Journal of Pharmacopuncture (대한약침학회지)

KOREAN PHARMACOPUNCTURE INSTITUTE (대한약침학회)
권호 표지
DOI QR코드

DOI QR Code

Reversal of Doxorubicin-induced Cardiotoxicity by Using Phytotherapy: A Review

  • Hosseini, Azar (Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences) ;
  • Sahebkar, Amirhossein (Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences)
  • Received : 2017.08.22
  • Accepted : 2017.11.09
  • Published : 2017.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Doxorubicin as a chemotherapeutic drug is widely used for the treatment of patients with cancer. However, clinical use of this drug is hampered by its cardiotoxicity, which is manifested as electrocardiographic abnormalities, arrhythmias, irreversible degenerative cardiomyopathy and congestive heart failure. The precise mechanisms underlying the cardiotoxicity of doxorubicin are not clear, but impairment of calcium homeostasis, generation of iron complexes, production of oxygen radicals, mitochondrial dysfunction and cell membrane damage have been suggested as potential etiologic factors. Compounds that can neutralize the toxic effect of doxorubicin on cardiac cells without reducing the drug's antitumor activity are needed. In recent years, numerous studies have shown that herbal medicines and bioactive phytochemicals can serve as effective add-on therapies to reduce the cardiotoxic effects of doxorubicin. This review describes different phytochemicals and herbal products that have been shown to counterbalance doxorubicin-induced cardiotoxicity.

Keywords

References

  1. Danesi R, Fogli S, Gennari A, Conte P, Del Tacca M. Pharmacokinetic-pharmacodynamic relationships of the anthracycline anticancer drugs. Clin Pharmacokinet. 2002;41(6):431-44. https://doi.org/10.2165/00003088-200241060-00004
  2. Wouters KA, Kremer L, Miller TL, Herman EH, Lipshultz SE. Protecting against anthracycline-induced myocardial damage: a review of the most promising strategies. Br J Haematol. 2005;131(5):561-78. https://doi.org/10.1111/j.1365-2141.2005.05759.x
  3. Lenneman AJ, Wang L, Wigger M, Frangoul H, Harrell FE, Silverstein C, et al. Heart transplant survival outcomes for adriamycin-dilated cardiomyopathy. Am J Cardiol. 2013;111(4):609-12. https://doi.org/10.1016/j.amjcard.2012.10.048
  4. Octavia Y, Tocchetti CG, Gabrielson KL, Janssens S, Crijns HJ, Moens AL. Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies. J Mol Cell Cardiol. 2012;52(6):1213-25. https://doi.org/10.1016/j.yjmcc.2012.03.006
  5. Chua CC, Liu X, Gao J, Hamdy RC, Chua BH. Multiple actions of pifithrin-$\alpha$ on doxorubicin-induced apoptosis in rat myoblastic H9c2 cells. Am J Physiol-Heart Circ Physiol. 2006;290(6):H2606-H13. https://doi.org/10.1152/ajpheart.01138.2005
  6. L'Ecuyer T, Sanjeev S, Thomas R, Novak R, Das L, Campbell W, et al. DNA damage is an early event in doxorubicin-induced cardiac myocyte death. Am J Physiol Heart Circ Physiol. 2006;291(3):H1273-H80. https://doi.org/10.1152/ajpheart.00738.2005
  7. Wattanapitayakul SK, Chularojmontri L, Herunsalee A, Charuchongkolwongse S, Niumsakul S, Bauer JA. Screening of antioxidants from medicinal plants for cardioprotective effect against doxorubicin toxicity. Basic Clin Pharmacol Toxicol. 2005;96(1):80-7. https://doi.org/10.1111/j.1742-7843.2005.pto960112.x
  8. Merten KE, Jiang Y, Feng W, Kang YJ. Calcineurin activation is not necessary for Doxorubicin-induced hypertrophy in H9c2 embryonic rat cardiac cells: involvement of the phosphoinositide 3-kinase-Akt pathway. J Pharmacol Exp Ther. 2006;319(2):934-40. https://doi.org/10.1124/jpet.106.108845
  9. Lushnikova E, Klinnikova M, Molodykh O, Nepomnyashchikh L. Morphological manifestations of heart remodeling in anthracycline-induced dilated cardiomyopathy Bull Exp Biol Med. 2004;138(6):607-12. https://doi.org/10.1007/s10517-005-0138-0
  10. Oliveira PJ, Bjork JA, Santos MS, Leino RL, Froberg MK, Moreno AJ, et al. Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicity. Toxicol Appl Pharmacol. 2004;200(2):159-68. https://doi.org/10.1016/j.taap.2004.04.005
  11. Spallarossa P, Garibaldi S, Altieri P, Fabbi P, Manca V, Nasti S, et al. Carvedilol prevents doxorubicin-induced free radical release and apoptosis in cardiomyocytes in vitro. J Mol Cell Cardiol. 2004;37(4):837-46. https://doi.org/10.1016/j.yjmcc.2004.05.024
  12. Swain SM, Whaley FS, Gerber MC, Weisberg S, York M, Spicer D, et al. Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J Clin Oncol. 1997;15(4):1318-32. https://doi.org/10.1200/JCO.1997.15.4.1318
  13. Nazish J, Shoukat A. Cardioprotective and antilipidemic potential of Cyperus rotundus in chemically induced cardiotoxicity. Int J Agric Biol. 2012;14(6):989-92.
  14. Hina S, Rehman K, Dogar Z-u-H, Jahan N, Hameed M, Khan ZI, et al. Cardioprotective effect of gemmotherapeutically treated Withania somnifera against chemically induced myocardial injury. Pak J Bot. 2010;42(2):1487-99.
