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 1/2018

Open Access 01-12-2018 | Research article

The protective effect of Er-Xian decoction against myocardial injury in menopausal rat model

Authors: Zhiguo Zhang, Lihua Xiang, Lanping Zhao, Hong Jiao, Zhen Wang, Yubo Li, Yanjing Chen

Published in: BMC Complementary Medicine and Therapies | Issue 1/2018

Login to get access

Abstract

Background

Er-Xian decoction (EXD), a formula of Chinese medicine, is often used to treat menopausal syndrome in China. The aim of the present study was to explore the potential cardioprotective mechanism of EXD against myocardial injury in an ovariectomy-induced menopausal rat model.

Methods

We divided the female Wistar rats into ovariectomy group and sham operation group (SHAM group). The ovariectomized (OVX) rats received treatment of vehicle (OVX group), EXD (EXD group) or 17β-estradiol (E2 group). After 12-week of treatment, the level of estradiol in serum was detected using an electrochemiluminescence immunoassay, and electrophysiologic changes in myocardial action potentials (AP) were evaluated using intracellular microelectrode technique. Changes in the histopathology of the left ventricle and the ultrastructure of the cardiomyocytes were observed by hematoxylin and eosin (HE) staining and transmission electronmicroscopy to assess myocardial injury. Microarrays were applied for the evaluation of gene expression profiles in ventricular muscle of the OVX and EXD rats. Further pathway analyses of the differential expression genes were carried out using the Kyoto Encyclopedia of Genes and Genomes (KEGG). And real-time quantitative RT-PCR (qRT-PCR) was used for verification of the key findings.

Results

The results from electrophysiological and histomorphological observations demonstrated that EXD had a substantial myocardial protective effect. The EXD-treated rats, in comparison with the OVX rats, demonstrated up-regulated expression of 28 genes yet down-regulated expression of 157 genes in the ventricular muscle. The qRT-PCR assay validated all selected differential expression genes. The KEGG pathway analysis showed that the down-regulated genes were relevant to cardiomyopathy and myocardial contractility. EXD could decrease the mRNA expressions of cardiac myosin (Myh7, Myl2) and integrin (Itgb5) in the ventricular myocardium.

