Full Text:   <4537>

Summary:  <2162>

CLC number: R542.2

On-line Access: 2024-08-27

Received: 2023-10-17

Revision Accepted: 2024-05-08

Crosschecked: 2015-04-09

Cited: 13

Clicked: 6699

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Hai-tao Yu

http://orcid.org/0000-0001-9955-8001

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2015 Vol.16 No.5 P.344-354

http://doi.org/10.1631/jzus.B1400204


Ginsenoside Rg1 ameliorates oxidative stress and myocardial apoptosis in streptozotocin-induced diabetic rats


Author(s):  Hai-tao Yu, Juan Zhen, Bo Pang, Jin-ning Gu, Sui-sheng Wu

Affiliation(s):  Department of Cardiovascular Medicine, the First Hospital of Jilin University, Changchun 130021, China; more

Corresponding email(s):   tedyu@foxmail.com, suishengwu@gmail.com

Key Words:  Ginsenoside Rg1, Diabetic cardiomyopathy, Oxidative stress, Apoptosis, Caspase-3 (CASP3)


Hai-tao Yu, Juan Zhen, Bo Pang, Jin-ning Gu, Sui-sheng Wu. Ginsenoside Rg1 ameliorates oxidative stress and myocardial apoptosis in streptozotocin-induced diabetic rats[J]. Journal of Zhejiang University Science B, 2015, 16(5): 344-354.

@article{title="Ginsenoside Rg1 ameliorates oxidative stress and myocardial apoptosis in streptozotocin-induced diabetic rats",
author="Hai-tao Yu, Juan Zhen, Bo Pang, Jin-ning Gu, Sui-sheng Wu",
journal="Journal of Zhejiang University Science B",
volume="16",
number="5",
pages="344-354",
year="2015",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1400204"
}

%0 Journal Article
%T Ginsenoside Rg1 ameliorates oxidative stress and myocardial apoptosis in streptozotocin-induced diabetic rats
%A Hai-tao Yu
%A Juan Zhen
%A Bo Pang
%A Jin-ning Gu
%A Sui-sheng Wu
%J Journal of Zhejiang University SCIENCE B
%V 16
%N 5
%P 344-354
%@ 1673-1581
%D 2015
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1400204

TY - JOUR
T1 - Ginsenoside Rg1 ameliorates oxidative stress and myocardial apoptosis in streptozotocin-induced diabetic rats
A1 - Hai-tao Yu
A1 - Juan Zhen
A1 - Bo Pang
A1 - Jin-ning Gu
A1 - Sui-sheng Wu
J0 - Journal of Zhejiang University Science B
VL - 16
IS - 5
SP - 344
EP - 354
%@ 1673-1581
Y1 - 2015
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1400204


Abstract: 
We evaluated the cardioprotective effects of ginsenoside Rg1 in a diabetic rat model induced with high-fat diet and intraperitoneal injection of streptozotocin. ginsenoside Rg1 was injected intraperitoneally for 12 weeks. Myocardial injury indices and oxidative stress markers were determined. Changes in cardiac ultrastructure were evaluated with transmission electron microscopy. Myocardial apoptosis was assessed via terminal deoxynucleotidyl transferase (TDT)-mediated DNA nick-end labeling (TUNEL) and immunohistochemistry. ginsenoside Rg1 was associated with a significant dose-dependent reduction in serum levels of creatinine kinase MB and cardiac troponin I, and lessened ultrastructural disorders in diabetic myocardium, relative to the untreated diabetic model rats. Also, compared with the untreated diabetic rats, significant reductions in serum and myocardial levels of malondialdehyde were noted in the ginsenoside Rg1-treated groups, and increased levels of the antioxidants (superoxide dismutase, catalase, and glutathione peroxidase) were detected. TUNEL staining indicated reduced myocardial apoptosis in ginsenoside Rg1-treated rats, which may be associated with reduced levels of caspase-3 (CASP3) and increased levels of B-cell lymphoma-extra-large (Bcl-xL) in the diabetic myocardium. ginsenoside Rg1 treatment of diabetic rats was associated with reduced oxidative stress and attenuated myocardial apoptosis, suggesting that ginsenoside Rg1 may be of potential preventative and therapeutic value for cardiovascular injury in diabetic patients.

