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Published in: BMC Complementary Medicine and Therapies 1/2015

Open Access 01-12-2015 | Research article

Effects of rhodiola crenulata on mice hearts under severe sleep apnea

Authors: Mei-Chih Lai, Jaung-Geng Lin, Pei-Ying Pai, Mei-Hsin Lai, Yueh-Min Lin, Yu-Lan Yeh, Shiu-Min Cheng, Yi-fan Liu, Chih-Yang Huang, Shin-Da Lee

Published in: BMC Complementary Medicine and Therapies | Issue 1/2015

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Abstract

Background

The goal of this study is to determine if Rhodiola Crenulata (RC) has protective effects on mice hearts with severe sleep apnea model.

Methods

Sixty-four C57BL/6 J mice 5–6 months old were distributed into 4 groups i.e. Control group (21 % O2, 24 h per day, 8 weeks, n = 16); Hypoxia group (Hypoxia: 7 % O2 60 s, 20 % O2 alternating 60 s, 8 h per day, 8 weeks, n = 16); Hypoxia + 90RC and Hypoxia + 270RC group (Hypoxia for 1st 4 weeks and hypoxia pretreated 90 mg/Kg and 270 mg/Kg Rhodiola Crenulata by oral gavage per day for 2nd 4 weeks, each n = 16). Excised hearts from 4 groups of mice were analyzed for heart weight index changes using H&E staining, TUNEL-positive assays and Western Blotting protein.

Results

Cardiac widely dispersed TUNEL-positive apoptotic cells in mice hearts were less in Hypoxia + RC90 and Hypoxia + RC270 than those in Hypoxia. Compared with Hypoxia, the protein levels of Fas ligand, Fas death receptors, Fas-Associated Death Domain (FADD), activated caspase 8, and activated caspase 3 (Fas dependent apoptotic pathways) were decreased in Hypoxia + RC90, Hypoxia + RC270. The protein levels of Bad, Bax, t-Bid, activated caspase 9, activated caspase 3 (mitochondria dependent apoptotic pathway) were less in Hypoxia + RC90, Hypoxia + RC270 than those in hypoxia. The protein levels of Bcl2, Bcl-xL, p-Bad (Bcl2-realted anti-apoptotic pathway) and VEGF, p-PI3k, p-AKT (VEGF-related pro-survival pathway) were higher in Hypoxia + RC90, Hypoxia + RC270 than those in hypoxia.

