Generic placeholder image

Combinatorial Chemistry & High Throughput Screening


ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Investigating the Effects and Mechanism of Rhodiola Rosea Injection on Cardiac Function in Rats with Chronic Heart Failure

Author(s): Xiuqin Li, Shaopeng Chen, Weihua Shao, Suxing Wang and Lixia Yao*

Volume 26, Issue 12, 2023

Published on: 27 February, 2023

Page: [2238 - 2246] Pages: 9

DOI: 10.2174/1386207326666230203145254

Price: $65


Aim: To study the effect of Rhodiola Rosea injection on cardiac function and the reninangiotensin- aldosterone system (RASS) in rats with chronic heart failure.

Background: Rhodiola Rosea injection, a traditional Chinese medication for relieving blood stasis and improving blood circulation, is an excellent therapeutic for treating coronary heart disease-angina pectoris. Rhodiola Rosea injection's major component, salidroside, protects the cardiovascular system. But there isn't much first-hand evidence about how injectable Rhodiola Rosea affects heart failure.

Objectives: In this study, a rat model of heart failure was established, and the effect of Rhodiola rosea injection on myocardial cell morphology, cardiac function, and ventricular remodelling in rats with heart failure was investigated.

Methods: 66 SD male rats were selected; 10 were randomly selected as a blank control group, and 56 were treated intraperitoneally with doxorubicin (4 g/g). After 6 weeks, all animals had LVEF 60%. Established a heart failure model. Each group had 14 rats: model control, low-dose, mediumdose, and high-dose Rhodiola Rosea injection. The 2 mL/kg of Rhodiola Rosea injection was injected into the tail vein once a day for 2 weeks. Both the blank and control groups received normal daily saline. After 2 weeks, the echocardiographic index, RASS-related index, and serum BNP level were assessed in all rats, and myocardial tissue morphology was observed. MiRNA423-5p, miRNA499-5p, and miRNA210-3p were extracted from peripheral blood. Rhodiola rosea injection on its expression was compared to healthy control rats.

Results: 6 mL/kg Rhodiola Rosea injection lowered LVEDV and LVESV while increasing LVEF and LVFS. Injections of 6 mL/kg Rhodiola Rosea reduce plasma levels of miR-210-3p, miR-423- 5p, miRNA-499, and BNP in heart failure model rats. The 6 mL/kg Rhodiola Rosea injection can restore the RASS indexes of heart failure rats to the level of the normal group.

Conclusion: The present study offers preliminary evidence supporting the use of Rhodiola Rosea injection in the treatment of heart failure and offers a solid foundation for clinical off-label medication use.

Keywords: Rhodiola rosea injection, chronic heart failure, miRNA, RASS, traditional Chinese medication, echocardiographic index.