  15. Branco AF, Sampaio SF, Moreira AC, Holy J, Wallace KB, Baldeiras I, et al. Differentiation-dependent doxorubicin toxicity on H9c2 cardiomyoblasts. Cardiovasc Toxicol. 2012;12(4):326-40. https://doi.org/10.1007/s12012-012-9177-8
  16. Dorsey JF, Kao GD. Aloe (-emodin) for cancer? More than just a comforting salve. Cancer Biol Ther. 2007;6(1):89-90. https://doi.org/10.4161/cbt.6.1.3845
  17. Zhang R, Kang KA, Piao MJ, Lee KH, Jang HS, Park MJ, et al. Rhapontigenin from Rheum undulatum protects against oxidative-stress-induced cell damage through antioxidant activity. J Toxicol Environ Health A. 2007;70(13):1155-66. https://doi.org/10.1080/15287390701252766
  18. Hosseini A, Rajabian A. Protective effect of Rheum turkestanikum root against doxorubicin-induced toxicity in H9c2 cells. Rev Bras de Farmacogn. 2016;26(3):347-51. https://doi.org/10.1016/j.bjp.2016.02.004
  19. Goreja W. Black seed: nature's miracle remedy: Karger Publishers; 2003.
  20. Ahmed MA, Hassanein KM. Cardio protective effects of Nigella sativa oil on lead induced cardio toxicity: Anti inflammatory and antioxidant mechanism. J Physiol Pathophysiol. 2013;4(5):72-80. https://doi.org/10.5897/JPAP2013.0083
  21. Ebru U, Burak U, Yusuf S, Reyhan B, Arif K, Faruk TH, et al. Cardioprotective effects of Nigella sativa oil on cyclosporine A‐ induced cardiotoxicity in rats. Basic Clin Pharmacol Toxicol. 2008;103(6):574-80. https://doi.org/10.1111/j.1742-7843.2008.00313.x
  22. Nicoll R, Henein MY. Ginger (Zingiber officinale Roscoe): a hot remedy for cardiovascular disease? Int J Cardio. 2009;131(3):408-9. https://doi.org/10.1016/j.ijcard.2007.07.107
  23. Bafna P, Balaraman R. Antioxidant activity of DHC‐1, an herbal formulation, in experimentally‐ induced cardiac and renal damage. Phytothe Res. 2005;19(3):216-21. https://doi.org/10.1002/ptr.1659
  24. Nakagawa K, Kishida H, Arai N, Nishiyama T, Mae T. Licorice flavonoids suppress abdominal fat accumulation and increase in blood glucose level in obese diabetic KK-Ay mice. Biol Pharm Bull. 2004;27(11):1775-8. https://doi.org/10.1248/bpb.27.1775
  25. Lim WYA, Chia YY, Liong SY, Ton SH, Kadir KA, Husain SNAS. Lipoprotein lipase expression, serum lipid and tissue lipid deposition in orally-administered glycyrrhizic acid-treated rats. Lipids Health Dis. 2009;8(1):31. https://doi.org/10.1186/1476-511X-8-31
  26. Hosseini A, Shafiee-Nick R, Mousavi SH. 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. 2014;17(12):993.
  27. Mahmoud F, Abul H, Onadeko B, Khadadah M, Haines D, Morgan G. In vitro effects of Ginkgolide B on lymphocyte activation in atopic asthma: comparison with cyclosporin A. Jpn J Pharmacol. 2001;83(3):241-5.
  28. Gao J, Chen T, Zhao D, Zheng J, Liu Z. Ginkgolide B exerts cardioprotective properties against doxorubicin-Induced cardiotoxicity by regulating reactive oxygen species, akt and calcium signaling pathways in vitro and in vivo. PloS one. 2016;11(12):e0168219. https://doi.org/10.1371/journal.pone.0168219
  29. Abraham SVPI, Palani A, Ramaswamy BR, Shunmugiah KP, Arumugam VR. Antiquorum sensing and antibiofilm potential of Capparis spinosa. Arch Med Res. 2011;42(8):658-68. https://doi.org/10.1016/j.arcmed.2011.12.002
  30. Boga C, Forlani L, Calienni R, Hindley T, Hochkoeppler A, Tozzi S, et al. On the antibacterial activity of roots of Capparis spinosa L. Nat Prod Res. 2011;25(4):417-21. https://doi.org/10.1080/14786419.2010.487189
  31. Siracusa L, Kulisic-Bilusic T, Politeo O, Krause I, Dejanovic B, Ruberto G. Phenolic composition and antioxidant activity of aqueous infusions from Capparis spinosa L. and Crithmum maritimum L. before and after submission to a two-step in vitro digestion model. J Agric Food Chem. 2011;59(23):12453-9. https://doi.org/10.1021/jf203096q
  32. Huseini HF, Hasani-Rnjbar S, Nayebi N, Heshmat R, Sigaroodi FK, Ahvazi M, et al. Capparis spinosa L.(Caper) fruit extract in treatment of type 2 diabetic patients: a randomized double-blind placebo-controlled clinical trial. Complement Ther Med. 2013;21(5):447-52. https://doi.org/10.1016/j.ctim.2013.07.003
  33. Aghel N, Rashidi I, Mombeini A. Hepatoprotective activity of Capparis spinosa root bark against CCl4 induced hepatic damage in mice. Iran J Pharm Res. 2010:285-90.
  34. Wu J-H, Chang F-R, Hayashi K-i, Shiraki H, Liaw C-C, Nakanishi Y, et al. Antitumor agents. Part 218: Cappamensin A, a new in vitro anticancer principle, from Capparis sikkimensis. Bioorganic Med Chem lett. 2003;13(13):2223-5. https://doi.org/10.1016/S0960-894X(03)00379-2
  35. Argentieri M, Macchia F, Papadia P, Fanizzi FP, Avato P. Bioactive compounds from Capparis spinosa subsp. Rupestris. Indust Crops Prod. 2012;36(1):65-9. https://doi.org/10.1016/j.indcrop.2011.08.007
  36. Mousavi SH, Hosseini A, Bakhtiari E, Rakhshandeh H. Capparis spinosa reduces Doxorubicin-induced cardio-toxicity in cardiomyoblast cells. Avicenna J Phytomed. 2016;6(5):488.
  37. Janbaz KH, Latif MF, Saqib F, Imran I, Zia-Ul-Haq M, De Feo V. Pharmacological effects of Lactuca serriola L. in experimental model of gastrointestinal, respiratory, and vascular ailments. Evid Based Complement Alternat Med. 2013;2013.
  38. Hosseini A, Mahdian D. PROTECTIVE EFFECT OF LACTUCA SERRIOLA ON DOXORUBICIN-INDUCED TOXICITY IN H9C2 CELLS. Acta Pol Pharm. 2016;73(3):659-66.
