Curcumin reduces cardiac fibrosis by inhibiting myofibroblast differentiation and decreasing transforming growth factor β1 and matrix metalloproteinase 9 / tissue inhibitor of metalloproteinase 1

Jin Ma; Shi-yu Ma; Chun-hua Ding

doi:10.1007/s11655-015-2159-5

Your Location：

Home >

Browse articles >

Curcumin reduces cardiac fibrosis by inhibiting myofibroblast differentiation and decreasing transforming growth factor β1 and matrix metalloproteinase 9 / tissue inhibitor of metalloproteinase 1

Updated：2021-08-27

- Curcumin reduces cardiac fibrosis by inhibiting myofibroblast differentiation and decreasing transforming growth factor β1 and matrix metalloproteinase 9 / tissue inhibitor of metalloproteinase 1
- Chinese Journal of Integrative Medicine Vol. 23, Issue 5, Pages: 362-369(2017)
- Affiliations：
  
  1. Cardiac Electrophysiology Research Lab, Guangdong Provincial Academy of Chinese Medical Sciences,Guangzhou,China
  2. Department of Critical Care Medicine, Guangdong Provincial Hospital of Chinese Medicine,Guangzhou,China
  3. Arrhythmia Center, Guangdong Provincial Hospital of Chinese Medicine,Guangzhou,China
- Author bio：
- Funds：
- DOI：10.1007/s11655-015-2159-5
  CLC：
- Published：2017，
  
  Published Online：8 March 2016，
Scan for full text
Ma, J., Ma, Sy. & Ding, Ch. Curcumin reduces cardiac fibrosis by inhibiting myofibroblast differentiation and decreasing transforming growth factor β1 and matrix metalloproteinase 9 / tissue inhibitor of metalloproteinase 1., Chin. J. Integr. Med. 23, 362–369 (2017). https://doi.org/10.1007/s11655-015-2159-5

Jin Ma, Shi-yu Ma, Chun-hua Ding. Curcumin reduces cardiac fibrosis by inhibiting myofibroblast differentiation and decreasing transforming growth factor β1 and matrix metalloproteinase 9 / tissue inhibitor of metalloproteinase 1. [J]. Chinese Journal of Integrative Medicine 23(5):362-369(2017)
Ma, J., Ma, Sy. & Ding, Ch. Curcumin reduces cardiac fibrosis by inhibiting myofibroblast differentiation and decreasing transforming growth factor β1 and matrix metalloproteinase 9 / tissue inhibitor of metalloproteinase 1., Chin. J. Integr. Med. 23, 362–369 (2017). https://doi.org/10.1007/s11655-015-2159-5 DOI：

Jin Ma, Shi-yu Ma, Chun-hua Ding. Curcumin reduces cardiac fibrosis by inhibiting myofibroblast differentiation and decreasing transforming growth factor β1 and matrix metalloproteinase 9 / tissue inhibitor of metalloproteinase 1. [J]. Chinese Journal of Integrative Medicine 23(5):362-369(2017) DOI： 10.1007/s11655-015-2159-5.

摘要

To study the effect of curcumin on fibroblasts in rats with cardiac fibrosis. The rats were randomly divided into 4 groups (n=12 in each group): the normal control

isoproterenol (ISO)

ISO combined with low-dose curcumin (ISO+Cur-L)

and ISO combined with high-dose curcumin (ISO+Cur-H) groups. ISO+Cur-L and ISO+Cur-H groups were treated with curcumin (150 or 300 mg•kg-1•day-1) for 28 days. The primary culture of rat cardiac fibroblast was processed by trypsin digestion method in vitro. The 3rd to 5th generation were used for experiment. Western blot method was used to test the expression of collagen type I/III

α-smooth muscle actin (α-SMA)

transforming growth factor (TGF)-β1

matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1. 3-(4

5-Dimethylthiazol-2-yl)-2

5-diphenyltetrazolium bromide (MTT) assay was applied to test the proliferation of fibroblast. Curcumin significantly decreased interstitial and perivascular myocardial collagen deposition and cardiac weight index with reducing protein expression of collagen type I/III in hearts (P<0.05). In addition

curcumin directly inhibited angiotensin (Ang) II-induced fibroblast proliferation and collagen type I/III expression in cardiac fibroblasts (P<0.05). Curcumin also inhibited fibrosis by inhibiting myofibroblast differentiation

decreased TGF-β1

MMP-9 and TIMP-1 expression (P<0.05) but had no effects on Smad3 in Ang II incubated cardiac fibroblasts. Curcumin reduces cardiac fibrosis in rats and Ang II-induced fibroblast proliferation by inhibiting myofibroblast differentiation

decreasing collagen synthesis and accelerating collagen degradation through reduction of TGF-β1

MMPs/TIMPs. The present findings also provided novel insights into the role of curcumin as an antifibrotic agent for the treatment of cardiac fibrosis.

Abstract

To study the effect of curcumin on fibroblasts in rats with cardiac fibrosis. The rats were randomly divided into 4 groups (n=12 in each group): the normal control

isoproterenol (ISO)

ISO combined with low-dose curcumin (ISO+Cur-L)

α-smooth muscle actin (α-SMA)

transforming growth factor (TGF)-β1

matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1. 3-(4

5-Dimethylthiazol-2-yl)-2

decreased TGF-β1

decreasing collagen synthesis and accelerating collagen degradation through reduction of TGF-β1

MMPs/TIMPs. The present findings also provided novel insights into the role of curcumin as an antifibrotic agent for the treatment of cardiac fibrosis.

关键词

Curcuminfibrosismyofibroblasttransforming growth factormatrix metalloproteinase

Keywords

Curcuminfibrosismyofibroblasttransforming growth factormatrix metalloproteinase

references

Cohn JN, Ferrari R, Sharpe N. Cardiac remodelingconcepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol 2000;35:569–582.

Dobaczewski M, Frangogiannis NG. Chemokines and cardiac fibrosis. Front Biosci (Schol ed) 2009;1:391–405.

Biernacka A, Frangogiannis NG. Aging and cardiac fibrosis. Aging Dis 2011;2:158–173.

Krenning G, Zeisberg EM, Kalluri R. The origin of fibroblasts and mechanism of cardiac fibrosis. J Cell Physiol 2010;225:631–637.

Spach MS, Boineau JP. Microfibrosis produces electrical load variations due to loss of side-to-side cell connections: a major mechanism of structural heart disease arrhythmias. Pacing Clin Electrophysio 1997;20:397–413.

Kehat I, Molkentin JD. Molecular pathways underlying cardiac remodeling during pathophysiological stimulation. Circulation 2010;122:2727–2235.

Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat ML, Gabbiani G. The myofibroblast: one function, multiple origins. Am J Pathol 2007;170:1807–1816.

Rosenkranz S. TGF-beta1 and angiotensin networking in cardiac remodeling. Cardiovasc Res 2004;63:423–432.

Li YY, McTiernan CF, Feldman AM. Interplay of matrix metalloproteinases, tissue inhibitors of metalloproteinases and their regulators in cardiac matrix remodeling. Cardiovasc Res 2000;46:214–224.

Nguyen DT, Ding C, Wilson E, Marcus GM, Olgin JE. Pirfenidone mitigates left ventricular fibrosis and dysfunction after myocardial infarction and reduces arrhythmias. Heart Rhythm 2010;7:1438–1445.

Noorafshan A, Ashkani-Esfahani S. A review of therapeutic effects of curcumin. Curr Pharm Des 2013;19:2032–2046.

Zhang Z, Guo Y, Zhang S, Zhang Y, Wang Y, Ni W, et al. Curcumin modulates cannabinoid receptors in liver fibrosis in vivo and inhibits extracellular matrix expression in hepatic stellate cells by suppressing cannabinoid receptor type-1 in vitro. Eur J Pharmacol 2013;721:133–140.

Pan Y, Wang Y, Cai L, Cai Y, Hu J, Yu C, et al. Inhibition of high glucose-induced inflammatory response and macrophage infiltration by a novel curcumin derivative prevents renal injury in diabetic rats. Br J Pharmacol 2012;166:1169–1182.

Bai J, Zhang N, Hua Y, Wang B, Ling L, Ferro A, et al. Metformin inhibits angiotensin II-induced differentiation of cardiac fibroblasts into myofibroblasts. PLoS One 2013;8:e72120.

Wei LH, Huang XR, Zhang Y, Li YQ, Chen HY, Heuchel R, et al. Deficiency of Smad7 enhances cardiac remodeling induced by angiotensin II infusion in a mouse model of hypertension. PloS One 2013;8:e70195.

Wang NP, Wang ZF, Tootle S, Philip T, Zhao ZQ. Curcumin promotes cardiac repair and ameliorates cardiac dysfunction following myocardial infarction. Br J Pharmacol 2012;167:1550–1562.

Li J, Shao ZH, Xie JT, Wang CZ, Ramachandran S, Yin JJ, et al. The effects of ginsenoside Rb1 on JNK in oxidative injury in cardiomyocytes. Arch Pharm Res 2012;35:1259–1267.

Cheng H, Liu W, Ai X. Protective effect of curcumin on myocardial ischemia reperfusion injury in rats. China J Chin Mater Med (Chin) 2005;28:920–922.

Yang X, Thomas DP, Zhang X, Culver BW, Alexander BM, Murdoch WJ, et al. Curcumin inhibits plateletderived growth factor-stimulated vascular smooth muscle cell function and injury-induced neointima formation. Arterioscler Thromb Vasc Biol 2006;26:85–90.

Soetikno V, Sari FR, Lakshmanan AP, Arumugam S, Harima M, Suzuki K, et al. Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2-keap1 pathway. Mol Nutr Food Res 2013;57:1649–1659.

Ma S, Yang D, Wang K, Tang B, Li D, Yang Y. Cryptotanshinone attenuates isoprenaline-induced cardiac fibrosis in mice associated with upregulation and activation of matrix metalloproteinase-2. Mol Med Rep 2012;6:145–150.

Jaiswal A, Kumar S, Seth S, Dinda AK, Maulik SK. Effect of U50,488H, a j-opioid receptor agonist on myocardial. a-and b-myosin heavy chain expression and oxidative stress associated with isoproterenol-induced cardiac hypertrophy in rat. Mol Cell Biochemi 2010;345:231–240.

Swaney JS, Roth DM, Olson ER, Naugle JE, Meszaros JG, Insel PA. Inhibition of cardiac myofibroblast formation and collagen synthesis by activation and overexpression of adenylyl cyclase. Proc Natl Acad Sci U S A 2005;102:437–442.

Lijnen PJ, Petrov VV, Fagard RH. Induction of cardiac fibrosis by angiotensin II. Methods Find Exp Clin Pharmacol 2000;22:709–723.

Fujita K, Maeda N, Sonoda M, Ohashi K, Hibuse T, Nishizawa H, et al. Adiponectin protects against angiotensin II-induced cardiac fibrosis through activation of PPARalpha. Arterioscler Thromb Vasc Biol 2008;28:863–870.

Zhou L, Shao Y, Huang Y, Yao T, Lu LM. 17Beta-estradiol inhibits angiotensin II-induced collagen synthesis of cultured rat cardiac fibroblasts via modulating angiotensin II receptors. Eur J Pharmacol 2007;567:186–192.

Xu X, Ding F, Pang J, Gao X, Xu RK, Hao W, et al. Chronic administration of hexarelin attenuates cardiac fibrosis in the spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol 2012;303:H703–H711.

Gay-Jordi G, Guash E, Benito B, Brugada J, Nattel S, Mont L, et al. Losartan prevents heart fibrosis induced by longterm intensive exercise in an animal model. PLoS One 2013;8:e55427.

Wu Q, Peng Y, Meng Q, Cui H, Wang X. Effects of salviandic acid B (SA-B) on activity of basement membranetype collagenase and impact of regulatory factors in rats with cardiac hypertrophy. China J Chin Meter Med (Chin) 2011;36:2388–2392.

FULL TEXT LINK

More>

Views

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

Effects of herbal compound 861 on collagen synthesis and degradation in rat mesangial cells exposed to high glucose

Effects of curcumin on pain threshold and on the expression of nuclear factor κ B and CX3C receptor 1 after sciatic nerve chronic constrictive injury in rats

Integrative oncology meets immunotherapy: New prospects for combination therapy grounded in Eastern medical knowledge

The theory of homogeny of liver and kidney in the treatment of kidney and liver fibrosis

In Vitro antimetastatic effect of Changweiqing (肠胃清) through antiinvasion of hypoxic colorectal carcinoma LoVo cells

Related Author

No data

Related Institution

Department of Gerontology, Beijing Friendship Hospital, Capital Medical University

Department of Anesthesiology, The Second Affiliated Hospital of Wenzhou Medical College

Department of Epidemiology, Mailman School of Public Health, Columbia University

Nuffield Department of Medicine and Department of Primary Health Care, University of Oxford

Global Initiative for Traditional Systems (GIFTS) of Health

Address：1 Caochang, xiyuan, Beijing, People's Republic of China Postal code：100091
Tel：010-62886827, 62877592 Fax：010-62874291
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备05067934号-1 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