Ukr.Biochem.J. 2024; Том 96, № 6, листопад-грудень, c. 17-28
doi: https://doi.org/10.15407/ubj96.06.017
Потенціал ізотіоціанату сульфорафану з хрестоцвітих рослин у боротьбі з ожирінням та цукровим діабетом 2 типу: залучення регуляторного шляху NRF2
М. В. Іваночко1, М. М. Байляк1, В. І. Лущак1,2*
1Кафедра біохімії та біотехнології, Прикарпатський національний університет
імені Василя Стефаника, Івано-Франківськ, Україна;
2Громадська організація «Університет досліджень та розробок»,
Івано-Франківськ, Україна;
*e-mail: volodymyr.lushchak@pnu.edu.ua
Отримано: 03 вересня 2024; Виправлено: 11 листопада 2024;
Затверджено: 21 листопада 2024; Доступно онлайн: 17 грудня 2024
Метою цього огляду було проаналізувати поточні дані щодо застосування ізотіоціанату сульфорафану, знайденого в броколі та інших хрестоцвітих рослинах, для лікування цукрового діабету 2 типу, ожиріння та їх супутніх захворювань із представленням встановлених молекулярних, особливо залежних від NF‑E2-пов’язаного фактора-2 (Nrf2), і сигнальних механізмів терапевтичних ефектів.
Ключові слова: Nrf2, дієтотерапія, ожиріння, проростки броколі, профілактика, сульфорафан, цукровий діабет 2 типу
Посилання:
- Ma Y, Chen Y, Ge A, Long G, Yao M, Shi Y, He X. Healthy lifestyle associated with dynamic progression of type 2 diabetes: A multi-state analysis of a prospective cohort. J Glob Health. 2024;14:04195. PubMed, PubMedCentral, CrossRef
- Wang M, Pu D, Zhao Y, Chen J, Zhu S, Lu A, Liao Z, Sun Y, Xiao Q. Sulforaphane protects against skeletal muscle dysfunction in spontaneous type 2 diabetic db/db mice. Life Sci. 2020;255:117823. PubMed, CrossRef
- Wu S, Wang H, Pan D, Guo J, Zhang F, Ning Y, Gu Y, Guo L. Navigating the future of diabetes: innovative nomogram models for predicting all-cause mortality risk in diabetic nephropathy. BMC Nephrol. 2024;25(1):127. PubMed, PubMedCentral, CrossRef
- Dilworth L, Facey A, Omoruyi F. Diabetes Mellitus and Its Metabolic Complications: The Role of Adipose Tissues. Int J Mol Sci. 2021;22(14):7644. PubMed, PubMedCentral, CrossRef
- Kleinert M, Clemmensen C, Hofmann SM, Moore MC, Renner S, Woods SC, Huypens P, Beckers J, de Angelis MH, Schürmann A, Bakhti M, Klingenspor M, Heiman M, Cherrington AD, Ristow M, Lickert H, Wolf E, Havel PJ, Müller TD, Tschöp MH. Animal models of obesity and diabetes mellitus. Nat Rev Endocrinol. 2018;14(3):140-162. PubMed, CrossRef
- Ali MK, Pearson-Stuttard J, Selvin E, Gregg EW. Interpreting global trends in type 2 diabetes complications and mortality. Diabetologia. 2022;65(1):3-13. PubMed, PubMedCentral, CrossRef
- Lushchak VI, Lushchak O. Interplay between reactive oxygen and nitrogen species in living organisms. Chem Biol Interact. 2021;349:109680. PubMed, CrossRef
- Lushchak VI, Covasa M, Abrat OB, Mykytyn TV, Tverdokhlib IZ, Storey KB, Semchyshyn H. Risks of obesity and diabetes development in the population of the Ivano-Frankivsk region in Ukraine. EXCLI J. 2023;22:1047-1054. PubMed, PubMedCentral, CrossRef
