Protective effect of mangiferin on doxorubicin-induced liver damage in animal model

Fauzul Husna; Wawaimuli Arozal; Hanifah Yusuf; Safarianti Safarianti

Protective effect of mangiferin on doxorubicin-induced liver damage in animal model

Abstract

Mangiferin is a bioactive compound which has antioxidant effect, but its effect on liver protection during chemotherapy with doxorubicin is understudied. The objective of this study was to assess the protective effect of mangiferin on liver injury induced by doxorubicin. The doxorubicin was injected intraperitoneally at a total dose of 15 mg/kg b.w, and then the animals were orally supplemented with mangiferin (either 50 and 100 mg/kg b.w) for five weeks. The activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), the level of malondialdehyde (MDA) and glutathione, and liver histopathology were examined to evaluate the liver damage. The results showed that doxorubicin could cause liver cell damage to the rats. In addition, the study revealed that the supplementation of mangiferin (50 and 100 mg/kg b.w) decreased ALT and AST activities, as well as lipid peroxidation. It also increased SOD and GSH levels of liver cells (p <0.05). Our study proved that the improvement in liver function and oxidative stress parameters caused by doxorubicin, indicates that the mangiferin has a protective effect against liver damage induced by doxorubicin.

Keywords

References

[1] Chabner BA, Bertino J, Cleary J, Ortiz T, Lane A, Supko JG, Ryan D. Cytotoxic agent. In: Brunton LL, Chabner BA, Knollmann BC, editors. Goodman & Gilman’s The Pharmacological Basic of Therapeutics. 12th ed. McGraw-Hill, United Stated, 2011, pp.1712-1715.
[2] Wenningmann N, Knapp M, Ande A, Vaidya TR, Ait-Oudhia S. Insights into doxorubicin-induced cardiotoxicity: Molecular mechanisms, preventive strategies, and early monitoring. Mol Pharmacol. 2019; 96: 219–32. [CrossRef]
[3] Molehin OR, Adeyanju AA, Adefegha SA, Oyeyemi AO, Idowu KA. Protective mechanisms of protocatechuic acid against doxorubicin-induced nephrotoxicity in rat model. J Basic Clin Physiol Pharmacol. 2019; 30(4). [CrossRef]
[4] Arozal W, Sari FR, Watanabe K, Arumugam S, Veeraveedu PT, Ma M, Thandavarayan RA, Sakumaran V, Lakshmanan AP, Kobayashi Y, Mito S, Soetikno V, Suzuki K. Carvedilol-afforded protection against daunorubisininduced cardiomyopathic rats in vivo: effect on cardiac fibrosis dan hypertrophy. ISRN Pharmacol. 2011; 14: 1-8. Article ID 430549. [CrossRef]
[5] Tacar O, Sriamornsak P, Dass CR. Doxorubicin: An update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol. 2012; 65: 157-70. [CrossRef]
[6] Molehin OR, Idowu KA, Olaoye AB, Fakayode AE, Adesua OO. Influence of Clerodendrum volubile leaf extract on doxorubicin-induced toxicity and inhibition of carbonyl reductase mediated metabolism. J. Complement. Integr. 2021: 5. [CrossRef]
[7] Shah KA, Patel MB, Patel RJ, Parmar PK. Mangifera indica (mango). Pharmacog Rev. 2010; 4(7): 42-48. [CrossRef]
[8] Guha S, Ghosal S, Chattopadhyay U. Antitumor, immunomodulatory and anti-HIV effect of mangiferin, a naturally occurring glucosylxanthone. Chemotherapy. 1996; 42: 443–451. [CrossRef]

[9] Yoosook C, Bunyapraphatsara N, Boonyakiat Y, Kantasuk C. Anti-herpes simplex virus activities of crude water extracts of Thai medicinal plants. Phytomedicine. 2000; 6: 411–419. [CrossRef]
[10] Muruganandan S, Gupta S, Kataria M, Lal J, Gupta PK. Mangiferin protect the streptozotocin-induced oxidative damage to cardiac and renal tissue in rats. Toxicol. 2002; 176: 165-173. [CrossRef]
[11] Shabani Z, Sayadi A. The antimicrobial in vitro effects of different concentrations of some plant extracts ıncluding tamarisk, march, acetone and mango kernel. J App Pharm Sci. 2014; 4(5): 75-79. [CrossRef]
[12] Leiro JM, Alvarez E, Arranz JA, Siso IG, Orallo F. In vitro effects of mangiferin on superoxide concentrations and expression of the inducible nitric oxide synthase, tumor necrosis factor-α and transforming growth factor- genes. Biochem Pharmacol. 2003; 65(8): 1361-1371. [CrossRef]
[13] Aderibigbe AO, Emudianughe TS, Lawal BA. Evaluation of antidiabetic action of mangifera indica in mice. Phytother Res. 2001; 15(5): 456–458. [CrossRef]
[14] Hossain MS, Ahmed M, Islam A. Hypolipidemic and hepatoprotective effect of different fraction of ethanolic extract of immature leave of Mangifera indica (Linn) in alloxan induced diabetic rats. IJPSR. 2010; 1(11): 132-138. [CrossRef]
[15] Pardo-Andreu G, Delgado R, Núñez-Sellés AJ, Vercesi AE. Dual mechanism of mangiferin protection against ironinduced damage to 2-deoxyribose and ascorbate oxidation. Pharmacol Res. 2006; 53(3): 253-260. [CrossRef]
[16] Purwaningsih EH, Hanani E, Wahidiyat PA, Krisnamurti DGB. The chelating effect of mangifera foetida water extract on serum thalassemic patients. J Indon Med Assoc. 2011; 61(8): 321-325.
[17] Cecen E, Dost T, Culhaci N, Karul A, Ergur B, Birincioglu M. Protective effect of silymarin against doxorubicininduced toxicity. Asian Pacific J cancer Prev. 2011; 12(10): 2697-2704. [CrossRef]
[18] Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S. The current state of serum biomarkers of hepatotoxicity. Toxicol. 2008; 245(3): 194-205. [CrossRef]
[19] Firat O, Kirdox O, Makay O, Caliskan C, Yilmaz F, Ilgezdi S, Karabulut B, Coker A, Zeytunlu M. Can hyperbaric oxygenation decrease doxorubicin hepatotoxicity and improve regeneration in the injured liver?. J Hepatobiliary Pancreat Surg. 2009; 16(3): 346-352. [CrossRef]
[20] Halliwell B, Gutteridge JMC. Free Radicals in Biology and Medicine, 3rd ed, Oxford Univ Press, New York, 2007.
[21] Pal PB, Sinha K, Sil PC. Mangiferin, a natural xanthone, protects murine liver in Pb(II) induced hepatic damage and cell death via MAP Kinase, NF-B and mitochondria dependent pathway. Plos one. 2013; 8(2): 1-17. [CrossRef]
[22] Yagmurca M, Bas O, Mollaoglu H, Sahin O, Nacar A, Karaman O, Songur A. Protective effect of erdostein on doxorubicin-induced hepatotoxicity in rats. Arch Med Res. 2007; 38(4): 380-385. [CrossRef]
[23] Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M. Free radicals, metals, and antioxidants in oxidative stressinduced cancer. Chem Biol Interact. 2006; 160(1): 1-40. [CrossRef]
[24] Mirończuk-Chodakowska I, Witkowska AM, Zujko ME. Endogenous non-enzymatic antioxidants in the human body. Adv Med Sci. 2018; 63(1): 68-78. [CrossRef]
[25] Liu X, Qiu Y, Liu Y, Huang N, Hua C, Wang Q, et al. Citronellal ameliorates doxorubicin-induced hepatotoxicity via antioxidative stress, antiapoptosis, and proangiogenesis in rats. J Biochem Mol Toxicol. 2021; 35(2): e22639. [CrossRef]
[26] Injac R, Perse M, Obermajer N, Djordjevic-Milic V, Prijatelj M, Djordjevic A, et al. Potential hepatoprotective effect of fullerenol C60(OH)24 in doxorubisin-induced hepatotoxicity in rats with mammary carcinoma. Biomaterials. 2008; 29: 3451-60.
[27] Kalender Y, Yel M, Kalender S. Doxorubicin hepatotoxicity and hepatic free radical metabolism in rats: the effect of vitamin E and catechin. Toxicol. 2005; 209: 39-45. [CrossRef]
[28] Arozal W, Suyatna FD, Juniantito V, Rosdiana DS, Amurugam S, Aulia R, et al. The effects of mangiferin (Mangifera indica L) in doxorubicin-induced cardiotoxicity in rats. Drug Res. 2014; 65(11): 574–580. [CrossRef]
[29] Fajri P, Estuningtyas A, Louisa M, Freisleben HJ. The preventive effect of Mangifera foetida L. leaf extract administered simultaneously to excess iron on markers of iron overload in Spraque-Dawley rats. Med. J. Indones. 2017; 26(4): 246–252. [CrossRef]
[30] Uchiyama M, Mihara M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 1978; 86(1): 271–278. [CrossRef]
[31] McCord JM, Fridovich I. The reduction of cytochrome c by milk xanthine oxidase. J Biol Chem. 1968; 243(21): 57535760. [CrossRef]
[32] Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959; 82(1): 70–77. [CrossRef]

Details

Primary Language

English

Subjects

Medical Pharmacology

Journal Section

Research Article

Authors

Fauzul Husna ^*
Indonesia

Wawaimuli Arozal This is me
Indonesia

Hanifah Yusuf This is me
Indonesia

Safarianti Safarianti This is me
Indonesia

Publication Date

June 28, 2025

Submission Date

June 2, 2021

Acceptance Date

December 13, 2021

Published in Issue

Year 2022 Volume: 26 Number: 1

IZ

https://izlik.org/JA58DG44TW

Cite

RIS / Bibtex

APA

Husna, F., Arozal, W., Yusuf, H., & Safarianti, S. (2025). Protective effect of mangiferin on doxorubicin-induced liver damage in animal model. Journal of Research in Pharmacy, 26(1), 44-51. https://izlik.org/JA58DG44TW

AMA

1.Husna F, Arozal W, Yusuf H, Safarianti S. Protective effect of mangiferin on doxorubicin-induced liver damage in animal model. J. Res. Pharm. 2025;26(1):44-51. https://izlik.org/JA58DG44TW

Chicago

Husna, Fauzul, Wawaimuli Arozal, Hanifah Yusuf, and Safarianti Safarianti. 2025. “Protective Effect of Mangiferin on Doxorubicin-Induced Liver Damage in Animal Model”. Journal of Research in Pharmacy 26 (1): 44-51. https://izlik.org/JA58DG44TW.

EndNote

Husna F, Arozal W, Yusuf H, Safarianti S (June 1, 2025) Protective effect of mangiferin on doxorubicin-induced liver damage in animal model. Journal of Research in Pharmacy 26 1 44–51.

IEEE

[1]F. Husna, W. Arozal, H. Yusuf, and S. Safarianti, “Protective effect of mangiferin on doxorubicin-induced liver damage in animal model”, J. Res. Pharm., vol. 26, no. 1, pp. 44–51, June 2025, [Online]. Available: https://izlik.org/JA58DG44TW

ISNAD

Husna, Fauzul - Arozal, Wawaimuli - Yusuf, Hanifah - Safarianti, Safarianti. “Protective Effect of Mangiferin on Doxorubicin-Induced Liver Damage in Animal Model”. Journal of Research in Pharmacy 26/1 (June 1, 2025): 44-51. https://izlik.org/JA58DG44TW.

JAMA

1.Husna F, Arozal W, Yusuf H, Safarianti S. Protective effect of mangiferin on doxorubicin-induced liver damage in animal model. J. Res. Pharm. 2025;26:44–51.

MLA

Husna, Fauzul, et al. “Protective Effect of Mangiferin on Doxorubicin-Induced Liver Damage in Animal Model”. Journal of Research in Pharmacy, vol. 26, no. 1, June 2025, pp. 44-51, https://izlik.org/JA58DG44TW.

Vancouver

1.Fauzul Husna, Wawaimuli Arozal, Hanifah Yusuf, Safarianti Safarianti. Protective effect of mangiferin on doxorubicin-induced liver damage in animal model. J. Res. Pharm. [Internet]. 2025 Jun. 1;26(1):44-51. Available from: https://izlik.org/JA58DG44TW