Capparis spinosa reduces Doxorubicin-induced cardio-toxicity in cardiomyoblast cells

Document Type : Short communication


1 Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Pharmacology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


Objective: Doxorubicin (DOX) is an effective anticancer drug but its clinical application is limited because it induces apoptosis in cardiomyocytes and leads to permanent degenerative cardiomyopathy and heart failure possibly due to oxidative stress. Recent studies showed that Capparis spinosa (C. spinose)exhibits potent antioxidant activity. So, in this study, we explored the protective effect of hydro-alcoholic extract of C. spinosa against DOX-induced cytotoxicity in H9c2 cells.
Materials and Methods: Cell viability was quantified by MTT assay. Apoptotic cells were determined using flow cytometry (sub-G1 peak) evaluation of DNA fragmentation following PI staining. Cells were cultured with 5 μM DOX for 24 hr to induce cell damage. H9c2 cells were pretreated with different concentrations (6-200 μg/ml) of C. spinosa extract for 4 hr before DOX treatment in all trials.
Results:  Pretreatment with 25, 50, 100 and 200 µg/ml of C. spinosa could increase the viability of H9C2 cells to 72.63 ± 2.8% (p< 0.05), 77.37 ± 1.8% (p< 0.05), 83.56 ± 2.6% (p< 0.001) and 90.9 ± 0.5% (p< 0.001) of control, respectively. Also, C. spinosa decreased apoptotic induction significantly, at the doses of 50 µg/ml (p<0.05), 100 µg/ml (p<0.01) and 200 µg/ml (p<0.001)
Conclusion: Our results showed that C. spinosa could exert cardioprotective effects against DOX-induced toxicity that might be mediated via its antioxidant activity.


