Skip to main content
Erschienen in: Endocrine 2/2013

01.04.2013 | Original Article

Ginkgo biloba L. extract enhances the effectiveness of syngeneic bone marrow mesenchymal stem cells in lowering blood glucose levels and reversing oxidative stress

verfasst von: Ming Ren, Shujuan Yang, Jianhui Li, Yulin Hu, Zhixing Ren, Shuping Ren

Erschienen in: Endocrine | Ausgabe 2/2013

Einloggen, um Zugang zu erhalten

Abstract

Bone marrow mesenchymal stem cells (BMSCs) are potential therapy for diabetes. Owing to the oxidative stress caused by hyperglycemia, these transplanted BMSCs are with high rate of apoptotic death after transplantation. Ginkgo biloba L. extract (EGB) is a potent antioxidant which can remove free radicals. The study was to investigate whether EGB can protect BMSCs from oxidative stress in vitro and enhance the efficacy of BMSCs in lowering blood glucose levels after transplantation. BMSCs were cultured with H2O2, EGB, or H2O2 and EGB. Cell viability, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and cell death rates were determined. Diabetes was induced by single injection of streptozotocin (STZ) in male Wistar rats. Diabetic rats received EGB, BMSCs, or EGB/BMSCs. The serum levels of glucose, insulin, interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), MDA, SOD, and GSH-Px were determined. PKCα expression and NF-κB activation in kidney were determined. The MDA levels and cell death rates in BMSCs cultured with H2O2 and EGB were significantly lower; cell viability, SOD, and GSH-Px activities were significantly higher compared with those with H2O2 alone. Compared with diabetic rats receiving BMSCs, diabetic rats receiving EGB before BMSCs transplantation showed (1) significantly lower levels of blood glucose, serum MDA, IL-6, and TNF-α, and higher levels of insulin, SOD, and GSH-Px activities; (2) significantly lower PKCα expression and NF-κB activation in the kidney. EGB administration before BMSC transplantation can enhance the effectiveness of BMSCs in lowering blood glucose levels and reversing oxidative stress in diabetic rats.
Literatur
2.
Zurück zum Zitat P.K. Mishra, S.R. Singh, I.G. Joshua, S.C. Tyagi, Stem cells as a therapeutic target for diabetes. Front. Biosci. 15, 461–477 (2010)PubMedCrossRef P.K. Mishra, S.R. Singh, I.G. Joshua, S.C. Tyagi, Stem cells as a therapeutic target for diabetes. Front. Biosci. 15, 461–477 (2010)PubMedCrossRef
3.
Zurück zum Zitat L. Vija, D. Farge, J.F. Gautier, P. Vexiau, C. Dumitrache, A. Bourgarit et al., Mesenchymal stem cells: stem cell therapy perspectives for type 1 diabetes. Diabetes Metab. 35, 85–93 (2009)PubMedCrossRef L. Vija, D. Farge, J.F. Gautier, P. Vexiau, C. Dumitrache, A. Bourgarit et al., Mesenchymal stem cells: stem cell therapy perspectives for type 1 diabetes. Diabetes Metab. 35, 85–93 (2009)PubMedCrossRef
4.
Zurück zum Zitat M. Mabed, M. Shahin, Mesenchymal stem cell-based therapy for the treatment of type 1 diabetes mellitus. Curr. Stem Cell Res. Ther. 7(3), 179–190 (2012)PubMedCrossRef M. Mabed, M. Shahin, Mesenchymal stem cell-based therapy for the treatment of type 1 diabetes mellitus. Curr. Stem Cell Res. Ther. 7(3), 179–190 (2012)PubMedCrossRef
5.