Conclusion

EXD had a protective effect against myocardial injury in OVX rats, and this cardioprotective effect may be associated with modulation of the expression of cardiac myosin or integrin at the mRNA level.
Appendix
Available only for authorised users
Literature
1.
Dogan U, Dogan NU, Basarir AO, Yildirim S, Celik C, Incesu F, Ozdemir K. P-wave parameters and cardiac repolarization indices: does menopausal status matter? J Cardiol. 2012;60:333–7.CrossRefPubMed
2.
Schillaci G, Verdecchia P, Borgioni C, Ciucci A, Porcellati C. Early cardiac changes after menopause. Hypertension. 1998;32:764–9.CrossRefPubMed
3.
Hinderliter AL, Sherwood A, Blumenthal JA, Light KC, Girdler SS, McFetridge J, Johnson K, Waugh R. Changes in hemodynamics and left ventricular structure after menopause. Am J Cardiol. 2002;89:830–3.CrossRefPubMed
4.
Matthews KA, Meilahn E, Kuller LH, Kelsey SF, Caggiula AW, Wing RR. Menopause and risk factors for coronary heart disease. N Engl J Med. 1989;321:641–6.CrossRefPubMed
5.
Bonithon-Kopp C, Scarabin PY, Darne B, Malmejac A, Guize L. Menopause-related changes in lipoproteins and some other cardiovascular risk factors. Int J Epidemiol. 1990;19:42–8.CrossRefPubMed
6.
Chien CL, Wu YW, Yang WS, Yang PC, Su HM, Wu YT. Myocardial perfusion image in asymptomatic postmenopausal women with physical inactivity and overweight. Obesity facts. 2011;4:372–8.CrossRefPubMed
7.
8.
Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med. 1999;340:1801–11.CrossRefPubMed
9.
Grodstein F, Manson JE, Colditz GA, Willett WC, Speizer FE, Stampfer MJ. A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease. Ann Intern Med. 2000;133:933–41.CrossRefPubMed
10.
Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The postmenopausal estrogen/progestin interventions (PEPI) trial. The writing group for the PEPI trial. JAMA. 1995;273:199–208.CrossRefPubMed
11.
Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and estrogen/progestin replacement study (HERS) research group. JAMA. 1998;280:605–13.CrossRefPubMed
12.
Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288:321–33.CrossRefPubMed
13.
Cushman M, Kuller LH, Prentice R, Rodabough RJ, Psaty BM, Stafford RS, Sidney S, Rosendaal FR. Women's Health Initiative I. Estrogen plus progestin and risk of venous thrombosis. JAMA. 2004;292:1573–80.CrossRefPubMed
14.
Hsia J, Criqui MH, Rodabough RJ, Langer RD, Resnick HE, Phillips LS, Allison M, Bonds DE, Masaki K, Caralis P, et al. Estrogen plus progestin and the risk of peripheral arterial disease: the Women's Health Initiative. Circulation. 2004;109:620–6.CrossRefPubMed
15.
Federici LM, Roth SD, Krier C, Fitz SD, Skaar T, Shekhar A, Carpenter JS, Johnson PL. Anxiogenic CO2 stimulus elicits exacerbated hot flash-like responses in a rat menopause model and hot flashes in postmenopausal women. Menopause. 2016;23:1257–66.CrossRefPubMedPubMedCentral
16.
Minami A, Matsushita H, Ieno D, Matsuda Y, Horii Y, Ishii A, Takahashi T, Kanazawa H, Wakatsuki A, Suzuki T. Improvement of neurological disorders in postmenopausal model rats by administration of royal jelly. Climacteric. 2016;19:568–73.CrossRefPubMed
17.
Tang Z, Wang Y, Zhu X, Ni X, Lu J. Exercise increases cystathionine-gamma-lyase expression and decreases the status of oxidative stress in myocardium of Ovariectomized rats. Int Heart J. 2016;57:96–103.CrossRefPubMed
18.
Irigoyen MC, Paulini J, Flores LJ, Flues K, Bertagnolli M, Moreira ED, Consolim-Colombo F, Bello-Klein A, De Angelis K. Exercise training improves baroreflex sensitivity associated with oxidative stress reduction in ovariectomized rats. Hypertension. 2005;46:998–1003.CrossRefPubMed
19.