- Bayliak MM, Abrat OB, Storey JM, Storey KB, Lushchak VI. Interplay between diet-induced obesity and oxidative stress: Comparison between Drosophila and mammals. Comp Biochem Physiol A Mol Integr Physiol. 2019;228:18-28. PubMed, CrossRef
- Bellezza I, Giambanco I, Minelli A, Donato R. Nrf2-Keap1 signaling in oxidative and reductive stress. Biochim Biophys Acta Mol Cell Res. 2018;1865(5):721-733. PubMed, CrossRef
- Seo HA, Lee IK. The role of Nrf2: adipocyte differentiation, obesity, and insulin resistance. Oxid Med Cell Longev. 2013;2013:184598. PubMed, PubMedCentral, CrossRef
- Shin S, Wakabayashi J, Yates MS, Wakabayashi N, Dolan PM, Aja S, Liby KT, Sporn MB, Yamamoto M, Kensler TW. Role of Nrf2 in prevention of high-fat diet-induced obesity by synthetic triterpenoid CDDO-imidazolide. Eur J Pharmacol. 2009;620(1-3):138-144. PubMed, PubMedCentral, CrossRef
- Vatashchuk MV, Bayliak MM, Hurza VV, Storey KB, Lushchak VI. Metabolic Syndrome: Lessons from Rodent and Drosophila Models. Biomed Res Int. 2022;2022:5850507. PubMed, PubMedCentral, CrossRef
- Moreno DA, Carvajal M, López-Berenguer C, García-Viguera C. Chemical and biological characterisation of nutraceutical compounds of broccoli. J Pharm Biomed Anal. 2006;41(5):1508-1522. PubMed, CrossRef
- Le TN, Luong HQ, Li HP, Chiu CH, Hsieh PC. Broccoli (Brassica oleracea L. var. italica) sprouts as the potential food source for bioactive properties: a comprehensive study on in vitro disease models. Foods. 2019;8(11):532. PubMed, PubMedCentral, CrossRef
- Xue M, Qian Q, Adaikalakoteswari A, Rabbani N, Babaei-Jadidi R, Thornalley PJ. Activation of NF-E2-related factor-2 reverses biochemical dysfunction of endothelial cells induced by hyperglycemia linked to vascular disease. Diabetes. 2008;57(10):2809-2817. PubMed, PubMedCentral, CrossRef
- Li J, Ichikawa T, Janicki JS, Cui T. Targeting the Nrf2 pathway against cardiovascular disease. Expert Opin Ther Targets. 2009;13(7):785-794. PubMed, CrossRef
- Tan Y, Ichikawa T, Li J, Si Q, Yang H, Chen X, Goldblatt CS, Meyer CJ, Li X, Cai L, Cui T. Diabetic downregulation of Nrf2 activity via ERK contributes to oxidative stress-induced insulin resistance in cardiac cells in vitro and in vivo. Diabetes. 2011;60(2):625-633. PubMed, PubMedCentral, CrossRef
- Evans JL. Antioxidants: do they have a role in the treatment of insulin resistance? Indian J Med Res. 2007;125(3):355-372. PubMed
- Glade MJ, Meguid MM. A Glance at… Broccoli, glucoraphanin, and sulforaphane. Nutrition. 2015;31(9):1175-1178. PubMed, CrossRef
- Houghton CA. Sulforaphane: its “coming of age” as a clinically relevant nutraceutical in the prevention and treatment of chronic disease. Oxid Med Cell Longev. 2019;2019:2716870. PubMed, PubMedCentral, CrossRef
- Costa-Pérez A, Núñez-Gómez V, Baenas N, Di Pede G, Achour M, Manach C, Mena P, Del Rio D, García-Viguera C, Moreno DA, Domínguez-Perles R. Systematic review on the metabolic Interest of Glucosinolates and Their Bioactive Derivatives for Human Health. Nutrients. 2023;15(6):1424. PubMed, PubMedCentral, CrossRef
