Attenuation of TNF-α and Iron Levels in Renal Hemosiderosis by Phaleria macrocarpa (Scheff.) Boerl Extract in a Rat Iron Overload Model

  • Nadia Larasinta Heriatmo Master Programme in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Ari Estuningtyas Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Vivian Soetikno Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Ernie H. Poerwaningsih Department of Pharmacy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Kusmardi Kusmardi Department of Pathology Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
Keywords: hemosiderosis, repeated transfusions, iron deposits, inflammation, iron chelator

Abstract

Regular blood transfusions are typically used to treat the genetic anemia known as thalassemia, which can lead to an increase in the body's total iron levels. The condition of excess iron can be toxic to the body due to the formation of free radicals that are harmful and can damage cells and tissues. So the availability of free iron will form the basis of iron toxicity because it accelerates the Fenton reaction to produce an increase in the amount of ROS that cannot be suppressed so that saturation of the antioxidant system can occur. Excess iron has been known to be a risk factor for organ dysfunction and damage that results in various organ diseases such as liver, heart and kidney, diabetes mellitus, and neurodegenerative diseases. Mangiferin is an active compound has been shown to act as an iron chelating agent by forming complexes with iron. The complex formed can reduce iron accumulation in thalassemia patients who receive blood transfusions on a regular basis. Mahkota Dewa (Phaleria macrocarpa) is a well-known medicinal plant native to Papua, Indonesia, and it also includes the active ingredient mangiferin. This study aims to determine the effectiveness of the ethanolic extract of Phaleria macrocarpa fruit as an iron chelating agent observed in the kidneys in a rat model of excess iron