Hamilton KL, Lin L, Wang Y, Knowlton AA. Effect of ovariectomy on cardiac gene expression: inflammation and changes in SOCS gene expression. Physiol Genomics. 2008;32:254–63.CrossRefPubMed
20.
Zhu X, Tang Z, Cong B, Du J, Wang C, Wang L, Ni X, Lu J. Estrogens increase cystathionine-gamma-lyase expression and decrease inflammation and oxidative stress in the myocardium of ovariectomized rats. Menopause. 2013;20:1084–91.CrossRefPubMed
21.
Campos C, Casali KR, Baraldi D, Conzatti A, Araujo AS, Khaper N, Llesuy S, Rigatto K, Bello-Klein A. Efficacy of a low dose of estrogen on antioxidant defenses and heart rate variability. Oxidative Med Cell Longev. 2014;2014:218749.CrossRef
22.
Zhong LL, Tong Y, Tang GW, Zhang ZJ, Choi WK, Cheng KL, Sze SC, Wai K, Liu Q, Yu BX. A randomized, double-blind, controlled trial of a Chinese herbal formula (Er-Xian decoction) for menopausal symptoms in Hong Kong perimenopausal women. Menopause. 2013;20:767–76.CrossRefPubMed
23.
Wang SW, Cheung HP, Tong Y, Lu J, Ng TB, Zhang YB, Zhang ZJ, Lee KF, Lam JK, Sze SC. Steroidogenic effect of Erxian decoction for relieving menopause via the p-Akt/PKB pathway in vitro and in vivo. J Ethnopharmacol. 2017;195:188–95.
24.
Sze SC, Tong Y, Zhang YB, Zhang ZJ, Lau AS, Wong HK, Tsang KW, Ng TB. A novel mechanism: Erxian decoction, a Chinese medicine formula, for relieving menopausal syndrome. J Ethnopharmacol. 2009;123:27–33.CrossRefPubMed
25.
Zhang ZG, Bai D, Liu MJ, Li Y, Pan JH, Liu H, Wang WL, Xiang LH, Xiao GG, Ju DH. Therapeutic effect of aqueous extract from Ecliptae herba on bone metabolism of ovariectomized rats. Menopause. 2013;20:232–40.PubMed
26.
27.
Lee A, Pickham D. Basic cardiac electrophysiology and common drug-induced arrhythmias. Crit Care Nurs Clin North Am. 2016;28:357–71.CrossRefPubMed
28.
Liu J, Laksman Z, Backx PH. The electrophysiological development of cardiomyocytes. Adv Drug Deliv Rev. 2016;96:253–73.CrossRefPubMed
29.
El Gebeily G, El Khoury N, Mathieu S, Brouillette J, Fiset C. Estrogen regulation of the transient outward K(+) current involves estrogen receptor alpha in mouse heart. J Mol Cell Cardiol. 2015;86:85–94.CrossRefPubMed
30.
Tanabe S, Hata T, Hiraoka M. Effects of estrogen on action potential and membrane currents in Guinea pig ventricular myocytes. Am J Phys. 1999;277:H826–33.
31.
Turdi S, Huff AF, Pang J, He EY, Chen X, Wang S, Chen Y, Zhang Y, Ren J. 17-beta estradiol attenuates ovariectomy-induced changes in cardiomyocyte contractile function via activation of AMP-activated protein kinase. Toxicol Lett. 2015;232:253–62.CrossRefPubMed
32.
Wong KC, Lee KS, Luk HK, Wan HY, Ho CK, Zhang Y, Wong MS. Er-xian decoction exerts estrogen-like osteoprotective effects in vivo and in vitro. Am J Chin Med. 2014;42:409–26.CrossRefPubMed
33.
Huang CY, Lin YY, Hsu CC, Cheng SM, Shyu WC, Ting H, Yang AL, Ho TJ, Lee SD. Antiapoptotic effect of exercise training on ovariectomized rat hearts. J Appl Physiol. 2016;121:457–65.CrossRefPubMed
34.
Rattanasopa C, Phungphong S, Wattanapermpool J, Bupha-Intr T. Significant role of estrogen in maintaining cardiac mitochondrial functions. J Steroid Biochem Mol Biol. 2015;147:1–9.CrossRefPubMed
35.
Jessup JA, Wang H, MacNamara LM, Presley TD, Kim-Shapiro DB, Zhang L, Chen AF, Groban L. Estrogen therapy, independent of timing, improves cardiac structure and function in oophorectomized mRen2.Lewis rats. Menopause. 2013;20:860–8.CrossRefPubMedPubMedCentral
36.
Ueyama T, Ishikura F, Matsuda A, Asanuma T, Ueda K, Ichinose M, Kasamatsu K, Hano T, Akasaka T, Tsuruo Y, et al. Chronic estrogen supplementation following ovariectomy improves the emotional stress-induced cardiovascular responses by indirect action on the nervous system and by direct action on the heart. Circ J. 2007;71:565–73.CrossRefPubMed
37.