Conclusions

Our findings suggest that Rhodiola Crenulata have protective effects on chronic intermittent hypoxia-induced cardiac widely dispersed apoptosis via Fas-dependent and mitochondria-dependent apoptotic and VEGF-related pro-survival pathway.
Literature
1.
go back to reference Chiang AA. Obstructive sleep apnea and chronic intermittent hypoxia: a review. Chin J Physiol. 2006;49:234–43.PubMed Chiang AA. Obstructive sleep apnea and chronic intermittent hypoxia: a review. Chin J Physiol. 2006;49:234–43.PubMed
2.
go back to reference Moore T. R.T., Wiklund U, Franklin KA, Eriksson P. Sleep-disordered breathing in men with coronary artery disease. Chest. 1996;109:659–63.CrossRef Moore T. R.T., Wiklund U, Franklin KA, Eriksson P. Sleep-disordered breathing in men with coronary artery disease. Chest. 1996;109:659–63.CrossRef
3.
go back to reference Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Nieto FJ, et al. Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med. 2001;163:19–25.CrossRefPubMed Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Nieto FJ, et al. Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med. 2001;163:19–25.CrossRefPubMed
4.
go back to reference Liu, X., Feng L., Cao G., Huang H., Yu J., Xu Q., Zhang S. and Zhou M. Noninvasive positive pressure ventilation therapy can improve cardiac structure and function in patients with coronary artery disease combined with severe obstructive sleep apnea/hypopnea syndrome. Cardiol J 2014. Liu, X., Feng L., Cao G., Huang H., Yu J., Xu Q., Zhang S. and Zhou M. Noninvasive positive pressure ventilation therapy can improve cardiac structure and function in patients with coronary artery disease combined with severe obstructive sleep apnea/hypopnea syndrome. Cardiol J 2014.
5.
go back to reference Lai, M.C., Lin J.G., Pai P.Y., Lai M.H., Lin Y.M., Yeh Y.L., Cheng S.M., Liu Y.F., Huang C.Y. and Lee S.D. Protective effect of salidroside on cardiac apoptosis in mice with chronic intermittent hypoxia. Int J Cardiol 2014. Lai, M.C., Lin J.G., Pai P.Y., Lai M.H., Lin Y.M., Yeh Y.L., Cheng S.M., Liu Y.F., Huang C.Y. and Lee S.D. Protective effect of salidroside on cardiac apoptosis in mice with chronic intermittent hypoxia. Int J Cardiol 2014.
6.
go back to reference Lee SD, Kuo WW, Lin JA, Chu YF, Wang CK, Yeh YL, et al. Effects of long-term intermittent hypoxia on mitochondrial and Fas death receptor dependent apoptotic pathways in rat hearts. Int J Cardiol. 2007;116:348–56.CrossRefPubMed Lee SD, Kuo WW, Lin JA, Chu YF, Wang CK, Yeh YL, et al. Effects of long-term intermittent hypoxia on mitochondrial and Fas death receptor dependent apoptotic pathways in rat hearts. Int J Cardiol. 2007;116:348–56.CrossRefPubMed
7.
go back to reference Kelly GS. Rhodiola rosea: a possible plant adaptogen. Altern Med Rev. 2001;6:293–302.PubMed Kelly GS. Rhodiola rosea: a possible plant adaptogen. Altern Med Rev. 2001;6:293–302.PubMed
8.
go back to reference Lee SY, Li MH, Shi LS, Chu H, Ho CW, Chang TC. Rhodiola crenulata Extract Alleviates Hypoxic Pulmonary Edema in Rats. Evid Based Complement Alternat Med. 2013;2013:718739.PubMedPubMedCentral Lee SY, Li MH, Shi LS, Chu H, Ho CW, Chang TC. Rhodiola crenulata Extract Alleviates Hypoxic Pulmonary Edema in Rats. Evid Based Complement Alternat Med. 2013;2013:718739.PubMedPubMedCentral
9.
