Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Effects of Pterostilbene on Diabetes, Liver Steatosis and Serum Lipids

Author(s): Saioa Gómez-Zorita, Iñaki Milton-Laskíbar, Leixuri Aguirre, Alfredo Fernández-Quintela*, Jianbo Xiao and María P. Portillo

Volume 28, Issue 2, 2021

Published on: 29 October, 2019

Page: [238 - 252] Pages: 15

DOI: 10.2174/0929867326666191029112626

Price: $65

conference banner
Abstract

Pterostilbene, a phenolic compound derived from resveratrol, possesses greater bioavailability than its parent compound due to the presence of two methoxyl groups. In this review, the beneficial effects of pterostilbene on diabetes, liver steatosis and dyslipidemia are summarized. Pterostilbene is a useful bioactive compound in preventing type 1 diabetes, insulin resistance and type 2 diabetes in animal models. Concerning type 1 diabetes, the main mechanisms described to justify the positive effects of this phenolic compound are increased liver glycogen content and hepatic glucokinase and phosphofructokinase activities, the recovery of pancreatic islet architecture, cytoprotection and a decrease in serum and pancreatic pro-inflammatory cytokines. As for type 2 diabetes, increased liver glucokinase and glucose-6-phosphatase and decreased fructose-1,6-biphosphatase activities are reported. When insulin resistance is induced by diets, a greater activation of insulin signaling cascade has been reported, increased cardiotrophin-1 levels and liver glucokinase and glucose- 6-phosphatase activities, and a decreased fructose-1,6-biphosphatase activity. Data concerning pterostilbene and liver steatosis are scarce so far, but the reduction in oxidative stress induced by pterostilbene may be involved since oxidative stress is related to the progression of steatosis to steatohepatitis. Finally, pterostilbene effectively reduces total cholesterol, LDL-cholesterol and serum triglyceride levels, while increases HDL-cholesterol in animal models of dyslipidemia.

Keywords: Pterostilbene, glycaemic control, insulin resistance, diabetes, dyslipidemia, liver steatosis, nonalcoholic fatty liver disease.