Rayment I, Holden HM, Whittaker M, Yohn CB, Lorenz M, Holmes KC, Milligan RA. Structure of the actin-myosin complex and its implications for muscle contraction. Science. 1993;261:58–65.CrossRefPubMed
38.
Yamauchi-Takihara K, Sole MJ, Liew J, Ing D, Liew CC. Characterization of human cardiac myosin heavy chain genes. Proc Natl Acad Sci U S A. 1989;86:3504–8.CrossRefPubMedPubMedCentral
39.
40.
Kararigas G, Bito V, Tinel H, Becher E, Baczko I, Knosalla C, Albrecht-Kupper B, Sipido KR, Regitz-Zagrosek V. Transcriptome characterization of estrogen-treated human myocardium identifies myosin regulatory light chain interacting protein as a sex-specific element influencing contractile function. J Am Coll Cardiol. 2012;59:410–7.CrossRefPubMed
41.
Pandit S, Woranush W, Wattanapermpool J, Bupha-Intr T. Significant role of female sex hormones in cardiac myofilament activation in angiotensin II-mediated hypertensive rats. J Physiol Sci. 2014;64:269–77.CrossRefPubMed
42.
Thawornkaiwong A, Pantharanontaga J, Wattanapermpool J. Hypersensitivity of myofilament response to Ca2+ in association with maladaptation of estrogen-deficient heart under diabetes complication. Am J Physiol Regul Integr Comp Physiol. 2007;292:R844–51.CrossRefPubMed
43.
Schwab K, Stein R, Scheler C, Theuring F. Dietary genistein enhances phosphorylation of regulatory myosin light chain in the myocardium of ovariectomized mice. Electrophoresis. 2012;33:1795–803.CrossRefPubMed
44.
Duft K, Schanz M, Pham H, Abdelwahab A, Schriever C, Kararigas G, Dworatzek E, Davidson MM, Regitz-Zagrosek V, Morano I, et al. 17beta-estradiol-induced interaction of estrogen receptor alpha and human atrial essential myosin light chain modulates cardiac contractile function. Basic Res Cardiol. 2017;112:1.CrossRefPubMed
45.
Bupha-Intr T, Wattanapermpool J. Cardioprotective effects of exercise training on myofilament calcium activation in ovariectomized rats. J Appl Physiol. 2004;96:1755–60.CrossRefPubMed
46.
Patten RD, Pourati I, Aronovitz MJ, Alsheikh-Ali A, Eder S, Force T, Mendelsohn ME, Karas RH. 17 Beta-estradiol differentially affects left ventricular and cardiomyocyte hypertrophy following myocardial infarction and pressure overload. J Card Fail. 2008;14:245–53.CrossRefPubMedPubMedCentral
47.
48.
49.
50.
51.
Chen C, Li R, Ross RS, Manso AM. Integrins and integrin-related proteins in cardiac fibrosis. J Mol Cell Cardiol. 2016;93:162–74.CrossRefPubMed
Metadata
Title
The protective effect of Er-Xian decoction against myocardial injury in menopausal rat model
Authors
Zhiguo Zhang
Lihua Xiang
Lanping Zhao
Hong Jiao
Zhen Wang
Yubo Li
Yanjing Chen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2018
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-018-2311-9

Other articles of this Issue 1/2018

BMC Complementary Medicine and Therapies 1/2018 Go to the issue

Research article

The health impact of residential retreats: a systematic review

Research article

Placebo by proxy expectations toward acupuncture change over time: a survey comparing parental expectations to acupuncture pre- and postoperatively

Research article

Steroidal alkaloids and conessine from the medicinal plant Holarrhena antidysenterica restore antibiotic efficacy in a Galleria mellonella model of multidrug-resistant Pseudomonas aeruginosa infection

Research article

Propolis improves pregnancy outcomes and placental oxidative stress status in streptozotocin-induced diabetic rats

Research article

Hand-foot-mouth disease and use of steroids, intravenous immunoglobulin, and traditional Chinese herbs in a tertiary hospital in Shantou, China

Research article

Associations between the use of herbal medicines and adverse pregnancy outcomes in rural Malawi: a secondary analysis of randomised controlled trial data