase-catalyzed trans-a-glucosylation Carbohydr. Res. 2017 440 51 62
39. M. te Poele T. Devlamynck M. Jager G. J. Gerwig D. Van de Walle K. Dewettinck A. K. H. Hirsch J. P. Kamerling W. Soetaert L. Dijkhuizen Glucansucrase (mutant) enzymes from Lactobacillus reuter i, 180 efficiently transglucosylate Stevia component rebaudioside A, resulting in a superior taste Sci. Rep. 2018 8 1516
40. A. Musa B. Jiang H. Ma M. A. A. Gasmalla M. H. Abdalhai A. Al-alfarga Di-glycosyl-stevioside production via Leuconostoc citreum sk24.002 alternansucrase enzymatic reaction and structural characterization J. Food Meas. Charact. 2019 13 1159 1165
41. Z. Yang B. Uhler T. Zheng K. M. Adams Enzymatic Synthesis and Characterization of a Novel a-1?6-Glucosyl Rebaudioside C Derivative Sweetener Biomolecules 2019 9 27
42. F. Y. Ye R. Yang X. Hua Q. Shen W. Zhao W. Zhang Modification of steviol glycosides using a-amylase LWT-Food Sci. Technol. 2014 57 400 405
43. S. V. Lobov R. Kasai K. Ohtani O. Tanaka K. Yamasaki Enzymic Production of Sweet Stevioside Derivatives: Transglucosylation by Glucosidases Agric. Biol. Chem. 1991 55 2959 2965
44. K. Yamamoto K. Yoshikawa S. Okada Effective production of glycosyl-steviosides by a-1,6 transglucosylation of dextrin dextranase Biosci., Biotechnol., Biochem. 1994 58 1657 1661
45. Y. Wang L. Chen Y. Li Y. Li M. Yan K. Chen N. Hao L. Xu Efficient enzymatic production of rebaudioside A from stevioside Biosci., Biotechnol., Biochem. 2016 80 67 73
46. R. Czinkoczky A. Nemeth Investigations into Enzymatic Bioconversion to Form Rebaudioside A from Stevioside Period. Polytech., Chem. Eng. 2018 62 396 402
47. L. Chen P. Sun F. Zhou Y. Li K. Chen H. Jia M. Yan D. Gong P. Ouyang Synthesis of rebaudioside D, using glycosyltransferase UGTSL2 and in situ UDP-glucose regeneration Food Chem. 2018 259 286 291
48. H. de Oliveira J. F. Packer M. Chimelli D. A. de Jesus Enzymatic modification of stevioside by cell-free extract of Gibberella fujikuroi J. Biotechnol. 2007 131 92 96
49. R. Adari S. Alavala S. A. George H. M. Meshram A. K. Tiwari A. V. S. Sarma Synthesis of rebaudioside-A by enzymatic transglycosylation of stevioside present in the leaves of Stevia rebaudian a, Bertoni Food Chem. 2016 200 154 158
50. K. V. Chkhan M. B. Moiseyak Effects of Enzymatic Transglycosylation of Steviol Glycosides on Their Taste Profile Storage Process. Farm Prod. 2019 1 86 97
51. X. Yu J. Yang B. Li H. Yuan High efficiency transformation of stevioside into a single mono-glycosylated product using a cyclodextrin glucanotransferase from Paenibacillus sp. CGMCC 5316 World J. Microbiol. Biotechnol. 2015 31 1983 1991
52. S. Li W. Li Q. Xiao Y. Xia Transglycosylation of stevioside to improve the edulcorant quality by lower substitution using cornstarch hydrolyzate and CGTase Food Chem. 2013 138 2064 2069
53. K. Ohtani Y. Aikawa H. Ishikawa R. Kasai S. Kitahata K. Mizutani S. Doi M. Nakaura O. Tanaka Further study on the 1,4-alpha-transglucosylation of rubusoside, a sweet steviol-bisglucoside from Rubus suavissimus Agric. Biol. Chem. 1991 55 449 453
54. J. A. Ko Y. M. Kim Y. B. Ryu H. J. Jeong T. S. Park S. J. Park Y. J. Wee J. S. Kim D. Kim W. S. Lee Mass Production of Rubusoside Using a Novel Stevioside-Specific ß-Glucosidase from Aspergillus aculeatus J. Agric. Food Chem. 2012 60 6210 6216
55. Z. W. Xu Y. Q. Li Y. H. Wang Y. Bo Z. X. Ning Production of ß-fructofuranosidase by Arthrobacter sp. and its application in the modification of stevioside and rebaudioside A Food Technol. Biotechnol. 2009 47 137 143
56. K. Suzuki T. Fukumura N. Shibasaki-Kitakawa T. Yonemoto Kinetic model for synthesis of fructosyl-stevioside using suspended ß-fructofuranosidase Biochem. Eng. J. 2002 10 207 215