go back to reference Yang YN, Liu ZZ, Feng ZM, Jiang JS, Zhang PC. Lignans from the root of Rhodiola crenulata. J Agric Food Chem. 2012;60:964–72.CrossRefPubMed Yang YN, Liu ZZ, Feng ZM, Jiang JS, Zhang PC. Lignans from the root of Rhodiola crenulata. J Agric Food Chem. 2012;60:964–72.CrossRefPubMed
10.
11.
go back to reference El-Ad B, Lavie P. Effect of sleep apnea on cognition and mood. Int Rev Psychiatry. 2005;17:277–82.CrossRefPubMed El-Ad B, Lavie P. Effect of sleep apnea on cognition and mood. Int Rev Psychiatry. 2005;17:277–82.CrossRefPubMed
12.
go back to reference Han X, Zhang T, Wei Y, Cao X, Ito Y. Separation of salidroside from Rhodiola crenulata by high-speed counter-current chromatography. J Chromatogr A. 2002;971:237–41.CrossRefPubMed Han X, Zhang T, Wei Y, Cao X, Ito Y. Separation of salidroside from Rhodiola crenulata by high-speed counter-current chromatography. J Chromatogr A. 2002;971:237–41.CrossRefPubMed
13.
go back to reference Wang XL, Wang X, Xiong LL, Zhu Y, Chen HL, Chen JX, et al. Salidroside improves doxorubicin-induced cardiac dysfunction by suppression of excessive oxidative stress and cardiomyocyte apoptosis. J Cardiovasc Pharmacol. 2013;62:512–23.CrossRefPubMed Wang XL, Wang X, Xiong LL, Zhu Y, Chen HL, Chen JX, et al. Salidroside improves doxorubicin-induced cardiac dysfunction by suppression of excessive oxidative stress and cardiomyocyte apoptosis. J Cardiovasc Pharmacol. 2013;62:512–23.CrossRefPubMed
14.
go back to reference Xing S, Yang X, Li W, Bian F, Wu D, Chi J, et al. Salidroside stimulates mitochondrial biogenesis and protects against H(2)O(2)-induced endothelial dysfunction. Oxid Med Cell Longev. 2014;2014:904834.CrossRefPubMedPubMedCentral Xing S, Yang X, Li W, Bian F, Wu D, Chi J, et al. Salidroside stimulates mitochondrial biogenesis and protects against H(2)O(2)-induced endothelial dysfunction. Oxid Med Cell Longev. 2014;2014:904834.CrossRefPubMedPubMedCentral
15.
go back to reference Li X, Erden O, Li L, Ye Q, Wilson A, Du W. Binding to WGR domain by salidroside activates PARP1 and protects hematopoietic stem cells from oxidative stress. Antioxid Redox Signal. 2014;20:1853–65.CrossRefPubMedPubMedCentral Li X, Erden O, Li L, Ye Q, Wilson A, Du W. Binding to WGR domain by salidroside activates PARP1 and protects hematopoietic stem cells from oxidative stress. Antioxid Redox Signal. 2014;20:1853–65.CrossRefPubMedPubMedCentral
16.
go back to reference Zheng KY, Zhang ZX, Guo AJ, Bi CW, Zhu KY, Xu SL, et al. Salidroside stimulates the accumulation of HIF-1alpha protein resulted in the induction of EPO expression: a signaling via blocking the degradation pathway in kidney and liver cells. Eur J Pharmacol. 2012;679:34–9.CrossRefPubMed Zheng KY, Zhang ZX, Guo AJ, Bi CW, Zhu KY, Xu SL, et al. Salidroside stimulates the accumulation of HIF-1alpha protein resulted in the induction of EPO expression: a signaling via blocking the degradation pathway in kidney and liver cells. Eur J Pharmacol. 2012;679:34–9.CrossRefPubMed
17.
go back to reference Narula J, Pandey P, Arbustini E, Haider N, Narula N, Kolodgie FD, Dal Bello B, Semigran MJ, Bielsa-Masdeu A, Dec GW, Israels S, Ballester M, Virmani R, Saxena S, Kharbanda S. Apoptosis in heart failure: release of cytochrome c from mitochondria and activation of caspase-3 in human cardiomyopathy. Proc Natl Acad Sci U S A. 1999;96(14):8144–9. PMID: 10393962.CrossRefPubMedPubMedCentral Narula J, Pandey P, Arbustini E, Haider N, Narula N, Kolodgie FD, Dal Bello B, Semigran MJ, Bielsa-Masdeu A, Dec GW, Israels S, Ballester M, Virmani R, Saxena S, Kharbanda S. Apoptosis in heart failure: release of cytochrome c from mitochondria and activation of caspase-3 in human cardiomyopathy. Proc Natl Acad Sci U S A. 1999;96(14):8144–9. PMID: 10393962.CrossRefPubMedPubMedCentral
