The anti-apoptotic and anti-inflammatory properties of puerarin attenuate 3-nitropropionic-acid induced neurotoxicity in rats

Canadian Journal of Physiology and Pharmacology

Volumn 92, Issue 3, 2014, Pages 252-258

  Mahdy, Heba M ^a   Mohamed, Mohamed R ^b   Emam, Manal A ^b   Karim, Amr M ^b   Abdel Naim, Ashraf ^a   Khalifa, Amani E ^a  

^a AIN SHAMS UNIVERSITY   (Egypt)

^b Ain Shams University   (Egypt)

Author keywords

3 nitropropionic acid; Apoptosis; ATP; Huntington's disease; Neuroinflammation; Nissl staining; Puerarin

Indexed keywords

3 NITROPROPIONIC ACID; ADENOSINE TRIPHOSPHATE; BIOLOGICAL MARKER; CASPASE 3; CYTOCHROME C; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDUCIBLE NITRIC OXIDE SYNTHASE; NEUROPROTECTIVE AGENT; PROTEIN BAX; PROTEIN BCL 2; PUERARIN; TUMOR NECROSIS FACTOR ALPHA;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; APOPTOSIS; ARTICLE; ATTENUATION; BODY MASS; BRAIN CORTEX; CORPUS STRIATUM; CYTOPLASM; CYTOSOL; ENZYME ACTIVITY; HIPPOCAMPUS; HISTOPATHOLOGY; MALE; NERVOUS SYSTEM INFLAMMATION; NEUROPROTECTION; NEUROTOXICITY; NISSL STAINING; NISSL SUBSTANCE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; TREATMENT DURATION;

ADENOSINE TRIPHOSPHATE; ANIMALS; ANTI-INFLAMMATORY AGENTS; APOPTOSIS; BRAIN; ISOFLAVONES; MALE; NEUROTOXICITY SYNDROMES; NITRO COMPOUNDS; PROPIONATES; RATS, WISTAR;

EID: 84900380715     PISSN: 00084212     EISSN: 12057541     Source Type: Journal    
DOI: 10.1139/cjpp-2013-0398     Document Type: Article

References (84)