57. H. Ishikawa S. Kitahata K. Ohtani O. Tanaka Transfructosylation of Rebaudioside A (a Sweet Glycoside of Stevia Leaves) with Microbacterium ß-Fructofuranosidase Chem. Pharm. Bull. 1991 39 2043 2045
58. S. Purkayastha G. Pugh Jr. B. Lynch A. Roberts D. Kwok S. M. Tarka Jr. In vitro metabolism of rebaudioside B, D, and M under anaerobic conditions: Comparison with rebaudioside A Regul. Toxicol. Pharmacol. 2014 68 259 268
59. K. K. Mahalak J. Firrman P. M. Tomasula A. Nunez J.-J. Lee K. Bittinger W. Rinaldi L. S. Liu Impact of Steviol Glycosides and Erythritol on the Human and Cebus apella Gut Microbiome J. Agric. Food Chem. 2020 68 13093 13101
60. E. Koyama K. Kitazawa Y. Ohori O. Izawa K. Kakegawa A. Fujino M. Ui In vitro metabolism of the glycosidic sweeteners, stevia mixture and enzymatically modified stevia in human intestinal microflora Food Chem. Toxicol. 2003 41 359 374
61. S. Purkayastha D. Kwok Metabolic fate in adult and pediatric population of steviol glycosides produced from stevia leaf extract by different production technologies Regul. Toxicol. Pharmacol. 2020 116 104727
62. S. Purkayastha A. Markosyan I. Prakash S. Bhusari G. Pugh Jr. B. Lynch A. Roberts Steviol glycosides in purified Stevia leaf extract sharing the same metabolic fate Regul. Toxicol. Pharmacol. 2016 77 125 133
63. E. Koyama N. Sakai Y. Ohori K. Kitazawa O. Izawa K. Kakegawa A. Fujino M. Ui Absorption and metabolism of glycosidic sweeteners of, stevia mixture and their aglycone, steviol, in rats and humans Food Chem. Toxicol. 2003 41 875 883
64. P. Simonetti, L. Bramati, C. Gardana and P. G. Pietta, in Proceedings of the first symposium on the safety of stevioside, ed. J Geuns and, J. G. Buyse, Heverlee-Leuven, Belgium, 2004, pp. 51-62
65. A. Roberts A. G. Renwick Comparative toxicokinetics and metabolism of rebaudioside A, stevioside, and steviol in rats Food Chem. Toxicol. 2008 46 S31 S39
66. C. Gardana P. Simonetti E. Canzi R. Zanchi P. Pietta Metabolism of stevioside and rebaudioside A from Stevia rebaudiana extracts by human microflora J. Agric. Food Chem. 2003 51 6618 6622
67. M. Wang J. Lu J. Li H. Qi Y. Wang H. Zhang Steviol glucuronidation and its potential interaction with UDP-glucuronosyltransferase 2B7 substrates Food Chem. Toxicol. 2014 64 135 143
68. M. Chen Y. M. Xia Y. D. Zhang T. T. Zhang Q. R. Peng Y. Fang Influence of substrates on the in vitro kinetics of steviol glucuronidation and interaction between steviol glycosides metabolites and UGT2B7 Int. J. Food Sci. Nutr. 2018 69 472 479
69. J. Dusek A. Carazo F. Trejtnar L. Hyrsova O. Holas T. Smutny S. Micuda P. Pavek Steviol, an aglycone of steviol glycoside sweeteners, interacts with the pregnane X (PXR) and aryl hydrocarbon (AHR) receptors in detoxification regulation Food Chem. Toxicol. 2017 109 130 142
70. R. Thogersen B. Petrat-Melin G. Zamaratskaia K. Grevsen J. F. Young M. K. Rasmussen In vitro effects of rebaudioside A, stevioside and steviol on porcine cytochrome p450 expression and activity Food Chem. 2018 258 245 253
71. M. Wang H. Qi J. Li Y. Xu H. Zhang Transmembrane transport of steviol glucuronide and its potential interaction with selected drugs and natural compounds Food Chem. Toxicol. 2015 86 217 224
72. D. Zhou Y. Xu Y. Wang J. Li C. Gui H. Zhang Interaction of organic anion transporter 3-mediated uptake of steviol acyl glucuronide, a major metabolite of rebaudioside A, with selected drugs J. Agric. Food Chem. 2020 68 1579 1587