18.
go back to reference Lee SD, Tzang BS, Kuo WW, Lin YM, Yang AL, Chen SH, et al. Cardiac fas receptor-dependent apoptotic pathway in obese Zucker rats. Obesity (Silver Spring). 2007;15:2407–15.CrossRef Lee SD, Tzang BS, Kuo WW, Lin YM, Yang AL, Chen SH, et al. Cardiac fas receptor-dependent apoptotic pathway in obese Zucker rats. Obesity (Silver Spring). 2007;15:2407–15.CrossRef
19.
go back to reference Lu, M.C., Tzang B.S., Kuo W.W., Wu F.L., Chen Y.S., Tsai C., Huang C.Y. and Lee S.D. More activated cardiac mitochondrial dependent apoptotic pathway in obese Zucker rat. Obesity in press: 2007. Lu, M.C., Tzang B.S., Kuo W.W., Wu F.L., Chen Y.S., Tsai C., Huang C.Y. and Lee S.D. More activated cardiac mitochondrial dependent apoptotic pathway in obese Zucker rat. Obesity in press: 2007.
20.
go back to reference Kuo WW, Wu CH, Lee SD, Lin JA, Chu CY, Hwang JM, et al. Second-hand smoke-induced cardiac fibrosis is related to the Fas death receptor apoptotic pathway without mitochondria-dependent pathway involvement in rats. Environ Health Perspect. 2005;113:1349–53.CrossRefPubMedPubMedCentral Kuo WW, Wu CH, Lee SD, Lin JA, Chu CY, Hwang JM, et al. Second-hand smoke-induced cardiac fibrosis is related to the Fas death receptor apoptotic pathway without mitochondria-dependent pathway involvement in rats. Environ Health Perspect. 2005;113:1349–53.CrossRefPubMedPubMedCentral
21.
go back to reference Lee SD, Kuo WW, Wu CH, Lin YM, Lin JA, Lu MC, et al. Effects of short- and long-term hypobaric hypoxia on Bcl2 family in rat heart. Int J Cardiol. 2006;108:376–84.CrossRefPubMed Lee SD, Kuo WW, Wu CH, Lin YM, Lin JA, Lu MC, et al. Effects of short- and long-term hypobaric hypoxia on Bcl2 family in rat heart. Int J Cardiol. 2006;108:376–84.CrossRefPubMed
22.
go back to reference Lin YM, Huang SK, Wang HF, Chen LM, Tsai FJ, Hsu HH, et al. Short-term versus long-term intermittent hypobaric hypoxia on cardiac fibrosis and Fas death receptor dependent apoptotic pathway in rat hearts. Chin J Physiol. 2008;51:308–16.PubMed Lin YM, Huang SK, Wang HF, Chen LM, Tsai FJ, Hsu HH, et al. Short-term versus long-term intermittent hypobaric hypoxia on cardiac fibrosis and Fas death receptor dependent apoptotic pathway in rat hearts. Chin J Physiol. 2008;51:308–16.PubMed
23.
go back to reference Bishopric NHA, Slepak P, Webster T. K. A. Molecular mechanisms of apoptosis in the cardiac myocyte. Curr Opin Pharmacol. 2001;1:141–50.CrossRefPubMed Bishopric NHA, Slepak P, Webster T. K. A. Molecular mechanisms of apoptosis in the cardiac myocyte. Curr Opin Pharmacol. 2001;1:141–50.CrossRefPubMed
24.
go back to reference Barnhart BC, Alappat EC, Peter ME. The CD95 type I/type II model. Semin Immunol. 2003;15(3):185–93.CrossRefPubMed Barnhart BC, Alappat EC, Peter ME. The CD95 type I/type II model. Semin Immunol. 2003;15(3):185–93.CrossRefPubMed
25.