- Tian Q, Rosselot RA, Schwartz SJ. Quantitative determination of intact glucosinolates in broccoli, broccoli sprouts, Brussels sprouts, and cauliflower by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Anal Biochem. 2005;343(1):93-99. PubMed, CrossRef
- McMahon M, Itoh K, Yamamoto M, Hayes JD. Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression. J Biol Chem. 2003;278(24):21592-21600. PubMed, CrossRef
- Dinkova-Kostova AT, Holtzclaw WD, Cole RN, Itoh K, Wakabayashi N, Katoh Y, Yamamoto M, Talalay P. Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proc Natl Acad Sci USA. 2002;99(18):11908-11913. PubMed, PubMedCentral, CrossRef
- Keum YS. Regulation of the Keap1/Nrf2 system by chemopreventive sulforaphane: implications of posttranslational modifications. Ann N Y Acad Sci. 2011;1229:184-189. PubMed, CrossRef
- Guerrero-Beltrán CE, Calderón-Oliver M, Pedraza-Chaverri J, Chirino YI. Protective effect of sulforaphane against oxidative stress: recent advances. Exp Toxicol Pathol. 2012;64(5):503-508. PubMed, CrossRef
- Evans PC. The influence of sulforaphane on vascular health and its relevance to nutritional approaches to prevent cardiovascular disease. EPMA J. 2011;2(1):9-14. PubMed, PubMedCentral, CrossRef
- Fahey JW, Talalay P. Antioxidant functions of sulforaphane: a potent inducer of Phase II detoxication enzymes. Food Chem Toxicol. 1999;37(9-10):973-979. PubMed, CrossRef
- Daniel M, Tollefsbol TO. Epigenetic linkage of aging, cancer and nutrition. J Exp Biol. 2015;218(Pt 1):59-70. PubMed, PubMedCentral, CrossRef
- Kim M, Lee JY. Beneficial Effects of Sulforaphane on Diabetes and Its Complications via Both Nrf2-Dependent and Independent Mechanisms. Food Suppl Biomater Health. 2023;3(1):e6. CrossRef
- Bai Y, Cui W, Xin Y, Miao X, Barati MT, Zhang C, Chen Q, Tan Y, Cui T, Zheng Y, Cai L. Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation. J Mol Cell Cardiol. 2013;57:82-95. PubMed, CrossRef
- Xu Z, Wang S, Ji H, Zhang Z, Chen J, Tan Y, Wintergerst K, Zheng Y, Sun J, Cai L. Broccoli sprout extract prevents diabetic cardiomyopathy via Nrf2 activation in db/db T2DM mice. Sci Rep. 2016;6:30252. PubMed, PubMedCentral, CrossRef
- Choi KM, Lee YS, Kim W, Kim SJ, Shin KO, Yu JY, Lee MK, Lee YM, Hong JT, Yun YP, Yoo HS. Sulforaphane attenuates obesity by inhibiting adipogenesis and activating the AMPK pathway in obese mice. J Nutr Biochem. 2014;25(2):201-207. PubMed, CrossRef
- Deng Z, Rong Y, Teng Y, Mu J, Zhuang X, Tseng M, Samykutty A, Zhang L, Yan J, Miller D, Suttles J, Zhang HG. Broccoli-Derived Nanoparticle Inhibits Mouse Colitis by Activating Dendritic Cell AMP-Activated Protein Kinase. Mol Ther. 2017;25(7):1641-1654. PubMed, PubMedCentral, CrossRef
- Li Z, Guo H, Li J, Ma T, Zhou S, Zhang Z, Miao L, Cai L. Sulforaphane prevents type 2 diabetes-induced nephropathy via AMPK-mediated activation of lipid metabolic pathways and Nrf2 antioxidative function. Clin Sci (Lond). 2020;134(18):2469-2487. PubMed, CrossRef
