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Protective Effects of Baicalin on Aβ1–42-Induced Learning and Memory Deficit, Oxidative Stress, and Apoptosis in Rat

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Abstract

The accumulation and deposition of β-amyloid peptide (Aβ) in senile plaques and cerebral vasculature is believed to facilitate the progressive neurodegeneration that occurs in the Alzheimer’s disease (AD). The present study sought to elucidate possible effects of baicalin, a natural phytochemical, on Aβ toxicity in a rat model of AD. By morris water maze test, Aβ1–42 injection was found to cause learning and memory deficit in rat, which was effectively improved by baicalin treatment. Besides, histological examination showed that baicalin could attenuate the hippocampus injury caused by Aβ. The neurotoxicity mechanism of Aβ is associated with oxidative stress and apoptosis, as revealed by increased malonaldehyde generation and TUNEL-positive cells. Baicalin treatment was able to increase antioxidant capabilities by recovering activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and up-regulating their gene expression. Moreover, baicalin effectively prevented Aβ-induced mitochondrial membrane potential decrease, Bax/Bcl-2 ratio increase, cytochrome c release, and caspase-9/-3 activation. In addition, we found that the anti-oxidative effect of baicalin was associated with Nrf2 activation. In conclusion, baicalin effectively improved Aβ-induced learning and memory deficit, hippocampus injury, and neuron apoptosis, making it a promising drug to preventive interventions for AD.

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References

  • Ataie A, Sabetkasaei M, Haghparast A, Moghaddam AH, Kazeminejad B (2010) Neuroprotective effects of the polyphenolic antioxidant agent, Curcumin, against homocysteine-induced cognitive impairment and oxidative stress in the rat. Pharmacol Biochem Behav 96:378–385

    Article  CAS  PubMed  Google Scholar 

  • Bagheri M, Joghataei MT, Mohseni S, Roghani M (2011) Genistein ameliorates learning and memory deficits in amyloid β(1-40) rat model of Alzheimer’s disease. Neurobiol Learn Mem 95:270–276

    Article  CAS  PubMed  Google Scholar 

  • Butterfield DA, Swomley AM, Sultana R (2013) Amyloid β-peptide (1-42)-induced oxidative stress in Alzheimer disease: importance in disease pathogenesis and progression. Antioxid Redox Signal 19:823–835

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cao Y, Li G, Wang YF, Fan ZK, Yu DS, Wang ZD, Bi YL (2010) Neuroprotective effect of baicalin on compression spinal cord injury in rats. Brain Res 1357:115–123

    Article  CAS  PubMed  Google Scholar 

  • Cao Y, Mao X, Sun C, Zheng P, Gao J, Wang X, Min D, Sun H, Xie N, Cai J (2011) Baicalin attenuates global cerebral ischemia/reperfusion injury in gerbils via anti-oxidative and anti-apoptotic pathways. Brain Res Bull 85:396–402

    Article  CAS  PubMed  Google Scholar 

  • Cappai R, Barnham KJ (2008) Delineating the mechanism of Alzheimer’s disease Aβ peptide neurotoxicity. Neurochem Res 33:526–532

    Article  CAS  PubMed  Google Scholar 

  • Cetin F, Dincer S (2007) The effect of intrahippocampal β amyloid (1-42) peptide injection on oxidant and antioxidant status in rat brain. Ann NY Acad Sci 1100:510–517

    Article  CAS  PubMed  Google Scholar 

  • Chen DL, Zhang P, Lin L, Shuai O, Zhang HM, Liu SH, Wang JY (2013) Protective effect of Bajijiasu against β-amyloid-induced neurotoxicity in pc12 cells. Cell Mol Neurobiol 33:837–850

    Article  PubMed  Google Scholar 

  • Cheng F, Lu Y, Zhong X, Song W, Wang X, Sun X, Qin J, Guo S, Wang Q (2013) Baicalin’s therapeutic time window of neuroprotection during transient focal cerebral ischemia and its antioxidative effects in vitro and in vivo. Evid Based Complement Alternat Med 2013:120261

    PubMed Central  PubMed  Google Scholar 

  • Cioanca O, Hritcu L, Mihasan M, Hancianu M (2013) Cognitive-enhancing and antioxidant activities of inhaled coriander volatile oil in amyloid β(1-42) rat model of Alzheimer’s disease. Physiol Behav 120:193–202

    Article  CAS  PubMed  Google Scholar 

  • Earnshaw WC, Martins LM, Kaufmann SH (1999) Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem 68:383–424

    Article  CAS  PubMed  Google Scholar 

  • Eftekharzadeh B, Ramin M, Khodagholi F, Moradi S, Tabrizian K, Sharif R, Azami K, Beyer C, Sharifzadeh M (2012) Inhibition of PKA attenuates memory deficits induced by β-amyloid (1-42), and decreases oxidative stress and NF-κB transcription factors. Behav Brain Res 226:301–308

    Article  CAS  PubMed  Google Scholar 

  • Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid β-peptide. Nat Rev Mol Cell Biol 8:101–112

