Phenylpropenoic Acid Glucoside from Rooibos Protects Pancreatic Beta Cells against Cell Death Induced by Acute Injury

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Objective:
Previous studies demonstrated that a phenylpropenoic acid glucoside (PPAG) from rooibos (Aspalathus linearis) extract had anti-hyperglycemic activity and significant protective effects on the pancreatic beta cell mass in a chronic diet-induced diabetes model. The present study evaluated the cytoprotective effect of the phytochemical on beta cells exposed to acute cell stress.

Methods:
Synthetically prepared PPAG was administered orally in mice treated with a single dose of streptozotocin to acutely induce beta cell death and hyperglycemia. Its effect was assessed on beta cell mass, proliferation and apoptotic cell death. Its cytoprotective effect was also studied in vitro on INS-1E beta cells and on human pancreatic islet cells.

Results:
Treatment with the phytochemical PPAG protected beta cells during the first days after the insult against apoptotic cell death, as evidenced by TUNEL staining, and prevented loss of expression of anti-apoptotic protein BCL2 in vivo. In vitro, PPAG protected INS-1E beta cells from streptozotocin-induced apoptosis and necrosis in a BCL2-dependent and independent way, respectively, depending on glucose concentration. PPAG also protected human pancreatic islet cells against the cytotoxic action of the fatty acid palmitate.

Conclusions:
These findings show the potential use of PPAG as phytomedicine which protects the beta cell mass exposed to acute diabetogenic stress.

Autoři: Eddy Himpe ^1*; Daniel A. Cunha ²; Imane Song ¹; Marco Bugliani ⁴; Piero Marchetti ⁴; Miriam Cnop ^2,3; Luc Bouwens ¹
Působiště autorů: Cell Differentiation Lab, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Brussels, Belgium ¹; ULB Center for Diabetes Research, Université Libre de Bruxelles (ULB), Brussels, Belgium ²; Division of Endocrinology, Erasmus Hospital, Brussels, Belgium ³; Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy ⁴
Vyšlo v časopise: PLoS ONE 11(6)
Kategorie: Research article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0157604

© 2016 Himpe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The electronic version of this article is the complete one and can be found online at: http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0157604

Souhrn

Conclusions:
These findings show the potential use of PPAG as phytomedicine which protects the beta cell mass exposed to acute diabetogenic stress.

Zdroje

1. Meier JJ, Bonadonna RC. Role of Reduced β-Cell Mass Versus Impaired β-Cell Function in the Pathogenesis of Type 2 Diabetes. Diabetes Care. 2013; 36:S113–S119. doi: 10.2337/dcS13-2008 PMID: 23882035

2. Song I, Muller C, Louw J, Bouwens L. Regulating the Beta Cell Mass as a Strategy for Type-2 Diabetes Treatment. Curr Drug Targets. 2015; 16:516–524. PMID: 25654737

3. McCarty MF. Nutraceutical resources for diabetes prevention—an update. Med Hypotheses. 2005; 64:151–8. PMID: 15533633

4. Muller CJ, Joubert E, Pheiffer C, Ghoor S, Sanderson M, Chellan N, et al. Z-2-(ß-D-glucopyranosyloxy)-3-phenylpropenoic acid, an α-hydroxy acid from rooibos (Aspalathus linearis) with hypoglycemic activity. Mol Nutr Food Res. 2013; 57:2216–2222. doi: 10.1002/mnfr.201300294 PMID: 23943314

5. Mathijs I, Da Cunha DA, Himpe E, Ladriere L, Chellan N, Roux CR, et al. Phenylpropenoic acid glucoside augments pancreatic beta cell mass in high-fat diet-fed mice and protects beta cells from ER stress-induced apoptosis. Mol Nutr Food Res. 2014; 58:1980–1990. doi: 10.1002/mnfr.201400211 PMID: 25044754

6. Joubert E, de Beer D, Malherbe CJ, Muller N, Bonnet SL, van der Westhuizen JH, et al. Occurrence and sensory perception of Z-2-(ß-D-glucopyranosyloxy)-3-phenylpropenoic acid in rooibos (Aspalathus linearis). Food Chem. 2013; 136:1078–1085. doi: 10.1016/j.foodchem.2012.09.014 PMID: 23122165

7. Marais C, Steenkamp JA, Ferreira D. Occurrence of phenylpyruvic acid in woody plants: biosynthetic significance and synthesis of an enolic glucoside derivative. J Chem Soc Perkin 1. 1996; 1:2915–2918.

8. Rooman I, Bouwens L. Combined gastrin and epidermal growth factor treatment induces islet regeneration and restores normoglycaemia in C57Bl6/J mice treated with alloxan. Diabetologia. 2004; 47:259–265. PMID: 14666367

9. Asfari M, Janjic D, Meda P, Li G, Halban PA, Wollheim CB. Establishment of 2-mercaptoethanoldependent differentiated insulin-secreting cell lines. Endocrinology. 1992; 130:167–178. PMID: 1370150

10. Lupi R, Dotta F, Marselli L, Del Guerra S, Masini M, Santangelo C, et al. Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets: evidence that β-cell death is caspase mediated, partially dependent on ceramide pathway, and Bcl-2 regulated. Diabetes. 2002; 51:1437–1442. PMID: 11978640

11. Cnop M, Abdulkarim B, Bottu G, Cunha DA, Igoillo-Esteve M, Masini M, et al. RNA sequencing identifies dysregulation of the human pancreatic islet transcriptome by the saturated fatty acid palmitate. Diabetes. 2014; 63:1978–93. doi: 10.2337/db13-1383 PMID: 24379348

12. Cunha DA, Hekerman P, Ladrière L, Bazarra-Castro A, Ortis F, Wakeham MC, et al. Initiation and execution of lipotoxic ER stress in pancreatic beta-cells. J Cell Sci. 2008; 121:2308–2318. doi: 10.1242/jcs.026062 PMID: 18559892

13. Cunha DA, Igoillo-Esteve M, Gurzov EN, Germano CM, Naamane N, Marhfour I, et al. Death protein 5 and p53-upregulated modulator of apoptosis mediate the endoplasmic reticulum stress mitochondrial dialog triggering lipotoxic rodent and human ß-cell apoptosis. Diabetes. 2012; 61:2763–2775. doi: 10.2337/db12-0123 PMID: 22773666

14. Cnop M, Ladriere L, Hekerman P, Ortis F, Cardozo AK, Dogusan Z, et al. Selective inhibition of eukaryotic translation initiation factor 2α dephosphorylation potentiates fatty acid-induced endoplasmic reticulum stress and causes pancreatic beta-cell dysfunction and apoptosis. J Biol Chem. 2007; 282:3989–3997. PMID: 17158450

15. Eizirik DL, Pipeleers DG, Ling Z, Welsh N, Hellerström C, Andersson A. Major species differences between humans and rodents in the susceptibility to pancreatic beta-cell injury. Proc Natl Acad Sci U S A. 1994; 91:9253–9256. PMID: 7937750

16. Wu J, Yan LY. Streptozotocin-induced type 1 diabetes in rodents as a model for studying mitochondrial mechanisms of diabetic β cell glucotoxicity. Diabetes Metab Syndr Obes. 2015; 8:181–188. doi: 10.2147/DMSO.S82272 PMID: 25897251

17. Hayashi K, Kojima R, Ito M. Strain differences in the diabetogenic activity of streptozotocin in mice. Biol Pharm Bull. 2006; 29:1110–1119. PMID: 16755002

18. Vetere A, Choudhary A, Burns SM, Wagner BK. Targeting the pancreatic ß cell to treat diabetes. Nat Rev Drug Discov. 2014; 13:278–289. doi: 10.1038/nrd4231 PMID: 24525781

19. Bensellam M, Laybutt DR, Jonas JC. The molecular mechanisms of pancreatic beta cell glucotoxicity: recent findings and future research directions. Mol Cell Endocrinol. 2012; 364:1–27. doi: 10.1016/j.mce.2012.08.003 PMID: 22885162

20. Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res. 2001; 50:537–46. PMID: 11829314

21. Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia. 2008; 51:216–26. PMID: 18087688

22. Morgan NG, Cable HC, Newcombe NR, Williams GT. Treatment of cultured pancreatic B-cells with streptozotocin induces cell death by apoptosis. Biosci Rep. 1994; 14:243–50. PMID: 7772717

23. Watanabe A, Nishijima K, Zhao S, Zhao Y, Tanaka Y, Takemoto H, et al. Quantitative determination of apoptosis of pancreatic β-cells in a murine model of type 1 diabetes mellitus. J Nucl Med. 2012; 53:1585–91. doi: 10.2967/jnumed.111.102459 PMID: 22930815

24. Zong WX, Ditsworth D, Bauer DE, Wang ZQ, Thompson SB. Alkylating DNA damage stimulates a regulated form of necrotic cell death. Genes Dev. 2004; 18:1272–1282. PMID: 15145826

25. Lenzen S, Drinkgern J, Tiedge M. Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues. Free Radic Bio Med. 1996; 20:463–6.

26. Tiedge M, Lortz S, Drinkgern J, Lenzen S. Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes. 1997; 46:1733–42. PMID: 9356019

27. LieberthalW, Menza SA, Levine JS. Graded ATP depletion can cause necrosis or apoptosis of cultured mouse proximal tubular cells. Am J Physiol. 1998; 274:F315–27. PMID: 9486226

28. Saito Y, Nishio K, Ogawa Y, Kimata J, Kinumi T, Yoshida Y, et al. Turning point in apoptosis/necrosis induced by hydrogen peroxide. Free Radic Res. 2006; 40:619–30. PMID: 16753840

29. Pipeleers D, Van De Winkel M. Pancreatic B cells possess defense mechanisms against cell-specific toxicity. Proc Natl Acad Sci U S A. 1986; 83:5267–5271. PMID: 2941762

30. Ahn C, An BS, Jeung EB. Streptozotocin induces endoplasmic reticulum stress and apoptosis via disruption of calcium homeostasis in mouse pancreas. Mol Cell Endocrinol. 2015; 412:302–308. doi: 10.1016/j.mce.2015.05.017 PMID: 26003140

31. Zhu M, Guo M, Fei L, Pan XQ, Liu QQ. 4-phenylbutyric acid attenuates endoplasmic reticulum stressmediated pancreatic β-cell apoptosis in rats with streptozotocin-induced diabetes. Endocrine. 2014; 47:129–37. doi: 10.1007/s12020-013-0132-7 PMID: 24347242

32. Afrin R, Arumugam S, Soetikno V, Thandavarayan RA, Pitchaimani V, Karuppagounder V, et al. Curcumin ameliorates streptozotocin-induced liver damage through modulation of endoplasmic reticulum stress-mediated apoptosis in diabetic rats. Free Radic Res. 2015; 49:279–89. doi: 10.3109/10715762. 2014.999674 PMID: 25536420

33. Uetake R, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Lesato Y, et al. Adrenomedullin-RAMP2 system suppresses ER stress-induced tubule cell death and is involved in kidney protection. PLoS One. 2014; 5:e87667.

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