Ethyl acetate extract of Wedelia chinensis inhibits tert-butyl hydroperoxide-induced damage in PC12 cells and D-galactose-induced neuronal cell loss in mice

BMC Complementary and Alternative Medicine

Tsui-Hwa Tseng⁵  Yean-Jang Lee¹  Hsing-Chun Kuo²  Ying-Jui Ho³  Shao-Ming Wang⁴  Wea-Lung Lin⁶ 

[1] Department of Chemistry, National Changhua University of Education, No. 1, Jin-De Road, Changhua 500, Taiwan;Department of Nursing, Chang Gung University of Science and Technology, Chia-Yi Campus No. 2, Chia-Pu Rd. West Sec. Putz, Chia-Yi 613, Taiwan;School of Psychology, Chung Shan Medical University, No. 110, Section 1, Chien-Kuo N. Road, Taichung 402, Taiwan;School of Medical Applied Chemistry, Chung Shan Medical University, No. 110, Section 1, Chien-Kuo N. Road, Taichung 402, Taiwan;Department of Medical Education, Chung Shan Medical University Hospital, No. 110, Section 1, Chien-Kuo N. Road, Taichung 402, Taiwan;School of Medicine, Chung Shan Medical University, No. 110, Section 1, Chien-Kuo N. Road, Taichung, Taiwan

关键词: Wedelolactone;    Wedelia chinensis;    Luteolin;    D-galactose;    t-butylhydroperoxide;    Apoptosis;   

Others  :  1084822
DOI  :  10.1186/1472-6882-14-491

 received in 2014-06-13, accepted in 2014-12-10,  发布年份 2014

【 摘 要 】

Background

Wedelia chinensis is traditionally used as a hepatoprotective herb in Taiwan. The aim of this study was to evaluate the neuroprotective potential of W. chinensis.

Methods

An ethyl acetate extract of W. chinensis (EAW) was prepared and analyzed by HPLC. The neuroprotective potential of EAW was assessed by tert-butylhydroperoxide (t-BHP)-induced damage in PC12 cells and D-galactose-induced damage in mouse cortex.

Results

EAW exhibited potent radical scavenging property and highly contained luteolin and wedelolactone. EAW decreased t-BHP-induced reactive oxygen species (ROS) accumulation, cytotoxicity and apoptosis in PC12 cells. EAW and its major constituents blocked t-BHP-induced cytochrome C release and Bcl-2 family protein ratio change. EAW and its major constituents increased the endogenous antioxidant capacity evaluated by the binding activity assay of nuclear factor E2-related factor 2 (Nrf2) to antioxidant response element (ARE) and nuclear translocation of Nrf2 respectively in PC12 cells. Finally, EAW inhibited D-galactose-induced lipid peroxidation, apoptosis and neuron loss in the cerebral cortex of mice.

Conclusion

These results demonstrate that W. chinensis has neuroprotective potential through blocking oxidative stress-induced damage and that luteolin and wedelolactone contribute to the protective action.