73. Y. Xu D. Zhou Y. Wang J. Li M. Wang J. Lu H. Zhang CYP2C8-mediated interaction between repaglinide and steviol acyl glucuronide: in vitro investigations using rat and human matrices and in vivo pharmacokinetic evaluation in rats Food Chem. Toxicol. 2016 94 138 147
74. S. Mathur N. Bulchandani S. Parihar G. S. Shekhawat Critical review on steviol glycosides: Pharmacological, toxicological and therapeutic aspects of high potency zero caloric sweetener Int. J. Pharmacol. 2017 13 916 928
75. +-channel activity Metabolism 2000 49 208 214
76. S. Bhasker H. Madhav M. Chinnamma Molecular evidence of insulinomimetic property exhibited by steviol and stevioside in diabetes induced L6 and 3 T3L1 cells Phytomedicine 2015 22 1037 1044
77. Z. Myint J. M. Chen Z. Y. Zhou Y. M. Xia J. Lin J. Zhang Structural dependence of antidiabetic effect of steviol glycosides and their metabolites on streptozocin-induced diabetic mice J. Sci. Food Agric. 2020 100 3841 3849
78. K. Philippaert A. Pironet M. Mesuere W. Sones L. Vermeiren S. Kerselaers S. Pinto A. Segal N. Antoine C. Gysemans J. Laureys K. Lemaire P. Gilon E. Cuypers J. Tytgat C. Mathieu F. Schuit P. Rorsman K. Talavera T. Voets R. Vennekens Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity Nat. Commun. 2017 8 14733
79. W. Gu A. Rebsdorf C. Anker S. Gregersen K. Hermansen J. M. C. Geuns P. B. Jeppesen Steviol glucuronide, a metabolite of steviol glycosides, potently stimulates insulin secretion from isolated mouse islets: Studies in vitro Endocrinol., Diabetes Metab. 2019 2 e00093
80. F. Zeni B. Freeman C. Natanson Anti-inflammatory therapies to treat sepsis and septic shock: A reassessment Crit. Care Med. 1997 25 1095 1100
81. T. Durack M. P. Glauser The inflammatory cytokines-New developments in the pathophysiology and treatment of septic shock-Discussion Drugs 1996 52 9 17
82. C. Boonkaewwan M. Ao C. Toskulkao M. C. Rao Specific immunomodulatory and secretory activities of stevioside and steviol in intestinal cells J. Agric. Food Chem. 2008 56 3777 3784
83. C. Boonkaewwan A. Burodom Anti-inflammatory and immunomodulatory activities of stevioside and steviol on colonic epithelial cells J. Sci. Food Agric. 2013 93 3820 3825
84. C. Boonkaewwan C. Toskulkao M. Vongsakul Anti-inflammatory and immunomodulatory activities of stevioside and its metabolite steviol on THP-1 cells J. Agric. Food Chem. 2006 54 785 789
85. U. Ahmad R. S. Ahmad M. S. Arshad Z. Mushtaq S. M. Hussain A. Hameed Antihyperlipidemic efficacy of aqueous extract of Stevia rebaudiana Bertoni in albino rats Lipids Health Dis. 2018 17 175
86. J. E. Park Y. S. Cha Stevia rebaudiana Bertoni extract supplementation improves lipid and carnitine profiles in C57BL/6J mice fed a high-fat diet J. Sci. Food Agric. 2010 90 1099 1105
87. T. Ranjbar A. A. Nekooeian N. Tanideh O. Koohi-Hosseinabadi S. J. Masoumi S. Amanat N. Azarpira A. Monabati A comparison of the effects of Stevia extract and metformin on metabolic syndrome indices in rats fed with a high-fat, high-sucrose diet J. Food Biochem. 2020 44 e13242
88. S. G. Yilmaz A. Uçar S. Yilmaz Do steviol glycosides affect the oxidative and genotoxicity parameters in BALB/c mice? Drug Chem. Toxicol. 2020 21 1 6
89. M. Ajami M. Seyfi F. Abdollah Pouri Hosseini P. Naseri A. Velayati F. Mahmoudnia M. Zahedirad M. Hajifaraji Effects of stevia on glycemic and lipid profile of type 2 diabetic patients: A randomized controlled trial Avicenna J. Phytomed. 2020 10 118 127
90. J. M. Kurek E. Krol Z. Krejpcio Steviol Glycosides Supplementation Affects Lipid Metabolism in High-Fat Fed STZ-Induced Diabetic Rats Nutrients 2021 13 112