- Wang X, Chen X, Zhou W, Men H, Bao T, Sun Y, Wang Q, Tan Y, Keller BB, Tong Q, Zheng Y, Cai L. Ferroptosis is essential for diabetic cardiomyopathy and is prevented by sulforaphane via AMPK/NRF2 pathways. Acta Pharm Sin B. 2022;12(2):708-722. PubMed, PubMedCentral, CrossRef
- Xin Y, Bai Y, Jiang X, Zhou S, Wang Y, Wintergerst KA, Cui T, Ji H, Tan Y, Cai L. Sulforaphane prevents angiotensin II-induced cardiomyopathy by activation of Nrf2 via stimulating the Akt/GSK-3ß/Fyn pathway. Redox Biol. 2018;15:405-417. PubMed, PubMedCentral, CrossRef
- Lei P, Tian S, Teng C, Huang L, Liu X, Wang J, Zhang Y, Li B, Shan Y. Sulforaphane improves lipid metabolism by enhancing mitochondrial function and biogenesis in vivo and in vitro. Mol Nutr Food Res. 2019;63(4):e1800795. PubMed, CrossRef
- Wang Y, Zhang Z, Sun W, Tan Y, Liu Y, Zheng Y, Liu Q, Cai L, Sun J. Sulforaphane attenuation of type 2 diabetes-induced aortic damage was associated with the upregulation of Nrf2 expression and function. Oxid Med Cell Longev. 2014;2014:123963. PubMed, PubMedCentral, CrossRef
- Axelsson AS, Tubbs E, Mecham B, Chacko S, Nenonen HA, Tang Y, Fahey JW, Derry JMJ, Wollheim CB, Wierup N, Haymond MW, Friend SH, Mulder H, Rosengren AH. Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes. Sci Transl Med. 2017;9(394):eaah4477. PubMed, CrossRef
- Kensler TW, Chen JG, Egner PA, Fahey JW, Jacobson LP, Stephenson KK, Ye L, Coady JL, Wang JB, Wu Y, Sun Y, Zhang QN, Zhang BC, Zhu YR, Qian GS, Carmella SG, Hecht SS, Benning L, Gange SJ, Groopman JD, Talalay P. Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo township, Qidong, People’s Republic of China. Cancer Epidemiol Biomarkers Prev. 2005;14(11 Pt 1):2605-2613. PubMed, CrossRef
- Shapiro TA, Fahey JW, Dinkova-Kostova AT, Holtzclaw WD, Stephenson KK, Wade KL, Ye L, Talalay P. Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: a clinical phase I study. Nutr Cancer. 2006;55(1):53-62. PubMed, CrossRef
- Singh K, Connors SL, Macklin EA, Smith KD, Fahey JW, Talalay P, Zimmerman AW. Sulforaphane treatment of autism spectrum disorder (ASD). Proc Natl Acad Sci USA. 2014;111(43):15550-15555. PubMed, PubMedCentral, CrossRef
- Brown RH, Reynolds C, Brooker A, Talalay P, Fahey JW. Sulforaphane improves the bronchoprotective response in asthmatics through Nrf2-mediated gene pathways. Respir Res. 2015;16(1):106. PubMed, PubMedCentral, CrossRef
- Lebovitz HE. Insulin resistance: definition and consequences. Exp Clin Endocrinol Diabetes. 2001;109(Suppl 2):S135-S148. PubMed, CrossRef
- Bayliak MM, Abrat OB. (2020). Role of Nrf2 in Oxidative and Inflammatory Processes in Obesity and Metabolic Diseases. In: Deng, H. (eds) Nrf2 and its Modulation in Inflammation. Progress in Inflammation Research. 2020;85:153-187. CrossRef
- Patel S, Santani D. Role of NF-kappa B in the pathogenesis of diabetes and its associated complications. Pharmacol Rep. 2009;61(4):595-603. PubMed, CrossRef
- Zhang Y, Wu Q, Liu J, Zhang Z, Ma X, Zhang Y, Zhu J, Thring RW, Wu M, Gao Y, Tong H. Sulforaphane alleviates high fat diet-induced insulin resistance via AMPK/Nrf2/GPx4 axis. Biomed Pharmacother. 2022;152:113273. PubMed, CrossRef