Zurück zum Zitat J.H. Ho, T.C. Tseng, W.H. Ma, W.K. Ong, Y.F. Chen, M.H. Chen, M.W. Lin, C.Y. Hong, O.K. Lee, Multiple intravenous transplantations of mesenchymal stem cells effectively restore long-term blood glucose homeostasis by hepatic engraftment and beta cell differentiation in streptozosin-induced diabetic mice. Cell Transplant. (2011). doi: 10.3727/096368911X603611 J.H. Ho, T.C. Tseng, W.H. Ma, W.K. Ong, Y.F. Chen, M.H. Chen, M.W. Lin, C.Y. Hong, O.K. Lee, Multiple intravenous transplantations of mesenchymal stem cells effectively restore long-term blood glucose homeostasis by hepatic engraftment and beta cell differentiation in streptozosin-induced diabetic mice. Cell Transplant. (2011). doi: 10.​3727/​096368911X603611​
6.
Zurück zum Zitat Martin Rodriguez-Porcel, Olivier Gheysens, Ramasamy Paulmurugan, Ian Y. Chen, Karen M. Peterson, Jürgen K. Willmann et al., Antioxidants improve early survival of cardiomyoblasts after transplantation to the myocardium. Mol. Imaging Biol. 12, 325–334 (2010)PubMedCrossRef Martin Rodriguez-Porcel, Olivier Gheysens, Ramasamy Paulmurugan, Ian Y. Chen, Karen M. Peterson, Jürgen K. Willmann et al., Antioxidants improve early survival of cardiomyoblasts after transplantation to the myocardium. Mol. Imaging Biol. 12, 325–334 (2010)PubMedCrossRef
7.
Zurück zum Zitat Keisuke Ito, Atsushi Hirao, Fumio Arai, Keiyo Takubo, Sahoko Matsuoka, Kana Miyamoto et al., Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat. Med. 12(4), 446–451 (2006)PubMedCrossRef Keisuke Ito, Atsushi Hirao, Fumio Arai, Keiyo Takubo, Sahoko Matsuoka, Kana Miyamoto et al., Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat. Med. 12(4), 446–451 (2006)PubMedCrossRef
8.
Zurück zum Zitat M.E.E. Shams, M.M.H. Al-Gayyar, E.A.M.E. Barakat, Type 2 diabetes mellitus-induced hyperglycemia in patients with NAFLD and normal LFTs: relationship to lipid profile, oxidative stress and pro-inflammatory cytokines. Sci. Pharm. 79, 623–634 (2011)PubMedCrossRef M.E.E. Shams, M.M.H. Al-Gayyar, E.A.M.E. Barakat, Type 2 diabetes mellitus-induced hyperglycemia in patients with NAFLD and normal LFTs: relationship to lipid profile, oxidative stress and pro-inflammatory cytokines. Sci. Pharm. 79, 623–634 (2011)PubMedCrossRef
9.
Zurück zum Zitat M. Zeyda, T.M. Stulnig, Obesity, inflammation, and insulin resistance––a mini-review. Gerontology 55, 379–386 (2009)PubMedCrossRef M. Zeyda, T.M. Stulnig, Obesity, inflammation, and insulin resistance––a mini-review. Gerontology 55, 379–386 (2009)PubMedCrossRef
10.
Zurück zum Zitat P.C. Chan, Q.S. Xia, P.P. FU, Ginkgo Biloba leave extract: biological, medicinal, and toxicological effects. J. Environ. Sci. Health C. 25, 211–244 (2007) P.C. Chan, Q.S. Xia, P.P. FU, Ginkgo Biloba leave extract: biological, medicinal, and toxicological effects. J. Environ. Sci. Health C. 25, 211–244 (2007)
11.
Zurück zum Zitat T. Mosmann, Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods. 65(1–2), 55–63 (1983)PubMedCrossRef T. Mosmann, Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods. 65(1–2), 55–63 (1983)PubMedCrossRef
12.
Zurück zum Zitat D.G. Hafeman, R.A. Sunde, W.G. Hoekstra, Effect of dietary selenium on erythrocyte and liver glutathione peroxidase in the rat. J. Nutr. 104, 580–587 (1974)PubMed D.G. Hafeman, R.A. Sunde, W.G. Hoekstra, Effect of dietary selenium on erythrocyte and liver glutathione peroxidase in the rat. J. Nutr. 104, 580–587 (1974)PubMed
13.