【 授权许可】

   
2014 Lin et al.; licensee BioMed Central.

【 图 表 】

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【 参考文献 】

• [1]Quintanilla RA, Orellana JA, von Bernhardi R: Understanding risk factors for Alzheimer’s disease: interplay of neuroinflammation, connexin-based communication and oxidative stress. Arch Med Res 2012, 43:632-644.
• [2]Adams JD Jr, Klaidman LK, Huang YM, Cheng JJ, Wang ZJ, Nguyen M, Knusel B, Kuda A: The neuropathology of intracerebroventricular t-butylhydroperoxide. Mol Chem Neuropathol 1994, 22:123-142.
• [3]Plas EK, Aw TY: Early redox imbalance mediates hydroperoxide-induced apoptosis in mitotic competent undifferentiated PC-12 cells. Cell Death Differ 2002, 9:1007-1016.
• [4]Iannone A, Bini A, Jin YG, Vannini V, Tomasi A: tert-Butylhydroperoxide bioactivation to methyl radical in rat liver mitochondria and submitochondrial particles. Free Radic Res Commun 1993, 19:S141-S147.
• [5]Guidarelli A, Clementi E, Sciorati C, Cattabeni F, Cantoni O: Calcium-dependent mitochondrial formation of species mediating DNA single strand breakage in U937 cells exposed to sublethal concentrations of tert-butylhydroperoxide. J Pharmacol Exp Ther 1997, 283:66-74.
• [6]Hsia CH, Wang CH, Kuo YW, HO YJ, Chen HL: Fructo-oligosaccharide systemically diminished D-galactose-induced oxidative molecule damage in BALB/cJ mice. Br J Nutr 2012, 107:1787-1792.
• [7]Zhong SZ, Ge QH, Qu R, Li Q, Ma SP: Paeonol attenuates neurotoxicity and ameliorates cognitive impairment induced by D-galactose in ICR mice. J Neurol Sci 2009, 277:58-64.
• [8]Lin SC, Lin CC, Lin YH, Shyuu SJ: Hepatoprotective effects of Taiwan folk medicine: Wedelia chinensis on three hepatotoxin-induced hepatotoxicity. Am J Chin Med 1994, 22:155-168.
• [9]Manjamalai A, Sardar-Sathyajith-Singh R, Guruvayoorappan C, Berlin-Grace VM: Analysis of phytochemical constituents and anti-microbial activity of some medicinal plants in Tamilnadu, India. Global J Biotech Biochem 2010, 5:120-128.
• [10]Haldar PK, Bhattacharya S, Dewanjee S, Mazumder UK: Chemopreventive efficacy of Wedelia calendulaceae against 20-methylcholanthrene- induced carcinogenesis in mice. Environ Toxicol Phar 2011, 31:10-17.
• [11]Prakash T, Rao NR, Viswanatha Swamy AH: Neuropharmacological studies on Wedelia calendulacea Less stem extract. Phytomedicine 2008, 15:959-970.
• [12]Lin FM, Chen LR, Lin EH, Ke FC, Chen HY, Tsai MJ, Hsiao PW: Compounds from Wedelia chinensis synergistically suppress androgen activity and growth in prostate cancer cells. Carcinogenesis 2007, 28:2521-2529.
• [13]Seelinger G, Merfort I, Schempp CM: Anti-oxidant, anti-inflammatroy and anti-allergic activities of luteolin. Planta Med 2008, 74:1667-1677.
• [14]Lin CW, Wu MJ, Liu IYC, Su JD, Yen JH: Neurotrophic and cytoprotective action of luteolin in PC12 cells through ERK-dependent induction of Nrf2-driven HO-1 expression. J Agric Food Chem 2010, 58:4477-4486.
• [15]Lin Y, Shi R, Wang X, Shen HM: Luteolin a flavonoid with potentials for cancer prevention and therapy. Curr Cancer Drug Targets 2008, 8:634-646.
• [16]Kobori M, Yang Z, Gong D, Heissmeyer V, Zhu H, Jung YK, Gakidis MA, Rao A, Sekine T, Ikegami F, Yuan C, Yuan J: Wedelolactone suppresses LPS-induced caspase-11 expression by directly inhibiting the IKK complex. Cell Death Differ 2004, 11:123-130.
• [17]Pôças ES, Lopes DV, da Silva AJ, Pimenta PH, Leitão FB, Netto CD, Buarque CD, Brito FV, Costa PR, Noël F: Structure–activity relationship of wedelolactone analogues: structural requirements for inhibition of Na+, K+-ATPase and binding to the central benzodiazepine receptor. Bioorg Med Chem 2006, 14:7962-7966.
• [18]Kaushik-Basu N, Bopda-Waffo A, Talele TT, Basu A, Costa PR, da Silva AJ, Sarafianos SG, Noel F: Identification and characterization of coumestans as novel HCV NS5B polymerase inhibitors. Nucleic Acids Res 2008, 36:1482-1496.
• [19]Benes P, Knopfova L, Trcka F, Nemajerova A, Pinheiro D, Soucek K, Fojta M, Smarda J: Inhibition of topoisomerase IIα: Novel function of wedelolactone. Cancer Lett 2011, 303:29-38.
• [20]Lee YJ, Lin WL, Chen NF, Chuang SK, Tseng TH: Demethylwedelolactone derivatives inhibit invasive growth in vitro and lung metastasis of MDA-MB-231 breast cancer cells in nude mice. Eur J Med Chem 2012, 56:361-367.
• [21]Chang CF, Yang LY, Chang SW, Fang YT, Lee YJ: Total synthesis of demethylwedelolactone and wedelolactone by Cu-mediated/Pd(0)-catalysis and oxidative-cyclization. Tetrahedron 2008, 64:3661-3666.
• [22]Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X: Prevention of apoptosis by Bcl-2: release of cytochrome C from mitochondria blocked. Science 1997, 75:1139-1142.
• [23]Sinha K, Das J, Pal PB, Sil PC: Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis. Arch Toxicol 2013, 87:1157-1180.
• [24]Dewson G, Kluck RM: Bcl-2 family-regulated apoptosis in health and disease. Cell Health and Cytoskeleton 2010, 2:9-22.
• [25]Perier C, Bove J, Wu DC, Dehay B, Choi DK, Jackson-Lewis V, Rathke-Hartlieb S, Bouillet P, Strasser A, Schulz JB, Przedborski S, Vila M: Two molecular pathways initiated mitochondria-dependent dopaminergic neurodegeneration in experimental Parkinson’s disease. Proc Natl Acad Sci U S A 2007, 104:8161-8166.
• [26]Scapagnini G, Sonya V, Nader AG, Calogero C, Zella D, Fabio G: Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neurodegerative disorders. Mol Neurobiol 2011, 44:192-201.
• [27]Majewska M, Skrzycki M, Podsiad M, Czeczot H: Evaluation of antioxidant potential of flavonoids: an in vitro study. Acta Pol Pharm 2011, 68:611-615.
• [28]Unnikrishnan KP, Fathima A, Hashim KM, Balachandran I: Antioxidant Studies and Determination of Wedelolactone in Eclipta alba. J Plant Sci 2007, 2:459-464.
• [29]Jellinger KA: Basic mechanisms of neurodegeneration: a critical update. J Cell Mol Med 2010, 14:457-487.
• [30]Uttara B, Singh AV, Zamboni P, Mahajan RT: Oxidative stress and neurodegenerative diseases: a review of upstream and down stream antioxidant therapeutic options. Curr Neuropharmacol 2009, 7:65-74.
• [31]Federico A, Cardaioli E, Da Pozzo P, Formichi P, Gallus GN, Radi E: Mitochondria, oxidative stress and neurodegeneration. J Neurol Sci 2012, 322:254-262.
• [32]Reagan-Shaw S, Nihal M, Ahmad N: Dose translation from animal to human studies revisited. FASEB J 2007, 22:659-661.