1. Ahuja, M., Chopra, K., and Bishnoi, M. 2008. Inflammatory and neurochemical changes associated with 3-nitropropionic acid neurotoxicity. Toxicol. Mech. Methods, 18(4): 335-339. doi:10.1080/15376510701563738. PMID:20020899
2. Antonawich, F.J., Fiore-Marasa, S.M., and Parker, C.P. 2002. Modulation of apoptotic regulatory proteins and early activation of cytochrome c following systemic 3-nitropropionic acid administration. Brain Res. Bull. 57(5): 647-649. doi:10.1016/S0361-9230(01)00761-4. PMID:11927368
3. Bancroft, J., and Stevens, A 1996. Theory and practice of histological techniques. 4th Ed. Churchil Livingstone, Edinburgh, UK
4. Bantubungi, K., and Blum, D. 2007. Mechanisms of neuronal death in Huntington's disease. First part: general considerations and histopathological features. Rev. Med. Brux. 28(5): 413-421. [In French] 18069515
5. Beal, M.F., Brouillet, E., Jenkins, B.G., Ferrante, R.J., Kowall, N.W., Miller, J.M., et al. 1993. Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J. Neurosci. 13(10): 4181-4192. PMID:7692009
6. Bhateja, D.K., Dhull, D.K., Gill, A., Sidhu, A., Sharma, S., Reddy, B.V., and Padi, S.S. 2012. Peroxisome proliferator-activated receptor-alpha activation attenuates 3-nitropropionic acid induced behavioral and biochemical alterations in rats: possible neuroprotective mechanisms. Eur. J. Pharmacol. 674(1): 33-43. doi:10.1016/j.ejphar.2011.10.029. PMID:22056833
7. Bortolatto, C.F., Jesse, C.R., Wilhelm, E.A., Chagas, P.M., and Nogueira, C.W. 2013. Organoselenium bis selenide attenuates 3-nitropropionic acid-induced neurotoxicity in rats. Neurotox. Res. 23(3): 214-224. doi:10.1007/s12640-012- 9336-5. PMID:22739838
8. Campbell, A. 2004. Inflammation, neurodegenerative diseases, and environmental exposures. Ann. N.Y. Acad. Sci. 1035: 117-132. doi:10.1196/annals.1332. 008. PMID:15681804
9. Canudas, A.M., Pubill, D., Sureda, F.X., Verdaguer, E., Camps, P., Munoz-Torrero, D., et al. 2003. Neuroprotective effects of (+/)-huprine Y on in vitro and in vivo models of excitoxicity damage. Exp. Neurol. 180(2): 123-130. doi:10.1016/S0014-4886(02)00029-8. PMID:12684026
10. Chan, A.S.-C., Chen, S.L., Li, Y., and Yang, D. 2006. Puerarin derivatives and their medical uses. WO Patent 2,006,042,454
11. Chang, Y., Hsieh, C.Y., Peng, Z.A., Yen, T.L., Hsiao, G., Chou, D.S., et al. 2009a. Neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats. J. Biomed. Sci. 16: 9. doi:10.1186/ 1423-0127-16-9. PMID:19272172
12. Chang, Y., Hsieh, C.Y., Peng, Z.A., Yen, T.L., Hsiao, G., Chou, D.S., et al. 2009b. Neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats. J. Biomed. Sci. 16: 9. doi:10.1186/ 1423-0127-16-9. PMID:19272172
13. Chen, C.M. 2011. Mitochondrial dysfunction, metabolic deficits, and increased oxidative stress in Huntington's disease. Chang Gung Med. J. 34(2): 135-152. PMID:21539755
14. Cheng, Y.F., Zhu, G.Q., Wang, M., Cheng, H., Zhou, A., Wang, N., et al. 2009. Involvement of ubiquitin proteasome system in protective mechanisms of Puerarin to MPP(+)-elicited apoptosis. Neurosci. Res. 63(1): 52-58. doi:10.1016/ j.neures.2008.10.009. PMID:19022306
15. Cheng, Y., Zhu, G., Guan, Y., Liu, Y., Hu, Y., and Li, Q. 2011. Protective effects of puerarin against 1-methyl-4-phenylpyridinium-induced mitochondrial apoptotic death in differentiated SH-SY5Y cells. Zhongguo Zhong Yao Za Zhi, 36(9): 1222-1226. [In Chinese] 21842654