  39. Chen CC, Chou FP, Ho YC, Lin WL, Wang CP, Kao ES, et al. Inhibitory effects of Hibiscus Sabdariffa L extract on low‐ density lipoprotein oxidation and anti‐hyperlipidemia in fructose‐pfed and cholesterol‐fed rats. J Sci Food Agric. 2004;84(15):1989-96. https://doi.org/10.1002/jsfa.1872
  40. Ali BH, Wabel NA, Blunden G. Phytochemical, pharmacological and toxicological aspects of Hibiscus sabdariffa L.: a review. Phytother Res. 2005;19(5):369-75. https://doi.org/10.1002/ptr.1628
  41. Serban C, Sahebkar A, Ursoniu S, Andrica F, Banach M. Effect of sour tea (Hibiscus sabdariffa L.) on arterial hypertension: a systematic review and meta-analysis of randomized controlled trials. J Hypertension. 2015;33(6):1119-27. https://doi.org/10.1097/HJH.0000000000000585
  42. Hossein A, Bakhtiari E, Mousavi SH. Protective Effect of Hibiscus Sabdariffa on Doxorubicin-induced Cytotoxicity in H9c2 Cardiomyoblast Cells (Spring 2017). Iran J Pharm Res. 2017.
  43. Li J-Z, Yu S-Y, Wu J-H, Shao Q-R, Dong X-M. Paeoniflorin protects myocardial cell from doxorubicin-induced apoptosis through inhibition of NADPH oxidase. Can J Physiol Pharmacol. 2012;90(12):1569-75. https://doi.org/10.1139/y2012-140
  44. Lu G, Wu Y, Mak YT, Wai SM, Feng ZT, Rudd JA, et al. Molecular evidence of the neuroprotective effect of Ginkgo biloba (EGb761) using bax/bcl-2 ratio after brain ischemia in senescence-accelerated mice, strain prone-8. Brain Res. 2006;1090(1):23-8. https://doi.org/10.1016/j.brainres.2006.02.138
  45. Trumbeckaite S, Bernatoniene J, Majiene D, Jaksas V, Savickas A, Toleikis A. Effect of Ginkgo biloba extract on the rat heart mitochondrial function. J Ethnopharmacol. 2007;111(3):512-6. https://doi.org/10.1016/j.jep.2006.12.028
  46. Liu T-J, Yeh Y-C, Ting C-T, Lee W-L, Wang L-C, Lee H-W, et al. Ginkgo biloba extract 761 reduces doxorubicin-induced apoptotic damage in rat hearts and neonatal cardiomyocytes. Cardiovasc Res. 2008;80(2):227-35. https://doi.org/10.1093/cvr/cvn192
  47. Haruenkit SPR. Investigation of limonoids, flavanones, total polyphenol content and antioxidant activity in seven thai pummelo cultivars. Kasetsart J. 2009;43:458-66.
  48. Chularojmontri L, Gerdprasert O, Wattanapitayakul SK. Pummelo protects doxorubicin-induced cardiac cell death by reducing oxidative stress, modifying glutathione transferase expression, and preventing cellular senescence. Evid Based Complement Alternat Med. 2013;2013.
  49. Chang WT, Shao ZH, Yin JJ, Mehendale S, Wang CZ, Qin Y, et al. Comparative effects of flavonoids on oxidant scavenging and ischemia-reperfusion injury in cardiomyocytes. Eur J Pharmacol. 2007;566(1-3):58-66. https://doi.org/10.1016/j.ejphar.2007.03.037
  50. Chang WT, Li J, Haung HH, Liu H, Han M, Ramachandran S, et al. Baicalein protects against doxorubicin-induced cardiotoxicity by attenuation of mitochondrial oxidant injury and JNK activation. J Cell Biochem. 2011;112(10):2873-81. https://doi.org/10.1002/jcb.23201
  51. Johnson R, Shabalala S, Louw J, Kappo AP, Muller CJF. Aspalathin Reverts Doxorubicin-Induced Cardiotoxicity through Increased Autophagy and Decreased Expression of p53/mTOR/p62 Signaling. Molecules. 2017;22(10).
  52. Johnson R, Dludla P, Joubert E, February F, Mazibuko S, Ghoor S, et al. Aspalathin, a dihydrochalcone C-glucoside, protects H9c2 cardiomyocytes against high glucose induced shifts in substrate preference and apoptosis. Mol Nut Food Res. 2016;60(4):922-34. https://doi.org/10.1002/mnfr.201500656
  53. Snijman PW, Joubert E, Ferreira D, Li XC, Ding Y, Green IR, et al. Antioxidant activity of the dihydrochalcones Aspalathin and Nothofagin and their corresponding flavones in relation to other Rooibos ( Aspalathus linearis ) Flavonoids, Epigallocatechin Gallate, and Trolox. J Agric Food Chem. 2009;57(15):6678-84. https://doi.org/10.1021/jf901417k
  54. Priyadarsini KI, Khopde SM, Kumar SS, Mohan H. Free radical studies of ellagic acid, a natural phenolic antioxidant. J Agric Food Chem. 2002;50(7):2200-6. https://doi.org/10.1021/jf011275g
  55. Tuk G, Atessahin A, Somez M, Cribasri AO, Yue A. Improvement of cisplatin-induced injuries to sperm quality, the oxidant-antioxidant system, and the histologic structure of the rat testis by ellagic acid. Fertil Steril. 2008;89(5):1474-81. https://doi.org/10.1016/j.fertnstert.2007.04.059
  56. Corbett S, Daniel J, Drayton R, Field M, Steinhardt R, Garrett N. Evaluation of the anti-inflammatory effects of ellagic acid. J Perianesth Nurs. 2010;25(4):214-20. https://doi.org/10.1016/j.jopan.2010.05.011
  57. Kannan MM, Quine SD. Ellagic acid ameliorates isoproterenol induced oxidative stress: Evidence from electrocardiological, biochemical and histological study. Eur J Pharmacol. 2011;659(1):45-52. https://doi.org/10.1016/j.ejphar.2011.02.037
  58. Warpe VS, Mali VR, Arulmozhi S, Bodhankar SL, Mahadik KR. Cardioprotective effect of ellagic acid on doxorubicin induced cardiotoxicity in wistar rats. J Acute Med. 2015;5(1):1-8. https://doi.org/10.1016/j.jacme.2015.02.003
  59. Sheena N, Ajith T, Janardhanan K. Anti-inflammatory and anti-nociceptive activities of Ganoderma lucidum occurring in South India. Pharm Biol. 2003;41(4):301-4. https://doi.org/10.1076/phbi.41.4.301.15677
  60. Jones S, Janardhanan KK. Antioxidant and antitumor activity of Ganoderma lucidum (Curt.: Fr.) P. Karst.-Reishi (Aphyllophoromycetideae) from South India. Int J Med Mushrooms. 2000;2(3).