91. P. Holvoet A. Rull A. Garcia-Heredia S. Lopez-Sanroma B. Geeraert J. Joven J. Camps Stevia-derived compounds attenuate the toxic effects of ectopic lipid accumulation in the liver of obese mice: A transcriptomic and metabolomic study Food Chem. Toxicol. 2015 77 22 33
92. M. I. Ragone P. Bonazzola G. A. Colareda M. L. Lazarte F. Bruno A. E. Consolini Cardioprotection of stevioside on stunned rat hearts: A mechano-energetical study Phytomedicine 2017 35 18 26
93. J. Schofield J. Ho H. Soran Cardiovascular risk in type 1 diabetes mellitus Diabetes Ther. 2019 10 773 789
94. C. Prata L. Zambonin B. Rizzo T. Maraldi C. Angeloni F. Vieceli Dalla Sega D. Fiorentini S. Hrelia Glycosides from Stevia rebaudiana Bertoni Possess Insulin-Mimetic and Antioxidant Activities in Rat Cardiac Fibroblasts Oxid. Med. Cell. Longevity 2017 2017 3724545
95. S. Casas-Grajales D. Alvarez-Suarez E. Ramos-Tovar L. Dayana Buendía-Montaño K. Reyes-Gordillo J. Camacho V. Tsutsumi M. R. Lakshman P. Muriel Stevioside inhibits experimental fibrosis by down-regulating profibrotic Smad pathways and blocking hepatic stellate cell activation Basic Clin. Pharmacol. Toxicol. 2019 124 670 680
96. J. Wang W. Shen J. Y. Zhang C. H. Jia M. L. Xie Stevioside attenuates isoproterenol-induced mouse myocardial fibrosis through inhibition of the myocardial NF-? B/TGF-ß1/Smad signaling pathway Food Funct. 2019 10 1179 1190
97. J. Wang C. H. Jia F. Wang M. L. Xie Stevioside inhibits transforming growth factor-ß1-induced cardiac fibroblast differentiation and collagen synthesis by modulation of Smad signaling pathway J. Funct. Foods 2018 49 384 390
98. R. Zhao J. Wang L. Qin X. Zhang Y. Mei Stevioside improved hyperglycemia-induced cardiac dysfunction by attenuating the development of fibrosis and promoting the degradation of established fibrosis Food Funct. 2020 68 103895
99. P. Pye S. M. Cobbe Mechanisms of ventricular arrhythmias in cardiac failure and hypertrophy Cardiovasc. Res. 1992 26 740 750
100. Z. Fan N. Lv X. Luo W. Tan Isosteviol prevents the prolongation of action potential in hypertrophied cardiomyoctyes by regulating transient outward potassium and L-type calcium channels Biochim. Biophys. Acta, Biomembr. 2017 1859 1872 1879
101. V. E. Torres P. C. Harris Autosomal dominant polycystic kidney disease: the last 3 years Kidney Int. 2009 76 149 168
102. C. Bergmann L. M. Guay-Woodford P. C. Harris S. Horie D. J. M. Peters V. E. Torres Polycystic kidney disease Nat. Rev. Dis. Primers 2018 4 50
103. C. Yuajit S. Homvisasevongsa L. Chatsudthipong S. Soodvilai C. Muanprasat V. Chatsudthipong Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation PLoS One 2013 8 e58871
104. C. Yuajit C. Muanprasat A. R. Gallagher S. V. Fedeles S. Kittayaruksakul S. Homvisasevongs S. Somlo V. Chatsudthipong Steviol retards renal cyst growth through reduction of CFTR expression and inhibition of epithelial cell proliferation in a mouse model of polycystic kidney disease Biochem. Pharmacol. 2014 88 412 421
105. C. Yuajit C. Muanprasat S. Homvisasevongsa V. Chatsudthipong Steviol stabilizes polycystin 1 expression and promotes lysosomal degradation of CFTR and ß-catenin proteins in renal epithelial cells Biomed. Pharmacother. 2017 94 820 826
106. R. Noitem C. Yuajit S. Soodvilai C. Muanprasat V. Chatsudthipong Steviol slows renal cyst growth by reducing AQP2 expression and promoting AQP2 degradation Biomed. Pharmacother. 2018 101 754 762
107. M. Shannon A. Rehfeld C. Frizzell C. Livingstone C. McGonagle N. E. Skakkebaek E. Wielogorska L. Connolly In vitro bioassay investigations of the endocrine disrupting potential of steviol glycosides and their metabolite steviol, components of the natural sweetener Stevia Mol. Cell. Endocrinol. 2016 427 65 72