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Planta Med 2017; 83(03/04): 224-231
DOI: 10.1055/s-0042-111521
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Protective Effects of Puerarin against Aβ 1–42-Induced Learning and Memory Impairments in Mice

Lidan Wu
1   School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, P. R. China
,
Tong Tong
1   School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, P. R. China
,
Shutong Wan
1   School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, P. R. China
,
Tingxu Yan
1   School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, P. R. China
,
Fangyi Ren
1   School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, P. R. China
,
Kaishun Bi
2   School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P. R. China
,
Ying Jia
3   School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, P. R. China
› Author Affiliations
Further Information

Publication History

received 13 April 2016
revised 17 June 2016

accepted 27 June 2016

Publication Date:
15 July 2016 (online)

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Abstract

Puerarin is a major isoflavone glycoside from the root of Pueraria lobata. It has been reported that puerarin can protect neurons from oxidative stress-induced apoptosis. Emerging evidence suggests that oxidative damage is associated with Aβ-induced neuronal death. In the current study, we evaluated the effect of puerarin on Alzheimerʼs disease induced by Aβ and explored the potential mechanisms underlying this effect. We found that the escape latency of the Morris water maze was decreased in groups treated with puerarin compared to the model group (p < 0.01). In addition, there were significant differences between treated groups and the model group mice in a Y-maze test (p < 0.01). Furthermore, puerarin recovered the levels of brain-derived neurotrophic factor, phosphorylated tau, malondialdehyde, acetylcholine esterase, glycogen synthase kinase-3beta, and the activity of superoxide dismutase to some extent in the hippocampus and cerebral cortex. Shrinkage of nuclei and swollen and eccentrically dispersed neuronal bodies were observed in the hippocampus of Aβ-treated mice. These data demonstrate that puerarin might protect against cognitive deficits, oxidative stress, and neurodegeneration induced by Aβ 1–42.

Key words

puerarin - Pueraria lobata - Fabaceae - Aβ 1–42 - Alzheimerʼs disease - cognitive impairment

Supporting Information

 

