Polyphenols and neuroprotection against ischemia and neurodegeneration

Mini-Reviews in Medicinal Chemistry

Volumn 11, Issue 14, 2011, Pages 1222-1238

  Lin, B ^a  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

Author keywords

Angiogenesis; Anti aggregation; Anti inflammation; Antioxidant; Chinese medicine; Ischemia; Neurogenesis; Vasodilation

Indexed keywords

1,2,3,4,6 PENTA O GALLOYL BETA DEXTRO GLUCOSE; AMYLOID BETA PROTEIN; ANGELICA EXTRACT; ANGELICA SINENSIS EXTRACT; ASTRAGALI EXTRACT; ASTRAGALUS MEMBRANACEUS EXTRACT; BAICALEIN; BAICALIN; FERULIC ACID; GLYCYRRHIZA EXTRACT; GLYCYRRHIZIC ACID; LIGUSTICUM WALLICHII EXTRACT; LIGUSTILIDE; OROXYLIN A; PAEONIA EXTRACT; PAEONIA SUFFRUTICOSA EXTRACT; PAEONIA VEITCHII EXTRACT; PAEONIFLORIN; PAEONOSIDE; PEONOL; PLANT EXTRACT; PLANT MEDICINAL PRODUCT; POLYPHENOL; PRUNUS PERSICA EXTRACT; SAFFLOWER EXTRACT; SAPONIN; SCUTELLARIA BAICALENSIS EXTRACT; TETRAMETHYLPYRAZINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; WOGONIN;

ALZHEIMER DISEASE; ANGELICA; ANGELICA SINENSIS; ANTICOAGULATION; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; ANTIPYRETIC ACTIVITY; ARTICLE; ASTRAGALI; ASTRAGALUS MEMBRANACEUS; ASTRAGALUS PLANT; BRAIN CIRCULATION; BRAIN INFARCTION; BRAIN ISCHEMIA; CELL PROTECTION; CHEMICAL STRUCTURE; CHINESE MEDICINE; DRUG TARGETING; ENDOTHELIUM CELL; FEVER; GLYCYRRHIZA; HEMOSTASIS; HUMAN; INFLAMMATORY CELL; LIGUSTICUM WALLICHII; MEDICINAL PLANT; MEMORY DISORDER; MYALGIA; NERVE DEGENERATION; NEUROPROTECTION; NONHUMAN; PAEONIA SUFFRUTICOSA; PAEONIA VEITCHII; PARKINSON DISEASE; PHYTOCHEMISTRY; PRUNUS PERSICA; SAFFLOWER; SCUTELLARIA; SCUTELLARIA BAICALENSIS; THROMBOCYTE AGGREGATION INHIBITION; VASOCONSTRICTION; VASODILATATION;

EID: 82955214576     PISSN: 13895575     EISSN: 18755607     Source Type: Journal    
DOI: 10.2174/13895575111091222     Document Type: Article

References (205)

