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Protection by chrysin, apigenin, and luteolin against oxidative stress is mediated by the Nrf2-dependent up-regulation of heme oxygenase 1 and glutamate cysteine ligase in rat primary hepatocytes.
Arch Toxicol. 2013 Jan; 87(1):167-78.AT

Abstract

Chrysin, apigenin, and luteolin are flavones that differ in their number of hydroxyl groups in the B ring. In this study, we investigated the protection by chrysin, apigenin, and luteolin against tert-butyl hydroperoxide (tBHP)-induced oxidative stress and the possible mechanisms involved in rat primary hepatocytes. Chrysin, apigenin, and luteolin dose-dependently up-regulated the protein expression of heme oxygenase 1 (HO-1) and glutamate cysteine ligase (GCL) catalytic (GCLC) and modifier subunit (GCLM) and increased the intracellular glutathione (GSH) content and the ratio of GSH to oxidized GSH. Among the flavones studied, chrysin showed the greatest induction of HO-1, GCLC, and GCLM protein expression and GSH content. Cellular reactive oxygen species production induced by tBHP was attenuated by pretreatment with chrysin, apigenin, and luteolin (P < .05), and this protection was reversed by the GCL inhibitor l-buthionine-S-sulfoximine and the HO-1 inhibitor zinc protoporphyrin. Chrysin, apigenin, and luteolin activated extracellular signal-regulated protein kinase 2 (ERK2), nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, nuclear Nrf2-antioxidant responsive element (ARE) binding activity, and ARE-dependent luciferase activity. Both ERK2 and Nrf2 siRNAs attenuated chrysin-induced HO-1, GCLC, and GCLM protein expression. Taken together, these results suggest that chrysin, apigenin, and luteolin inhibit tBHP-induced oxidative stress by up-regulating HO-1, GCLC, and GCLM gene transcription via the ERK2/Nrf2/ARE signaling pathways in rat primary hepatocytes.

Authors+Show Affiliations

Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan, ROC.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22864849

Citation

Huang, Chin-Shiu, et al. "Protection By Chrysin, Apigenin, and Luteolin Against Oxidative Stress Is Mediated By the Nrf2-dependent Up-regulation of Heme Oxygenase 1 and Glutamate Cysteine Ligase in Rat Primary Hepatocytes." Archives of Toxicology, vol. 87, no. 1, 2013, pp. 167-78.
Huang CS, Lii CK, Lin AH, et al. Protection by chrysin, apigenin, and luteolin against oxidative stress is mediated by the Nrf2-dependent up-regulation of heme oxygenase 1 and glutamate cysteine ligase in rat primary hepatocytes. Arch Toxicol. 2013;87(1):167-78.
Huang, C. S., Lii, C. K., Lin, A. H., Yeh, Y. W., Yao, H. T., Li, C. C., Wang, T. S., & Chen, H. W. (2013). Protection by chrysin, apigenin, and luteolin against oxidative stress is mediated by the Nrf2-dependent up-regulation of heme oxygenase 1 and glutamate cysteine ligase in rat primary hepatocytes. Archives of Toxicology, 87(1), 167-78. https://doi.org/10.1007/s00204-012-0913-4
Huang CS, et al. Protection By Chrysin, Apigenin, and Luteolin Against Oxidative Stress Is Mediated By the Nrf2-dependent Up-regulation of Heme Oxygenase 1 and Glutamate Cysteine Ligase in Rat Primary Hepatocytes. Arch Toxicol. 2013;87(1):167-78. PubMed PMID: 22864849.
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TY - JOUR T1 - Protection by chrysin, apigenin, and luteolin against oxidative stress is mediated by the Nrf2-dependent up-regulation of heme oxygenase 1 and glutamate cysteine ligase in rat primary hepatocytes. AU - Huang,Chin-Shiu, AU - Lii,Chong-Kuei, AU - Lin,Ai-Hsuan, AU - Yeh,Yu-Wen, AU - Yao,Hsien-Tsung, AU - Li,Chien-Chun, AU - Wang,Tsu-Shing, AU - Chen,Haw-Wen, Y1 - 2012/08/05/ PY - 2012/05/10/received PY - 2012/07/24/accepted PY - 2012/8/7/entrez PY - 2012/8/7/pubmed PY - 2013/6/8/medline SP - 167 EP - 78 JF - Archives of toxicology JO - Arch Toxicol VL - 87 IS - 1 N2 - Chrysin, apigenin, and luteolin are flavones that differ in their number of hydroxyl groups in the B ring. In this study, we investigated the protection by chrysin, apigenin, and luteolin against tert-butyl hydroperoxide (tBHP)-induced oxidative stress and the possible mechanisms involved in rat primary hepatocytes. Chrysin, apigenin, and luteolin dose-dependently up-regulated the protein expression of heme oxygenase 1 (HO-1) and glutamate cysteine ligase (GCL) catalytic (GCLC) and modifier subunit (GCLM) and increased the intracellular glutathione (GSH) content and the ratio of GSH to oxidized GSH. Among the flavones studied, chrysin showed the greatest induction of HO-1, GCLC, and GCLM protein expression and GSH content. Cellular reactive oxygen species production induced by tBHP was attenuated by pretreatment with chrysin, apigenin, and luteolin (P < .05), and this protection was reversed by the GCL inhibitor l-buthionine-S-sulfoximine and the HO-1 inhibitor zinc protoporphyrin. Chrysin, apigenin, and luteolin activated extracellular signal-regulated protein kinase 2 (ERK2), nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, nuclear Nrf2-antioxidant responsive element (ARE) binding activity, and ARE-dependent luciferase activity. Both ERK2 and Nrf2 siRNAs attenuated chrysin-induced HO-1, GCLC, and GCLM protein expression. Taken together, these results suggest that chrysin, apigenin, and luteolin inhibit tBHP-induced oxidative stress by up-regulating HO-1, GCLC, and GCLM gene transcription via the ERK2/Nrf2/ARE signaling pathways in rat primary hepatocytes. SN - 1432-0738 UR - https://www.unboundmedicine.com/medline/citation/22864849/Protection_by_chrysin_apigenin_and_luteolin_against_oxidative_stress_is_mediated_by_the_Nrf2_dependent_up_regulation_of_heme_oxygenase_1_and_glutamate_cysteine_ligase_in_rat_primary_hepatocytes_ L2 - https://doi.org/10.1007/s00204-012-0913-4 DB - PRIME DP - Unbound Medicine ER -