go back to reference Gross A, McDonnell JM, Korsmeyer SJ. BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 1999;13(15):1899–911. Review. PMID:10444588.CrossRefPubMed Gross A, McDonnell JM, Korsmeyer SJ. BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 1999;13(15):1899–911. Review. PMID:10444588.CrossRefPubMed
26.
27.
go back to reference Kubasiak LA, Hernandez OM, Bishopric NH, Webster KA. Hypoxia and acidosis activate cardiac myocyte death through the Bcl-2 family protein BNIP3. Proc Natl Acad Sci USA. 2002;99:12825–30.CrossRefPubMedPubMedCentral Kubasiak LA, Hernandez OM, Bishopric NH, Webster KA. Hypoxia and acidosis activate cardiac myocyte death through the Bcl-2 family protein BNIP3. Proc Natl Acad Sci USA. 2002;99:12825–30.CrossRefPubMedPubMedCentral
28.
go back to reference Abid MR, Guo S, Minami T, Spokes KC, Ueki K, Skurk C, et al. Vascular endothelial growth factor activates PI3K/Akt/forkhead signaling in endothelial cells. Arterioscler Thromb Vasc Biol. 2004;24:294–300.CrossRefPubMed Abid MR, Guo S, Minami T, Spokes KC, Ueki K, Skurk C, et al. Vascular endothelial growth factor activates PI3K/Akt/forkhead signaling in endothelial cells. Arterioscler Thromb Vasc Biol. 2004;24:294–300.CrossRefPubMed
29.
go back to reference Chen T, Zhou G, Zhu Q, Liu X, Ha T, Kelley JL, et al. Overexpression of vascular endothelial growth factor 165 (VEGF165) protects cardiomyocytes against doxorubicin-induced apoptosis. J Chemother. 2010;22:402–6.CrossRefPubMed Chen T, Zhou G, Zhu Q, Liu X, Ha T, Kelley JL, et al. Overexpression of vascular endothelial growth factor 165 (VEGF165) protects cardiomyocytes against doxorubicin-induced apoptosis. J Chemother. 2010;22:402–6.CrossRefPubMed
30.
31.
go back to reference Chiu T, Chen L, Su D, Lo H, Chen C, Wang S, et al. 57 Rhodiola Crenulata Extract Prophylaxis for Acute Mountain Sickness: A Randomized, Double Blind, Placebo Controlled, Crossover Trial. Ann Emerg Med. 2012;60:S22.CrossRef Chiu T, Chen L, Su D, Lo H, Chen C, Wang S, et al. 57 Rhodiola Crenulata Extract Prophylaxis for Acute Mountain Sickness: A Randomized, Double Blind, Placebo Controlled, Crossover Trial. Ann Emerg Med. 2012;60:S22.CrossRef
32.
go back to reference Wang J, Rong X, Li W, Yang Y, Yamahara J, Li Y. Rhodiola crenulata root ameliorates derangements of glucose and lipid metabolism in a rat model of the metabolic syndrome and type 2 diabetes. J Ethnopharmacol. 2012;142:782–8.CrossRefPubMed Wang J, Rong X, Li W, Yang Y, Yamahara J, Li Y. Rhodiola crenulata root ameliorates derangements of glucose and lipid metabolism in a rat model of the metabolic syndrome and type 2 diabetes. J Ethnopharmacol. 2012;142:782–8.CrossRefPubMed
33.
go back to reference Cheng YZ, Chen LJ, Lee WJ, Chen MF, Jung LH, Cheng JT. Increase of myocardial performance by Rhodiola-ethanol extract in diabetic rats. J Ethnopharmacol. 2012;144:234–9.CrossRefPubMed Cheng YZ, Chen LJ, Lee WJ, Chen MF, Jung LH, Cheng JT. Increase of myocardial performance by Rhodiola-ethanol extract in diabetic rats. J Ethnopharmacol. 2012;144:234–9.CrossRefPubMed
34.
go back to reference Zhang J, Liu A, Hou R, Jia X, Jiang W, Chen J. Salidroside protects cardiomyocyte against hypoxia-induced death: a HIF-1alpha-activated and VEGF-mediated pathway. Eur J Pharmacol. 2009;607:6–14.CrossRefPubMed Zhang J, Liu A, Hou R, Jia X, Jiang W, Chen J. Salidroside protects cardiomyocyte against hypoxia-induced death: a HIF-1alpha-activated and VEGF-mediated pathway. Eur J Pharmacol. 2009;607:6–14.CrossRefPubMed