人参皂苷Rg1对糖尿病大鼠心肌氧化应激及细胞凋亡的影响

目的:探讨人参皂苷Rg1对高血糖所致心肌损害的保护作用及其机制。
创新点:使用糖尿病大鼠为实验对象,探讨三种浓度的人参皂苷Rg1对糖尿病心肌损伤的保护作用及其机制,检测其是否具有浓度依赖性。
方法:将60只Wistar大鼠随机分组,其中空白对照组10只,另50只给予高脂高糖饲养,4周后腹腔注射40mg/kg链脲佐菌素(STZ)。成功制备糖尿病大鼠模型40只,再随机分为糖尿病模型组,糖尿病大鼠+低剂量人参皂苷Rg1(10mg/(kg•d)),糖尿病大鼠+中剂量人参皂苷Rg1(15mg/(kg•d)),糖尿病大鼠+高剂量人参皂苷Rg1(20mg/(kg•d))。12周后处死大鼠,取血测定空腹血糖、总胆固醇(TC)、甘油三酯(TG)、心肌酶及氧化应激水平,留取心肌组织使用透射电镜观察心肌细胞超微结构改变,应用TUNEL法检测心肌细胞凋亡,免疫组化检测细胞凋亡相关蛋白半胱氨酸天冬氨酸蛋白酶3(CASP3)和Bcl-xL的表达。
结论:人参皂苷Rg1对糖尿病大鼠糖脂代谢无明显影响,人参皂苷Rg1可降低糖尿病大鼠血清肌钙蛋白(cTnI)和肌酸激酶同工酶(CK-MB)水平,改善心肌细胞超微结构,减少心肌细胞凋亡,降低大鼠血清和心肌组织中丙二醛(MDA)含量,提高超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH)水平,降低凋亡蛋白CASP3的表达,同时提高Bcl-xL蛋白表达。总之,人参皂苷Rg1能显著保护糖尿病大鼠心肌损伤,其机制可能与其抗氧化及抗细胞凋亡作用有关。

关键词:人参皂苷Rg1;糖尿病心肌病;氧化应激;细胞凋亡;半胱氨酸天冬氨酸蛋白酶3(CASP3)

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Aneja, A., Tang, W., Bansilal, S., et al., 2008. Diabetic cardiomyopathy: insights into pathogenesis, diagnostic challenges, and therapeutic options. Am. J. Med., 121(9):748-757.

[2]Asrih, M., Steffens, S., 2013. Emerging role of epigenetics and miRNA in diabetic cardiomyopathy. Cardiovasc. Pathol., 22(2):117-125.

[3]Bäcklund, T., Palojoki, E., Saraste, A., et al., 2004. Sustained cardiomyocyte apoptosis and left ventricular remodelling after myocardial infarction in experimental diabetes. Diabetologia, 47(2):325-330.

[4]Beulens, J.W., Grobbee, D.E., Nealb, B., 2010. The global burden of diabetes and its complications: an emerging pandemic. Eur. J. Cardiovasc. Prev. Rehabil., 17(Suppl. 1):S3-S8.

[5]Boyer, J.K., Thanigaraj, S., Schechtman, K.B., et al., 2004. Prevalence of ventricular diastolic dysfunction in asymptomatic, normotensive patients with diabetes mellitus. Am. J. Cardiol., 93(7):870-875.

[6]Brownlee, M., 2001. Biochemistry and molecular cell biology of diabetic complications. Nature, 414(6865):813-820.

[7]Cai, L., Wang, Y., Zhou, G., et al., 2006. Attenuation by metallothionein of early cardiac cell death via suppression of mitochondrial oxidative stress results in a prevention of diabetic cardiomyopathy. J. Am. Coll. Cardiol., 48(8):1688-1697.

[8]Carrington, E.M., McKenzie, M.D., Jansen, E., et al., 2009. Islet β-cells deficient in Bcl-xL develop but are abnormally sensitive to apoptotic stimuli. Diabetes, 58(10):2316-2323.

[9]Chen, J., Cha-Molstad, H., Szabo, A., et al., 2009. Diabetes induces and calcium channel blockers prevent cardiac expression of proapoptotic thioredoxin-interacting protein. Am. J. Physiol. Endocrinol. Metab., 296(5):E1133-E1139.

