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Asiatic acid enhances Nrf2 signaling to protect HepG2 cells from oxidative damage through Akt and ERK activation.
Biomed Pharmacother. 2017 Apr; 88:252-259.BP

Abstract

Asiatic acid (AA), a natural triterpene isolated from the plant Centella asiatica, have antioxidative potential, but the molecular mechanism of AA against oxidative stress remains unclear. Our study was performed to investigate the antioxidative effect of AA against oxidative stress and the antioxidative mechanism in tert-butyl hydroperoxide (t-BHP) -stimulated the HepG2 cells. The results showed that AA suppressed t-BHP-induced cytotoxicity, apoptosis, and reactive oxygen species (ROS) generation. Additionally, AA activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signal, which was closely related to induction Nrf2 nuclear translocation, reduction the expression of Keap1 and up-regulation the activity of the antioxidant response element (ARE). Meanwhile, activation of Nrf2 signal upregulated the protein expressions of antioxidant genes, including heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidase (NQO-1), and glutamyl cysteine ligase catalytic subunit (GCLC). Excitingly, Knockout of Nrf2 almost abolished AA-mediated antioxidant activity and cytoprotection against t-BHP. Further studies showed the mechanism underlying that AA induced Nrf2 activation in HepG2 cells via Akt and ERK signal activation. We found Akt and ERK inhibitors treatment attenuated AA-mediated Nrf2 nuclear translocation. Furthermore, treatment with either Akt or ERK inhibitor also decreased AA-mediated cytoprotection against t-BHP-induced cellular damage. Collectively, these results presented in this study indicate that AA has the protective effect against t-BHP-induced cellular damage and oxidative stress by modulating Nrf2 signaling through activating the signals of Akt and ERK.

Authors+Show Affiliations

Institute of Translational Medicine, The First Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun, 130061, China.Institute of Translational Medicine, The First Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun, 130061, China.Department of Traditional Chinese Medicine, The First Hospital of Jilin University, Changchun, 130061, China.Institute of Translational Medicine, The First Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun, 130061, China.Institute of Translational Medicine, The First Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun, 130061, China.Department of Dermatology and Venereology, The First Hospital of Jilin University, Changchun, 130061, China. Electronic address: 646603407@qq.com.Institute of Translational Medicine, The First Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun, 130061, China. Electronic address: dengxm@jlu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28110191

Citation

Qi, Zhimin, et al. "Asiatic Acid Enhances Nrf2 Signaling to Protect HepG2 Cells From Oxidative Damage Through Akt and ERK Activation." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 88, 2017, pp. 252-259.
Qi Z, Ci X, Huang J, et al. Asiatic acid enhances Nrf2 signaling to protect HepG2 cells from oxidative damage through Akt and ERK activation. Biomed Pharmacother. 2017;88:252-259.
Qi, Z., Ci, X., Huang, J., Liu, Q., Yu, Q., Zhou, J., & Deng, X. (2017). Asiatic acid enhances Nrf2 signaling to protect HepG2 cells from oxidative damage through Akt and ERK activation. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 88, 252-259. https://doi.org/10.1016/j.biopha.2017.01.067
Qi Z, et al. Asiatic Acid Enhances Nrf2 Signaling to Protect HepG2 Cells From Oxidative Damage Through Akt and ERK Activation. Biomed Pharmacother. 2017;88:252-259. PubMed PMID: 28110191.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Asiatic acid enhances Nrf2 signaling to protect HepG2 cells from oxidative damage through Akt and ERK activation. AU - Qi,Zhimin, AU - Ci,Xinxin, AU - Huang,Jingbo, AU - Liu,Qinmei, AU - Yu,Qinlei, AU - Zhou,Junfeng, AU - Deng,Xuming, Y1 - 2017/01/19/ PY - 2016/11/28/received PY - 2017/01/04/revised PY - 2017/01/10/accepted PY - 2017/1/23/pubmed PY - 2017/3/14/medline PY - 2017/1/23/entrez KW - Asiatic acid KW - HepG2 cells KW - Nrf2 KW - Oxidative stress SP - 252 EP - 259 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 88 N2 - Asiatic acid (AA), a natural triterpene isolated from the plant Centella asiatica, have antioxidative potential, but the molecular mechanism of AA against oxidative stress remains unclear. Our study was performed to investigate the antioxidative effect of AA against oxidative stress and the antioxidative mechanism in tert-butyl hydroperoxide (t-BHP) -stimulated the HepG2 cells. The results showed that AA suppressed t-BHP-induced cytotoxicity, apoptosis, and reactive oxygen species (ROS) generation. Additionally, AA activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signal, which was closely related to induction Nrf2 nuclear translocation, reduction the expression of Keap1 and up-regulation the activity of the antioxidant response element (ARE). Meanwhile, activation of Nrf2 signal upregulated the protein expressions of antioxidant genes, including heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidase (NQO-1), and glutamyl cysteine ligase catalytic subunit (GCLC). Excitingly, Knockout of Nrf2 almost abolished AA-mediated antioxidant activity and cytoprotection against t-BHP. Further studies showed the mechanism underlying that AA induced Nrf2 activation in HepG2 cells via Akt and ERK signal activation. We found Akt and ERK inhibitors treatment attenuated AA-mediated Nrf2 nuclear translocation. Furthermore, treatment with either Akt or ERK inhibitor also decreased AA-mediated cytoprotection against t-BHP-induced cellular damage. Collectively, these results presented in this study indicate that AA has the protective effect against t-BHP-induced cellular damage and oxidative stress by modulating Nrf2 signaling through activating the signals of Akt and ERK. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/28110191/Asiatic_acid_enhances_Nrf2_signaling_to_protect_HepG2_cells_from_oxidative_damage_through_Akt_and_ERK_activation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(16)32511-2 DB - PRIME DP - Unbound Medicine ER -