« Previous Next »
[1]
Scartezzini, P.; Speroni, E. Review on some plants of Indian traditional medicine with antioxidant activity. J. Ethnopharmacol., 2000, 71(1-2), 23-43.
[http://dx.doi.org/10.1016/S0378-8741(00)00213-0] [PMID: 10904144]
[2]
Modak, M.; Dixit, P.; Londhe, J.; Ghaskadbi, S.; Devasagayam, T.P. Indian herbs and herbal drugs used for the treatment of diabetes. J. Clin. Biochem. Nutr., 2007, 40(3), 163-173.
[http://dx.doi.org/10.3164/jcbn.40.163] [PMID: 18398493]
[3]
Späth, E.; Schläger, J. Über die Inhaltsstoffe des roten Sandelholzes. I. Mitteil.: Die Konstitution des Homopterocarpins. Ber. Dtsch. Chem. Ges., 1940, 73(1), 881.
[http://dx.doi.org/10.1002/cber.19400730808]
[4]
Rimando, A.M.; Kalt, W.; Magee, J.B.; Dewey, J.; Ballington, J.R. Resveratrol, pterostilbene, and piceatannol in vaccinium berries. J. Agric. Food Chem., 2004, 52(15), 4713-4719.
[http://dx.doi.org/10.1021/jf040095e] [PMID: 15264904]
[5]
Pezet, R.; Pont, V. Ultrastructural observations of pterostilbene fungitoxicity in dormant conidia of botrytis cinerea pers. J. Phytopathol., 1990, 129(1), 19-30.
[http://dx.doi.org/10.1111/j.1439-0434.1990.tb04286.x]
[6]
Kapetanovic, I.M.; Muzzio, M.; Huang, Z.; Thompson, T.N.; McCormick, D.L. Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats. Cancer Chemother. Pharmacol., 2011, 68(3), 593-601.
[http://dx.doi.org/10.1007/s00280-010-1525-4] [PMID: 21116625]
[7]
American diabetes association. Diagnosis and classification of diabetes mellitus. Diabetes Care, 2009, 32(Suppl. 1), S62-S67.
[http://dx.doi.org/10.2337/dc09-S062] [PMID: 19118289]
[8]
Guariguata, L.; Whiting, D.R.; Hambleton, I.; Beagley, J.; Linnenkamp, U.; Shaw, J.E. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res. Clin. Pract., 2014, 103(2), 137-149.
[http://dx.doi.org/10.1016/j.diabres.2013.11.002] [PMID: 24630390]
[9]
Johnson, J.D.; Luciani, D.S. Mechanisms of pancreatic beta-cell apoptosis in diabetes and its therapies. Adv. Exp. Med. Biol., 2010, 654, 447-462.
[http://dx.doi.org/10.1007/978-90-481-3271-3_19] [PMID: 20217509]
[10]
Bugianesi, E.; McCullough, A.J.; Marchesini, G. Insulin resistance: a metabolic pathway to chronic liver disease. Hepatology, 2005, 42(5), 987-1000.
[http://dx.doi.org/10.1002/hep.20920] [PMID: 16250043]
[11]
Kotronen, A.; Juurinen, L.; Tiikkainen, M.; Vehkavaara, S.; Yki-Järvinen, H. Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes. Gastroenterology, 2008, 135(1), 122-130.
[http://dx.doi.org/10.1053/j.gastro.2008.03.021] [PMID: 18474251]
[12]
Deeds, M.C.; Anderson, J.M.; Armstrong, A.S.; Gastineau, D.A.; Hiddinga, H.J.; Jahangir, A.; Eberhardt, N.L.; Kudva, Y.C. Single dose streptozotocin-induced diabetes: considerations for study design in islet transplantation models. Lab. Anim., 2011, 45(3), 131-140.
[http://dx.doi.org/10.1258/la.2010.010090] [PMID: 21478271]
[13]
Grover, J.K.; Vats, V.; Yadav, S. Effect of feeding aqueous extract of Pterocarpus marsupium on glycogen content of tissues and the key enzymes of carbohydrate metabolism. Mol. Cell. Biochem., 2002, 241(1-2), 53-59.
[http://dx.doi.org/10.1023/A:1020870526014] [PMID: 12482025]
[14]
Manickam, M.; Ramanathan, M.; Jahromi, M.A.; Chansouria, J.P.; Ray, A.B. Antihyperglycemic activity of phenolics from Pterocarpus marsupium. J. Nat. Prod., 1997, 60(6), 609-610.
