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Geraniin exerts cytoprotective effect against cellular oxidative stress by upregulation of Nrf2-mediated antioxidant enzyme expression via PI3K/AKT and ERK1/2 pathway.
Biochim Biophys Acta. 2015 Sep; 1850(9):1751-61.BB

Abstract

BACKGROUND

Geraniin, an active compound with remarkable antioxidant activity, was isolated from Geranium sibiricum. The present study aimed to investigate whether geraniin has the ability to activate Nrf2, induce antioxidant enzyme expression and protect cells from oxidative damage.

METHODS

The cells were pretreated with geraniin for 24h and exposed to hydrogen peroxide (H₂O₂) for 4h. Intracellular reactive oxygen species (ROS) levels, mitochondrial membrane potential and apoptosis were measured. We also investigated intracellular glutathione (GSH) levels and changes in nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated signaling cascade in cells treated with geraniin.

RESULTS

We investigated the protective effects of geraniin against H₂O₂-induced apoptosis in HepG2 cells. Geraniin significantly reduced H₂O₂-induced oxidative damage in a dose dependent manner. Further, geraniin induced the expression of heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1) and level of glutathione (GSH) in a concentration- and time-dependent manner, and increased Nrf2 nuclear translocation. The Nrf2-related cytoprotective effects of geraniin were PI3K/AKT and extracellular signal-regulated protein kinase1/2 (ERK1/2) pathway-dependent. However, inhibitors of PI3K/AKT and ERK1/2 (LY294002 or U0126) not only suppressed geraniin-induced nuclear translocation of Nrf2 but also abolished the expression of HO-1, NQO1 and GSH.

CONCLUSIONS

These results demonstrated that geraniin induced Nrf2-mediated expression of antioxidant enzymes HO-1 and NQO1, presumably via PI3K/AKT and ERK1/2 signaling pathways, thereby protecting cells from H₂O₂-induced oxidative cell death.

GENERAL SIGNIFICANCE

Geraniin, at least in part, offers an antioxidant defense capacity to protect cells from the oxidative stress-related diseases.

Authors+Show Affiliations

Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China; Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Heilongjiang Province, PR China.Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China. Electronic address: yujie_fu2002@yahoo.com.Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.

Pub Type(s)

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

Language

eng

PubMed ID

25917210

Citation

Wang, Peng, et al. "Geraniin Exerts Cytoprotective Effect Against Cellular Oxidative Stress By Upregulation of Nrf2-mediated Antioxidant Enzyme Expression Via PI3K/AKT and ERK1/2 Pathway." Biochimica Et Biophysica Acta, vol. 1850, no. 9, 2015, pp. 1751-61.
Wang P, Peng X, Wei ZF, et al. Geraniin exerts cytoprotective effect against cellular oxidative stress by upregulation of Nrf2-mediated antioxidant enzyme expression via PI3K/AKT and ERK1/2 pathway. Biochim Biophys Acta. 2015;1850(9):1751-61.
Wang, P., Peng, X., Wei, Z. F., Wei, F. Y., Wang, W., Ma, W. D., Yao, L. P., Fu, Y. J., & Zu, Y. G. (2015). Geraniin exerts cytoprotective effect against cellular oxidative stress by upregulation of Nrf2-mediated antioxidant enzyme expression via PI3K/AKT and ERK1/2 pathway. Biochimica Et Biophysica Acta, 1850(9), 1751-61. https://doi.org/10.1016/j.bbagen.2015.04.010
Wang P, et al. Geraniin Exerts Cytoprotective Effect Against Cellular Oxidative Stress By Upregulation of Nrf2-mediated Antioxidant Enzyme Expression Via PI3K/AKT and ERK1/2 Pathway. Biochim Biophys Acta. 2015;1850(9):1751-61. PubMed PMID: 25917210.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Geraniin exerts cytoprotective effect against cellular oxidative stress by upregulation of Nrf2-mediated antioxidant enzyme expression via PI3K/AKT and ERK1/2 pathway. AU - Wang,Peng, AU - Peng,Xiao, AU - Wei,Zuo-Fu, AU - Wei,Fu-Yao, AU - Wang,Wei, AU - Ma,Wei-Dong, AU - Yao,Li-Ping, AU - Fu,Yu-Jie, AU - Zu,Yuan-Gang, Y1 - 2015/04/23/ PY - 2014/11/26/received PY - 2015/03/29/revised PY - 2015/04/16/accepted PY - 2015/4/29/entrez PY - 2015/4/29/pubmed PY - 2015/9/29/medline KW - Antioxidant gene KW - Cytoprotection KW - Geraniin KW - Human hepatocarcinoma cell line KW - Nrf2 KW - Oxidative stress SP - 1751 EP - 61 JF - Biochimica et biophysica acta JO - Biochim Biophys Acta VL - 1850 IS - 9 N2 - BACKGROUND: Geraniin, an active compound with remarkable antioxidant activity, was isolated from Geranium sibiricum. The present study aimed to investigate whether geraniin has the ability to activate Nrf2, induce antioxidant enzyme expression and protect cells from oxidative damage. METHODS: The cells were pretreated with geraniin for 24h and exposed to hydrogen peroxide (H₂O₂) for 4h. Intracellular reactive oxygen species (ROS) levels, mitochondrial membrane potential and apoptosis were measured. We also investigated intracellular glutathione (GSH) levels and changes in nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated signaling cascade in cells treated with geraniin. RESULTS: We investigated the protective effects of geraniin against H₂O₂-induced apoptosis in HepG2 cells. Geraniin significantly reduced H₂O₂-induced oxidative damage in a dose dependent manner. Further, geraniin induced the expression of heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1) and level of glutathione (GSH) in a concentration- and time-dependent manner, and increased Nrf2 nuclear translocation. The Nrf2-related cytoprotective effects of geraniin were PI3K/AKT and extracellular signal-regulated protein kinase1/2 (ERK1/2) pathway-dependent. However, inhibitors of PI3K/AKT and ERK1/2 (LY294002 or U0126) not only suppressed geraniin-induced nuclear translocation of Nrf2 but also abolished the expression of HO-1, NQO1 and GSH. CONCLUSIONS: These results demonstrated that geraniin induced Nrf2-mediated expression of antioxidant enzymes HO-1 and NQO1, presumably via PI3K/AKT and ERK1/2 signaling pathways, thereby protecting cells from H₂O₂-induced oxidative cell death. GENERAL SIGNIFICANCE: Geraniin, at least in part, offers an antioxidant defense capacity to protect cells from the oxidative stress-related diseases. SN - 0006-3002 UR - https://www.unboundmedicine.com/medline/citation/25917210/Geraniin_exerts_cytoprotective_effect_against_cellular_oxidative_stress_by_upregulation_of_Nrf2_mediated_antioxidant_enzyme_expression_via_PI3K/AKT_and_ERK1/2_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-4165(15)00115-4 DB - PRIME DP - Unbound Medicine ER -