References

Akter, S., Moni, A., Faisal, G. M., Uddin, M. R., Jahan, N., Hannan, M. A., Rahman, A., & Uddin, M. J. (2022). Renoprotective Effects of Mangiferin: Pharmacological Advances and Future Perspectives. International Journal of Environmental Research and Public Health, 19(3), 0–15. https://doi.org/10.3390/ijerph19031864
Andreu, G. P., Delgado, R., Velho, J. A., Curti, C., & Vercesi, A. E. (2005). Iron complexing activity of mangiferin, a naturally occurring glucosylxanthone, inhibits mitochondrial lipid peroxidation induced by Fe 2+-citrate. European Journal of Pharmacology, 513(1–2), 47–55. https://doi.org/10.1016/j.ejphar.2005.03.007
Baccan, M. M., Chiarelli-Neto, O., Pereira, R. M. S., & Espósito, B. P. (2012). Quercetin as a shuttle for labile iron. Journal of Inorganic Biochemistry, 107(1), 34–39. https://doi.org/10.1016/j.jinorgbio.2011.11.014
Borgna-Pignatti, C., & Marsella, M. (2015). Iron Chelation in Thalassemia Major. Clinical Therapeutics, 37(12), 2866–2877. https://doi.org/10.1016/j.clinthera.2015.10.001
Estuningtyas, A., Setiabudy, R., Wahidiyat, P. A., & Freisleben, H. J. (2019). The Role of Mangiferin in the Prevention of Experimentally Induced Iron Overload in an Animal Model. Drug Research, 69(4), 234–240. https://doi.org/10.1055/a-0667-8530
Estuningtyas, A., Wahyuni, T., Wahidiyat, P. A., Poerwaningsih, E. H., & Freisleben, H. J. (2019). Mangiferin and mangiferin-containing leaf extract from Mangifera foetida L for therapeutic attenuation of experimentally induced iron overload in a rat model. Journal of HerbMed Pharmacology, 8(1), 21–27. https://doi.org/10.15171/jhp.2019.04
Gowda, S., Desai, P. B., Kulkarni, S. S., Hull, V. V, Math, A. A. K., & Vernekar, S. N. (2010). Markers of renal function tests. North American Journal of Medical Sciences, 2(4), 170–173. http://www.ncbi.nlm.nih.gov/pubmed/22624135%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3354405
Guo, H., Chen, M., Li, M., Hu, M., Chen, B., & Zhou, C. (2019). Pharmacokinetic Comparisons of Mangiferin and Mangiferin Monosodium Salt in Rat Plasma by UPLC-MS/MS. Journal of Chemistry, 2019. https://doi.org/10.1155/2019/9272710
Hanif M Q, Yuandani, H. U. (2020). Evaluation of Toxic Effect of Phaleria macrocarpa (Scheff.) Boerl Leaf Extract on Hematological Parameters. Asian Journal of Pharmaceutical Research and Development, 8(3), 1–4.
Hashim, A., Harun, N., & Adam, F. (2017). MALAYSIAN JOURNAL OF ANALYTICAL SCIENCES EXTRACTION OF BIOACTIVE COMPOUNDS ( MANGIFERIN ) FROM MAHKOTA DEWA ( Phaleria macrocarpa ) EXTRACTION OF BIOACTIVE COMPOUNDS ( MANGIFERIN ) FROM MAHKOTA DEWA ( Phaleria macrocarpa ) FRUITS USING SUBCRITICAL WATER : June. https://doi.org/10.17576/mjas-2017-2103-22
Ho, W. L., Chung, K. P., Yang, S. S., Lu, M. Y., Jou, S. T., Chang, H. H., Yang, Y. L., Lin, D. T., & Lin, K. H. (2013). A pharmaco-economic evaluation of deferasirox for treating patients with iron overload caused by transfusion-dependent thalassemia in Taiwan. Journal of the Formosan Medical Association, 112(4), 221–229. https://doi.org/10.1016/j.jfma.2011.08.020
Ige, A. O., Ongele, F. A., Adele, B. O., Emediong, I. E., Odetola, A. O., & Adewoye, E. O. (2019). Pathophysiology of iron overload-induced renal injury and dysfunction: Roles of renal oxidative stress and systemic inflammatory mediators. Pathophysiology, 26(2), 175–180. https://doi.org/10.1016/j.pathophys.2019.03.002
Jeong, J. J., Jang, S. E., Hyam, S. R., Han, M. J., & Kim, D. H. (2014). Mangiferin ameliorates colitis by inhibiting IRAK1 phosphorylation in NF-κB and MAPK pathways. European Journal of Pharmacology, 740, 652–661. https://doi.org/10.1016/j.ejphar.2014.06.013
Khurana, R. K., Kaur, R., Kaur, M., Kaur, R., Kaur, J., Kaur, H., & Singh, B. (2017). Exploring and validating physicochemical properties of mangiferin through GastroPlus® software. Future Science OA, 3(1). https://doi.org/10.4155/fsoa-2016-0055
Laksmitawati, D. R., Handayani, S., Udyaningsih-Freisleben, S. K., Kurniati, V., Adhiyanto, C., Hidayat, J., Kusnandar, S., Dillon, H. S. D., Munthe, B. G., Wirawan, R., Soegianto, R. R., Ramelan, W., & Freisleben, H. J. (2003). Iron status and oxidative stress in β-thalassemia patients in Jakarta. BioFactors, 19(1–2), 53–62. https://doi.org/10.1002/biof.5520190107
Li, X., Yan, Z., Carlström, M., Tian, J., Zhang, X., Zhang, W., Wu, S., & Ye, F. (2020). Mangiferin ameliorates hyperuricemic nephropathy which is associated with downregulation of AQP2 and increased urinary uric acid excretion. Frontiers in Pharmacology, 11(February), 1–12. https://doi.org/10.3389/fphar.2020.00049
Limtrakul, P., Khantamat, O., & Pintha, K. (2005). Inhibition of P-glycoprotein function and expression by kaempferol and quercetin. Journal of Chemotherapy, 17(1), 86–95. https://doi.org/10.1179/joc.2005.17.1.86
Pardo-Andreu, G. L., Sánchez-Baldoquín, C., Ávila-González, R., Delgado, R., Naal, Z., & Curti, C. (2006). Fe(III) improves antioxidant and cytoprotecting activities of mangiferin. European Journal of Pharmacology, 547(1–3), 31–36. https://doi.org/10.1016/j.ejphar.2006.07.040
Rodrigo, E., Martín de Francisco, A. L., Escallada, R., Ruiz, J. C., Fresnedo, G. F., Piñera, C., & Arias, M. (2002). Measurement of renal function in pre-ESRD patients. Kidney International, Supplement, 61(80), 11–17. https://doi.org/10.1046/j.1523-1755.61.s80.4.x
Rujito, L. (2019). Talasemia : Genetik Dasar dan Pengelolaan Terkini. In Universitas Jenderal Soedirman. Universitas Jenderal Soedirman.
Sumneang, N., Siri-Angkul, N., Kumfu, S., Chattipakorn, S. C., & Chattipakorn, N. (2020). The effects of iron overload on mitochondrial function, mitochondrial dynamics, and ferroptosis in cardiomyocytes. Archives of Biochemistry and Biophysics, 680(October 2019), 108241. https://doi.org/10.1016/j.abb.2019.108241
Sundari, N., Soetikno, V., Louisa, M., Wardhani, B. W., & Tjandrawinata, R. R. (2018). Protective Effect of Phaleria macrocarpa Water Extract (Proliverenol) against Carbon Tetrachloride-Induced Liver Fibrosis in Rats: Role of TNF-α and TGF-β1. Journal of Toxicology, 2018, 11–18. https://doi.org/10.1155/2018/2642714
Taher, A. T., & Cappellini, M. D. (2021). Luspatercept for β-thalassemia: beyond red blood cell transfusions. Expert Opinion on Biological Therapy, 00(00), 1–9. https://doi.org/10.1080/14712598.2021.1968825
Udani, K., Chris-Olaiya, A., Ohadugha, C., Malik, A., Sansbury, J., & Paari, D. (2021). Cardiovascular manifestations in hospitalized patients with hemochromatosis in the United States. International Journal of Cardiology, July. https://doi.org/10.1016/j.ijcard.2021.07.060
Wani, N., & Pasha, T. (2021). Laboratory tests of renal function. Anaesthesia and Intensive Care Medicine, 22(7), 393–397. https://doi.org/10.1016/j.mpaic.2021.05.010
Published
2024-06-24
How to Cite
Heriatmo, N. L., Estuningtyas, A., Soetikno, V., Poerwaningsih, E. H., & Kusmardi, K. (2024). Attenuation of TNF-α and Iron Levels in Renal Hemosiderosis by Phaleria macrocarpa (Scheff.) Boerl Extract in a Rat Iron Overload Model. Indonesian Journal of Pharmacy. https://doi.org/10.22146/ijp.6811
Section
Research Article