[http://dx.doi.org/10.1021/np9607013] [PMID: 9214733]
[15]
Ren, G.; Rimando, A.M.; Mathews, S.T. AMPK activation by pterostilbene contributes to suppression of hepatic gluconeogenic gene expression and glucose production in H4IIE cells. Biochem. Biophys. Res. Commun., 2018, 498(3), 640-645.
[http://dx.doi.org/10.1016/j.bbrc.2018.03.035] [PMID: 29524400]
[16]
Zhang, B.B.; Zhou, G.; Li, C. AMPK: an emerging drug target for diabetes and the metabolic syndrome. Cell Metab., 2009, 9(5), 407-416.
[http://dx.doi.org/10.1016/j.cmet.2009.03.012] [PMID: 19416711]
[17]
Puigserver, P.; Spiegelman, B.M. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr. Rev., 2003, 24(1), 78-90.
[http://dx.doi.org/10.1210/er.2002-0012] [PMID: 12588810]
[18]
Bhakkiyalakshmi, E.; Shalini, D.; Sekar, T.V.; Rajaguru, P.; Paulmurugan, R.; Ramkumar, K.M. Therapeutic potential of pterostilbene against pancreatic beta-cell apoptosis mediated through Nrf2. Br. J. Pharmacol., 2014, 171(7), 1747-1757.
[http://dx.doi.org/10.1111/bph.12577] [PMID: 24417315]
[19]
Tarantino, G.; Scopacasa, F.; Colao, A.; Capone, D.; Tarantino, M.; Grimaldi, E.; Savastano, S. Serum Bcl-2 concentrations in overweight-obese subjects with nonalcoholic fatty liver disease. World J. Gastroenterol., 2011, 17(48), 5280-5288.
[http://dx.doi.org/10.3748/wjg.v17.i48.5280] [PMID: 22219597]
[20]
Kanda, T.; Matsuoka, S.; Yamazaki, M.; Shibata, T.; Nirei, K.; Takahashi, H.; Kaneko, T.; Fujisawa, M.; Higuchi, T.; Nakamura, H.; Matsumoto, N.; Yamagami, H.; Ogawa, M.; Imazu, H.; Kuroda, K.; Moriyama, M. Apoptosis and non-alcoholic fatty liver diseases. World J. Gastroenterol., 2018, 24(25), 2661-2672.
[http://dx.doi.org/10.3748/wjg.v24.i25.2661] [PMID: 29991872]
[21]
Bhakkiyalakshmi, E.; Sireesh, D.; Sakthivadivel, M.; Sivasubramanian, S.; Gunasekaran, P.; Ramkumar, K.M. Anti-hyperlipidemic and anti-peroxidative role of pterostilbene via Nrf2 signaling in experimental diabetes. Eur. J. Pharmacol., 2016, 777, 9-16.
[http://dx.doi.org/10.1016/j.ejphar.2016.02.054] [PMID: 26921755]
[22]
Elango, B.; Dornadula, S.; Paulmurugan, R.; Ramkumar, K.M. Pterostilbene ameliorates streptozotocin-induced diabetes through enhancing antioxidant signaling pathways mediated by Nrf2. Chem. Res. Toxicol., 2016, 29(1), 47-57.
[http://dx.doi.org/10.1021/acs.chemrestox.5b00378] [PMID: 26700463]
[23]
Mythili, M.D.; Vyas, R.; Akila, G.; Gunasekaran, S. Effect of streptozotocin on the ultrastructure of rat pancreatic islets. Microsc. Res. Tech., 2004, 63(5), 274-281.
[http://dx.doi.org/10.1002/jemt.20039] [PMID: 15170757]
[24]
Haligur, M.; Topsakal, S.; Ozmen, O. Early degenerative effects of diabetes mellitus on pancreas, liver, and kidney in rats: an immunohistochemical study. Exp. Diabetes Res., 2012, 2012120645
[http://dx.doi.org/10.1155/2012/120645] [PMID: 22844268]
[25]
Sireesh, D.; Ganesh, M.R.; Dhamodharan, U.; Sakthivadivel, M.; Sivasubramanian, S.; Gunasekaran, P.; Ramkumar, K.M. Role of pterostilbene in attenuating immune mediated devastation of pancreatic beta cells via Nrf2 signaling cascade. J. Nutr. Biochem., 2017, 44, 11-21.
[http://dx.doi.org/10.1016/j.jnutbio.2017.02.015] [PMID: 28343084]
[26]
Dornadula, S.; Thiruppathi, S.; Palanisamy, R.; Umapathy, D.; Suzuki, T.K.; Mohanram, R. Differential proteomic profiling identifies novel molecular targets of pterostilbene against experimental diabetes. J. Cell. Physiol., 2019, 234(3), 1996-2012.
[http://dx.doi.org/10.1002/jcp.26835] [PMID: 30171690]
[27]
Szkudelski, T. Streptozotocin-nicotinamide-induced diabetes in the rat. Characteristics of the experimental model. Exp. Biol. Med. (Maywood), 2012, 237(5), 481-490.
[http://dx.doi.org/10.1258/ebm.2012.011372] [PMID: 22619373]
[28]
Pari, L.; Satheesh, M.A. Effect of pterostilbene on hepatic key enzymes of glucose metabolism in streptozotocin- and nicotinamide-induced diabetic rats. Life Sci., 2006, 79(7), 641-645.
[http://dx.doi.org/10.1016/j.lfs.2006.02.036] [PMID: 16616938]
[29]
Amarnath Satheesh, M.; Pari, L. The antioxidant role of pterostilbene in streptozotocin-nicotinamide-induced type 2 diabetes mellitus in Wistar rats. J. Pharm. Pharmacol., 2006, 58(11), 1483-1490.
[http://dx.doi.org/10.1211/jpp.58.11.0009] [PMID: 17132211]
[30]
Elliott, S.S.; Keim, N.L.; Stern, J.S.; Teff, K.; Havel, P.J. Fructose, weight gain, and the insulin resistance syndrome. Am. J. Clin. Nutr., 2002, 76(5), 911-922.
[http://dx.doi.org/10.1093/ajcn/76.5.911] [PMID: 12399260]
[31]
Grover, J.K.; Vats, V.; Yadav, S.S. Pterocarpus marsupium extract (Vijayasar) prevented the alteration in metabolic patterns induced in the normal rat by feeding an adequate diet containing fructose as sole carbohydrate. Diabetes Obes. Metab., 2005, 7(4), 414-420.
[http://dx.doi.org/10.1111/j.1463-1326.2005.00414.x] [PMID: 15955128]
[32]
Freedland, R.A.; Harper, A.E. Metabolic adaptations in higher animals. I. Dietary effects on liver glucose-6-phosphatase. J. Biol. Chem., 1957, 228(2), 743-751.
[PMID: 13475356]
[33]
Blumenthal, M.D.; Abraham, S.; Chaikoff, I.L. Dietary control of liver glucokinase activity in the normal rat. Arch. Biochem. Biophys., 1964, 104, 215-224.
[http://dx.doi.org/10.1016/S0003-9861(64)80006-0] [PMID: 14163885]
[34]
Gómez-Zorita, S.; Fernández-Quintela, A.; Aguirre, L.; Macarulla, M.T.; Rimando, A.M.; Portillo, M.P. Pterostilbene improves glycaemic control in rats fed an obesogenic diet: involvement of skeletal muscle and liver. Food Funct., 2015, 6(6), 1968-1976.
[http://dx.doi.org/10.1039/C5FO00151J] [PMID: 25998070]
[35]
Zorzano, A.; Sevilla, L.; Tomàs, E.; Camps, M.; Gumà, A.; Palacín, M. Trafficking pathway of GLUT4 glucose transporters in muscle.review Int. J. Mol. Med., 1998, 2(3), 263-271.
[http://dx.doi.org/10.3892/ijmm.2.3.263] [PMID: 9855697]
[36]
Pérez-Martin, A.; Raynaud, E.; Mercier, J. Insulin resistance and associated metabolic abnormalities in muscle: effects of exercise. Obes. Rev., 2001, 2(1), 47-59.
[http://dx.doi.org/10.1046/j.1467-789x.2001.00024.x] [PMID: 12119637]
[37]
Garvey, W.T.; Maianu, L.; Zhu, J.H.; Brechtel-Hook, G.; Wallace, P.; Baron, A.D. Evidence for defects in the trafficking and translocation of GLUT4 glucose transporters in skeletal muscle as a cause of human insulin resistance. J. Clin. Invest., 1998, 101(11), 2377-2386.
[http://dx.doi.org/10.1172/JCI1557] [PMID: 9616209]
[38]
van Dam, E.M.; Govers, R.; James, D.E. Akt activation is required at a late stage of insulin-induced GLUT4 translocation to the plasma membrane. Mol. Endocrinol., 2005, 19(4), 1067-1077.
[http://dx.doi.org/10.1210/me.2004-0413] [PMID: 15650020]
[39]
Moreno-Aliaga, M.J.; Pérez-Echarri, N.; Marcos-Gómez, B.; Larequi, E.; Gil-Bea, F.J.; Viollet, B.; Gimenez, I.; Martínez, J.A.; Prieto, J.; Bustos, M. Cardiotrophin-1 is a key regulator of glucose and lipid metabolism. Cell Metab., 2011, 14(2), 242-253.
[http://dx.doi.org/10.1016/j.cmet.2011.05.013] [PMID: 21803294]
[40]
Moreno-Aliaga, M.J.; Romero-Lozano, M.A.; Castaño, D.; Prieto, J.; Bustos, M. Role of cardiotrophin-1 in obesity and insulin resistance. Adipocyte, 2012, 1(2), 112-115.
[http://dx.doi.org/10.4161/adip.19696] [PMID: 23700521]
[41]
Latha, M.; Pari, L. Antihyperglycaemic effect of Cassia auriculata in experimental diabetes and its effects on key metabolic enzymes involved in carbohydrate metabolism. Clin. Exp. Pharmacol. Physiol., 2003, 30(1-2), 38-43.
[http://dx.doi.org/10.1046/j.1440-1681.2003.03785.x] [PMID: 12542451]
[42]
Bera, T.K.; Ali, K.M.; Jana, K.; Ghosh, A.; Ghosh, D. Protective effect of aqueous extract of seed of Psoralea corylifolia (Somraji) and seed of Trigonella foenum-graecum L. (Methi) in streptozotocin-induced diabetic rat: A comparative evaluation. Pharmacol. Res., 2013, 5(4), 277-285.
[http://dx.doi.org/10.4103/0974-8490.118840] [PMID: 24174822]
[43]
Gancedo, J.M.; Gancedo, C. Fructose-1,6-diphosphatase, phosphofructokinase and glucose-6-phosphate dehydrogenase from fermenting and non fermenting yeasts. Arch. Mikrobiol., 1971, 76(2), 132-138.
[http://dx.doi.org/10.1007/BF00411787] [PMID: 4324161]
[44]
Mithieux, G.; Vidal, H.; Zitoun, C.; Bruni, N.; Daniele, N.; Minassian, C. Glucose-6-phosphatase mRNA and activity are increased to the same extent in kidney and liver of diabetic rats. Diabetes, 1996, 45(7), 891-896.
[http://dx.doi.org/10.2337/diab.45.7.891] [PMID: 8666139]
[45]
Renjith, R.S.; Rajamohan, T. Young inflorescence of Cocos nucifera contributes to improvement of glucose homeostasis and antioxidant status in diabetic rats. Int. J. Diabetes Dev. Ctries., 2012, 32(4), 193-198.
[http://dx.doi.org/10.1007/s13410-012-0088-9]
[46]
Cho, S.J.; Jung, U.J.; Choi, M.S. Differential effects of low-dose resveratrol on adiposity and hepatic steatosis in diet-induced obese mice. Br. J. Nutr., 2012, 108(12), 2166-2175.
[http://dx.doi.org/10.1017/S0007114512000347] [PMID: 22414733]
[47]
Ahmed, D.; Sharma, M.; Mukerjee, A.; Ramteke, P.W.; Kumar, V. Improved glycemic control, pancreas protective and hepatoprotective effect by traditional poly-herbal formulation “Qurs Tabasheer” in streptozotocin induced diabetic rats. BMC Complement. Altern. Med., 2013, 13, 10.
[http://dx.doi.org/10.1186/1472-6882-13-10] [PMID: 23305114]
[48]
Kosuru, R.; Singh, S. Pterostilbene ameliorates insulin sensitivity, glycemic control and oxidative stress in fructose-fed diabetic rats. Life Sci., 2017, 182, 112-121.
[http://dx.doi.org/10.1016/j.lfs.2017.06.015] [PMID: 28629731]
[49]
Reagan-Shaw, S.; Nihal, M.; Ahmad, N. Dose translation from animal to human studies revisited. FASEB J., 2008, 22(3), 659-661.
[http://dx.doi.org/10.1096/fj.07-9574LSF] [PMID: 17942826]
[50]
Uppal, V.; Mansoor, S.; Furuya, K.N. Pediatric non-alcoholic fatty liver disease. Curr. Gastroenterol. Rep., 2016, 18(5), 24.
[http://dx.doi.org/10.1007/s11894-016-0498-9] [PMID: 27086005]
[51]
Duvnjak, M.; Lerotić, I.; Barsić, N.; Tomasić, V.; Virović Jukić, L.; Velagić, V. Pathogenesis and management issues for non-alcoholic fatty liver disease. World J. Gastroenterol., 2007, 13(34), 4539-4550.
[http://dx.doi.org/10.3748/wjg.v13.i34.4539] [PMID: 17729403]
[52]
Day, C.P.; James, O.F. Steatohepatitis: a tale of two “hits”? Gastroenterology, 1998, 114(4), 842-845.
[http://dx.doi.org/10.1016/S0016-5085(98)70599-2] [PMID: 9547102]
[53]
Buzzetti, E.; Pinzani, M.; Tsochatzis, E.A. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism, 2016, 65(8), 1038-1048.
[http://dx.doi.org/10.1016/j.metabol.2015.12.012] [PMID: 26823198]
[54]
Ahmed, M. Non-alcoholic fatty liver disease in 2015. World J. Hepatol., 2015, 7(11), 1450-1459.
[http://dx.doi.org/10.4254/wjh.v7.i11.1450] [PMID: 26085906]
[55]
Tarantino, G.; Saldalamacchia, G.; Conca, P.; Arena, A. Non-alcoholic fatty liver disease: further expression of the metabolic syndrome. J. Gastroenterol. Hepatol., 2007, 22(3), 293-303.
[http://dx.doi.org/10.1111/j.1440-1746.2007.04824.x] [PMID: 17295757]
[56]
López-Velázquez, J.A.; Silva-Vidal, K.V.; Ponciano-Rodríguez, G.; Chávez-Tapia, N.C.; Arrese, M.; Uribe, M.; Méndez-Sánchez, N. The prevalence of nonalcoholic fatty liver disease in the Americas. Ann. Hepatol., 2014, 13(2), 166-178.
[http://dx.doi.org/10.1016/S1665-2681(19)30879-8] [PMID: 24552858]
[57]
Zelber-Sagi, S.; Godos, J.; Salomone, F. Lifestyle changes for the treatment of nonalcoholic fatty liver disease: a review of observational studies and intervention trials. Therap. Adv. Gastroenterol., 2016, 9(3), 392-407.
[http://dx.doi.org/10.1177/1756283X16638830] [PMID: 27134667]
[58]
Satheesh, M.A.; Pari, L. Effect of pterostilbene on lipids and lipid profiles in streptozotocin-nicotinamide induced type 2 diabetes mellitus., 2008, 6, 31-37..
[http://dx.doi.org/10.32725/jab.2008.005]
[59]
Browning, J.D.; Horton, J.D. Molecular mediators of hepatic steatosis and liver injury. J. Clin. Invest., 2004, 114(2), 147-152.
[http://dx.doi.org/10.1172/JCI200422422] [PMID: 15254578]
[60]
Rimando, A.M.; Nagmani, R.; Feller, D.R.; Yokoyama, W. Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor alpha-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamsters. J. Agric. Food Chem., 2005, 53(9), 3403-3407.
[http://dx.doi.org/10.1021/jf0580364] [PMID: 15853379]
[61]
Rimando, A.M.; Khan, S.I.; Mizuno, C.S.; Ren, G.; Mathews, S.T.; Kim, H.; Yokoyama, W. Evaluation of PPARα activation by known blueberry constituents. J. Sci. Food Agric., 2016, 96(5), 1666-1671.
[http://dx.doi.org/10.1002/jsfa.7269] [PMID: 25996649]
[62]
Riche, D.M.; Riche, K.D.; Blackshear, C.T.; McEwen, C.L.; Sherman, J.J.; Wofford, M.R.; Griswold, M.E. Pterostilbene on metabolic parameters: a randomized, double-blind, and placebo-controlled trial. Evid. Based Complement. Alternat. Med., 2014, 2014459165
[http://dx.doi.org/10.1155/2014/459165] [PMID: 25057276]

Rights & Permissions Print Cite
Article Metrics
92
1
Wayfinder Image
World Antimicrobial Awareness Week
© 2024 Bentham Science Publishers | Privacy Policy