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Activation of Akt and JNK/Nrf2/NQO1 pathway contributes to the protective effect of coptisine against AAPH-induced oxidative stress.
Biomed Pharmacother. 2017 Jan; 85:313-322.BP

Abstract

Coptisine (COP) is one of the main active constituents of Coptidis Rhizoma. Previous studies have clarified that COP possesses antioxidant activity, but its defensive effects against pathological characteristics accompanied by oxidative damage in animal models and antioxidant mechanism are still unclear. Therefore, our purpose was to confirm the antioxidant activity of COP and explore its mechanism of action. We first detected the effects of COP on intracellular reactive oxygen species (ROS), heart beating rate, lipid peroxidation and cell death in zebrafish model with AAPH-induced oxidative stress. The results showed that COP of 10μg/mL significantly reduced ROS production, the increase of heart beating rate, lipid peroxidation and cell death by 41.3%, 24.5%, 26.5% and 30.0%, respectively. In addition, COP of 0.8μg/mL also decreased ROS, increased glutathione (GSH) content and elevated activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) by 40.1%, 19.8%, 18.3% and 49.3%, respectively in HepG2 cells. Further assays were carried out to explore the mRNA expression in zebrafish and protein expression of key factors in HepG2 cells. We demonstrated that COP up-regulated phase II antioxidant enzymes NAD(P)H/quinone oxidoreductase 1 (NQO1) through activating the nuclear factor erythroid-2 related factor 2 (Nrf2). Moreover, as the upstream signalings of Nrf2, the protein kinase B (Akt) and c-Jun NH2-terminal kinase (JNK) signalings were also induced by COP. And up-regulating Nrf2-mediated NQO1 expression of COP was in Akt and JNK-dependent manner. Taken together, COP exerted its antioxidant activity against AAPH-induced toxicity involving in activating Akt and JNK/Nrf2/NQO1 pathway.

Authors+Show Affiliations

College of Pharmaceutical Sciences, Southwest University, Chongqing, 400716, China; Chongqing Productivity Promotion Centre for the Modernization of Chinese Medicine, Chongqing, 400716, China; Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control, Chongqing, 400716, China.College of Pharmaceutical Sciences, Southwest University, Chongqing, 400716, China; Chongqing Productivity Promotion Centre for the Modernization of Chinese Medicine, Chongqing, 400716, China; Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control, Chongqing, 400716, China.College of Pharmaceutical Sciences, Southwest University, Chongqing, 400716, China; Chongqing Productivity Promotion Centre for the Modernization of Chinese Medicine, Chongqing, 400716, China; Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control, Chongqing, 400716, China.College of Pharmaceutical Sciences, Southwest University, Chongqing, 400716, China; Chongqing Productivity Promotion Centre for the Modernization of Chinese Medicine, Chongqing, 400716, China; Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control, Chongqing, 400716, China.College of Pharmaceutical Sciences, Southwest University, Chongqing, 400716, China; Chongqing Productivity Promotion Centre for the Modernization of Chinese Medicine, Chongqing, 400716, China; Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control, Chongqing, 400716, China.School of Life Sciences, Southwest University, Chongqing, 400715, China.College of Pharmaceutical Sciences, Southwest University, Chongqing, 400716, China; Chongqing Productivity Promotion Centre for the Modernization of Chinese Medicine, Chongqing, 400716, China; Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control, Chongqing, 400716, China.School of Life Sciences, Southwest University, Chongqing, 400715, China.College of Pharmaceutical Sciences, Southwest University, Chongqing, 400716, China; Chongqing Productivity Promotion Centre for the Modernization of Chinese Medicine, Chongqing, 400716, China; Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control, Chongqing, 400716, China. Electronic address: xuegangli@swu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27903425