  61. Han X, Gao S, Cheng Y, Sun Y, Liu W, Tang L, et al. Protective effect of naringenin-7-O-glucoside against oxidative stress induced by doxorubicin in H9c2 cardiomyocytes. Biosci Trends. 2012;6(1):19-25.
  62. Sheena N, Ajith T, Janardhanan K. Protective effect of methanolic extract of Ganoderma lucidum P. Karst. Reishi from South India against doxorubicin-induced cardiotoxicity in rats. Orient Pharm Exp Med. 2005;5(1):62-8. https://doi.org/10.3742/OPEM.2005.5.1.062
  63. Putri H, Nagadi S, Larasati YA, Wulandari N, Hermawan A. Cardioprotective and hepatoprotective effects of Citrus hystrix peels extract on rats model. Asian Pac J Trop Biomed. 2013;3(5):371-5. https://doi.org/10.1016/S2221-1691(13)60079-9
  64. Prashanth D, Asha M, Amit A. Antibacterial activity of Punica granatum. Fitoterapia. 2001;72(2):171-3. https://doi.org/10.1016/S0367-326X(00)00270-7
  65. Ross RG, Selvasubramanian S, Jayasundar S. Immunomodulatory activity of Punica granatum in rabbits-a preliminary study. J Ethnopharmacol. 2001;78(1):85-7. https://doi.org/10.1016/S0378-8741(01)00287-2
  66. Chidambara Murthy KN, Jayaprakasha GK, Singh RP. Studies on antioxidant activity of pomegranate (Punica granatum) peel extract using in vivo models. J Agric Food Chem. 2002;50(17):4791-5. https://doi.org/10.1021/jf0255735
  67. Hassanpour Fard M, Ghule AE, Bodhankar SL, Dikshit M. Cardioprotective effect of whole fruit extract of pomegranate on doxorubicin-induced toxicity in rat. Pharm Biol. 2011;49(4):377-82. https://doi.org/10.3109/13880209.2010.517758
  68. Xia E-Q, Deng G-F, Guo Y-J, Li H-B. Biological activities of polyphenols from grapes. Int J Mol Sci. 2010;11(2):622-46. https://doi.org/10.3390/ijms11020622
  69. Khoshbaten M, Aliasgarzadeh A, Masnadi K, Farhang S, Tarzamani MK, Babaei H, et al. Grape seed extract to improve liver function in patients with nonalcoholic fatty liver change. Saudi J Gastroenterol. 2010;16(3):194. https://doi.org/10.4103/1319-3767.65197
  70. Najafi M, Vaez H, Zahednezhad F, Samadzadeh M, Babaei H. Study the effects of hydroalcoholic extract of grape seed (Vitis vinifera) on infarct size and cardiac arrhythmias in ischemic-reperfused isolated rat heart. Pharmaceut Sci. 2011;16:187-94.
  71. Babaei H, Aliasgarzadeh A, Poorabdollahi P. Effect of supplementation with grape seed extract (vitis vinifera) on serum lipid profiles in patient with type 2 diabetes. Iran J Endocrin Metab. 2013;15(1):59-66.
  72. Bagchi D, Swaroop A, Preuss HG, Bagchi M. Free radical scavenging, antioxidant and cancer chemoprevention by grape seed proanthocyanidin: An overview. Mutat Res.2014;768:69-73. https://doi.org/10.1016/j.mrfmmm.2014.04.004
  73. Bagchi D, Bagchi M, Stohs SJ, Das DK, Ray SD, Kuszynski CA, et al. Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention. Toxicol. 2000;148(2):187-97. https://doi.org/10.1016/S0300-483X(00)00210-9
  74. Razmaraii N, Babaei H, Nayebi AM, Assadnassab G, Helan JA, Azarmi Y. Cardioprotective Effect of Grape Seed Extract on Chronic Doxorubicin-Induced Cardiac Toxicity in Wistar Rats. Adv Pharm Bull. 2016;6(3):423. https://doi.org/10.15171/apb.2016.055
  75. Arthan D, Svasti J, Kittakoop P, Pittayakhachonwut D, Tanticharoen M, Thebtaranonth Y. Antiviral isoflavonoid sulfate and steroidal glycosides from the fruits of Solanum torvum. Phytochem. 2002;59(4):459-63. https://doi.org/10.1016/S0031-9422(01)00417-4
  76. Israf D, Lajis NH, Somchit M, Sulaiman M. Enhancement of ovalbumin-specific IgA responses via oral boosting with antigen co-administered with an aqueous Solanum torvum extract. Life Sci. 2004;75(4):397-406. https://doi.org/10.1016/j.lfs.2003.10.038
  77. Sivapriya M, Leela S. Isolation and purification of a novel antioxidant protein from the water extract of Sundakai (Solanum torvum) seeds. Food Chem. 2007;104(2):510-7. https://doi.org/10.1016/j.foodchem.2006.11.060
  78. Nguelefack TB, Feumebo CB, Ateufack G, Watcho P, Tatsimo S, Atsamo AD, et al. Anti-ulcerogenic properties of the aqueous and methanol extracts from the leaves of Solanum torvum Swartz (Solanaceae) in rats. J Ethnopharmacol. 2008;119(1):135-40. https://doi.org/10.1016/j.jep.2008.06.008
  79. ValaviovaR, KondrovaE, EhrlichovaM, Boumendjel A, Kova rJ, Stopka P, et al. The effect of flavonoid derivatives on doxorubicin transport and metabolism. Bioorganic Med Chem. 2008;16(4):2034-42. https://doi.org/10.1016/j.bmc.2007.10.093
  80. Kamble S, Mohan M, Kasture S. Protective effect of Solanum torvum on doxorubicin- induced cardiactoxicity in rats. Pharmacologyonline. 2009;2:1192-204.
  81. Komolafe K, Akinmoladun A, Olaleye T. Methanolic leaf extract of Parkia biglobosa protects against doxorubicin-induced cardiotoxicity in rats. Int J Appl Res Nat Prod. 2013;6(3):39-47.
  82. Millogo-Kone H, Guissou I, Nacoulma O, Traore A. Comparative study of leaf and stem bark extracts of Parkia biglobosa against enterobacteria. Afr J Tradit Complement Altern Med. 2008;5(3):238-43.
  83. Atanu F, Ebiloma U, Ajayi E. A review of the pharmacological aspects of Solanum nigrum Linn. Biotechnol Mol Biol Rev. 2011;6(1):1-8.
  84. Ravi V, Saleem TM, Patel S, Raamamurthy J, Gauthaman K. Anti-inflammatory effect of methanolic extract of Solanum nigrum Linn berries. Int J Appl Res Nat Prod. 2009;2(2):33-6.
  85. Patel S, Gheewala N, Suthar A, Shah A. In-vitro cytotoxicity activity of Solanum nigrum extract against Hela cell line and Vero cell line. Int J Pharm Pharm Sci. 2009;1(1):38-46.
  86. Kumar V, Sharma S, Modi PK. Exploration of hepatoprotective activity of aqueous extract of Solanum nigrum-an experimental study. Int J Pharm Sci Res. 2013;4(1):464.
  87. Nitish B, Pratim MP, Abhinit K, Atul T, Tasneem A, Uzzaman KM. Evaluation of cardio protective Activity of Methanolic Extract Of Solanum Nigrum Linn. in Rats. Int J Drug Dev Res. 2011.
  88. Varshney P, Vishwakarma P, Sharma M, Saini M, Bhatt S, Singh G, et al. Cardioprotective effect of Solanum nigrum against doxorubicin induced cardiotoxicity-an experimental study. Int J Basic Clin Pharmacol. 2016;5(3):748-53.
  89. Frank J, George TW, Lodge JK, Rodriguez-Mateos AM, Spencer JP, Minihane AM, et al. Daily consumption of an aqueous green tea extract supplement does not impair liver function or alter cardiovascular disease risk biomarkers in healthy men. J Nutr. 2009;139(1):58-62. https://doi.org/10.3945/jn.108.096412
  90. Zheng J, Lee HCM, bin Sattar MM, Huang Y, Bian J-S. Cardioprotective effects of epigallocatechin-3-gallate against doxorubicin-induced cardiomyocyte injury. Eur J Pharmacol. 2011;652(1):82-8. https://doi.org/10.1016/j.ejphar.2010.10.082
  91. Khan G, Haque SE, Anwer T, Ahsan MN, Safhi MM, Alam M. Cardioprotective effect of green tea extract on doxorubicin-induced cardiotoxicity in rats. Acta Pol Pharm. 2014;71(5):861-8.
  92. Mishra L-C, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Altern Med Rev. 2000;5(4):334-46.
  93. Scartezzini P, Speroni E. Review on some plants of Indian traditional medicine with antioxidant activity. J Ethnopharmacol. 2000;71(1):23-43. https://doi.org/10.1016/S0378-8741(00)00213-0
  94. Jahanbakhsh SP, Manteghi AA, Emami SA, Mahyari S, Gholampour B, Mohammadpour AH, et al. Evaluation of the efficacy of Withania somnifera (Ashwagandha) root extract in patients with obsessive-compulsive disorder: A randomized double-blind placebo-controlled trial. Complement Ther Med. 2016;27:25-9. https://doi.org/10.1016/j.ctim.2016.03.018
  95. Dhuley JN. RETRACTED: adaptogenic and cardioprotective action of ashwagandha in rats and frogs. J Ethnopharmacol. 2000;70(1):57-63. https://doi.org/10.1016/S0378-8741(99)00177-4
  96. Davis L, Kuttan G. Effect of Withania somnifera on cyclophosphamide-induced urotoxicity. Cancer lett. 2000;148(1):9-17. https://doi.org/10.1016/S0304-3835(99)00252-9
  97. Hamza A, Amin A, Daoud S. The protective effect of a purified extract of Withania somnifera against doxorubicin-induced cardiac toxicity in rats. Cell Biol Toxicol. 2008;24(1):63-73. https://doi.org/10.1007/s10565-007-9016-z
  98. Fryer RA, Galustian C, Dalgelish AG. Recent advances and developments in treatment strategies against pancreatic cancer. Curr Clin Pharmacol. 2009;4(2):102-12. https://doi.org/10.2174/157488409788185007
  99. Maheshwari RK, Singh AK, Gaddipati J, Srimal RC. Multiple biological activities of curcumin: a short review. Life Sci. 2006;78(18):2081-7. https://doi.org/10.1016/j.lfs.2005.12.007
  100. Ramsewak R, DeWitt D, Nair M. Cytotoxicity, antioxidant and anti-inflammatory activities of curcumins I– III from Curcuma longa. Phytomed. 2000;7(4):303-8. https://doi.org/10.1016/S0944-7113(00)80048-3
  101. Ganjali S, Blesso CN, Banach M, Pirro M, Majeed M, Sahebkar A. Effects of curcumin on HDL functionality. Pharmacol Res. 2017;119:208-18. https://doi.org/10.1016/j.phrs.2017.02.008
  102. Ganjali S, Sahebkar A, Mahdipour E, Jamialahmadi K, Torabi S, Akhlaghi S, et al. Investigation of the effects of curcumin on serum cytokines in obese individuals: a randomized controlled trial. TheScientificWorldJournal. 2014;2014:898361.