- Putnam W, Buhariwalla F, Lacey K, Goodfellow M, Goodine RA, Hall J, Macdonald I, Murray M, Smith P, Burge F, Natarajan N, Lawson B. Drug management for hypertension in type 2 diabetes in family practice. Can Fam Physician. 2009;55(7):728-734. PubMed, PubMedCentral
- Wu L, Noyan Ashraf MH, Facci M, Wang R, Paterson PG, Ferrie A, Juurlink BH. Dietary approach to attenuate oxidative stress, hypertension, and inflammation in the cardiovascular system. Proc Natl Acad Sci USA. 2004;101(18):7094-7099. PubMed, PubMedCentral, CrossRef
- Zakkar M, Van der Heiden K, Luong le A, Chaudhury H, Cuhlmann S, Hamdulay SS, Krams R, Edirisinghe I, Rahman I, Carlsen H, Haskard DO, Mason JC, Evans PC. Activation of Nrf2 in endothelial cells protects arteries from exhibiting a proinflammatory state. Arterioscler Thromb Vasc Biol. 2009;29(11):1851-1857. PubMed, CrossRef
- Shan Y, Zhao R, Geng W, Lin N, Wang X, Du X, Wang S. Protective effect of sulforaphane on human vascular endothelial cells against lipopolysaccharide-induced inflammatory damage. Cardiovasc Toxicol. 2010;10(2):139-145. PubMed, CrossRef
- Miao X, Bai Y, Sun W, Cui W, Xin Y, Wang Y, Tan Y, Miao L, Fu Y, Su G, Cai L. Sulforaphane prevention of diabetes-induced aortic damage was associated with the up-regulation of Nrf2 and its down-stream antioxidants. Nutr Metab (Lond). 2012;9(1):84. PubMed, PubMedCentral, CrossRef
- Valk EJ, Bruijn JA, Bajema IM. Diabetic nephropathy in humans: pathologic diversity. Curr Opin Nephrol Hypertens. 2011;20(3):285-289. PubMed, CrossRef
- Kashihara N, Haruna Y, Kondeti VK, Kanwar YS. Oxidative stress in diabetic nephropathy. Curr Med Chem. 2010;17(34):4256-4269. PubMed, PubMedCentral, CrossRef
- Zheng H, Whitman SA, Wu W, Wondrak GT, Wong PK, Fang D, Zhang DD. Therapeutic potential of Nrf2 activators in streptozotocin-induced diabetic nephropathy. Diabetes. 2011;60(11):3055-3066. PubMed, PubMedCentral, CrossRef
- Li B, Liu S, Miao L, Cai L. Prevention of diabetic complications by activation of Nrf2: diabetic cardiomyopathy and nephropathy. Exp Diabetes Res. 2012;2012:216512. PubMed, PubMedCentral, CrossRef
- Cui W, Bai Y, Miao X, Luo P, Chen Q, Tan Y, Rane MJ, Miao L, Cai L. Prevention of diabetic nephropathy by sulforaphane: possible role of Nrf2 upregulation and activation. Oxid Med Cell Longev. 2012;2012:821936. PubMed, PubMedCentral, CrossRef
- Ha H, Kim KH. Pathogenesis of diabetic nephropathy: the role of oxidative stress and protein kinase C. Diabetes Res Clin Pract. 1999;45(2-3):147-151. PubMed, CrossRef
- Chiang DJ, Pritchard MT, Nagy LE. Obesity, diabetes mellitus, and liver fibrosis. Am J Physiol Gastrointest Liver Physiol. 2011;300(5):G697-G702. PubMed, PubMedCentral, CrossRef
- Oh CJ, Kim JY, Min AK, Park KG, Harris RA, Kim HJ, Lee IK. Sulforaphane attenuates hepatic fibrosis via NF-E2-related factor 2-mediated inhibition of transforming growth factor-β/Smad signaling. Free Radic Biol Med. 2012;52(3):671-682. PubMed, CrossRef
- Tian S, Li X, Wang Y, Lu Y. The protective effect of sulforaphane on type II diabetes induced by high-fat diet and low-dosage streptozotocin. Food Sci Nutr. 2020;9(2):747-756. PubMed, PubMedCentral, CrossRef
- Teng W, Li Y, Du M, Lei X, Xie S, Ren F. Sulforaphane prevents hepatic insulin resistance by blocking serine palmitoyltransferase 3-mediated ceramide biosynthesis. Nutrients. 2019;11(5):1185. PubMed, PubMedCentral, CrossRef
- Negi G, Kumar A, Sharma SS. Nrf2 and NF-κB modulation by sulforaphane counteracts multiple manifestations of diabetic neuropathy in rats and high glucose-induced changes. Curr Neurovasc Res. 2011;8(4):294-304. PubMed, CrossRef
- Moustafa PE, Abdelkader NF, El Awdan SA, El-Shabrawy OA, Zaki HF. Extracellular matrix remodeling and modulation of inflammation and oxidative stress by sulforaphane in experimental diabetic peripheral neuropathy. Inflammation. 2018;41(4):1460-1476. PubMed, CrossRef
- Subedi L, Lee JH, Yumnam S, Ji E, Kim SY. Anti-inflammatory effect of sulforaphane on LPS-activated microglia potentially through JNK/AP-1/NF-κB inhibition and Nrf2/HO-1 activation. Cells. 2019;8(2):194. PubMed, PubMedCentral, CrossRef
- Checker R, Gambhir L, Thoh M, Sharma D, Sandur SK. Sulforaphane, a naturally occurring isothiocyanate, exhibits anti-inflammatory effects by targeting GSK3β/Nrf-2 and NF-κB pathways in T cells. J Funct Foods. 2015;19(part A):426-438. CrossRef
- Zhang YK, Yeager RL, Tanaka Y, Klaassen CD. Enhanced expression of Nrf2 in mice attenuates the fatty liver produced by a methionine- and choline-deficient diet. Toxicol Appl Pharmacol. 2010;245(3):326-334. PubMed, PubMedCentral, CrossRef
- Huang J, Tabbi-Anneni I, Gunda V, Wang L. Transcription factor Nrf2 regulates SHP and lipogenic gene expression in hepatic lipid metabolism. Am J Physiol Gastrointest Liver Physiol. 2010;299(6):G1211-G1221. PubMed, PubMedCentral, CrossRef
- Tavares V, Hirata MH, Hirata RD. Peroxisome proliferator-activated receptor gamma (PPARgamma): molecular study in glucose homeostasis, lipid metabolism and therapeutic approach. Arq Bras Endocrinol Metabol. 2007;51(4):526-533. PubMed, CrossRef
- Steinberg GR, Hardie DG. New insights into activation and function of the AMPK. Nat Rev Mol Cell Biol. 2023;24(4):255-272. PubMed, CrossRef
- Loh K, Tam S, Murray-Segal L, Huynh K, Meikle PJ, Scott JW, van Denderen B, Chen Z, Steel R, LeBlond ND, Burkovsky LA, O’Dwyer C, Nunes JRC, Steinberg GR, Fullerton MD, Galic S, Kemp BE. Inhibition of adenosine monophosphate-activated protein kinase-3-hydroxy-3-methylglutaryl coenzyme A reductase signaling leads to hypercholesterolemia and promotes hepatic steatosis and insulin resistance. Hepatol Commun. 2018;3(1):84-98. PubMed, PubMedCentral, CrossRef
- Lee JH, Moon MH, Jeong JK, Park YG, Lee YJ, Seol JW, Park SY. Sulforaphane induced adipolysis via hormone sensitive lipase activation, regulated by AMPK signaling pathway. Biochem Biophys Res Commun. 2012;426(4):492-497. PubMed, CrossRef
- Men X, Han X, Lee SJ, Oh G, Park KT, Han JK, Choi SI, Lee OH. Anti-obesogenic effects of sulforaphane-rich broccoli (Brassica oleracea var. italica) sprouts and myrosinase-rich mustard (Sinapis alba L.) seeds in vitro and in vivo. Nutrients. 2022;14(18):3814. PubMed, PubMedCentral, CrossRef
- Liu Y, Fu X, Chen Z, Luo T, Zhu C, Ji Y, Bian Z. The protective effects of sulforaphane on high-fat diet-induced obesity in mice through browning of white fat. Front Pharmacol. 2021;12:665894. PubMed, PubMedCentral, CrossRef
- Yao A, Shen Y, Wang A, Chen S, Zhang H, Chen F, Chen Z, Wei H, Zou Z, Shan Y, Zhang X. Sulforaphane induces apoptosis in adipocytes via Akt/p70s6k1/Bad inhibition and ERK activation. Biochem Biophys Res Commun. 2015;465(4):696-701. PubMed, CrossRef
- Kahlon TS, Chapman MH, Smith GE. In vitro binding of bile acids by spinach, kale, brussels sprouts, broccoli, mustard greens, green bell pepper, cabbage and collards. Food Chem. 2007;100(4):1531-1536. CrossRef
- Dunn SE, LeBlanc GA. Hypocholesterolemic properties of plant indoles. Inhibition of acyl-CoA:cholesterol acyltransferase activity and reduction of serum LDL/VLDL cholesterol levels by glucobrassicin derivatives. Biochem Pharmacol. 1994;47(2):359-364. PubMed, CrossRef
- Lee JJ, Shin HD, Lee YM, Kim AR, Lee MY. Effect of broccoli sprouts on cholesterol-lowering and anti-obesity effects in rats fed high fat diet. J Korean Soc Food Sci Nutr. 2009;38(3):309-318. CrossRef
- Maiyoh GK, Kuh JE, Casaschi A, Theriault AG. Cruciferous indole-3-carbinol inhibits apolipoprotein B secretion in HepG2 cells. J Nutr. 2007;137(10):2185-2189. PubMed, CrossRef
- Nicolucci A, De Berardis G, Sacco M, Tognoni G. Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association: response to Buse et al. Diabetes Care. 2007;30(6):e57. PubMed, CrossRef
- Bahadoran Z, Mirmiran P, Hosseinpanah F, Rajab A, Asghari G, Azizi F. Broccoli sprouts powder could improve serum triglyceride and oxidized LDL/LDL-cholesterol ratio in type 2 diabetic patients: a randomized double-blind placebo-controlled clinical trial. Diabetes Res Clin Pract. 2012;96(3):348-354. PubMed, CrossRef
- Murashima M, Watanabe S, Zhuo XG, Uehara M, Kurashige A. Phase 1 study of multiple biomarkers for metabolism and oxidative stress after one-week intake of broccoli sprouts. Biofactors. 2004;22(1-4):271-275. PubMed, CrossRef
- Christiansen B, Bellostas Muguerza N, Petersen AM, Kveiborg B, Madsen CR, Thomas H, Ihlemann N, Sørensen JC, Køber L, Sørensen H, Torp-Pedersen C, Domínguez H. Ingestion of broccoli sprouts does not improve endothelial function in humans with hypertension. PLoS One. 2010;5(8):e12461. PubMed, PubMedCentral, CrossRef
- Nagata N, Xu L, Kohno S, Ushida Y, Aoki Y, Umeda R, Fuke N, Zhuge F, Ni Y, Nagashimada M, Takahashi C, Suganuma H, Kaneko S, Ota T. Glucoraphanin ameliorates obesity and insulin resistance through adipose tissue browning and reduction of metabolic endotoxemia in mice. Diabetes. 2017;66(5):1222-1236. PubMed, CrossRef