16. Cuello, A., C. 1993. Immunohistochemistry II. 1st Ed. John Wiley & Sons, Hobken, N.J
17. Duran-Vilaregut, J., Manich, G., del Valle, J., Pallas, M., Camins, A., Pelegri, C., and Vilaplana, J. 2011. Neuronal apoptosis in the striatum of rats treated with 3-nitropropionic acid is not triggered by cell-cycle re-entry. Neurotoxicology, 32(6): 734-741. doi:10.1016/j.neuro.2011.07.009. PMID:21827787
18. Eidelberg, D., and Surmeier, D.J. 2011. Brain networks in Huntington disease. J Clin. Invest. 121(2): 484-492. doi:10.1172/JCI45646. PMID:21285521
19. Ferreira, I.L., Nascimento, M.V., Ribeiro, M., Almeida, S., Cardoso, S.M., Grazina, M., et al. 2010. Mitochondrial-dependent apoptosis in Huntington's disease human cybrids. Exp. Neurol. 222(2): 243-255. doi:10.1016/j.expneurol. 2010.01.002. PMID:20079354
20. Gao, L., Ji, X., Song, J., Liu, P., Yan, F., Gong, W., et al. 2009. Puerarin protects against ischemic brain injury in a rat model of transient focal ischemia. Neurol. Res. 31(4): 402-406. doi:10.1179/174313209X444017. PMID:19508827
21. Garrido, C., Galluzzi, L., Brunet, M., Puig, P.E., Didelot, C., and Kroemer, G. 2006. Mechanisms of cytochrome c release from mitochondria. Cell Death Differ. 13(9): 1423-1433. doi:10.1038/sj.cdd.4401950. PMID:16676004
22. Gil, J.M., and Rego, A.C. 2008. Mechanisms of neurodegeneration in Huntington's disease. Eur. J. Neurosci. 27(11): 2803-2820. doi:10.1111/j.1460-9568.2008. 06310.x. PMID:18588526.
23. Hickey, M.A., and Chesselet, M.F. 2003. Apoptosis in Huntington's disease. Prog. Neuropsychopharmacol. Biol. Psychiatry, 27(2): 255-265. doi:10.1016/S0278- 5846(03)00021-6. PMID:12657365
24. Hu, W., Zhang, Q., Yang, X., Wang, Y., and Sun, L. 2010. Puerarin inhibits adhesion molecule expression in tnf-alpha-stimulated human endothelial cells via modulation of the nuclear factor kappaB pathway. Pharmacology, 85(1): 27-35. doi:10.1159/000264938. PMID:20016245
25. Hu, W., Yang, X., Zhe, C., Zhang, Q., Sun, L., and Cao, K. 2011. Puerarin inhibits iNOS, COX-2 and CRP expression via suppression of NF-kappaB activation in LPS-induced RAW264.7 macrophage cells. Pharmacol. Rep. 63(3): 781-789. PMID:21857089
26. Jin, S.E., Son, Y.K., Min, B.S., Jung, H.A., and Choi, J.S. 2012. Anti-inflammatory and antioxidant activities of constituents isolated from Pueraria lobata roots. Arch. Pharm. Res. 35(5): 823-837. doi:10.1007/s12272-012-0508-x. PMID:22644850
27. Johri, A., and Beal, M.F. 2012. Antioxidants in Huntington's disease. Biochim. Biophys. Acta, 1822(5): 664-674. doi:10.1016/j.bbadis.2011.11.014. PMID:22138129
28. Khan, H.A. 2003. Bioluminometric assay of ATP in mouse brain: Determinant factors for enhanced test sensitivity. J. Biosci. 28(4): 379-382. doi:10.1007/ BF02705114. PMID:12799486
29. Kumar, P., and Kumar, A. 2010. Protective effect of hesperidin and naringin against 3-nitropropionic acid induced Huntington's like symptoms in rats: possible role of nitric oxide. Behav. Brain Res. 206(1): 38-46. doi:10.1016/j.bbr. 2009.08.028. PMID:19716383
30. Kumar, P., Kalonia, H., and Kumar, A. 2011. Role of LOX/COX pathways in 3- nitropropionic acid-induced Huntington's disease-like symptoms in rats: protective effect of licofelone. Br. J. Pharmacol. 164(2b): 644-654. doi:10.1111/j. 1476-5381.2011.01418.x. PMID:21486276
31. Lacor, P.N., Buniel, M.C., Furlow, P.W., Clemente, A.S., Velasco, P.T., Wood, M., et al. 2007. Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease. J. Neurosci. 27(4): 796-807. doi:10.1523/JNEUROSCI.3501-06. 2007. PMID:17251419
32. Lee, S.T., Chu, K., Park, J.E., Hong, N.H., Im, W.S., Kang, L., et al. 2008a. Atorvastatin attenuates mitochondrial toxin-induced striatal degeneration, with decreasing iNOS/c-Jun levels and activating ERK/Akt pathways. J. Neurochem. 104(5): 1190-1200. doi:10.1111/j.1471-4159.2007.05044.x. PMID:17976163
33. Lee, S.T., Park, J.E., Kim, D.H., Kim, S., Im, W.S., Kang, L., et al. 2008b. Granulocyte-colony stimulating factor attenuates striatal degeneration with activating survival pathways in 3-nitropropionic acid model of Huntington's disease. Brain Res. 1194: 130-137. doi:10.1016/j.brainres.2007.11.058. PMID: 18166168
34. Li, Y., Pan, W.S., Chen, S.L., Xu, H.X., Yang, D.J., and Chan, A.S. 2006. Pharmacokinetic, tissue distribution, and excretion of puerarin and puerarinphospholipid complex in rats. Drug Dev. Ind. Pharm. 32(4): 413-422. doi:10. 1080/03639040600559123. PMID:16638679
35. Li, J., Wang, G., Liu, J., Zhou, L., Dong, M., Wang, R., et al. 2010. Puerarin attenuates amyloid-beta-induced cognitive impairment through suppression of apoptosis in rat hippocampus in vivo. Eur. J. Pharmacol. 649(1-3): 195-201. doi:10.1016/j.ejphar.2010.09.045. PMID:20868658.
36. Lim, S., Chesser, A.S., Grima, J.C., Rappold, P.M., Blum, D., Przedborski, S., and Tieu, K. 2011. D-β-Hydroxybutyrate is protective in mouse models of Huntington's disease. PLoS One, 6(9): e24620. doi:10.1371/journal.pone.0024620. PMID:21931779
37. Liot, G., Bossy, B., Lubitz, S., Kushnareva, Y., Sejbuk, N., and Bossy-Wetzel, E. 2009. Complex II inhibition by 3-NP causes mitochondrial fragmentation and neuronal cell death via an NMDA- and ROS-dependent pathway. Cell Death Differ. 16(6): 899-909. doi:10.1038/cdd.2009.22. PMID:19300456
38. Liu, X.J., Zhao, J., and Gu, X.Y. 2010. The effects of genistein and puerarin on the activation of nuclear factor-kappaB and the production of tumor necrosis factor-alpha in asthma patients. Pharmazie, 65(2): 127-131. PMID:20225658
39. Lu, J., Ren, J., and Yao, S. 2004. Protective effect of puerarin on myocardial ischemia and reperfusion injury. Chin. J. Mod. Appl. Pharm. 04
40. Mahdy, H.M., Tadros, M.G., Mohamed, M.R., Karim, A.M., and Khalifa, A.E. 2011. The effect of ginkgo biloba extract on 3-nitropropionic acid-induced neurotoxicity in rats. Neurochem. Int. 59(6): 770-778. doi:10.1016/j.neuint.2011.07. 012. PMID:21827809
41. Mandavilli, B.S., Boldogh, I., and Van Houten, B. 2005. 3-nitropropionic acidinduced hydrogen peroxide, mitochondrial DNA damage, and cell death are attenuated by Bcl-2 overexpression in PC12 cells. Brain Res. Mol. Brain Res. 133(2): 215-223. doi:10.1016/j.molbrainres.2004.10.033. PMID:15710238
42. McCoy, M.K., and Tansey, M.G. 2008. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease. J. Neuroinflammation, 5: 45. doi:10.1186/1742-2094-5-45. PMID:18925972
43. Mealer, R.G., Subramaniam, S., and Snyder, S.H. 2013. Rhes deletion is neuroprotective in the 3-nitropropionic acid model of Huntington's disease. J. Neurosci. 33(9): 4206-4210. doi:10.1523/JNEUROSCI.3730-12.2013. PMID: 23447628
44. Menze, E.T., Tadros, M.G., Abdel-Tawab, A.M., and Khalifa, A.E. 2012. Potential neuroprotective effects of hesperidin on 3-nitropropionic acid-induced neurotoxicity in rats. Neurotoxicology, 33(5): 1265-1275. doi:10.1016/j.neuro.2012. 07.007. PMID:22850463
45. Milakovic, T., and Johnson, G.V. 2005. Mitochondrial respiration and ATP production are significantly impaired in striatal cells expressing mutant huntingtin. J. Biol. Chem. 280(35): 30773-30782. doi:10.1074/jbc.M504749200. PMID:15983033
46. Mrak, R.E., and Griffin, W.S. 2005. Potential inflammatory biomarkers in Alzheimer's disease. J. Alzheimers Dis. 8(4): 369-375. PMID:16556968
47. Napolitano, M., Zei, D., Centonze, D., Palermo, R., Bernardi, G., Vacca, A., et al. 2008. NF-kB/NOS cross-talk induced by mitochondrial complex II inhibition: implications for Huntington's disease. Neurosci. Lett. 434(3): 241-246. doi:10. 1016/j.neulet.2007.09.056. PMID:18329171
48. Nonaka, M., Chen, X.H., Pierce, J.E., Leoni, M.J., McIntosh, T.K., Wolf, J.A., and Smith, D.H. 1999. Prolonged activation of NF-kappaB following traumatic brain injury in rats. J. Neurotrauma, 16(11): 1023-1034. doi:10.1089/neu.1999. 16.1023. PMID:10595819
49. Pan, H.P., and Li, G. 2008. Protecting mechanism of puerarin on the brain neurocyte of rat in acute local ischemia brain injury and local cerebral ischemia-reperfusion injury. Yakugaku Zasshi, 128(11): 1689-1698. doi:10.1248/yakushi. 128.1689. PMID:18981705
50. Park, J.E., Lee, S.T., Im, W.S., Chu, K., and Kim, M. 2008. Galantamine reduces striatal degeneration in 3-nitropropionic acid model of Huntington's disease. Neurosci. Lett. 448(1): 143-147. doi:10.1016/j.neulet.2008.10.020. PMID:18938211
51. Pedraza-Chaverri, J., Reyes-Fermin, L.M., Nolasco-Amaya, E.G., Orozco-Ibarra, M., Medina-Campos, O.N., Gonzalez-Cuahutencos, O., et al. 2009. ROS scavenging capacity and neuroprotective effect of alphamangostin against 3-nitropropionic acid in cerebellar granule neurons. Exp. Toxicol. Pathol. 61(5): 491-501. doi:10.1016/j.etp.2008.11.002. PMID:19108999
52. Prasad, K., and Prabhu, G.K. 2012. Image analysis tools for evaluation of microscopic views of immunohistochemically stained specimen in medical research-a review. J. Med. Syst. 36(4): 2621-2631. doi:10.1007/s10916-011-9737-7. PMID:21584771
53. Puneet, K., Padi, S.S.V., Naidu, P.S., and Kumar, A. 2007. 3-Nitropropionic acid induced neurotoxicity: an animal model for Huntington's disease. J. Cell Tissue Res. 7(1): 853-860
54. Ramos-Vara, J.A. 2005. Technical aspects of immunohistochemistry. Vet. Pathol. 42(4): 405-426. doi:10.1354/vp.42-4-405. PMID:16006601
55. Rangan, G.K., and Tesch, G.H. 2007. Quantification of renal pathology by image analysis. Nephrology (Carlton), 12(6): 553-558. doi:10.1111/j.1440-1797.2007. 00855.x. PMID:17995580
56. Rego, A.C., and Oliveira, C.R. 2003. Mitochondrial dysfunction and reactive oxygen species in excitotoxicity and apoptosis: implications for the patho- genesis of neurodegenerative diseases. Neurochem. Res. 28(10): 1563-1574. doi:10.1023/A:1025682611389. PMID:14570402
57. Rosenstock, T.R., Carvalho, A.C., Jurkiewicz, A., Frussa-Filho, R., and Smaili, S.S. 2004. Mitochondrial calcium, oxidative stress and apoptosis in a neurodegenerative disease model induced by 3-nitropropionic acid. J. Neurochem. 88(5): 1220-1228. doi:10.1046/j.1471-4159.2003.02250.x. PMID:15009678
58. Ross, C.A., and Shoulson, I. 2009. Huntington disease: pathogenesis, biomarkers, and approaches to experimental therapeutics. Parkinsonism Relat. Disord. 15(Suppl. 3): S135-S138. doi:10.1016/S1353-8020(09)70800-4. PMID: 20082975