  103. Mirzaei H, Naseri G, Rezaee R, Mohammadi M, Banikazemi Z, Mirzaei HR, et al. Curcumin: A new candidate for melanoma therapy? Int J Cancer. 2016;139(8):1683-95. https://doi.org/10.1002/ijc.30224
  104. Panahi Y, Alishiri GH, Parvin S, Sahebkar A. Mitigation of Systemic Oxidative Stress by Curcuminoids in Osteoarthritis: Results of a Randomized Controlled Trial. J Diet Suppl. 2016;13(2):209-20. https://doi.org/10.3109/19390211.2015.1008611
  105. Panahi Y, Ghanei M, Bashiri S, Hajihashemi A, Sahebkar A. Short-term Curcuminoid Supplementation for Chronic Pulmonary Complications due to Sulfur Mustard Intoxication: Positive Results of a Randomized Double-blind Placebo-controlled Trial. Drug Res. 2015;65(11):567-73. https://doi.org/10.1055/s-0034-1389986
  106. Panahi Y, Hosseini MS, Khalili N, Naimi E, Majeed M, Sahebkar A. Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in subjects with metabolic syndrome: A randomized controlled trial and an updated meta-analysis. Clin Nutr. 2015;34(6):1101-8. https://doi.org/10.1016/j.clnu.2014.12.019
  107. Panahi Y, Kianpour P, Mohtashami R, Jafari R, Simental-Mendia LE, Sahebkar A. Curcumin Lowers Serum Lipids and Uric Acid in Subjects With Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial. J Cardiovasc Pharmacol. 2016;68(3):223-9. https://doi.org/10.1097/FJC.0000000000000406
  108. Rahmani S, Asgary S, Askari G, Keshvari M, Hatamipour M, Feizi A, et al. Treatment of Non-alcoholic Fatty Liver Disease with Curcumin: A Randomized Placebo-controlled Trial. Phytother Res : PTR. 2016;30(9):1540-8. https://doi.org/10.1002/ptr.5659
  109. Sahebkar A. Curcuminoids for the management of hypertriglyceridaemia. Nat Rev Cardiol. 2014;11(2):123.
  110. Sahebkar A, Cicero AFG, Simental-Mendia LE, Aggarwal BB, Gupta SC. Curcumin downregulates human tumor necrosis factor-alpha levels: A systematic review and meta-analysis ofrandomized controlled trials. Pharmacol Res. 2016;107:234-42. https://doi.org/10.1016/j.phrs.2016.03.026
  111. El-Sayed EM, El-azeem ASA, Afify AA, Shabana MH, Ahmed HH. Cardioprotective effects of Curcuma longa L. extracts against doxorubicin-induced cardiotoxicity in rats. J Med Plants Res. 2011;5(17):4049-58.
  112. Alavizadeh SH, Hosseinzadeh H. Bioactivity assessment and toxicity of crocin: a comprehensive review. Food Chem Toxicol. 2014;64:65-80. https://doi.org/10.1016/j.fct.2013.11.016
  113. Jam IN, Sahebkar AH, Eslami S, Mokhber N, Nosrati M, Khademi M, et al. The effects of crocin on the symptoms of depression in subjects with metabolic syndrome. Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2017;26(6):925-30.
  114. Hosseinzadeh H, Karimi G, Niapoor M, editors. Antidepressant effect of Crocus sativus L. stigma extracts and their constituents, crocin and safranal, in mice. I International Symposium on Saffron Biology and Biotechnology 650; 2003.
  115. Pitsikas N, Boultadakis A, Georgiadou G, Tarantilis P, Sakellaridis N. Effects of the active constituents of Crocus sativus L., crocins, in an animal model of anxiety. Phytomed. 2008;15(12):1135-9. https://doi.org/10.1016/j.phymed.2008.06.005
  116. Ghadrdoost B, Vafaei AA, Rashidy-Pour A, Hajisoltani R, Bandegi AR, Motamedi F, et al. Protective effects of saffron extract and its active constituent crocin against oxidative stress and spatial learning and memory deficits induced by chronic stress in rats. Eur J Pharmacol. 2011;667(1):222-9. https://doi.org/10.1016/j.ejphar.2011.05.012
  117. Khalili M, Hamzeh F. Effects of active constituents of Crocus sativus L., crocin on streptozocin-induced model of sporadic Alzheimer's disease in male rats. Iran Biomed J. 2010;14(1-2):59.
  118. Razmaraii N, Babaei H, Nayebi AM, Assadnassab G, Helan JA, Azarmi Y. Crocin treatment prevents doxorubicin-induced cardiotoxicity in rats. Life Sci. 2016;157:145-51. https://doi.org/10.1016/j.lfs.2016.06.012
  119. Goodman J, Hochstein P. Generation of free radicals and lipid peroxidation by redox cycling of adriamycin and daunomycin. Biochem Biophysic Res Communications. 1977;77(2):797-803. https://doi.org/10.1016/S0006-291X(77)80048-X
  120. Naidu M, Kumar KV, Mohan IK, Sundaram C, Singh S. Protective effect of Gingko biloba extract against doxorubicin-induced cardiotoxicity in mice. 2002.
  121. Devi V, Shanbhag TV, Bairy K, Rao N, Shenoy S. Effect of Phyllanthus niruri on wound healing in rats. Indian J Physiol Pharmacol. 2004;49(4):487-90.
  122. Islam A, Selvan T, Mazumder U, Gupta M, Ghosal S. Antitumour effect of phyllanthin and hypophyllanthin from Phyllanthus amarus against Ehrlich ascites carcinoma in mice. Pharmacologyonline. 2008;2:796-807.
  123. Joshi H, Parle M. Pharmacological evidences for antiamnesic potentials of Phyllanthus amarus in mice. Afr J Biomed Res. 2007;10(2).
  124. Sharma A, Singh RT, Handa SS. Estimation of phyllanthin and hypophyllanthin by high performance liquid chromatography in Phyllanthus amarus. Phytochem Analysis. 1993;4(5):226-9. https://doi.org/10.1002/pca.2800040507
  125. Thippeswamy A, Shirodkar A, Koti B, Sadiq AJ, Praveen D, Swamy AV, et al. Protective role of Phyllantus niruri extract in doxorubicin-induced myocardial toxicity in rats. Indian J Pharmacol. 2011;43(1):31. https://doi.org/10.4103/0253-7613.75663
  126. Mohajeri SA, Hosseinzadeh H, Keyhanfar F, Aghamohammadian J. Extraction of crocin from saffron (Crocus sativus) using molecularly imprinted polymer solid‐Hphase extraction. J Sep Sci. 2010;33(15):2302-9. https://doi.org/10.1002/jssc.201000183
  127. Hosseinzadeh H, Sadeghnia HR. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. J Pharm Pharm Sci. 2005;8(3):394-9.