[10]Chowdhry, M.F., Vohra, H.A., Galiñanes, M., 2007. Diabetes increases apoptosis and necrosis in both ischemic and nonischemic human myocardium: role of caspases and poly-adenosine diphosphate-ribose polymerase. J. Thorac. Cardiovasc. Surg., 134(1):124-131.

[11]Deng, J., Wang, Y.W., Chen, W.M., et al., 2010. Role of nitric oxide in ginsenoside Rg1-induced protection against left ventricular hypertrophy produced by abdominal aorta coarctation in rats. Biol. Pharm. Bull., 33(4):631-635.

[12]Falcão-Pires, I., Leite-Moreira, A.F., 2012. Diabetic cardiomyopathy: understanding the molecular and cellular basis to progress in diagnosis and treatment. Heart Fail. Rev., 17(3):325-344.

[13]Giacco, F., Brownlee, M., 2010. Oxidative stress and diabetic complications. Circ. Res., 107(9):1058-1070.

[14]Halliwell, B., 2007. Biochemistry of oxidative stress. Biochem. Soc. Trans., 35(5):1147-1150.

[15]Hamblin, M., Friedman, D.B., Hill, S., et al., 2007. Alterations in the diabetic myocardial proteome coupled with increased myocardial oxidative stress underlies diabetic cardiomyopathy. J. Mol. Cell. Cardiol., 42(4):884-895.

[16]Huang, Y., Wu, D., Fan, W., 2014. Protection of ginsenoside Rg1 on chondrocyte from IL-1β-induced mitochondria-activated apoptosis through PI3K/Akt signaling. Mol. Cell. Biochem., 392(1-2):249-257.

[17]Kannel, W.B., McGee, D.L., 1979. Diabetes and cardiovascular disease: the Framingham study. JAMA, 241(19):2035-2038.

[18]Khullar, M., Al-Shudiefat, A.A.R.S., Ludke, A., et al., 2010. Oxidative stress: a key contributor to diabetic cardiomyopathy. Can. J. Physiol. Pharmacol., 88(3):233-240.

[19]Korivi, M., Hou, C.W., Huang, C.Y., et al., 2012. Ginsenoside-Rg1 protects the liver against exhaustive exercise-induced oxidative stress in rats. Evid. Based Complement. Alternat. Med., 2012:932165.

[20]Leung, K.W., Pon, Y.L., Wong, R.N., et al., 2006. Ginsenoside-Rg1 induces vascular endothelial growth factor expression through the glucocorticoid receptor-related phosphatidylinositol 3-kinase/Akt and β-catenin/T-cell factor-dependent pathway in human endothelial cells. J. Biol. Chem., 281(47):36280-36288.

[21]Li, C.Y., Deng, W., Liao, X.Q., et al., 2013. The effects and mechanism of ginsenoside Rg1 on myocardial remodeling in an animal model of chronic thromboembolic pulmonary hypertension. Eur. J. Med. Res., 18:16.

[22]Li, J.H., Zhang, N., Wang, J.A., 2008. Improved anti-apoptotic and anti-remodeling potency of bone marrow mesenchymal stem cells by anoxic pre-conditioning in diabetic cardiomyopathy. J. Endocrinol. Invest., 31(2):103-110.

[23]Liu, H.R., Tao, L., Gao, E., et al., 2009. Rosiglitazone inhibits hypercholesterolaemia-induced myeloperoxidase upregulation—a novel mechanism for the cardioprotective effects of PPAR agonists. Cardiovasc. Res., 81(2):344-352.

[24]Liu, J.W., Liu, D., Cui, K.Z., et al., 2012. Recent advances in understanding the biochemical and molecular mechanism of diabetic cardiomyopathy. Biochem. Biophys. Res. Commun., 427(3):441-443.

[25]Lü, J.M., Yao, Q., Chen, C., 2009. Ginseng compounds: an update on their molecular mechanisms and medical applications. Curr. Vasc. Pharmacol., 7(3):293.

[26]Ma, J., Liu, J., Wang, Q., et al., 2013. The beneficial effect of ginsenoside Rg1 on Schwann cells subjected to hydrogen peroxide induced oxidative injury. Int. J. Biol. Sci., 9(6):624-636.

[27]Matsui, T., Davidoff, A.J., 2007. Assessment of PI-3 kinase and Akt in ischemic heart diseases in diabetes. Methods Mol. Med., 139:329-338.