Citation

Hu, Yin-Ran, et al. "Activation of Akt and JNK/Nrf2/NQO1 Pathway Contributes to the Protective Effect of Coptisine Against AAPH-induced Oxidative Stress." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 85, 2017, pp. 313-322.
Hu YR, Ma H, Zou ZY, et al. Activation of Akt and JNK/Nrf2/NQO1 pathway contributes to the protective effect of coptisine against AAPH-induced oxidative stress. Biomed Pharmacother. 2017;85:313-322.
Hu, Y. R., Ma, H., Zou, Z. Y., He, K., Xiao, Y. B., Wang, Y., Feng, M., Ye, X. L., & Li, X. G. (2017). Activation of Akt and JNK/Nrf2/NQO1 pathway contributes to the protective effect of coptisine against AAPH-induced oxidative stress. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 85, 313-322. https://doi.org/10.1016/j.biopha.2016.11.031
Hu YR, et al. Activation of Akt and JNK/Nrf2/NQO1 Pathway Contributes to the Protective Effect of Coptisine Against AAPH-induced Oxidative Stress. Biomed Pharmacother. 2017;85:313-322. PubMed PMID: 27903425.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of Akt and JNK/Nrf2/NQO1 pathway contributes to the protective effect of coptisine against AAPH-induced oxidative stress. AU - Hu,Yin-Ran, AU - Ma,Hang, AU - Zou,Zong-Yao, AU - He,Kai, AU - Xiao,Yu-Bo, AU - Wang,Yue, AU - Feng,Min, AU - Ye,Xiao-Li, AU - Li,Xue-Gang, Y1 - 2016/11/27/ PY - 2016/08/04/received PY - 2016/11/07/revised PY - 2016/11/08/accepted PY - 2016/12/3/pubmed PY - 2017/2/14/medline PY - 2016/12/2/entrez KW - Akt KW - Antioxidation KW - Coptisine KW - Coptisine (PubChem CID: 72322) KW - JNK KW - L-ascorbic acid (PubChem CID: 54670067) KW - NQO1 KW - Nrf2 SP - 313 EP - 322 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 85 N2 - Coptisine (COP) is one of the main active constituents of Coptidis Rhizoma. Previous studies have clarified that COP possesses antioxidant activity, but its defensive effects against pathological characteristics accompanied by oxidative damage in animal models and antioxidant mechanism are still unclear. Therefore, our purpose was to confirm the antioxidant activity of COP and explore its mechanism of action. We first detected the effects of COP on intracellular reactive oxygen species (ROS), heart beating rate, lipid peroxidation and cell death in zebrafish model with AAPH-induced oxidative stress. The results showed that COP of 10μg/mL significantly reduced ROS production, the increase of heart beating rate, lipid peroxidation and cell death by 41.3%, 24.5%, 26.5% and 30.0%, respectively. In addition, COP of 0.8μg/mL also decreased ROS, increased glutathione (GSH) content and elevated activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) by 40.1%, 19.8%, 18.3% and 49.3%, respectively in HepG2 cells. Further assays were carried out to explore the mRNA expression in zebrafish and protein expression of key factors in HepG2 cells. We demonstrated that COP up-regulated phase II antioxidant enzymes NAD(P)H/quinone oxidoreductase 1 (NQO1) through activating the nuclear factor erythroid-2 related factor 2 (Nrf2). Moreover, as the upstream signalings of Nrf2, the protein kinase B (Akt) and c-Jun NH2-terminal kinase (JNK) signalings were also induced by COP. And up-regulating Nrf2-mediated NQO1 expression of COP was in Akt and JNK-dependent manner. Taken together, COP exerted its antioxidant activity against AAPH-induced toxicity involving in activating Akt and JNK/Nrf2/NQO1 pathway. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/27903425/Activation_of_Akt_and_JNK/Nrf2/NQO1_pathway_contributes_to_the_protective_effect_of_coptisine_against_AAPH_induced_oxidative_stress_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(16)31211-2 DB - PRIME DP - Unbound Medicine ER -