  128. Hosseinzadeh H, Sadeghnia H. Protective effect of safranal on pentylenetetrazol-induced seizures in the rat: involvement of GABAergic and opioids systems. Phytomed. 2007;14(4):256-62. https://doi.org/10.1016/j.phymed.2006.03.007
  129. Mousavi SH, Tayarani N, Parsaee H. Protective effect of saffron extract and crocin on reactive oxygen species-mediated high glucose-induced toxicity in PC12 cells. Cell Mol Neurobiol. 2010;30(2):185-91. https://doi.org/10.1007/s10571-009-9441-z
  130. Ochiai T, Ohno S, Soeda S, Tanaka H, Shoyama Y, Shimeno H. Crocin prevents the death of rat pheochromyctoma (PC-12) cells by its antioxidant effects stronger than those of $\alpha$-tocopherol. Neurosci lett. 2004;362(1):61-4. https://doi.org/10.1016/j.neulet.2004.02.067
  131. Hosseinzadeh H, Modaghegh MH, Saffari Z. Crocus sativus L.(Saffron) extract and its active constituents (crocin and safranal) on ischemia-reperfusion in rat skeletal muscle. . Evid Based Complement Alternat Med. 2009;6(3):343-50. https://doi.org/10.1093/ecam/nem125
  132. Molnar J, Szabo D, Pusztai R, Mucsi I, Berek L, Ocsovszki I, et al. Membrane associated antitumor effects of crocine-, ginsenoside-and cannabinoid derivates. Anticancer Res. 2000;20(2A):861-7.
  133. Moshiri E, Basti AA, Noorbala A-A, Jamshidi A-H, Abbasi SH, Akhondzadeh S. Crocus sativus L.(petal) in the treatment of mild-to-moderate depression: A double-blind, randomized and placebo-controlled trial. Phytomed. 2006;13(9):607-11. https://doi.org/10.1016/j.phymed.2006.08.006
  134. Akhondzadeh S, Fallah-Pour H, Afkham K, Jamshidi A-H, Khalighi-Cigaroudi F. Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial [ISRCTN45683816]. BMC Complement Alternat Med. 2004;4(1):12. https://doi.org/10.1186/1472-6882-4-12
  135. Javadi B, Sahebkar A, Emami SA. A survey on saffron in major islamic traditional medicine books. Iran J Basic Med Sci. 2013;16(1):1-11.
  136. Shafiee M, Arekhi S, Omranzadeh A, Sahebkar A. Saffron in the treatment of depression, anxiety and other mental disorders: Current evidence and potential mechanisms of action. J Affect Disord. 2017;227:330-7.
  137. Hosseinzadeh H, Sadeghnia HR, Ghaeni FA, Motamedshariaty VS, Mohajeri SA. Effects of saffron (Crocus sativus L.) and its active constituent, crocin, on recognition and spatial memory after chronic cerebral hypoperfusion in rats. Phytother Res. 2012;26(3):381-6. https://doi.org/10.1002/ptr.3566
  138. Chahine N, Hanna J, Makhlouf H, Duca L, Martiny L, Chahine R. Protective effect of saffron extract against doxorubicin cardiotoxicity in isolated rabbit heart. Pharm Biol. 2013;51(12):1564-71. https://doi.org/10.3109/13880209.2013.802812
  139. Chahine N, Makhlouf H, Duca L, Martiny L, Chahine R. Cardioprotective effect of saffron extracts against acute doxorubicin toxicity in isolated rabbit hearts submitted to ischemia-reperfusion injury. Z Naturforsch C.2014;69(11-12):459-70.
  140. Lin S-P, Tsai S-Y, Hou Y-C, Chao P-DL. Glycyrrhizin and licorice significantly affect the pharmacokinetics of methotrexate in rats. J Agric Food Chem. 2009;57(5):1854-9. https://doi.org/10.1021/jf8029918
  141. Sheela M, Ramakrishna M, Salimath BP. Angiogenic and proliferative effects of the cytokine VEGF in Ehrlich ascites tumor cells is inhibited by Glycyrrhiza glabra. Int Immunopharmacol. 2006;6(3):494-8. https://doi.org/10.1016/j.intimp.2005.07.002
  142. Kim J-Y, Park SJ, Yun K-J, Cho Y-W, Park H-J, Lee K-T. Isoliquiritigenin isolated from the roots of Glycyrrhiza uralensis inhibits LPS-induced iNOS and COX-2 expression via the attenuation of $NF-{\kappa}B$ in RAW 264.7 macrophages. Eur J Pharmacol. 2008;584(1):175-84. https://doi.org/10.1016/j.ejphar.2008.01.032
  143. Agarwal R, Wang ZY, Mukhtar H. Inhibition of mouse skin tumor‐initiating activity of DMBA by chronic oral feeding of glycyrrhizin in drinking water. 1991.
  144. Isbrucker R, Burdock G. Risk and safety assessment on the consumption of Licorice root (Glycyrrhiza sp.), its extract and powder as a food ingredient, with emphasis on the pharmacology and toxicology of glycyrrhizin. Regul Toxicol Pharmacol. 2006;46(3):167-92. https://doi.org/10.1016/j.yrtph.2006.06.002
  145. Zhang L, Yang Y, Yu L, Wang Y, Liu L, Fan X. Cardioprotective effects of Glycyrrhiza uralensis extract against doxorubicin-induced toxicity. Int J Toxicol. 2011;30(2):181-9. https://doi.org/10.1177/1091581810393033
  146. Ali-Shtayeh MS, Yaniv Z, Mahajna J. Ethnobotanical survey in the Palestinian area: a classification of the healing potential of medicinal plants. J Ethnopharmacol. 2000;73(1):221-32. https://doi.org/10.1016/S0378-8741(00)00316-0
  147. Shatoor AS, Ahmed MAAS. Cardioprotective effect of Crataegus aronia syn. Azarolus (L) Aqueous Extract Against Doxorubicin-Induced Cardiotoxicity and Heart Failure in Wistar Rats. J Basic Appl Sci Res. 2014;4:102-14.
  148. Gorinstein S, Leontowicz H, Leontowicz M, Drzewiecki J, Najman K, Katrich E, et al. Raw and boiled garlic enhances plasma antioxidant activity and improves plasma lipid metabolism in cholesterol-fed rats. Life Sci. 2006;78(6):655-63. https://doi.org/10.1016/j.lfs.2005.05.069
  149. Al-Numair KS. Hypocholesteremic and antioxidant effects of garlic (Allium sativum L.) extract in rats fed high cholesterol diet. Pak J Nutr. 2009;8(2):161-6. https://doi.org/10.3923/pjn.2009.161.166
  150. Rahman K. Historical perspective on garlic and cardiovascular disease. J Nutr. 2001;131(3):977S-9S. https://doi.org/10.1093/jn/131.3.977S
  151. Hosseini A, Hosseinzadeh H. A review on the effects of Allium sativum (Garlic) in metabolic syndrome. J Endocrinolo Invest. 2015;38(11):1147-57. https://doi.org/10.1007/s40618-015-0313-8
  152. Alkreathy H, Damanhouri ZA, Ahmed N, Slevin M, Ali SS, Osman A-MM. Aged garlic extract protects against doxorubicin-induced cardiotoxicity in rats. Food Chem Toxicol. 2010;48(3):951-6. https://doi.org/10.1016/j.fct.2010.01.005
  153. Wang Y-X, Korth M. Effects of doxorubicin on excitation-contraction coupling in guinea pig ventricular myocardium. Circulation Res. 1995;76(4):645-53. https://doi.org/10.1161/01.RES.76.4.645
  154. Okuda T, Yoshida T, Hatano T. Hydrolyzable tannins and related polyphenols. Fortschritte der Chemie organischer Naturstoffe/Progress in the Chemistry of Organic Natural Products: Springer; 1995. p. 1-117.
  155. Singal P, Li T, Kumar D, Danelisen I, Iliskovic N. Adriamycin-induced heart failure: mechanisms and modulation. Mol Cell Biochem. 2000;207(1):77-86. https://doi.org/10.1023/A:1007094214460
  156. Manach C, Scalbert A, Morand C, Reey C, Jimeez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr. 2004;79(5):727-47. https://doi.org/10.1093/ajcn/79.5.727
  157. Rather SA, Saravanan N. Protective effect of gallic acid on immobilization induced stress in encephalon and myocardium of male albino Wistar rats. Int J Nutr, Pharmacol, Neurol Dis. 2013;3(3):269. https://doi.org/10.4103/2231-0738.114854
  158. Kulkarni J, Swamy AV. Cardioprotective effect of gallic acid against doxorubicin-induced myocardial toxicity in albino rats. Indian J Health Sci Biomed Res. 2015;8(1):28. https://doi.org/10.4103/2349-5006.158219
  159. Banerjee S, Mullick H, Banerjee J, Ghosh A. Zingiber officinale:‘a natural gold’. Int J Pharmaceutical Bio-Sci. 2011;2:283-94.
  160. Gala AAA. Protective effect of Zingiber officinale (ginger) on doxorubicin induced oxidative cardiotoxicity in rats. Life Sci J. 2013.
  161. Kumar MV, Gupta Y. Effect of different extracts of Centella asiatica on cognition and markers of oxidative stress in rats. J Ethnopharmacol. 2002;79(2):253-60. https://doi.org/10.1016/S0378-8741(01)00394-4
  162. Incandela L, Belcaro G, Nicolaides A, Cesarone M. Modification of the echogenicity of femoral plaques after treatment with total triterpenic fraction of Centalla asiatica: A prospective, randomized, placebo-controlled trial. Angiology. 2001;52:S69. https://doi.org/10.1177/0003319701052003S13
  163. De Sanctis M, Belcaro G, Incandela L, Cesarone M. Treatment of edema and increased capillary filtration in venous hypertension with total triterpenic fraction of Centella asiatica: A clincial, prospective, placebo-controlled, randomized, dose-ranging trial. Angiology. 2001;52:S55. https://doi.org/10.1177/000331970105202S11
  164. Inamdar P, Yeole R, Ghogare A, De Souza N. Determination of biologically active constituents in Centella asiatica. J Chromatogr A. 1996;742(1-2):127-30. https://doi.org/10.1016/0021-9673(96)00237-3
  165. Gnanapragasam A, Ebenezar KK, Sathish V, Govindaraju P, Devaki T. Protective effect of Centella asiatica on antioxidant tissue defense system against adriamycin induced cardiomyopathy in rats. Life Sci. 2004;76(5):585-97. https://doi.org/10.1016/j.lfs.2004.09.009
  166. Radhakrishnan R, Wadsworth R, Gray A. Terminalia arjuna, an Ayurvedic cardiotonic, increases contractile force of rat isolated atria. Phytother Res. 1993;7(3):266-8. https://doi.org/10.1002/ptr.2650070314
  167. Bharani A, Ganguli A, Mathur L, Jamra Y, Raman P. Efficacy of Terminalia arjuna in chronic stable angina: a double-blind, placebo-controlled, crossover study comparing Terminalia arjuna with isosorbide mononitrate. Indian Heart J. 2002;54(2):170-5.
  168. Singh N, Kapur K, Singh S, Shanker K, Sinha J, Kohli R. Mechanism of cardiovascular action of Terminalia arjuna. Planta Med. 1982;45(06):102-4. https://doi.org/10.1055/s-2007-971255
  169. Singh G, Singh AT, Abraham A, Bhat B, Mukherjee A, Verma R, et al. Protective effects of Terminalia arjuna against Doxorubicin-induced cardiotoxicity. J Ethnopharmacol. 2008;117(1):123-9. https://doi.org/10.1016/j.jep.2008.01.022
  170. Wu SJ, Ng LT, Lin CC. Antioxidant activities of some common ingredients of traditional chinese medicine, Angelica sinensis, Lycium barbarum and Poria cocos. Phytother Res. 2004;18(12):1008-12. https://doi.org/10.1002/ptr.1617
  171. Luo Q, Cai Y, Yan J, Sun M, Corke H. Hypoglycemic and hypolipidemic effects and antioxidant activity of fruit extracts from Lycium barbarum. Life Sci. 2004;76(2):137-49. https://doi.org/10.1016/j.lfs.2004.04.056
  172. Xin YF, Zhou GL, Deng ZY, Chen YX, Wu YG, Xu PS, et al. Protective effect of Lycium barbarum on doxorubicin‐0induced cardiotoxicity. Phytother Res. 2007;21(11):1020-4. https://doi.org/10.1002/ptr.2186

Cited by

  1. Natural Product Interventions for Chemotherapy and Radiotherapy-Induced Side Effects vol.9, pp.1663-9812, 2018, https://doi.org/10.3389/fphar.2018.01253