[28]Morrissy, S., Xu, B., Aguilar, D., et al., 2010. Inhibition of apoptosis by progesterone in cardiomyocytes. Aging Cell, 9(5):799-809.

[29]Ogata, Y., Takahashi, M., 2003. Bcl-xL as an antiapoptotic molecule for cardiomyocytes. Drug News Perspect., 16(7):446-452.

[30]Park, S.H., Jang, J.H., Chen, C.Y., et al., 2010. A formulated red ginseng extract rescues PC12 cells from PCB-induced oxidative cell death through Nrf2-mediated upregulation of heme oxygenase-1 and glutamate cysteine ligase. Toxicology, 278(1):131-139.

[31]Rubler, S., Dlugash, J., Yuceoglu, Y.Z., et al., 1972. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am. J. Cardiol., 30(6):595-602.

[32]Shi, C., Zheng, D.D., Fang, L., et al., 2012. Ginsenoside Rg1 promotes nonamyloidgenic cleavage of APP via estrogen receptor signaling to MAPK/ERK and PI3K/Akt. Biochim. Biophys. Acta, 1820(4):453-460.

[33]Singal, P.K., Bello-Klein, A., Farahmand, F., et al., 2001. Oxidative stress and functional deficit in diabetic cardiomyopathy. Adv. Exp. Med. Biol., 498:213-220.

[34]Thandavarayan, R.A., Watanabe, K., Ma, M., et al., 2009. Dominant-negative p38α mitogen-activated protein kinase prevents cardiac apoptosis and remodeling after streptozotocin-induced diabetes mellitus. Am. J. Physiol. Heart Circ. Physiol., 297(3):H911-H919.

[35]Voulgari, C., Papadogiannis, D., Tentolouris, N., 2010. Diabetic cardiomyopathy: from the pathophysiology of the cardiac myocytes to current diagnosis and management strategies. Vasc. Health Risk Manag., 6:883-903.

[36]Wang, Q.Y., Liu, F., Wu, F.J., et al., 2013. Effects of ginsenoside Rg1 on the expressions of p-eRK1/2 and p-JNK in local cerebral ischemia/reperfusion injury rats. Chin. J. Integr. Tradit. West. Med., 33(2):229-234 (in Chinese).

[37]Wang, Y., Liu, Y., Zhang, X.Y., et al., 2014. Ginsenoside Rg1 regulates innate immune responses in macrophages through differentially modulating the NF-κB and PI3K/ Akt/mTOR pathways. Int. Immunopharmacol., 23(1):77-84.

[38]Watanabe, I.S., Yamada, E., 1983. The fine structure of lamellated nerve endings found in the rat gingiva. Arch. Histol. Jpn., 46(2):173-182.

[39]Xia, R., Zhao, B., Wu, Y., et al., 2011. Ginsenoside Rb1 preconditioning enhances eNOS expression and attenuates myocardial ischemia/reperfusion injury in diabetic rats. J. Biomed. Biotechnol., 2011:767930.

[40]Xu, J., Wang, G., Wang, Y., et al., 2009. Diabetes- and angiotensin II-induced cardiac endoplasmic reticulum stress and cell death: metallothionein protection. J. Cell. Mol. Med., 13(8A):1499-1512.

[41]Yan, J., Liu, Q., Dou, Y., et al., 2013. Activating glucocorticoid receptor-ERK signaling pathway contributes to ginsenoside Rg1 protection against β-amyloid peptide-induced human endothelial cells apoptosis. J. Ethnopharmacol., 147(2):456-466.

[42]Yang, W., Lu, J., Weng, J., et al., 2010. Prevalence of diabetes among men and women in China. N. Engl. J. Med., 362(12):1090-1101.

[43]Yin, H., Liu, Z., Li, F., et al., 2011. Ginsenoside-Rg1 enhances angiogenesis and ameliorates ventricular remodeling in a rat model of myocardial infarction. J. Mol. Med., 89(4):363-375.

[44]Zhang, Y.J., Zhang, X.L., Li, M.H., et al., 2013. The ginsenoside Rg1 prevents transverse aortic constriction-induced left ventricular hypertrophy and cardiac dysfunction by inhibiting fibrosis and enhancing angiogenesis. J. Cardiovasc. Pharmacol., 62(1):50-57.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE