Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2016

Open Access 01-12-2016 | Research article

Protective effect of Sheng-Mai Yin, a traditional Chinese preparation, against doxorubicin-induced cardiac toxicity in rats

Authors: Shaojun Ma, Xiaojiang Li, Liang Dong, Jinli Zhu, He Zhang, Yingjie Jia

Published in: BMC Complementary Medicine and Therapies | Issue 1/2016

Login to get access

Abstract

Background

Sheng-Mai Yin (SMY), a modern Chinese formula based on Traditional Chinese Medicine theory, has been used to treat cardiovascular diseases in Eastern Asia. Our study focuses on the cardioprotection of SMY against doxorubicin (DOX)-induced cardiac toxicity in vivo.

Methods

Rats were injected with DOX (2.5 mg/kg) in six injections over a 2-week period. SMY was administrated intragastrically at the dose of 8.35, 16.7 and 33.4 g/kg, or 16.7 g/kg only twice a day concurrently with DOX for the 2-weeks. A series of assays were performed to detect the effects of SMY on: (i) heart weight index (HWI) and left ventricular mass index (LVMI); (ii) cardiac function; (iii) heart tissue morphology; (iv) the contents of carboxy terminal propeptide of procollagen typeI (PICP), amino terminal propeptide of procollagen type III (PШNP), transforming growth factor-β1 (TGF-β1), B-type natriuretic peptide (BNP), monocyte chemoattractant protein-1 (MCP-1), interferon gamma (INF-γ) and interleukin 6 (IL-6) by ELISA; (v) the mRNA levels of TGF-β1 and toll-like receptor-2 (TLR2); and (vi) protein level of TGF-β1.

Results

Rats treated with SMY displayed the reductions of BNP and CK-MB increased by DOX in a dose-dependent manner. Moderate dose of SMY exhibited the correction for the increased HWI, LVMI, and the injured cardiac function, as well as the collagen accumulation. In addition, cardioprotection of SMY against DOX-induced cardiac toxicity was demonstrated by the reduction of myocardial fibrosis, characterized by the suppression of PICP, PШNP and TGF-β1, as well as the anti-inflammation and the regulation for cardiac immune microenvironment, characterized by the inhibition of TLR2, MCP-1, INF-γ and IL-6.

Conclusions

SMY may protect heart function through the restriction of myocardial fibrosis induced by DOX, which suggests the potentially therapeutic effect of SMY on DOX-induced cardiomyopathy.
Literature
1.
De Angelis A, Piegari E, Cappetta D, Marino L, Filippelli A, Berrino L, et al. Anthracycline cardiomyopathy is mediated by depletion of the cardiac stem cell pool and is rescued by restoration of progenitor cell function. Circulation. 2010;121(2):276–92.PubMedCentralCrossRefPubMed
2.
Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 2004;56(2):185–229.CrossRefPubMed
3.
Shuai Y, Guo JB, Peng SQ, Zhang LS, Guo J, Han G, et al. Metallothionein protects against doxorubicin-induced cardiomyopathy through inhibition of superoxide generation and related nitrosative impairment. Toxicol Lett. 2007;170(1):66–74.CrossRefPubMed
4.
Singal PK, Iliskovic N, Li T, Kumar D. Adriamycin cardiomyopathy: pathophysiology and prevention. FASEB J. 1997;11(12):931–6.PubMed
5.
Singal PK, Li T, Kumar D, Danelisen I, Iliskovic N. Adriamycin-induced heart failure: mechanism and modulation. Mol Cell Biochem. 2000;207(1–2):77–86.CrossRefPubMed
6.
Swerdlow AJ, Higgins CD, Smith P, Cunningham D, Hancock BW, Horwich A, et al. Myocardial infarction mortality risk after treatment for Hodgkin disease: a collaborative British cohort study. J Natl Cancer Inst. 2007;99(3):206–14.CrossRefPubMed
7.
Das J, Ghosh J, Manna P, Sil PC. Taurine suppresses doxorubicin-triggered oxidative stress and cardiac apoptosis in rat via up-regulation of PI3-K/Akt and inhibition of p53, p38-JNK. Biochem Pharmacol. 2011;81(7):891–909.CrossRefPubMed
8.
Ichihara S, Yamada Y, Kawai Y, Osawa T, Furuhashi K, Duan Z, et al. Roles of oxidative stress and Akt signaling in doxorubicin cardiotoxicity. Biochem Biophys Res Commun. 2007;359(1):27–33.CrossRefPubMed
9.
Li T, Singal PK. Adriamycin-induced early changes in myocardial antioxidant enzymes and their modulation by probucol. Circulation. 2000;102(17):2105–10.CrossRefPubMed
10.
Jin Z, Zhang J, Zhi H, Hong B, Zhang S, Guo H, et al. Beneficial effects of tadalafil on left ventricular dysfunction in doxorubicin-induced cardiomyopathy. J Cardiol. 2013;62(2):110–6.CrossRefPubMed
11.
Lam W, Bussom S, Guan F, Jiang Z, Zhang W, Gullen EA, et al. The four-herb Chinese medicine PHY906 reduces chemotherapy-induced gastrointestinal toxicity. Sci Transl Med. 2010;2(45):45ra59.CrossRefPubMed
12.
Yan X, Zhang L, Guo J, Cao Y, Shang E, Tang Y, et al. Processing of kansui roots stir-baked with vinegar reduces kansui-induced hepatocyte cytotoxicity by decreasing the contents of toxic terpenoids and regulating the cell apoptosis pathway. Molecules. 2014;19(6):7237–54.CrossRefPubMed
13.
Ma L, Yang L, Chen TD. Influence of large amount of shengmai injection on blood coagulation in patients with chronic heart failure. Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban. 2003;23(4):275–7.
14.
Daowu W, Yingdong L. Protective effects of Shengmai San against myocardial damage induced by adriamycin in rats. Pharmacol Clinics Chinese Materia Medica. 1999;15(4):9–11.
15.
Hai J, Limin S. Protective effects of shengmai injection on myocardium injury induced by adriamycin in rats. LiShiZhen Med Materia Medica Res. 2006;17(3):329–30.
16.
Xiaodong Y, Wanqing S, Shuibing Y. Protective ef fect of Shengmai injection on adriamycin-induced myocardium injury in rats and its mechanism. Central South Pharm. 2008;6(2):162–5.
17.
Zhang GQ, Wang H, Liu WT, Dong H, Fong WF, Tang LM, et al. Long-term treatment with a Chinese herbal formula, Sheng-Mai-San, improves cardiac contractile function in aged rats: the role of Ca (2+) homeostasis. Rejuvenation Res. 2008;11(6):991–1000.CrossRefPubMed
18.
Arafa MH, Mohammad NS, Atteia HH, Abd-Elaziz HR. Protective effect of resveratrol against doxorubicin-induced cardiac toxicity and fibrosis in male experimental rats. J Physiol Biochem. 2014;70(3):701–11.CrossRefPubMed
19.
Wu Z, Chen Q, Ke D, Li G, Deng W. Emodin protects against diabetic cardiomyopathy by regulating the AKT/GSK-3beta signaling pathway in the rat model. Molecules. 2014;19(9):14782–93.CrossRefPubMed
20.
Lin YC, Leu S, Sun CK, Yen CH, Kao YH, Chang LT, et al. Early combined treatment with sildenafil and adipose-derived mesenchymal stem cells preserves heart function in rat dilated cardiomyopathy. J Transl Med. 2010;8:88.PubMedCentralCrossRefPubMed
21.
Wang J, Yuan Z, Zhao H, Ju D, Chen Y, Chen X, et al. Ferulic acid promotes endothelial cells proliferation through up-regulating cyclin D1 and VEGF. J Ethnopharmacol. 2011;137(2):992–7.CrossRefPubMed
22.
Migrino RQ, Aggarwal D, Konorev E, Brahmbhatt T, Bright M, Kalyanaraman B. Early detection of doxorubicin cardiomyopathy using two-dimensional strain echocardiography. Ultrasound Med Biol. 2008;34(2):208–14.PubMedCentralCrossRefPubMed
23.
24.
Horenstein MS, Vander Heide RS, L'Ecuyer TJ. Molecular basis of anthracycline-induced cardiotoxicity and its prevention. Mol Genet Metab. 2000;71(1–2):436–44.CrossRefPubMed
25.
Psaltis PJ, Carbone A, Leong DP, Lau DH, Nelson AJ, Kuchel T, et al. Assessment of myocardial fibrosis by endoventricular electromechanical mapping in experimental nonischemic cardiomyopathy. Int J Cardiovasc Imaging. 2011;27(1):25–37.CrossRefPubMed
26.
Zhou Q, Qin WZ, Liu SB, Kwong JS, Zhou J, Chen J. Shengmai (a traditional Chinese herbal medicine) for heart failure. Cochrane Database Syst Rev. 2014;4:CD005052.PubMed
27.
Zhan S, Fan X, Zhang F, Wang Y, Kang L, Li Z. A proteomic study of Shengmai injection's mechanism on preventing cardiac ischemia-reperfusion injury via energy metabolism modulation. Mol BioSyst. 2015;11(2):540–8.CrossRefPubMed
28.
Zhang YC, Lu BJ, Zhao MH, Rong YZ, Chen RM. Effect of Shengmai injection on vascular endothelial and heart functions in patients with coronary heart disease complicated with diabetes mellitus. Chin J Integr Med. 2008;14(4):281–5.CrossRefPubMed
29.
Imbaby S, Ewais M, Essawy S, Farag N. Cardioprotective effects of curcumin and nebivolol against doxorubicin-induced cardiac toxicity in rats. Hum Exp Toxicol. 2014;33(8):800–13.CrossRefPubMed
30.
Swamy AV, Gulliaya S, Thippeswamy A, Koti BC, Manjula DV. Cardioprotective effect of curcumin against doxorubicin-induced myocardial toxicity in albino rats. Indian J Pharmacol. 2012;44(1):73–7.PubMedCentralCrossRefPubMed
31.
Ertracht O, Liani E, Bachner-Hinenzon N, Bar-Am O, Frolov L, Ovcharenko E, et al. The cardioprotective efficacy of TVP1022 in a rat model of ischaemia/reperfusion. Br J Pharmacol. 2011;163(4):755–69.PubMedCentralCrossRefPubMed
32.
Haubner BJ, Neely GG, Voelkl JG, Damilano F, Kuba K, Imai Y, et al. PI3Kgamma protects from myocardial ischemia and reperfusion injury through a kinase-independent pathway. PLoS One. 2010;5(2):e9350.PubMedCentralCrossRefPubMed
33.
Galeotti L, Strauss DG, Ubachs JF, Pahlm O, Heiberg E. Development of an automated method for display of ischemic myocardium from simulated electrocardiograms. J Electrocardiol. 2009;42(2):204–12.CrossRefPubMed
34.
Hanninen H, Takala P, Rantonen J, Makijarvi M, Virtanen K, Nenonen J, et al. ST-T integral and T-wave amplitude in detection of exercise-induced myocardial ischemia evaluated with body surface potential mapping. J Electrocardiol. 2003;36(2):89–98.CrossRefPubMed
35.
Merino H, Singla DK. Notch-1 mediated cardiac protection following embryonic and induced pluripotent stem cell transplantation in doxorubicin-induced heart failure. PLoS One. 2014;9(7):e101024.PubMedCentralCrossRefPubMed
36.
Unverferth DV, Magorien RD, Unverferth BP, Talley RL, Balcerzak SP, Baba N. Human myocardial morphologic and functional changes in the first 24 hours after doxorubicin administration. Cancer Treatment Rep. 1981;65(11–12):1093–7.
37.
Yan CJ, Li SM, Xiao Q, Liu Y, Hou J, Chen AF, et al. Influence of serum adiponectin level and SNP +45 polymorphism of adiponectin gene on myocardial fibrosis. J Zhejiang Univ Sci B. 2013;14(8):721–8.PubMedCentralCrossRefPubMed
38.
Horslev-Petersen K, Kim KY, Pedersen LR, Bentsen KD, Uldbjerg N, Oxlund H, et al. Serum aminoterminal type III procollagen peptide. Relation to biosynthesis of collagen type III in experimentally induced granulation tissue in rats. APMIS. 1988;96(9):793–804.CrossRefPubMed
39.
Lin YH, Shiau YC, Yen RF, Lin LC, Wu CC, Ho YL, et al. The relation between myocardial cyclic variation of integrated backscatter and serum concentrations of procollagen propeptides in hypertensive patients. Ultrasound Med Biol. 2004;30(7):885–91.CrossRefPubMed
40.
Wang B, Hao J, Jones SC, Yee MS, Roth JC, Dixon IM. Decreased Smad 7 expression contributes to cardiac fibrosis in the infarcted rat heart. Am J Physiol Heart Circ Physiol. 2002;282(5):H1685–1696.CrossRefPubMed
41.
Kawano H, Do YS, Kawano Y, Starnes V, Barr M, Law RE, et al. Angiotensin II has multiple profibrotic effects in human cardiac fibroblasts. Circulation. 2000;101(10):1130–7.CrossRefPubMed
42.
Zhang W, Lavine KJ, Epelman S, Evans SA, Weinheimer CJ, Barger PM, et al. Necrotic myocardial cells release damage-associated molecular patterns that provoke fibroblast activation in vitro and trigger myocardial inflammation and fibrosis in vivo. J Am Heart Assoc. 2015;4(6):e001993.PubMedCentralCrossRefPubMed
43.
Ma Y, Zhang X, Bao H, Mi S, Cai W, Yan H, et al. Toll-like receptor (TLR) 2 and TLR4 differentially regulate doxorubicin induced cardiomyopathy in mice. PLoS One. 2012;7(7):e40763.PubMedCentralCrossRefPubMed
44.
Beutler B, Jiang Z, Georgel P, Crozat K, Croker B, Rutschmann S, et al. Genetic analysis of host resistance: Toll-like receptor signaling and immunity at large. Annu Rev Immunol. 2006;24:353–89.CrossRefPubMed
Metadata
Title
Protective effect of Sheng-Mai Yin, a traditional Chinese preparation, against doxorubicin-induced cardiac toxicity in rats
Authors
Shaojun Ma
Xiaojiang Li
Liang Dong
Jinli Zhu
He Zhang
Yingjie Jia
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2016
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-016-1037-9

Other articles of this Issue 1/2016

BMC Complementary Medicine and Therapies 1/2016 Go to the issue

Research article

An assessment of the impact of herb-drug combinations used by cancer patients

Research article

Antinociceptive effect of methanol extract of Celosia cristata Linn. in mice

Research article

Aqueous extract of Lithospermi radix attenuates oxaliplatin-induced neurotoxicity in both in vitro and in vivo models

Research article

Chalepin: isolated from Ruta angustifolia L. Pers induces mitochondrial mediated apoptosis in lung carcinoma cells

Research article

Mucosal and blood-brain barrier transport kinetics of the plant N-alkylamide spilanthol using in vitro and in vivo models

Research article

Bactericidal and antioxidant properties of essential oils from the fruits Dennettia tripetala G. Baker