  • References

  • 1 Xie S, Chen J, Li X, Su T, Wang Y, Wang Z, Huang L. Synthesis and evaluation of selegiline derivatives as monoamine oxidase inhibitor, antioxidant and metal chelator against Alzheimerʼs disease. Bioorg Med Chem 2015; 23: 3722-3729
    CrossrefPubMedGoogle Scholar
  • 2 Banji OJF, Banji D, Ch K. Curcumin and hesperidin improve cognition by suppressing mitochondrial dysfunction and apoptosis induced by D-galactose in rat brain. Food Chem Toxicol 2014; 74: 51-59
    CrossrefPubMedGoogle Scholar
  • 3 Rottkamp CA, Raina AK, Zhu X, Gaier E, Bush AI, Atwood CS, Chevion M, Perry G, Smith MA. Redox-active iron mediates amyloid-beta toxicity. Free Radic Bio Med 2001; 30: 447-450
    CrossrefPubMedGoogle Scholar
  • 4 Block ML, Zecca L, Hong JS. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 2007; 8: 57-69
    CrossrefPubMedGoogle Scholar
  • 5 Uttara B, Singh AV, Zamboni P, Mahajan RT. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 2009; 7: 65-74
    CrossrefPubMedGoogle Scholar
  • 6 Wang DM, Liu L, Zhu XY, Wu WL, Wang Y. Hesperidin alleviates cognitive impairment, mitochondrial dysfunction and oxidative stress in a mouse model of Alzheimerʼs disease. Cell Mol Neurobiol 2014; 34: 1209-1221
    CrossrefPubMedGoogle Scholar
  • 7 Xia CY, Dong XW, Zhao Y, Xu Y, Hao L, Zhang ZX. Ginkgo biloba extract 50 inhibited beta-amyloid-induced oxidative stress in ratsʼ hippocampal neurons: an experimental study. Zhongguo Zhong Xi Yi Jie He Za Zhi 2014; 34: 833-838
    PubMedGoogle Scholar
  • 8 Huh E, Kim HG, Park H, Kang MS, Lee B, Oh MS. Houttuynia cordata improves cognitive deficits in cholinergic dysfunction Alzheimerʼs disease-like models. Biomol Ther (Seoul) 2014; 22: 176-183
    CrossrefPubMedGoogle Scholar
  • 9 Levi-Montalcini R. The nerve growth factor: its mode of action on sensory and sympathetic nerve cells. Harvey Lect 1966; 60: 217-259
    PubMedGoogle Scholar
  • 10 Choi SM, Kim BC, Cho YH, Choi KH, Chang J, Park MS. Effects of flavonoid compounds on beta-amyloid-peptide-induced neuronal death in cultured mouse cortical neurons. Chonnam Med J 2014; 50: 45-51
    CrossrefPubMedGoogle Scholar
  • 11 Flaherty DB, Soria JP, Tomasiewicz HG, Wood JG. Phosphorylation of human tau protein by microtubule-associated kinases: GSK3β and cdk5 are key participants. J Neurosci Res 2000; 62: 463-472
    CrossrefPubMedGoogle Scholar
  • 12 Dajani R, Fraser E, Roe SM, Young N, Good V, Dale TC, Pearl LH. Crystal structure of glycogen synthase kinase 3β: structural basis for phosphate-primed substrate specificity and autoinhibition. Cell 2001; 105: 721-732
    CrossrefPubMedGoogle Scholar
  • 13 Fahnestock M. Brain-derived neurotrophic factor: the link between amyloid-β and memory loss. Future Neurol 2011; 6: 627-639
    CrossrefPubMedGoogle Scholar
  • 14 Chueh FS, Chang CP, Chio CC, Lin MT. Puerarin acts through brain serotonergic mechanisms to induce thermal effects. J Pharmacol Sci 2004; 96: 420-427
    CrossrefPubMedGoogle Scholar
  • 15 Chung MJ, Sung NJ, Park CS, Kweon DK, Mantovani A, Moon TW, Lee SJ. Antioxidative and hypocholesterolemic activities of water-soluble puerarin glycosides in Hepg2 cells and in C57 B1/6j mice. Eur J Pharmacol 2008; 578: 159-170
    CrossrefPubMedGoogle Scholar
  • 16 Liu Z, Zhao X, Liu B, Liu AJ, Li H, Mao X, Wu B, Bi KS, Jia Y. Jujuboside A, a neuroprotective agent from semen Ziziphi Spinosae ameliorates behavioral disorders of the dementia mouse model induced by Aβ 1–42. Eur J Pharmacol 2014; 738: 206-213
    CrossrefPubMedGoogle Scholar
  • 17 Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimerʼs disease: progress and problems on the road to therapeutics. Science 2002; 297: 353-356
    CrossrefPubMedGoogle Scholar
  • 18 Lu XL, Liu JX, Wu Q, Long SM, Zheng MY, Yao XL, Ren H, Wang YG, Su WW, Fai Cheung RT, Zeng JS, Su H, Pei Z. Protective effects of puerarin against Aβ40-induced vascular dysfunction in zebrafish and human endothelial cells. Eur J Pharmacol 2014; 732: 76-85
    CrossrefPubMedGoogle Scholar
  • 19 Brawn K, Fridovich I. Superoxide radical and superoxide dismutases: threat and defense. Acta Physiol Scand 1980; 492: 9-18
    PubMedGoogle Scholar
  • 20 Zhang X, Xiong J, Liu S, Wang L, Huang J, Liu L, Yang J, Zhang G, Guo K, Zhang Z, Wu P, Wang D, Lin Z, Xiong N, Wang T. Puerarin protects dopaminergic neurons in Parkinsonʼs disease models. Neuroscience 2014; 280: 88-98
    CrossrefPubMedGoogle Scholar
  • 21 Baptista FI, Henriques AG, Silva AMS, Wiltfang J, Slva O. Flavonoids as therapeutic compounds targeting key proteins involved in Alzheimerʼs disease. ACS Chem Neurosci 2014; 5: 83-92
    CrossrefPubMedGoogle Scholar
  • 22 Slater TF. Overview of methods used for detecting lipid peroxidation. Methods Enzymol 1984; 105: 283-293
    PubMedGoogle Scholar
  • 23 Elahi M, Motoi Y, Matsumoto SE, Hasan Z, Ishiguro K, Hattori N. Short-term treadmill exercise increased tau insolubility and neuroinflammation in tauopathy model mice. Neurosci Lett 2016; 610: 207-212
    CrossrefPubMedGoogle Scholar
  • 24 Drechsel DN, Hyman AA, Cobb MH, Kirschner MW. Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau. Mol Biol Cell 1992; 3: 1141-1154
    CrossrefPubMedGoogle Scholar
  • 25 Iqbal K, Alonso ADC, Chen S, Chohan MO, El-Akkad E, Gong CX. Tau pathology in Alzheimer disease and other tauopathies. Biochim Biophys Acta 2005; 1739: 198-210
    CrossrefPubMedGoogle Scholar
  • 26 Uchida K, Shiraishi M, Naito Y, Torii Y, Nakamura Y, Osawa T. Activation of stress signaling intracellular peroxide production. J Biol Chem 1999; 274: 2234-2242
    CrossrefPubMedGoogle Scholar
  • 27 Li CC, Pan Z, Xu TJ, Zhang C, Wu Q, Niu YC. Puerarin induces the upregulation of glutathione levels and nuclear translocation of Nrf2 through PI3K/Akt/GSK-3β signaling events in PC12 cells exposed to lead. Neurotoxicol Teratol 2014; 46: 1-9
    CrossrefPubMedGoogle Scholar
  • 28 Qu Z, Zhang J, Yang H, Huo L, Gao J, Chen H, Gao WY. Protective effect of tetrahydropalmatine against d-galactose induced memory impairment in rat. Physiol Behav 2016; 154: 114-125
    CrossrefPubMedGoogle Scholar
  • 29 Numakawa T, Suzuki S, Kumamaru E, Adachi N, Richards M, Kunugi H. BDNF function and intracellular signaling in neurons. Histol Histopathol 2010; 25: 237-258
    PubMedGoogle Scholar
  • 30 Levi-Montalcini R. The nerve growth factor: its mode of action on sensory and sympathetic nerve cells. Harvey Lect 1966; 60: 217-259
    PubMedGoogle Scholar
  • 31 Li J, Wang G, Liu J, Zhou L, Dong M, Wang R, Li XY, Lin CR, Niu YC. Puerarin attenuates amyloid-beta-induced cognitive impairment through suppression of apoptosis in rat hippocampus in vivo . Eur J Pharmacol 2010; 649: 195-201
    CrossrefPubMedGoogle Scholar
  • 32 Silveyra MX, Garcia-Ayllon MS, de Barreda EG, Small DH, Martinez S, Avila J. Altered expression of brain acetylcholinesterase in FTDP-17 human tau transgenic mice. Neurobiol Aging 2012; 33: 12
    PubMedGoogle Scholar
  • 33 Craig LA, Hong NS, McDonald RJ. Revisiting the cholinergic in the development of Alzheimerʼs disease. Neurosci Biobehav Rev 2011; 35: 1397-1409
    CrossrefPubMedGoogle Scholar
  • 34 Song JH, Yu JT, Tan L. Brain-derived neurotrophic factor in Alzheimerʼs disease: risk, mechanisms, and therapy. Mol Neurobiol 2015; 52: 1477-1493
    CrossrefPubMedGoogle Scholar
  • 35 Li QS, Yang W, Pan YF, Min J, Zhang Z, Gao HZ. Brain-derived neurotrophic factor prevents against amyloid beta protein-induced impairment of hippocampal in vivo long-term potentiation in rats. Zhongguo Zhong Xi Yi Jie He Za Zhi 2012; 28: 425-429
    PubMedGoogle Scholar
  • 36 Sharma M, Gupta YK. Effect of chronic treatment of melatonin on learning, memory and oxidative deficiencies induced by intracerebroventricular streptozotocin in rats. Pharmacol Biochem Behav 2001; 70: 325-331
    CrossrefPubMedGoogle Scholar
  • 37 Kim DH, Jeon SJ, Son KH, Jung JW, Lee S, Yoon BH, Lee JJ, Cho YW, Cheong JH, Ko KH, Ryu JH. The ameliorating effect of oroxylin A on scopolamine-induced memory impairment in mice. Neurobiol Learn Mem 2007; 87: 536-546
    CrossrefPubMedGoogle Scholar
  • 38 Mutlu O, Akar F, Celikyurt IK, Tanyeri P, Ulak G, Erden F. 7-NI and ODQ disturbs memory in the elevated plus maze, Morris water maze, and radial arm maze tests in mice. Drug Target Insights 2015; 9: 1-8
    PubMedGoogle Scholar
  • 39 Ahmad M, Saleem S, Ahmad AS, Yousuf S, Ansari MA, Khan MB. Ginkgo biloba affords dose-dependent protection against 6-hydroxydopamine-induced parkinsonism in rats: neurobehavioural, neurochemical and immunohistochemimac evidences. J Neurochem 2005; 93: 94-104
    CrossrefPubMedGoogle Scholar