EFFECT OF FLAVONOIDS ON OXIDATIVE STRESS, APOPTOSIS, AND CELL MARKERS OF PERIPHERAL BLOOD-DERIVED ENDOTHELIAL PROGENITOR CELLS: AN IN VITRO STUDY

  • WAHYU WIDOWATI Faculty of Medicine, Maranatha Christian University, Bandung 40164, West Java, Indonesia
  • RIMONTA F. GUNANEGARA Faculty of Medicine, Maranatha Christian University, Bandung 40164, West Java, Indonesia
  • TERESA LILIANA WARGASETIA Faculty of Medicine, Maranatha Christian University, Bandung 40164, West Java, Indonesia
  • HANNA SARI WIDYA KUSUMA Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung, 40163, West Java, Indonesia
  • SEILA ARUMWARDANA Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung, 40163, West Java, Indonesia
  • CINTANI DEWI WAHYUNI Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung, 40163, West Java, Indonesia
  • ERMI GIRSANG Faculty of Medicine, Universitas Prima Indonesia, Medan 20118, North Sumatera, Indonesia
  • I NYOMAN EHRICH LISTER Faculty of Medicine, Universitas Prima Indonesia, Medan 20118, North Sumatera, Indonesia
  • CHRISMIS NOVALINDA GINTING Faculty of Medicine, Universitas Prima Indonesia, Medan 20118, North Sumatera, Indonesia
  • RIZAL RIZAL Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung, 40163, West Java, Indonesia, Biomedical Engineering, Department of Electrical Engineering, Faculty of Engineering, Universitas Indonesia, Depok 16426, West Java, Indonesia
  • INDRA BACHTIAR Stem Cell and Cancer Institute, Jakarta, 13210, Indonesia
  • HARRY MURTI Stem Cell and Cancer Institute, Jakarta, 13210, IndonesiaHARRY MURTI
  • YOUNG HO KIM College of Pharmacy, Chungnam National University, Republic of Korea

Abstract

Objective: Circulating EPCs (endothelial progenitor cells) play a role in neovascularization and vascular repair. Oxidative stress impairs endothelial progenitor. Flavonoid is a phytochemical compound for antioxidant activity. Flavonoid effects toward oxidative stress, apoptosis, and expression of the cell markers on EPCs are not fully understood. This study was aimed to elucidate the effects of quercetin, kaempferol, and myricetin toward oxidative stress, apoptosis, and cell markers of peripheral blood-derived-EPCs.


Methods: EPCs (endothelial progenitor cells) were isolated from peripheral blood mononuclear cells (PBMNCs) using cultivation under EPCs spesific media. Oxidative stress in EPCs was induced by H2O2 and then treated by quercetin, kaempferol, and myricetin. Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, while intracellular reactive oxygen species (ROS), apoptosis and characterization of cells, which expressed CD133 and KDR, was measured using flow cytometry.


Results: Quercetin, kaempferol, and myricetin at concentration 12.50 µmol/l were not toxic on EPCs as the cells viability were 96.11±4.03%, 95.42±7.75%, and 94.22±9.49%, respectively. Flavonoids decreased intracellular ROS level in EPCs (quercetin: 14.38±1.47%, kaempferol: 20.21±6.25%, and myricetin: 13.88±4.02%) compared to EPCs treated with H2O2 (30.70%±1.04). Percetage of EPCs apoptosis was not significantly different among each treatment. Immunophenotyping showed the increasing of CD133 and KDR expression in EPCs treated with flavonoids.


Conclusion: Quercetin, kaempferol, and myricetin were safe for EPCs, decreased ROS levels, and increased CD133 and KDR expression. However, the flavonoids did not significantly affect EPCs apoptosis.

Keywords: Apoptosis, Endothelial progenitor cells, Flavonoids, Reactive oxygen species

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WIDOWATI, W., GUNANEGARA, R. F., WARGASETIA, T. L., KUSUMA, H. S. W., ARUMWARDANA, S., WAHYUNI, C. D., GIRSANG, E., LISTER, I. N. E., GINTING, C. N., RIZAL, R., BACHTIAR, I., MURTI, H., & KIM, Y. H. (2021). EFFECT OF FLAVONOIDS ON OXIDATIVE STRESS, APOPTOSIS, AND CELL MARKERS OF PERIPHERAL BLOOD-DERIVED ENDOTHELIAL PROGENITOR CELLS: AN IN VITRO STUDY. International Journal of Applied Pharmaceutics, 13(3), 39-42. https://doi.org/10.22159/ijap.2021.v13s3.07
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