Molecular Targets of Combined Natural Antioxidants Against Diabetes in Streptozotocin-induced Diabetic Mice

高等学校化学研究 ›› 2012, Vol. 28 ›› Issue (1): 96-102.

Molecular Targets of Combined Natural Antioxidants Against Diabetes in Streptozotocin-induced Diabetic Mice

SONG Yang^1,2, GAO Zhong-li², DU Zhen-wu¹, PIAO Song-lan¹, WANG Ling-ling¹, WANG Qing^3*, ZHANG Gui-zhen^1*

1. Central Research Department, China-Japan Union Hospital of Jilin University, Changchun 130033, P. R. China;
2. Department of Orthopaedics, China-Japan Union Hospital of Jilin University, Changchun 130033, P. R. China;
3. Department of Endocrinology, China-Japan Union Hospital of Jilin University, Changchun 130033, P. R. China

收稿日期:2011-05-23 修回日期:2011-08-04 出版日期:2012-01-25 发布日期:2011-12-27
基金资助:
Supported by the National Natural Science Foundation of China(No.39870667), the Scientific Research Foundation of Jilin Province, China(Nos.2007-0722, 2007-05265, 2008-2123, 20100942) and the Project of Developing and Reforming Community of Jilin Province, China (Nos.2006-1550, 2003-1268, 2010-1928, 20080925, 20101928).

Molecular Targets of Combined Natural Antioxidants Against Diabetes in Streptozotocin-induced Diabetic Mice

SONG Yang^1,2, GAO Zhong-li², DU Zhen-wu¹, PIAO Song-lan¹, WANG Ling-ling¹, WANG Qing^3*, ZHANG Gui-zhen^1*

1. Central Research Department, China-Japan Union Hospital of Jilin University, Changchun 130033, P. R. China;
2. Department of Orthopaedics, China-Japan Union Hospital of Jilin University, Changchun 130033, P. R. China;
3. Department of Endocrinology, China-Japan Union Hospital of Jilin University, Changchun 130033, P. R. China

Received:2011-05-23 Revised:2011-08-04 Online:2012-01-25 Published:2011-12-27
Contact: guizhen zhang E-mail:zhangguizhenjlu@yahoo.com; qingwang@yahoo.com.cn
Supported by:
Supported by the National Natural Science Foundation of China(No.39870667), the Scientific Research Foundation of Jilin Province, China(Nos.2007-0722, 2007-05265, 2008-2123, 20100942) and the Project of Developing and Reforming Community of Jilin Province, China (Nos.2006-1550, 2003-1268, 2010-1928, 20080925, 20101928).

摘要/Abstract

摘要： Natural antioxidants, due to the different chemical structures and their unique biological protection effects on islet cell, have been received much attention in applied chemistry field for developing a new diabetic drug. However, the molecular targets of the islet cell protection have been remained obscure. For investigating molecular targets of combined natural antioxidant's(CNA) roles in against diabetes, type 1 diabetic mouse model was made by multiple injection of low doses of streptozotocin into C57BL mice. Two combinations of natural antioxidants were orally supplemented to the mice. Blood glucose level, glutathione peroxidase(GSH-Px) and superoxide dismutase (SOD) activities, and malondialdehyde(MDA) contents were measured via biochemical assays. Tumor necrosis factor α(TNF-α), interferon γ(IFN-γ) and Interleukin-12(IL-12) in CD4⁺ Peripheral blood mononuclear cells(PBMC) were evaluated with flow cytometry(FCM). In situ hybridization(ISH) and immunohistochemistry(IHC) were used to detect insulin gene expression. The results demonstrate both the combinations significantly: increased GSH-px and SOD, but decreased MDA levels in pancreas(p<0.05―0.01); up-regulated insulin expression at both mRNA and protein levels in islet cells(p<0.05―0.01); down-regulated TNF-α and IL-12 expression in PBMC(p<0.05―0.01). Our data suggest that the CAN may regulate multiple key molecular targets related to β cell function, including reduction of oxidative stress and pre-inflammatory cytokines, and upregulate insulin gene expression to reduce the development of diabetes.

关键词: Combined natural antioxidant, Diabetes, Insulin gene expression, Oxidative stress, Pro-inflammatory cytokine

Abstract: Natural antioxidants, due to the different chemical structures and their unique biological protection effects on islet cell, have been received much attention in applied chemistry field for developing a new diabetic drug. However, the molecular targets of the islet cell protection have been remained obscure. For investigating molecular targets of combined natural antioxidant's(CNA) roles in against diabetes, type 1 diabetic mouse model was made by multiple injection of low doses of streptozotocin into C57BL mice. Two combinations of natural antioxidants were orally supplemented to the mice. Blood glucose level, glutathione peroxidase(GSH-Px) and superoxide dismutase (SOD) activities, and malondialdehyde(MDA) contents were measured via biochemical assays. Tumor necrosis factor α(TNF-α), interferon γ(IFN-γ) and Interleukin-12(IL-12) in CD4⁺ Peripheral blood mononuclear cells(PBMC) were evaluated with flow cytometry(FCM). In situ hybridization(ISH) and immunohistochemistry(IHC) were used to detect insulin gene expression. The results demonstrate both the combinations significantly: increased GSH-px and SOD, but decreased MDA levels in pancreas(p<0.05―0.01); up-regulated insulin expression at both mRNA and protein levels in islet cells(p<0.05―0.01); down-regulated TNF-α and IL-12 expression in PBMC(p<0.05―0.01). Our data suggest that the CAN may regulate multiple key molecular targets related to β cell function, including reduction of oxidative stress and pre-inflammatory cytokines, and upregulate insulin gene expression to reduce the development of diabetes.

Key words: Combined natural antioxidant, Diabetes, Insulin gene expression, Oxidative stress, Pro-inflammatory cytokine

SONG Yang, GAO Zhong-li, DU Zhen-wu, PIAO Song-lan, WANG Ling-ling, WANG Qing, ZHANG Gui-zhen. Molecular Targets of Combined Natural Antioxidants Against Diabetes in Streptozotocin-induced Diabetic Mice[J]. 高等学校化学研究, 2012, 28(1): 96-102.

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Molecular Targets of Combined Natural Antioxidants Against Diabetes in Streptozotocin-induced Diabetic Mice

Molecular Targets of Combined Natural Antioxidants Against Diabetes in Streptozotocin-induced Diabetic Mice

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