Possible Cardioprotective Effect of Iraqi Ammi Majus Seed Extract on Doxorubicin Induced Cardiotoxicity in Mice
DOI:
https://doi.org/10.48047/Keywords:
Ammi1 majus, DOX, SOD, GSH, ROSAbstract
Highly anticancer anthracyclines, including doxorubicin, have a long history of usage as chemotherapy drugs. However, its potent cardiotoxic sides, which include dilated cardiomyopathy and congestive cardiac failure, which are dose-dependent, restrict its therapeutic usefulness. Due to the presence of various active ingredients like quercetin, marmesinin, kempefrol, and other substances that inhibit cytochrome p450 like xanthotoxin, bergapten, imperatorin, and isoimpinellin, Ammi majus exhibits an antioxidant effect in diabetic nephropathy and myocardial injury. As a result, the objective of this study was to determine whether the seed extract of Ammi majus provided cardioprotection against DOX-induced heart injury in mice.
48 mature male mice were separated into six groups and distributed as follows: For 14 days, Group I—the "negative control"—mice received D.W. 2. Group II mice received a single oral dose of 64 mg/kg of Ammi majus seed extract. 3. Group III mice received a single oral daily dose of 128 mg/kg of Ammi majus seed extract. 4. Mice in the positive control (Group IV) group received a single oral dose of 2 ml/kg D.W. every day for 14 days. On day 15, the mice got a single IP dose of 15 mg/kg DOX. The mice were then terminated using anesthetic ether 24 hours later. 5. Group V were given a single dose of 15 mg/kg DOX on day 15 after receiving 64 mg/kg/day of Ammi majus ethanolic extract for 14 days. 6. Finally, group (Group VI) mice received 128 mg/kg of Ammi majus seed extract for 14 days, and on day 15 they got a single dosage of 15 mg/kg DOX. The mice were then slaughtered 24 hours after receiving the DOX.
To analyze GSH, SOD, GPx, and catalase as indicators of cardiotoxicity, the hearts of mice were collected for the manufacture of tissue homogenate. Analysis of the data showed that mice pre-treated with different doses of Ammi majus extract (64 mg and 128 mg/kg/day for 14 days) significantly reduced oxidative stress as compared to group IV of animals intoxicated by DOX, as demonstrated by a decrease in GSH, SOD, GPx, and catalase levels in heart tissue homogenate.
Downloads
References
Abdulrazzaq MH (2007) Protective Effect of Benfotiamine against DoxorubicinInduced Cardiotoxicity in Rabbits. Iraqi Journal of Pharmaceutical Sciences 16: 14–17.
Adham AN (2015) Comparative extraction methods, fluorescence, qualitative and quantitative evaluation of Ammi majus seed extracts. Journal of Pharmacognosy and
Phytochemistry 4: 41–44.
Akolkar G, da Silva Dias D, Ayyappan P, Bagchi AK, Jassal DS, Salemi VMC, Irigoyen MC, De Angelis K, Singal PK (2017) Vitamin C mitigates oxidative/nitrosative stress and inflammation in doxorubicin-induced cardiomyopathy. American Journal of Physiology-Heart and Circulatory Physiology 313: H795–H809.
Al-Snafi AE (2013) Chemical constituents and pharmacological activities of Ammi majus and Ammi visnaga. A review. International Journal of Pharmacy and Industrial Research 3: 257–265.
Ali N, AlAsmari AF, Imam F, Ahmed MZ, Alqahtani F, Alharbi M, AlSwayyed M, AlAsmari F, Alasmari M, Alshammari A (2021) Protective effect of diosmin against doxorubicin-induced nephrotoxicity. Saudi Journal of Biological Sciences 28: 4375–4383.
Aniogo EC, George BPA, Abrahamse H (2017) Phthalocyanine induced phototherapy coupled with Doxorubicin; a promising novel treatment for breast cancer. Expert review of anticancer therapy 17: 693–702.
Anjaneyulu M, Chopra K (2004) Quercetin, an anti-oxidant bioflavonoid, attenuates diabetic nephropathy in rats. Clinical and experimental pharmacology & physiology 31: 244–248. https://doi.org/10.1111/j.1440 1681. 2004. 03982.x
Attyah AM, Ismail SH (2012) Protective Effect of Ginger Extract Against CisplatinInduced Hepatotoxicity and Cardiotoxicity in Rats. Iraqi Journal of Pharmaceutical
Sciences (P-ISSN 1683-3597 E-ISSN 2521-3512) 21: 27–33.