    Article  CAS  PubMed  Google Scholar 

  • Han M, Liu Y, Tan Q, Zhang B, Wang W, Liu J, Zhang XJ, Wang YY, Zhang JM (2011) Therapeutic efficacy of stemazole in a beta-amyloid injection rat model of Alzheimer’s disease. Eur J Pharmacol 657:104–110

    Article  CAS  PubMed  Google Scholar 

  • Hawkes CA, Ng V, Mclaurin J (2009) Small molecule inhibitors of Aβ-Aggregation and neurotoxicity. Drug Dev Res 70:111–124

    Article  CAS  Google Scholar 

  • Hur J, Pak SC, Koo BS, Jeon S (2013) Borneol alleviates oxidative stress via upregulation of Nrf2 and Bcl-2 in SH-SY5Y cells. Pharm Biol 51:30–35

    Article  CAS  PubMed  Google Scholar 

  • Jacotot E, Costantini P, Laboureau E, Zamzami N, Susin SA, Kroemer G (1999) Mitochondrial membrane permeabilization during the apoptotic process. Ann NY Acad Sci 887:18–30

    Article  CAS  PubMed  Google Scholar 

  • Jhoo JH, Kim HC, Nabeshima T, Yamada K, Shin EJ, Jhoo WK, Kim W, Kang KS, Jo SA, Woo JI (2004) β-amyloid (1-42)-induced learning and memory deficits in mice: involvement of oxidative burdens in the hippocampus and cerebral cortex. Behav Brain Res 155:185–196

    Article  CAS  PubMed  Google Scholar 

  • Karkkainen V, Pomeshchik Y, Savchenko E, Dhungana H, Kurronen A, Lehtonen S, Naumenko N, Tavi P, Levonen AL, Yamamoto M, Malm T, Magga J, Kanninen KM, Koistinaho J (2014) Nrf2 regulates neurogenesis and protects neural progenitor cells against Aβ toxicity. Stem Cells

  • Kaur R, Arora S, Singh B (2008) Antioxidant activity of the phenol rich fractions of leaves of Chukrasia tabularis A. Juss. Bioresour Technol 99:7692–7698

    Article  CAS  PubMed  Google Scholar 

  • Keeble JA, Gilmore AP (2007) Apoptosis commitment—translating survival signals into decisions on mitochondria. Cell Res 17:976–984

    Article  CAS  PubMed  Google Scholar 

  • Kensler TW, Wakabayashi N, Biswal S (2007) Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol 47:89–116

    Article  CAS  PubMed  Google Scholar 

  • Kubli DA, Gustafsson AB (2012) Mitochondria and mitophagy: the yin and yang of cell death control. Circ Res 111:1208–1221

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lauren J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM (2009) Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature 457:1128–1132

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lee S, Fernandez EJ, Good TA (2007) Role of aggregation conditions in structure, stability, and toxicity of intermediates in the Aβ fibril formation pathway. Protein Sci 16:723–732

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lee B, Sur B, Shim I, Lee H, Hahm DH (2014) Baicalin improves chronic corticosterone-induced learning and memory deficits via the enhancement of impaired hippocampal brain-derived neurotrophic factor and cAMP response element-binding protein expression in the rat. J Nat Med 68:132–143

    Article  CAS  PubMed  Google Scholar 

  • Li W, Kong AN (2009) Molecular mechanisms of Nrf2-mediated antioxidant response. Mol Carcinog 48:91–104

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91:479–489

    Article  CAS  PubMed  Google Scholar 

  • Liu YF, Gao F, Li XW, Jia RH, Meng XD, Zhao R, Jing YY, Wang Y, Jiang W (2012) The anticonvulsant and neuroprotective effects of baicalin on pilocarpine-induced epileptic model in rats. Neurochem Res 37:1670–1680

    Article  CAS  PubMed  Google Scholar 

  • Mebane-Sims I (2009) 2009 Alzheimer’s disease facts and figures. Alzheimer’s Dement 5:234–270

    Article  Google Scholar 

  • Olariu A, Tran MH, Yamada K, Mizuno M, Hefco V, Nabeshima T (2001) Memory deficits and increased emotionality induced by β-amyloid(25-35) are correlated with the reduced acetylcholine release and altered phorbol dibutyrate binding in the hippocampus. J Neural Transm 108:1065–1079

    Article  CAS  PubMed  Google Scholar 

  • Park SY (2010) Potential therapeutic agents against Alzheimer’s disease from natural sources. Arch Pharm Res 33:1589–1609

    Article  CAS  PubMed  Google Scholar 

  • Qin L, Zhang J, Qin M (2013) Protective effect of cyanidin 3-O-glucoside on β-amyloid peptide-induced cognitive impairment in rats. Neurosci Lett 534:285–288

    Article  CAS  PubMed  Google Scholar 

  • Ruan CJ, Zhang L, Chen DH, Li Z, Du GH, Sun L (2010) Effects of trans-2,4-dimethoxystibene against the neurotoxicity induced by Aβ(25-35) both in vitro and in vivo. Neurosci Res 67:209–214