Graphical Abstract
Bard, M.; Woods, R.A.; Bartón, D.H.R.; Corrie, J.E.T.; Widdowson, D.A. Sterol mutants of Saccharomyces cerevisiae: Chromatographic analyses. Lipids, 1977, 12(8), 645-654.
[] [PMID: 331007]
Zhang, W.; Brombosz, S.M.; Mendoza, J.L.; Moore, J.S. A high-yield, one-step synthesis of o-phenylene ethynylene cyclic trimer via precipitation-driven alkyne metathesis. J. Org. Chem., 2005, 70(24), 10198-10201.
[] [PMID: 16292873]
Guan, H.; Dai, G.H.; Gao, W.L.; Zhao, X.; Cai, Z.H.; Zhang, J.Z.; Yao, J.X. A 5-year survival prediction model for chronic heart failure patients induced by coronary heart disease with traditional chinese medicine intervention. Evid. Based Complement. Alternat. Med., 2021, 2021, 1-10.
[] [PMID: 34239577]
Ambrosy, A.P.; Fonarow, G.C.; Butler, J.; Chioncel, O.; Greene, S.J.; Vaduganathan, M.; Nodari, S.; Lam, C.S.P.; Sato, N.; Shah, A.N.; Gheorghiade, M. The global health and economic burden of hospitalizations for heart failure: Lessons learned from hospitalized heart failure registries. J. Am. Coll. Cardiol., 2014, 63(12), 1123-1133.
[] [PMID: 24491689]
McDonagh, T.A.; Metra, M.; Adamo, M.; Gardner, R.S.; Baumbach, A.; Böhm, M.; Burri, H.; Butler, J.; Čelutkienė, J.; Chioncel, O.; Cleland, J.G.F.; Coats, A.J.S.; Crespo-Leiro, M.G.; Farmakis, D.; Gilard, M.; Heymans, S.; Hoes, A.W.; Jaarsma, T.; Jankowska, E.A.; Lainscak, M.; Lam, C.S.P.; Lyon, A.R.; McMurray, J.J.V.; Mebazaa, A.; Mindham, R.; Muneretto, C.; Francesco Piepoli, M.; Price, S.; Rosano, G.M.C.; Ruschitzka, F.; Kathrine Skibelund, A.; de Boer, R.A.; Christian Schulze, P.; Abdelhamid, M.; Aboyans, V.; Adamopoulos, S.; Anker, S.D.; Arbelo, E.; Asteggiano, R.; Bauersachs, J.; Bayes-Genis, A.; Borger, M.A.; Budts, W.; Cikes, M.; Damman, K.; Delgado, V.; Dendale, P.; Dilaveris, P.; Drexel, H.; Ezekowitz, J.; Falk, V.; Fauchier, L.; Filippatos, G.; Fraser, A.; Frey, N.; Gale, C.P.; Gustafsson, F.; Harris, J.; Iung, B.; Janssens, S.; Jessup, M.; Konradi, A.; Kotecha, D.; Lambrinou, E.; Lancellotti, P.; Landmesser, U.; Leclercq, C.; Lewis, B.S.; Leyva, F.; Linhart, A.; Løchen, M-L.; Lund, L.H.; Mancini, D.; Masip, J.; Milicic, D.; Mueller, C.; Nef, H.; Nielsen, J-C.; Neubeck, L.; Noutsias, M.; Petersen, S.E.; Sonia Petronio, A.; Ponikowski, P.; Prescott, E.; Rakisheva, A.; Richter, D.J.; Schlyakhto, E.; Seferovic, P.; Senni, M.; Sitges, M.; Sousa-Uva, M.; Tocchetti, C.G.; Touyz, R.M.; Tschoepe, C.; Waltenberger, J.; Adamo, M.; Baumbach, A.; Böhm, M.; Burri, H.; Čelutkienė, J.; Chioncel, O.; Cleland, J.G.F.; Coats, A.J.S.; Crespo-Leiro, M.G.; Farmakis, D.; Gardner, R.S.; Gilard, M.; Heymans, S.; Hoes, A.W.; Jaarsma, T.; Jankowska, E.A.; Lainscak, M.; Lam, C.S.P.; Lyon, A.R.; McMurray, J.J.V.; Mebazaa, A.; Mindham, R.; Muneretto, C.; Piepoli, M.F.; Price, S.; Rosano, G.M.C.; Ruschitzka, F.; Skibelund, A.K. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J., 2021, 42(36), 3599-3726.
[] [PMID: 34447992]
Mao, J.Y.; Zhu, M.J. Expert consensus on diagnosis and treatment of chronic heart failure in traditional Chinese medicine. J. Tradit. Chin. Med., 2014, 55, 1258-1260.
Chen, K.J..; Wu, Z.G.; Zhu, M.J. Expert consensus on the diagnosis and treatment of chronic heart failure with integrated traditional Chinese and Western medicine. Chin. J. Integr. Trad. West. Med., 2016, 36, 133-141.
Liu, L.; Gao, J.; Jin, J. Clinical experience of professor LIU Li in the treatment of chronic heart failure with Shenqi Yixin Tang. Clin. J. Trad. Chin. Med., 2015, 27, 1243-1245.
Jin, J.; Cui, L.; Zou, G.L. Effects of shenqi yixin fang on myocardial structure and cytokines in doxorubicin-induced chronic heart failure rats. Zhongguo Shiyan Fangjixue Zazhi, 2014, 20, 128-132.