Box VGS (2007) The intercalation of DNA double helices with doxorubicin and nagalomycin. Journal of Molecular Graphics and Modelling 26: 14–19.
Chakravarty HL (1976) Plant wealth of Iraq. Ministry of agriculture and agrarian reform. Iraq. Baghdad 505.
Chattopadhyay RR (2003) Possible mechanism of hepatoprotective activity of Azadirachta indica leaf extract: part II. Journal of ethnopharmacology 89: 217–219.
https://doi.org/10.1016/j.jep.2003.08.006
Chen J-Y, Hu R-Y, Chou H-C (2013) Quercetin-induced cardioprotection against doxorubicin cytotoxicity. Journal of biomedical science 20: 1–11.
Coimbra S, Figueiredo A, Castro E, Rocha‐Pereira P, Santos‐Silva A (2012) The roles of cells and cytokines in the pathogenesis of psoriasis. International journal of dermatology 51: 389–398.
Das J, Ghosh J, Manna P, Sil PC (2011) Taurine suppresses doxorubicin-triggered oxidative stress and cardiac apoptosis in rat via up-regulation of PI3-K/Akt and inhibition of p53, p38-JNK. Biochemical pharmacology 81: 891–909.
El-Dakroory SA, El-Ashry R, Mesbah A, El-Farahaty RM (2014) Doxorubicin Cardiotoxicity in acute lymphoblastic leukemia: possible protective role of grape seed extract Proanthocyanidins. British Journal of Medicine and Medical Research 4: 2555.
Erden Inal M, Kahraman A (2000) The protective effect of flavonol quercetin against ultraviolet a induced oxidative stress in rats. Toxicology 154: 21–29. https://doi.org/10.1016/s0300-483x(00)00268-7
Galisteo M, García-Saura MF, Jiménez R, Villar IC, Zarzuelo A, Vargas F, Duarte J
(2004) Effects of chronic quercetin treatment on antioxidant defence system and
oxidative status of deoxycorticosterone acetate-salt-hypertensive rats. Molecular and Cellular Biochemistry 259: 91–99.
https://doi.org/10.1023/B:MCBI.0000021360.89867.64
Hossain MA, Al Touby S (2020) Ammi majus an endemic medicinal plant: a review of the medicinal uses, pharmacological and phytochemicals. Annual toxicology 2: 9–14.
Hu Y-B, Zhang Y-F, Wang H, Ren R-J, Cui H-L, Huang W-Y, Cheng Q, Chen H-Z, Wang G (2019) miR-425 deficiency promotes necroptosis and dopaminergicneurodegeneration in Parkinson’s disease. Cell death & disease 10: 589.
Hussain I, Khan S, Khan MI, Rehman IU, Ahmed M (2012) Investigation of fatty acid composition of ammi majus seed oil by gas chromatography mass spectrometry. Journal of the Chinese Chemical Society 59: 655–658.
Hussein HM, Hameed IH, Ubaid JM (2016) Analysis of the secondary metabolite products of ammi majus and evaluation anti-insect activity.
Jawad B, Poudel L, Podgornik R, Steinmetz NF, Ching W-Y (2019) Molecular mechanism and binding free energy of doxorubicin intercalation in DNA. Physical Chemistry Chemical Physics 21: 3877–3893.
Koriem KMM, Asaad GF, Megahed HA, Zahran H, Arbid MS (2012) Evaluation of the antihyperlipidemic, anti-inflammatory, analgesic, and antipyretic activities of ethanolic extract of Ammi majus seeds in albino rats and mice. International Journal of Toxicology 31: 294–300.
Li S, E M, Yu B (2008) Adriamycin induces myocardium apoptosis through activation of nuclear factor κB in rat. Molecular biology reports 35: 489–494.
Liu W, Zhi D, Wang L, Yang A, Zhang L, Ahiasi‐Mensah J, He X (2020) Differences in xanthotoxin metabolites in seven mammalian liver microsomes. Experimental and Therapeutic Medicine 20: 3846–3852.
Lubrano V, Balzan S (2015) Enzymatic antioxidant system in vascular inflammation and coronary artery disease. World journal of experimental medicine 5: 218.
Mishra S, Pandey A, Manvati S (2020) Coumarin: An emerging antiviral agent. Heliyon 6: e03217.
Mitry MA, Edwards JG (2016) Doxorubicin induced heart failure: Phenotype and molecular mechanisms. IJC heart & vasculature 10: 17–24.
Mutlag SH (2012) Dose dependent anti-inflammatory effect of Ammi majus alcoholic extract in rat: chronic study. Iraqi Journal of Pharmaceutical Sciences (P-ISSN: 1683-3597, E-ISSN: 2521-3512) 21: 82–86.
Mutlag SH, Ismael DK, Al-Shawi NN (2011) Study the possible hepatoprotective effect of different doses of Ammi majus seeds’ extract against CCl4 induced liver damage in rats. Pharm Glob (IJCP) 9: 1–5.
Muttlag SH, Kasim AA, Jassim AR (2012) The Possible Protective Effect of Simultaneous Administration of Alcoholic Ammi majus Seeds’ Extract Against Gentamicininduced Nephrotoxicity in Rats. Al Mustansiriyah Journal of Pharmaceutical Sciences 11: 71–78.
Nagata H, Takekoshi S, Takagi T, Honma T, Watanabe K (1999) Antioxidative action of flavonoids, quercetin and catechin, mediated by the activation of glutathione peroxidase. The Tokai journal of experimental and clinical medicine 24: 1–11.
Naik PM, Al-Khayri JM (2016) Abiotic and biotic elicitors role in secondary metabolites production through in vitro culture of medicinal plants. Abiotic and biotic stress in plants—recent advances and future perspectives. Rijeka: InTech: 247–277.
Ng TB, Liu F, Wang ZT (2000) Antioxidative activity of natural products from plants. Life sciences 66: 709–723.
Octavia Y, Tocchetti CG, Gabrielson KL, Janssens S, Crijns HJ, Moens AL (2012) Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeuticstrategies. Journal of molecular and cellular cardiology 52: 1213–1225.
Oliveira AP, Valentão P, Pereira JA, Silva BM, Tavares F, Andrade PB (2009) Ficus carica L.: Metabolic and biological screening. Food and Chemical Toxicology 47:2841–2846.
Piao XL, Park IH, Baek SH, Kim HY, Park MK, Park JH (2004) Antioxidative activity of furanocoumarins isolated from Angelicae dahuricae. Journal of Ethnopharmacology 93: 243–246.
Pieniazek A, Gwozdzinski L, Hikisz P, Gwozdzinski K (2018) Indoxyl sulfate generates free radicals, decreases antioxidant defense, and leads to damage to mononuclear blood cells. Chemical research in toxicology 31: 869–875.
Scharf G, Prustomersky S, Knasmuller S, Schulte-Hermann R, Huber WW (2003) Enhancement of glutathione and g-glutamylcysteine synthetase, the rate limiting enzyme of glutathione synthesis, by chemoprotective plant-derived food and beverage components in the human hepatoma cell line HepG2. Nutrition and cancer 45: 74–83. https://doi.org/10.1207/S15327914NC4501_9
Sritharan S, Sivalingam N (2021) A comprehensive review on time-tested anticancer drug doxorubicin. Life sciences 278: 119527.
Su L-J, Zhang J-H, Gomez H, Murugan R, Hong X, Xu D, Jiang F, Peng Z-Y (2019) Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis. Oxidative medicine and cellular longevity 2019.
Thandavarayan RA, Giridharan V V, Arumugam S, Suzuki K, Ko KM, Krishnamurthy P, Watanabe K, Konishi T (2015) Schisandrin B prevents doxorubicin induced cardiac dysfunction by modulation of DNA damage, oxidative stress and inflammation through inhibition of MAPK/p53 signaling. PLoS One 10: e0119214.
Wiegand H, Boesch-Saadatmandi C, Regos I, Treutter D, Wolffram S, Rimbach G (2009) Effects of quercetin and catechin on hepatic glutathione-S transferase (GST),
NAD (P) H quinone oxidoreductase 1 (NQO1), and antioxidant enzyme activity levels in rats. Nutrition and cancer 61: 717–722.
Downloads
Published
Issue
Section
License
Copyright (c) 2023 AUTHOR

This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format for any purpose, even commercially.
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
- The licensor cannot revoke these freedoms as long as you follow the license terms.
Under the following terms:
- Attribution — You must give appropriate credit , provide a link to the license, and indicate if changes were made . You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
Notices:
You do not have to comply with the license for elements of the material in the public domain or where your use is permitted by an applicable exception or limitation .
No warranties are given. The license may not give you all of the permissions necessary for your intended use. For example, other rights such as publicity, privacy, or moral rights may limit how you use the material.