Main Subjects

Aghel N, Rashidi I, Mombeini A. 2007. Hepatoprotective activity of Capparis spinosa root bark against CCl4 induced hepatic damage in mice. Iranian J Pharm Res, 4: 285-90.
Al-Assady AAB. 2007. Cytotoxic and cytogenetic effect of Capparis spinosa extract on tumor cell lines in vitro and in vivo. Ph.D. thesis. College of Education. University Of Duhok.Duhok,Iraq.
Argentieri M, Macchia F, Papadia P, Fanizzi FP, Avato P. 2012. Bioactive compounds from Capparis spinosa subsp. Rupestris. Ind Crop Prod, 36: 65–69.
Bakhtiari E, Hosseini A, Mousavi SH.2015. Protective effect of Hibiscus sabdariffa against serum/glucosedeprivation-induced PC12 cells injury. Avicenna J Phytomed, 5: 231-237.
Boga C, Forlani L, Calienni R. 2011. On the antibacterial activity of roots of Capparis spinosa L. Nat Prod Res, 4: 417-21.
Bryant J, Picot J, Levitt G, Sullivan I, Baxter L, Clegg A. 2007. Cardioprotection against the toxic effects of anthracyclines given to children with cancer: a systematic review.  Health Technol Assess, 11:1-84.
Eddouks  M,  Lemhadri  A,  Michel  J  B.  2004. Caraway  and  caper:Potential  anti-hyperglycaemic  plants  in  diabetic  rats.  J  Ethnopharmacol, 94: 143–148.
Eddouks M, Lemhadri A, Michel JB. 2005.Hypolipidemic activity of aqueous  extract  of  Capparis spinosa L. in normal and diabetic rats. J Ethnopharmacol, 98: 345–350.
Feng X, Lu J, Xin H, Zhang L, Wang Y, Tang K. 2011. Anti-arthritic active  fraction  of  Capparis spinosa  L.  fruits and  its  chemical constituents.  YakugakuZasshi  J Pharmaceut Soc  Japan, 131:423–429.
Hosseini A, Ghorbani A, Sadeghnia HR, Rajabian A and Rakhshandeh H. 2014. Potentiating effects of Lactuca serriola on pentobarbital-induced sleep. Res Opin Anim Vet Sci, 4: 601-07.
Hosseini A, Shafiee-Nick R, Mousavi SH. 2014. Combination of Nigella sativa with Glycyrrhiza glabra and Zingiber officinale augments their protective effects on doxorubicin-induced toxicity in h9c2 cells. Iran J Basic Med Sci, 17: 993-1000.
Huseini HF, Hasani-Rnjbar S, Nayebi N. 2013. Capparis spinosa L. (Caper) fruit extract in treatment of type 2 diabetic patients:  a randomized double-blind placebo-controlled clinical trial. Complement Ther Med, 5: 447-52.
Issac Abraham SV,Palani A, Ramaswamy BR. 2011. Antiquorum sensing and antibiofilm potential of Capparis spinosa. Arch Med Res, 8: 658-68.
Kang YJ, Chen Y, Epstein PN. 1996. Suppression of doxorubicin cardiotoxicity by overexpression of catalase in the heart of transgenic mice. J Biol Chem, 271: 12610-12616.
Lam SK, Han QFand Ng TB. 2009. Isolation and characterization of a lectin with potentially exploitable activities from caper (Capparis spinosa) seeds. J Art, 29:293-299. 
Lemhadri A,  Eddouks  M,  Sulpice  T,    Burcelin  R.  2007. Anti-hyperglycaemic  and  anti-obesity  effects  of  Capparis spinosa and Chamaemelumnobile  aqueous  extracts  in  HFD  mice.  Am J Pharmacol Toxicol, 2: 106-110.
Li H, Horke S, Forstermann U. 2013. Oxidative stress in vascular disease and its pharmacological prevention. Trends in Pharmacol Sci, 34: 313-319.
Panico  AM  ,  Cardileb  T  V,  Garufia    F,  Pugliaa  C,  Bonina  F, Ronsisvalle G. 2005. Protective effect of Capparis spinosa on chondrocytes Life Sciences, 77: 2479–2488.
Rashedi H, Amiri H, Gharezi A.2015.Assessment of phytochemical and antioxidant properties of the Capparis spinosa L. in Khuzestan province. J Qazvin Univ Med Sci, 18: 11-17.
Sheng R, Gu ZL, Xie ML, Zhou WX, Guo CY. 2010. Epigallocatechingallate protects H9c2 cardiomyoblasts against hydrogen dioxides-induced apoptosis and telomere attrition. Eur J Pharmacol,641: 199-206.
Siracusa L, Kulisic-Bilusic T, Politeo O. 2011.Phenoliccomposition and antioxidant activity of aqueous infusions from Capparis spinosa L. and Crithmummaritimum L. before and after submission to a two-step in vitro digestion model. J Agric Food Chem, 23: 12453-9.
Takemura G, Fujiwara H. 2007.Doxorubicin-induced cardiomyopathy from Cardiotoxic mechanisms to management. Prog Cardiovasc Dis, 49: 330–52.
Tesriere L, Butera D, Gentile C, Livrea MA. 2007. Bioactive Components of Caper (Capparis spinosa L.) from Sicily and Antioxidant Effects in a Red Meat Simulated Gastric Digestion. J Agric Food Chem, 55: 8465–8471.
Tlili N, Khaldi A, Triki S. 2010. Phenolic compounds and vitamin antioxidants of caper (Capparis spinosa).Plant Foods Human Nutr, 3: 260-5.
Winstead MW, Lucas KK, Dennis EA. 2005. Group IV cytosolic phospholipase A2 mediates arachidonic acid release in H9c2 rat cardiomyocyte cells in response to hydrogen peroxide. Prostaglandins Other Lipid Mediat, 78: 55-66.
Wu  S,  Ko  YS,  Teng  MS,  Ko  YL,  Hsu  LA,  Hsueh  C. 2002. Adriamycin-induced    cardiomyocyte    and endothelial cell apoptosis:  In vitro and in vivo studies.  J  Mol  Cell Cardiol, 34:1595–1607.
Wu JH, Chang FR, Hayashi KI. 2003. Antitumor Agents. Part 218: Cappamensin A, a new in vitro anticancer principle, from C. sikkimensisy. Bioorg Med Chem Lett, 13: 2223-5.
YuJI, Mo K, Wang and Zou Xiang .2008. Study on inhibitory effect by total alkaloids in Capparis spinosa on SGC-7901 in vitro. J Shenyang Pharm Univ, 25: 74-75.
Yu-Bin J, Lei Y. 2014.N-Butanol Extract of Capparis spinosa L. Induces Apoptosis Primarily through a Mitochondrial Pathway Involving mPTP Open, Cytochrome C Release and Caspase Activation. Asian Pac J Cancer Prev, 15: 9153-9157.