Nasi-Er, B.; Lou, X.; Zhang, Y.; Sun, H.; Zhou, X.; Li, Y.; Zhou, Q.; Zhang, J.; Tang, B.; Lu, Y. Renal sympathetic denervation improves outcomes in a canine myocardial infarction model. Med. Sci. Monit., 2019, 25, 3887-3893.
[] [PMID: 31127792]
Chang, S.N.; Chang, S.H.; Yu, C.C.; Wu, C.K.; Lai, L.P.; Chiang, F.T.; Hwang, J.J.; Lin, J.L.; Tsai, C.T. Renal denervation decreases susceptibility to arrhythmogenic cardiac alternans and ventricular arrhythmia in a rat model of post-myocardial infarction heart failure. JACC Basic Transl. Sci., 2017, 2(2), 184-193.
[] [PMID: 30167565]
Liao, S.Y.; Zhen, Z.; Liu, Y.; Au, K.W.; Lai, W.H.; Tsang, A.; Tse, H.F. Improvement of myocardial function following catheter-based renal denervation in heart failure. JACC Basic Transl. Sci., 2017, 2(3), 270-281.
[] [PMID: 30062148]
Sharp, T.E., III; Polhemus, D.J.; Li, Z.; Spaletra, P.; Jenkins, J.S.; Reilly, J.P.; White, C.J.; Kapusta, D.R.; Lefer, D.J.; Goodchild, T.T. Renal denervation prevents heart failure progression via inhibition of the renin-angiotensin system. J. Am. Coll. Cardiol., 2018, 72(21), 2609-2621.
[] [PMID: 30466519]
Battistelli, M.; De Sanctis, R.; De Bellis, R.; Cucchiarini, L.; Dachà, M.; Gobbi, P. Rhodiola rosea as antioxidant in red blood cells: ultrastructural and hemolytic behaviour. Eur. J. Histochem., 2005, 49(3), 243-254.
[PMID: 16216810]
Cheng, Y.Z.; Chen, L.J.; Lee, W.J.; Chen, M.F.; Jung Lin, H.; Cheng, J.T. Increase of myocardial performance by Rhodiola–ethanol extract in diabetic rats. J. Ethnopharmacol., 2012, 144(2), 234-239.
[] [PMID: 23044195]
Baba, M.; Yoshida, K.; Ieda, M. Clinical applications of natriuretic peptides in heart failure and atrial fibrillation. Int. J. Mol. Sci., 2019, 20(11), 2824.
[] [PMID: 31185605]
Santaguida, P.L.; Don-Wauchope, A.C.; Oremus, M.; McKelvie, R.; Ali, U.; Hill, S.A.; Balion, C.; Booth, R.A.; Brown, J.A.; Bustamam, A.; Sohel, N.; Raina, P. BNP and NT-proBNP as prognostic markers in persons with acute decompensated heart failure: A systematic review. Heart Fail. Rev., 2014, 19(4), 453-470.
[] [PMID: 25062653]
Peng, Y.; Croce, C.M. The role of MicroRNAs in human cancer. Signal Transduct. Target. Ther., 2016, 1(1), 15004.
[] [PMID: 29263891]
Saliminejad, K.; Khorram Khorshid, H.R.; Soleymani Fard, S.; Ghaffari, S.H. An overview of microRNAs: Biology, functions, therapeutics, and analysis methods. J. Cell. Physiol., 2019, 234(5), 5451-5465.
[] [PMID: 30471116]
Barwari, T.; Joshi, A.; Mayr, M. MicroRNAs in cardiovascular disease. J. Am. Coll. Cardiol., 2016, 68(23), 2577-2584.
[] [PMID: 27931616]
Hanna, J.; Hossain, G.S.; Kocerha, J. The potential for microRNA therapeutics and clinical research. Front. Genet., 2019, 10, 478.
[] [PMID: 31156715]
Mehta, S.; Sharma, A.K.; Singh, R.K. Ethnobotany, pharmacological activities and bioavailability studies on “King of Bitters” (Kalmegh): A review (2010-2020). Comb. Chem. High Throughput Screen., 2022, 25(5), 788-807.
[] [PMID: 33745423]
Mehta, S.; Sharma, A.K.; Singh, R.K. Therapeutic journey of Andrographis paniculata (Burm.f.) Nees from natural to synthetic and nanoformulations. Mini Rev. Med. Chem., 2021, 21(12), 1556-1577.
[] [PMID: 33719961]
Mehta, S.; Sharma, A.K.; Singh, R.K. Advances in ethnobotany, synthetic phytochemistry and pharmacology of endangered herb Picrorhiza kurroa (Kutki): A comprehensive review (2010-2020). Mini Rev. Med. Chem., 2021, 21(19), 2976-2995.
[] [PMID: 33797375]
Mehta, S.; Sharma, A.K.; Singh, R.K. Pharmacological activities and molecular mechanisms of pure and crude extract of Andrographis paniculata: An update. Phytomedicine Plus, 2021, 1(4)100085
Zhang, W.; Huai, Y.; Miao, Z.; Chen, C.; Shahen, M.; Rahman, S.U.; Alagawany, M.; El-Hack, M.E.A.; Zhao, H.; Qian, A. Systems pharmacology approach to investigate the molecular mechanisms of herb Rhodiola rosea L. radix. Drug Dev. Ind. Pharm., 2019, 45(3), 456-464.
[] [PMID: 30449200]
Liu, S.H.; Hsiao, Y.W.; Chong, E.; Singhal, R.; Fong, M.C.; Tsai, Y.N.; Hsu, C.P.; Chen, Y.C.; Chen, Y.J.; Chiou, C.W.; Chiang, S.J.; Chang, S.L.; Chen, S.A. Rhodiola inhibits atrial arrhythmogenesis in a heart failure model. J. Cardiovasc. Electrophysiol., 2016, 27(9), 1093-1101.
[] [PMID: 27255210]
Chen, Y.; Tang, M.; Yuan, S.; Fu, S.; Li, Y.; Li, Y.; Wang, Q.; Cao, Y.; Liu, L.; Zhang, Q. Rhodiola rosea: A therapeutic candidate on cardiovascular diseases. Oxid. Med. Cell. Longev., 2022, 2022, 1-14.
[] [PMID: 35265260]
Wiedenfeld, H.; Dumaa, M.; Malinowski, M.; Furmanowa, M.; Narantuya, S. Phytochemical and analytical studies of extracts from Rhodiola rosea and Rhodiola quadrifida. Pharmazie, 2007, 62(4), 308-311.
[PMID: 17484290]
Han, F.; Li, Y.; Mao, X.; Xu, R.; Yin, R. Characterization of chemical constituents in Rhodiola crenulate by high-performance liquid chromatography coupled with Fourier-transform ion cyclotron resonance mass spectrometer (HPLC-FT-ICR MS). J. Mass Spectrom., 2016, 51(5), 363-368.
[] [PMID: 27194521]
Chen, X.; Zhang, Q.; Cheng, Q.; Ding, F. Protective effect of salidroside against H2O2-induced cell apoptosis in primary culture of rat hippocampal neurons. Mol. Cell. Biochem., 2009, 332(1-2), 85-93.
[] [PMID: 19554425]
Wu, T.; Zhou, H.; Jin, Z.; Bi, S.; Yang, X.; Yi, D.; Liu, W. Cardioprotection of salidroside from ischemia/reperfusion injury by increasing N-acetylglucosamine linkage to cellular proteins. Eur. J. Pharmacol., 2009, 613(1-3), 93-99.
[] [PMID: 19376110]
Wong, L.; Wang, J.; Liew, O.; Richards, A.; Chen, Y.T. MicroRNA and heart failure. Int. J. Mol. Sci., 2016, 17(4), 502.
[] [PMID: 27058529]
Tijsen, A.J.; Creemers, E.E.; Moerland, P.D.; de Windt, L.J.; van der Wal, A.C.; Kok, W.E.; Pinto, Y.M. MiR423-5p as a circulating biomarker for heart failure. Circ. Res., 2010, 106(6), 1035-1039.
[] [PMID: 20185794]
Luo, P.; He, T.; Jiang, R.; Li, G. MicroRNA-423-5p targets O-GlcNAc transferase to induce apoptosis in cardiomyocytes. Mol. Med. Rep., 2015, 12(1), 1163-1168.
[] [PMID: 25776937]
Goren, Y.; Kushnir, M.; Zafrir, B.; Tabak, S.; Lewis, B.S.; Amir, O. Serum levels of microRNAs in patients with heart failure. Eur. J. Heart Fail., 2012, 14(2), 147-154.
[] [PMID: 22120965]
Dickinson, B.A.; Semus, H.M.; Montgomery, R.L.; Stack, C.; Latimer, P.A.; Lewton, S.M.; Lynch, J.M.; Hullinger, T.G.; Seto, A.G.; van Rooij, E. Plasma microRNAs serve as biomarkers of therapeutic efficacy and disease progression in hypertension-induced heart failure. Eur. J. Heart Fail., 2013, 15(6), 650-659.
[] [PMID: 23388090]
Thum, T.; Galuppo, P.; Wolf, C.; Fiedler, J.; Kneitz, S.; van Laake, L.W.; Doevendans, P.A.; Mummery, C.L.; Borlak, J.; Haverich, A.; Gross, C.; Engelhardt, S.; Ertl, G.; Bauersachs, J. MicroRNAs in the human heart: A clue to fetal gene reprogramming in heart failure. Circulation, 2007, 116(3), 258-267.
[] [PMID: 17606841]
Wang, J.X.; Jiao, J.Q.; Li, Q.; Long, B.; Wang, K.; Liu, J.P.; Li, Y.R.; Li, P.F. miR-499 regulates mitochondrial dynamics by targeting calcineurin and dynamin-related protein-1. Nat. Med., 2011, 17(1), 71-78.
[] [PMID: 21186368]
Corsten, M.F.; Dennert, R.; Jochems, S.; Kuznetsova, T.; Devaux, Y.; Hofstra, L.; Wagner, D.R.; Staessen, J.A.; Heymans, S.; Schroen, B. Circulating MicroRNA-208b and MicroRNA-499 reflect myocardial damage in cardiovascular disease. Circ. Cardiovasc. Genet., 2010, 3(6), 499-506.
[] [PMID: 20921333]
Sluijter, J.P.G.; van Mil, A.; van Vliet, P.; Metz, C.H.G.; Liu, J.; Doevendans, P.A.; Goumans, M.J. MicroRNA-1 and -499 regulate differentiation and proliferation in human-derived cardiomyocyte progenitor cells. Arterioscler. Thromb. Vasc. Biol., 2010, 30(4), 859-868.
[] [PMID: 20081117]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy