酰化4-羟基查耳酮对H2O2诱导的PC12细胞凋亡的抗氧化保护作用及初步机制

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Abstract Objective: To investigate the protective function of previously synthesized and screened chalcones B1 and B2 against PC12 cells apoptosis induced by H2O2, and their impact on Nrf2/ARE signaling pathway. Methods: A model that PC12 cells were damaged by H2O2 was established, and MTT assay was used to detect the antioxidant activity as well as cytotoxicity of compounds B1 and B2. Real-time PCR was used to determine mRNA expression of Nrf-2 regulated genes GCLC and HO-1. Hoechst staining was applied to test the inhibitory ability against H2O2-mediated PC12 cells apoptosis. Results: B1 and B2 showed no protection on PC12 cells induced by H2O2 in case of 1 hour incubation, while they represented potent antioxidant efficiency after incubation for 24 hours, and both were nontoxic at 10 μmol/L. B1 showed no obvious effect on the expression of GCLC and HO-1 which were Nrf2-regulated downstream genes. B2 significantly prevented the PC12 cells apoptosis caused by H2O2 with activating the expression of GCLC and HO-1. Conclusion: B1 and B2 show a significant antioxidant activity against H2O2-induced PC12 cells injury. The possible mechanism of B2 may be its activation of Nrf2/ARE signaling pathways while B1 may perform the antioxidant action via other route.

Key words： chalcone synthesis antioxidant H2O2 induction Nrf2/ARE

Received: 03 June 2014

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	Articles by authors
	WANG Yanan1
	SHEN Lailai2
	WANG Zhankun3
	ZHOU Jiabei2
	CHENG Chanchan2
	HU Qiongqiong1
	FANG Pengcheng1
	QIU Peihong2
	WU Jianzhang2
	LIANG Guang2.

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https://xb.wmu.edu.cn/EN/ OR https://xb.wmu.edu.cn/EN/Y2015/V45/I1/26

[1] Gilgun-Sherki Y, Rosenbaum Z, Melamed E, et al. Antioxidant therapy in acute central nervous system injury: current state[J]. Pharmacol Rev, 2002, 54(2): 271-284.
[2] Halliwell B. Reactive species and antioxidants. Redox biology is a fundamental theme of aerobic life[J]. Plant Physiol, 2006, 141(2): 312-322.
[3] Sahu NK, Balbhadra SS, Choudhary J, et al. Exploring pharmacological significance of chalcone scaffold: a review[J].Curr Med Chem, 2012, 19(2): 209-225.
[4] 吴建章, 李物兰, 陈玲姿, 等. 查尔酮及其螺杂环衍生物的合成、晶体结构、抗氧化活性研究[J]. 有机化学, 2012, 32: 2141-2147.
[5] Kumar V, Kumar S, Hassan M, et al. Novel chalcone derivatives as potent Nrf2 activators in mice and human lung epithelial cells[J]. J Med Chem, 2011, 54(12): 4147-4159.
[6] Sawle P, Moulton BE, Jarzykowska M, et al. Structure-activity relationships of methoxychalcones as inducers of heme oxygenase-1[J]. Chem Res Toxicol, 2008, 21(7): 1484-1494.
[7] Shenvi S, Kumar K, Hatti KS, et al. Synthesis, anticancer and antioxidant activities of 2,4,5-trimethoxy chalcones and analogues from asaronaldehyde: structure-activity relationship[J]. Eur J Med Chem, 2013, 62: 435-442.
[8] Gacche R, Khsirsagar M, Kamble S, et al. Antioxidant and anti-inflammatory related activities of selected synthetic chalcones: structure-activity relationship studies usin computational tools[J]. Chem Pharm Bull (Tokyo), 2008, 56(7): 897-901.
[9] Wu JZ, Cheng CC, Shen LL, et al. Synthetic chalcones with potent antioxidant ability on H2O2-induced apoptosis in PC12 cells[J]. Int J Mol Sci, 2014, 15(10): 18525-18539.
[10] Wu J, Li J, Cai Y, et al. Evaluation and discovery of novel synthetic chalcone derivatives as anti-inflammatory agents [J]. J Med Chem, 2011, 54(23): 8110-8123.
[11] Kumar A, Sharma S, Tripathi VD, et al. Synthesis of chalcones and flavanones using Julia-Kocienski olefination[J].Tetrahedron, 2010, 66(48): 9445-9449.
[12] Scapagnini G, Vasto S, Abraham NG, et al. Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neurodegenerative disorders[J]. Mol Neurobiol, 2011, 44(2): 192-201.
[13] Zhao J, Moore AN, Redell JB, et al. Enhancing expression of Nrf2-driven genes protects the blood brain barrier after brain injury[J]. J Neurosci, 2007, 27(38): 10240-10248.
[14] Yang YC, Lii CK, Lin AH, et al. Induction of glutathione synthesis and heme oxygenase 1 by the flavonoids butein and phloretin is mediated through the ERK/Nrf2 pathway and protects against oxidative stress[J]. Free Radic Biol Med, 2011, 51(11): 2073-2081.
[15] Padhye S, Ahmad A, Oswal N, et al. Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs[J]. J Hematol Oncol, 2009, 2: 38.