59. Sugino, T., Nozaki, K., Takagi, Y., Hattori, I., Hashimoto, N., and Yodoi, J. 1999. Expression and distribution of redox regulatory protein, thioredoxin after metabolic impairment by 3-nitropropionic acid in rat brain. Neurosci. Lett. 275(2): 145-148. doi:10.1016/S0304-3940(99)00763-6. PMID:10568520
60. Tadros, M.G., Khalifa, A.E., Abdel-Naim, A.B., and Arafa, H.M. 2005. Neuroprotective effect of taurine in 3-nitropropionic acid-induced experimental animal model of Huntington's disease phenotype. Pharmacol. Biochem. Behav. 82(3): 574-582. doi:10.1016/j.pbb.2005.10.018. PMID:16337998.
61. Tian, F., Xu, L.H., Zhao, W., Tian, L.J., and Ji, X.L. 2013. The neuroprotective mechanism of puerarin treatment of acute spinal cord injury in rats. Neurosci. Lett. 543: 64-68. doi:10.1016/j.neulet.2013.03.039. PMID:23570727
62. Tobinick, E.L., and Gross, H. 2008. Rapid cognitive improvement in Alzheimer's disease following perispinal etanercept administration. J. Neuroinflammation, 5: 2. doi:10.1186/1742-2094-5-2. PMID:18184433
63. Tunez, I., and Santamaria, A. 2009. Model of Huntington's disease induced with 3-nitropropionic acid. Rev. Neurol. 48(8): 430-434. [In Spanish] 19340784
64. Tunez, I., Tasset, I., Perez-De La Cruz, V., and Santamaria, A. 2010. 3-Nitropropionic acid as a tool to study the mechanisms involved in Huntington's disease: past, present and future. Molecules, 15(2): 878-916. doi:10.3390/molecules 15020878. PMID:20335954
65. Turner, C., and Schapira, A.H. 2010. Mitochondrial matters of the brain: the role in Huntington's disease. J. Bioenerg. Biomembr. 42(3): 193-198. doi:10.1007/ s10863-010-9290-y. PMID:20480217
66. Valor, L.M., and Guiretti, D. 2013. What's wrong with epigenetics in Huntington's disease? Neuropharmacology. In press. doi:10.1016/j.neuropharm.2013. 10.025. PMID:24184315
67. Vis, J.C., Verbeek, M.M., de Waal, R.M., ten Donkelaar, H.J., and Kremer, B. 2001. The mitochondrial toxin 3-nitropropionic acid induces differential expression patterns of apoptosis-related markers in rat striatum. Neuropathol. Appl. Neurobiol. 27(1): 68-76. doi:10.1046/j.0305-1846.2001.00305.x. PMID: 11299004
68. Wang, J.-W., Wang, H.-D., Cong, Z.-X., Zhou, X.-M., Xu, J.-G., Jia, Y., and Ding, Y. 2014. Puerarin ameliorates oxidative stress in a rodent model of traumatic brain injury. J. Surg. Res. 186(1): 328-337. doi:10.1016/j.jss.2013.08.027. PMID: 24079811
69. Wenli, Y., Yaping, Z., and Bo, S. 2004. The radical scavenging activities of radix puerariae isoflavonoids: A chemiluminescence study. Food Chem. 86(4): 525-529. doi:10.1016/j.foodchem.2003.09.005
70. Wu, H.Q., Wang, H.Q., Zhang, B., Zhang, G.L., Zhang, R., and Zhang, L.F. 2012. Puerarin decreases hypoxia inducible factor-1 alpha in the hippocampus of vascular dementia rats. Neural Regener. Res. 7(6): 421-425. doi:10.3969/j.issn. 1673-5374.2012.06.003
71. Xiao, L.Z., Huang, Z., Ma, S.C., Zen, Z., Luo, B., Lin, X., and Xu, X. 2004. Study on the effect and mechanism of puerarin on the size of infarction in patients with acute myocardial infarction. Zhongguo Zhong Xi Yi Jie He Za Zhi, 24(9): 790-792. PMID:15495821
72. Xing, G., Dong, M., Li, X., Zou, Y., Fan, L., Wang, X., et al. 2011. Neuroprotective effects of puerarin against beta-amyloid-induced neurotoxicity in PC12 cells via a PI3K-dependent signaling pathway. Brain Res. Bull. 85(3-4): 212-218. doi:10.1016/j.brainresbull.2011.03.024. PMID:21473901
73. Xu, C., Xu, W., Xu, H., Xiong, W., Gao, Y., Li, G., et al. 2012. Role of puerarin in the signalling of neuropathic pain mediated by P2X3 receptor of dorsal root ganglion neurons. Brain Res. Bull. 87(1): 37-43. doi:10.1016/j.brainresbull. 2011.10.007. PMID:22044944
74. Yan, B., Wang, W., Zhang, L., Xing, D., Wang, D., and Du, L. 2006. Determination of puerarin in rat cortex by high-performance liquid chromatography after intravenous administration of Puerariae flavonoids. Biomed. Chromatogr. 20(2): 180-184. doi:10.1002/bmc.549. PMID:16078309
75. Yang, J., Liu, Q., Wu, S., Xi, Q., and Cai, Y. 2013. Effects of lanthanum chloride on glutamate level, intracellular calcium concentration and caspases expression in the rat hippocampus. Biometals, 26(1): 43-59. doi:10.1007/s10534-012- 9593-z. PMID:23097080
76. Yang, X., Hu, W., Zhang, Q., Wang, Y., and Sun, L. 2010. Puerarin inhibits C-reactive protein expression via suppression of nuclear factor kappaB activation in lipopolysaccharide-induced peripheral blood mononuclear cells of patients with stable angina pectoris. Basic Clin. Pharmacol. Toxicol. 107(2): 637-642. doi:10.1111/j.1742-7843.2010.00548.x. PMID:20346059
77. Yuan, J., and Yankner, B.A. 2000. Apoptosis in the nervous system. Nature, 407(6805): 802-809. doi:10.1038/35037739. PMID:11048732
78. Zhang, H.Y., Liu, Y.H., Wang, H.Q., Xu, J.H., and Hu, H.T. 2008. Puerarin protects PC12 cells against beta-amyloid-induced cell injury. Cell Biol. Int. 32(10): 1230-1237. doi:10.1016/j.cellbi.2008.07.006. PMID:18675923
79. Zhang, H., Liu, Y., Lao, M., Ma, Z., and Yi, X. 2011a. Puerarin protects Alzheimer's disease neuronal cybrids from oxidant-stress induced apoptosis by inhibiting pro-death signaling pathways. Exp. Gerontol. 46(1): 30-37. doi:10.1016/j.exger. 2010.09.013. PMID:20933077
80. Zhang, H., Liu, Y., Lao, M., Ma, Z., and Yi, X. 2011b. Puerarin protects Alzheimer's disease neuronal cybrids from oxidant-stress induced apoptosis by inhibiting pro-death signaling pathways. Exp. Gerontol. 46(1): 30-37. doi:10.1016/j.exger. 2010.09.013. PMID:20933077
81. Zhang, Z., Lam, T.N., and Zuo, Z. 2013. Radix Puerariae: an overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. J. Clin. Pharmacol. 53(8): 787-811. doi:10.1002/jcph.96. PMID:23677886
82. Zhao, L.X., Liu, A.C., Yu, S.W., Wang, Z.X., Lin, X.Q., Zhai, G.X., and Zhang, Q.Z. 2013. The permeability of puerarin loaded poly(butylcyanoacrylate) nanoparticles coated with polysorbate 80 on the blood-brain barrier and its protective effect against cerebral ischemia/reperfusion injury. Biol. Pharm. Bull. 36(8): 1263-1270. doi:10.1248/bpb.b12-00769. PMID:23902970
83. Zhou, J., Wang, H., Xiong, Y., Li, Z., Feng, Y., and Chen, J. 2010. Puerarin attenuates glutamate-induced neurofilament axonal transport impairment. J. Ethnopharmacol. 132(1): 150-156. doi:10.1016/j.jep.2010.08.005. PMID:20727960
84. Zhu, G., Wang, X., Chen, Y., Yang, S., Cheng, H., Wang, N., and Li, Q. 2010. Puerarin protects dopaminergic neurons against 6-hydroxydopamine neurotoxicity via inhibiting apoptosis and upregulating glial cell line-derived neurotrophic factor in a rat model of Parkinson's disease. Planta Med. 76(16): 1820-1826. doi:10.1055/s-0030-1249976. PMID:20509103