    Article  CAS  PubMed  Google Scholar 

  • Sabbagh MN (2009) Drug development for Alzheimer’s disease: where are we now and where are we headed? Am J Geriatr Pharmacother 7:167–185

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Selkoe DJ (1991) Amyloid protein and Alzheimer’s disease. Sci Am 265:68–71, 74–66, 78

  • Seo JS, Kim TK, Leem YH, Lee KW, Park SK, Baek IS, Kim KS, Im GJ, Lee SM, Park YH, Han PL (2009) SK-PC-B70M confers anti-oxidant activity and reduces Aβ levels in the brain of Tg2576 mice. Brain Res 1261:100–108

    Article  CAS  PubMed  Google Scholar 

  • Song Y, Chen X, Wang LY, Gao W, Zhu MJ (2013) Rho kinase inhibitor fasudil protects against beta-amyloid-induced hippocampal neurodegeneration in rats. CNS Neurosci Ther 19:603–610

    Article  CAS  PubMed  Google Scholar 

  • Srivareerat M, Tran TT, Salim S, Aleisa AM, Alkadhi KA (2011) Chronic nicotine restores normal Aβ levels and prevents short-term memory and E-LTP impairment in Aβ rat model of Alzheimer’s disease. Neurobiol Aging 32:834–844

    Article  CAS  PubMed  Google Scholar 

  • Tarrago T, Kichik N, Claasen B, Prades R, Teixido M, Giralt E (2008) Baicalin, a prodrug able to reach the CNS, is a prolyl oligopeptidase inhibitor. Bioorg Med Chem 16:7516–7524

    Article  CAS  PubMed  Google Scholar 

  • Tusi SK, Khalaj L, Ashabi G, Kiaei M, Khodagholi F (2011) Alginate oligosaccharide protects against endoplasmic reticulum- and mitochondrial-mediated apoptotic cell death and oxidative stress. Biomaterials 32:5438–5458

    Article  CAS  PubMed  Google Scholar 

  • Vomhof-Dekrey EE, Picklo MJ Sr (2012) The Nrf2-antioxidant response element pathway: a target for regulating energy metabolism. J Nutr Biochem 23:1201–1206

    Article  CAS  PubMed  Google Scholar 

  • Wang C, Yang XM, Zhuo YY, Zhou H, Lin HB, Cheng YF, Xu JP, Zhang HT (2012) The phosphodiesterase-4 inhibitor rolipram reverses Aβ-induced cognitive impairment and neuroinflammatory and apoptotic responses in rats. Int J Neuropsychopharmacol 15:749–766

    Article  CAS  PubMed  Google Scholar 

  • Xue X, Qu XJ, Yang Y, Sheng XH, Cheng F, Jiang EN, Wang JH, Bu W, Liu ZP (2010) Baicalin attenuates focal cerebral ischemic reperfusion injury through inhibition of nuclear factor kappaB p65 activation. Biochem Biophys Res Commun 403:398–404

    Article  CAS  PubMed  Google Scholar 

  • Yankner BA (1989) Amyloid and Alzheimer’s disease—cause or effect? Neurobiol Aging 10:470–471 discussion 477–478

    Article  CAS  PubMed  Google Scholar 

  • Yankner BA, Dawes LR, Fisher S, Villa-Komaroff L, Oster-Granite ML, Neve RL (1989) Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer’s disease. Science 245:417–420

    Article  CAS  PubMed  Google Scholar 

  • Yin F, Liu J, Ji X, Wang Y, Zidichouski J, Zhang J (2011) Baicalin prevents the production of hydrogen peroxide and oxidative stress induced by Aβ aggregation in SH-SY5Y cells. Neurosci Lett 492:76–79

    Article  CAS  PubMed  Google Scholar 

  • Zheng WX, Wang F, Cao XL, Pan HY, Liu XY, Hu XM, Sun YY (2014) Baicalin protects PC-12 cells from oxidative stress induced by hydrogen peroxide via anti-apoptotic effects. Brain Inj 28:227–234

    Article  PubMed  Google Scholar 

  • Zhou QB, Duan CZ, Jia Q, Liu P, Li LY (2014) Baicalin attenuates focal cerebral ischemic reperfusion injury by inhibition of protease-activated receptor-1 and apoptosis. Chin J Integr Med 20:116–122

    Article  CAS  PubMed  Google Scholar 

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    Authors and Affiliations

    1. Linyi City Yishui Central Hospital, Linyi, 276400, Shandong, China

      Haitao Ding, Haitao Wang, Yexia Zhao & Deke Sun

    2. The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, Liaoning, China

      Xu Zhai

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    1. Haitao Ding
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    2. Haitao Wang
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    Correspondence to Xu Zhai.

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    Ding Haitao and Wang Haitao have contributed equally to the study.

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    Ding, H., Wang, H., Zhao, Y. et al. Protective Effects of Baicalin on Aβ1–42-Induced Learning and Memory Deficit, Oxidative Stress, and Apoptosis in Rat. Cell Mol Neurobiol 35, 623–632 (2015). https://doi.org/10.1007/s10571-015-0156-z

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