35.
go back to reference Zhang L, Ding W, Sun H, Zhou Q, Huang J, Li X, et al. Salidroside protects PC12 cells from MPP(+)-induced apoptosis via activation of the PI3K/Akt pathway. Food Chem Toxicol. 2012;50:2591–7.CrossRefPubMed Zhang L, Ding W, Sun H, Zhou Q, Huang J, Li X, et al. Salidroside protects PC12 cells from MPP(+)-induced apoptosis via activation of the PI3K/Akt pathway. Food Chem Toxicol. 2012;50:2591–7.CrossRefPubMed
36.
go back to reference Hanus M, Lafon J, Mathieu M. Double-blind, randomised, placebo-controlled study to evaluate the efficacy and safety of a fixed combination containing two plant extracts (Crataegus oxyacantha and Eschscholtzia californica) and magnesium in mild-to-moderate anxiety disorders. Curr Med Res Opin. 2004;20:63–71.CrossRefPubMed Hanus M, Lafon J, Mathieu M. Double-blind, randomised, placebo-controlled study to evaluate the efficacy and safety of a fixed combination containing two plant extracts (Crataegus oxyacantha and Eschscholtzia californica) and magnesium in mild-to-moderate anxiety disorders. Curr Med Res Opin. 2004;20:63–71.CrossRefPubMed
37.
go back to reference Zhu Y, Shi YP, Wu D, Ji YJ, Wang X, Chen HL, et al. Salidroside protects against hydrogen peroxide-induced injury in cardiac H9c2 cells via PI3K-Akt dependent pathway. DNA Cell Biol. 2011;30:809–19.CrossRefPubMed Zhu Y, Shi YP, Wu D, Ji YJ, Wang X, Chen HL, et al. Salidroside protects against hydrogen peroxide-induced injury in cardiac H9c2 cells via PI3K-Akt dependent pathway. DNA Cell Biol. 2011;30:809–19.CrossRefPubMed
38.
go back to reference Sun L, Isaak CK, Zhou Y, Petkau JC. O K., Liu Y. and Siow Y.L. Salidroside and tyrosol from Rhodiola protect H9c2 cells from ischemia/reperfusion-induced apoptosis. Life Sci. 2012;91:151–8.CrossRefPubMed Sun L, Isaak CK, Zhou Y, Petkau JC. O K., Liu Y. and Siow Y.L. Salidroside and tyrosol from Rhodiola protect H9c2 cells from ischemia/reperfusion-induced apoptosis. Life Sci. 2012;91:151–8.CrossRefPubMed
39.
go back to reference Murabe Y, Sano Y. Morphological studies on neuroglia. V. Microglial cells in the cerebral cortex of the rat, with special reference to their possible involvement in synaptic function. Cell Tissue Res. 1982;223:493–506.CrossRefPubMed Murabe Y, Sano Y. Morphological studies on neuroglia. V. Microglial cells in the cerebral cortex of the rat, with special reference to their possible involvement in synaptic function. Cell Tissue Res. 1982;223:493–506.CrossRefPubMed
40.
go back to reference Yin X, Zheng Y, Liu Q, Cai J, Cai L. Cardiac response to chronic intermittent hypoxia with a transition from adaptation to maladaptation: the role of hydrogen peroxide. Oxid Med Cell Longev. 2012;2012:569520.CrossRefPubMedPubMedCentral Yin X, Zheng Y, Liu Q, Cai J, Cai L. Cardiac response to chronic intermittent hypoxia with a transition from adaptation to maladaptation: the role of hydrogen peroxide. Oxid Med Cell Longev. 2012;2012:569520.CrossRefPubMedPubMedCentral
Metadata
Title
Effects of rhodiola crenulata on mice hearts under severe sleep apnea
Authors
Mei-Chih Lai
Jaung-Geng Lin
Pei-Ying Pai
Mei-Hsin Lai
Yueh-Min Lin
Yu-Lan Yeh
Shiu-Min Cheng
Yi-fan Liu
Chih-Yang Huang
Shin-Da Lee
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2015
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-015-0698-0

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