Zurück zum Zitat K. Suzuki, B. Murtuza, J.R. Beauchamp, R.T. Smolenski, A. Varela-Carver, S. Fukushima et al., Dynamics and mediators of acute graft attrition after myoblast transplantation to the heart. FASEB J. 18, 1153–1155 (2004)PubMed K. Suzuki, B. Murtuza, J.R. Beauchamp, R.T. Smolenski, A. Varela-Carver, S. Fukushima et al., Dynamics and mediators of acute graft attrition after myoblast transplantation to the heart. FASEB J. 18, 1153–1155 (2004)PubMed
14.
Zurück zum Zitat X.H. Wu, C.P. Liu, K.F. Xu, X.D. Mao, J. Zhu, J.J. Jiang et al., Reversal of hyperglycemia in diabetic rats by portal vein transplantation of islet-like cells generated from bone marrow mesenchymal stem cells. World J. Gastroenterol. 13(24), 3342–3349 (2007)PubMed X.H. Wu, C.P. Liu, K.F. Xu, X.D. Mao, J. Zhu, J.J. Jiang et al., Reversal of hyperglycemia in diabetic rats by portal vein transplantation of islet-like cells generated from bone marrow mesenchymal stem cells. World J. Gastroenterol. 13(24), 3342–3349 (2007)PubMed
15.
Zurück zum Zitat M.F. El-Azab, F.M. Attia, A.M. El-Mowafy, Novel role of curcumin combined with bone marrow transplantation in reversing experimental diabetes: effects on pancreatic islet regeneration, oxidative stress, and inflammatory cytokines. Eur. J. Pharmacol. 658, 41–48 (2011)PubMedCrossRef M.F. El-Azab, F.M. Attia, A.M. El-Mowafy, Novel role of curcumin combined with bone marrow transplantation in reversing experimental diabetes: effects on pancreatic islet regeneration, oxidative stress, and inflammatory cytokines. Eur. J. Pharmacol. 658, 41–48 (2011)PubMedCrossRef
16.
Zurück zum Zitat M. Valko, D. Leibfritz, J. Moncol, M.T.D. Cronin, M. Mazur, J. Telser, Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol. 39, 44–84 (2007)PubMedCrossRef M. Valko, D. Leibfritz, J. Moncol, M.T.D. Cronin, M. Mazur, J. Telser, Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol. 39, 44–84 (2007)PubMedCrossRef
17.
Zurück zum Zitat D.K. Singh, P. Winocour, K. Farrington, Oxidative stress in early diabetic nephropathy: fueling the fire. Nat. Rev. Endocrinol. 7, 176–184 (2011)PubMedCrossRef D.K. Singh, P. Winocour, K. Farrington, Oxidative stress in early diabetic nephropathy: fueling the fire. Nat. Rev. Endocrinol. 7, 176–184 (2011)PubMedCrossRef
18.
Zurück zum Zitat C. Guijarro, J. Egido, Transcription factor-kB (NF-kB) and renal disease. Kidney Int. 59, 415–424 (2001)PubMedCrossRef C. Guijarro, J. Egido, Transcription factor-kB (NF-kB) and renal disease. Kidney Int. 59, 415–424 (2001)PubMedCrossRef
19.
Zurück zum Zitat M. Romagnoli, M.C. Gomez-Cabrera, M.G. Perrelli, F. Biasi, F.V. Pallardó, J. Sastre, G. Poli, J. Viña, Xanthine oxidase-induced oxidative stress causes activation of NF-κB and inflammation in the liver of type I diabetic rats. Free Radic. Biol. Med. 49, 171–177 (2010)PubMedCrossRef M. Romagnoli, M.C. Gomez-Cabrera, M.G. Perrelli, F. Biasi, F.V. Pallardó, J. Sastre, G. Poli, J. Viña, Xanthine oxidase-induced oxidative stress causes activation of NF-κB and inflammation in the liver of type I diabetic rats. Free Radic. Biol. Med. 49, 171–177 (2010)PubMedCrossRef
Metadaten
Titel
Ginkgo biloba L. extract enhances the effectiveness of syngeneic bone marrow mesenchymal stem cells in lowering blood glucose levels and reversing oxidative stress
verfasst von
Ming Ren
Shujuan Yang
Jianhui Li
Yulin Hu
Zhixing Ren
Shuping Ren
Publikationsdatum
01.04.2013
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 2/2013
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-012-9745-5

Weitere Artikel der Ausgabe 2/2013

Endocrine 2/2013 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.