1. De la Torre, JC. Vascular basis of Alzheimer's pathogenesis. Ann.N.Y. Acad. Sci., 2002, 977, 196-215.
2. Nakano, S.; Kogure, K.; Fujikura, H. Ischemia-induced slowlyprogressive neuronal damage in the rat brain. Neuroscience, 1992, 38, (1), 115-124.
3. Lin, B.; Levy, S.; Raval, A.P.; Perez-Pinzon, M.A.; Defazio, R. A. Forebrain ischemia triggers GABAergic system degeneration insubstantia nigra at chronic stages in rats. Cardiovasc. Psychiatry. Neurol., 2010.
4. Gong, X.; Sucher, N.J. Stroke therapy in traditional Chinesemedicine (TCM): prospects for drug discovery and development. Phytomedicine, 2002, 9(5), 478-484.
5. Kim, H. Neuroprotective herbs for stroke therapy in traditionaleastern medicine. Neurological Res., 2005, 27(3), 287-301.
6. Shi, F.L.; Hart, R.G.; Sherman, D.G., Tegeler, C.H. Stroke in thePeople's Republic of China. Stroke, 1989, 20(1), 1581-1585.
7. rd, ed.; People's Health Publisher: Beijing, 1994. (inChinese)
8. nd,ed.; Li, Y.K.;and Jiang, M.Y.; Eds.; Chinese Medicine of China: Beijing, 1993;pp.129-146. (in Chinese)
9. Cai, Q.; Li, X.; Wang, H. Astragali and angelica protect the kidneyagainst ischemia and reperfusion injury and accelerate recovery. Chin. Med. J., [Eng] 2001, 114(2), 119-123.
10. Xue, J.X.; Yan, Y.Q.; Jiang, Y. Effects of the combination ofastragulus membranaceus[Fisch.] Bge.[AM], angelicasinensis[Oliv.]diels[TAS], cyperus rotundus L.[CR], ligusticumchuanxiong[LC] and peaonia veitchii lynch[PV] on thehemorheological changes in "blood stagnation" rats. ZhongguoZhong Yao Za Zhi, 1994, 19(2), 108-128. (in Chinese).
11. Yim, T.K.; Wu, W.K.; Pak, W.F.; Mak, D.H.F.; Liang, S.M.; Ko, K.M. Myocardial protection against ischemia-reperfusion injury bya Polygonum multiflrum extract supplemented 'Dang-Guidecoction for enriching blood', a compound formulation, ex vivo. Phytotherapy. Res., 2000, 14(3), 195-199.
12. Li, X.; Bai, X.; Qin, L.; Huang, H.; Xiao, Z.; Gao, T. Neuroprotective effects of Buyang huanwu decoction on neuronalinjury in hippocampus after transient forebrain ischemia in rats. Neurosci. Lett., 2003, 346(1-2), 29-32.
13. nd,ed.; CRCPress LLC: Boca Raton, 1999.
14. nd,ed.;Li, Y, and Jiang, M. Eds.; Chinese Medicine of China: Beijing, 1993, pp. 177-205. (in Chinese)
15. Mena, H.; Cadavid, D.; Rushing, E.J. Human cerebral infarct: aproposed histopathologic classification based on 137 cases. ActaNeuropathol., 2004, 108(6), 524-530.
16. Lin, B.; Ginsberg, M.D. Quantitative assessment of the normalmicrovasculature by endothelial barrier antigen (EBA)immunohistochemistry: application to focal cerebral ischemia. Brain Res., 2000, 865(2), 237-244.
17. Garcia, J.H.; Liu, K.F.; Yoshida, Y.; Chen, S.; Lian, J. Brainmicrovessel: factors altering their patency after the occlusion of amiddle cerebral artery (Wistar rat). Am. J. Pathol., 1994, 145(3), 728-740.
18. Garcia, J.H.; Liu, K.F.; Yoshida, Y.; Lian, J.; Chen, S.; del Zoppo, G.J. Influx of leukocytes and platelets in an evolving brain infarct(Wistar rat). Am. J. Pathol., 1994, 144(1), 188-199.
19. Heye, N.; Paetzold, C.; Cerbos-Navarro, J. The role ofmicrothrombi and microcirculatory factors in localization andevolution of focal cerebral ischemia. Neurosurg. Rev., 1991, 14(1), 7-16.
20. Zhang, Z.G.; Zhang, L.; Tsang, W.; Goussev, A.; Powers, C.; Ho, K.L.; Morris, D.; Smyth, S.S.; Coller, B.S.; Chopp, M. Dynamicplatelet accumulation at the site of the occluded middle cerebralartery and in downstream microvessel is associated with loss ofmicrovascular integrity after embolic middle cerebral arteryocclusion. Brain Res., 2001, 912(2), 181-194.
21. Akopov, S.; Sercombe, R.; Seylaz, J. Cerebraovascular reactivity:role of endothelium /platelet/lekocyte interactions. Cerebrovasc. Brain Metab. Rev., 1996, 8(1), 11-94.
22. Mehta, J.L.; Nicolini, F.A.; Donnelly, W.H.; Nichols, W.W. Platelet-leukocyte-endothelial interactions in coronary arterydisease. Am. J. Cardiol., 1992, 69(7), 8B-13B.
23. Kudo, T.; Takeda, M.; Tanimukai, S.; Nishimura, T. Neuropathologic changes in the gerbil brain after chronichypoperfusion. Stroke., 1993, 24(2), 259-265.
24. Lin, B. Postischemic-anoxic encephalopathy after global forebrainischemia. J. Central Nervous System Agents in MedicinalChemistry, 2008, 8(3), 177-186.
25. Damjanov I. In: The Pathology for the health-related professions.W.B. Saunders Co. Philadelphia, 1996; pp. 24-43.
26. O'Banion, M.K. Cyclooxygenase-2: molecular biology, pharmacology, and neurobiology. Crit. Rev. Neurobiol., 1999, 13(1), 45-82.
27. Nogawa, S.; Forster, C.; Zhang, F.; Nagayama, M.; Ross, M.E.;Iadecola, C. Interaction between inducible nitric oxide synthase andcyclooxygenase-2 after cerebral ischemia. Proc. Natl. Acad. Sci. US A., 1998, 95(18), 10966-10971.
28. Iadecola, C.; Alexander, M. Cerebral ischemia and inflammation. Curr. Opin. Neurol., 2001, 14(1), 89-94.
29. Chan, P.H. Mitochondrial dysfunction and oxidative stress asdeterminants of cell death/survival in stroke. Ann. N.Y. Acad. Sci., 2005 May, 1042, 203-209.
30. Iadecola, C.; Forster, C.; Nogawa, S.; Clark, H.B.; Ross, M.E. Cyclooxygenase-2 immunoreactivity in the human brain followingcerebral ischemia. Acta Neuropathol., 1999, 98(1), 9-14.
31. Michiels, C.; Arnould, T.; Knott, I.; Dieu, M.; Remacle, J. Stimulation of prostaglandin synthesis by human endothelial cellsexposed to hypoxia. Am. J. Physiol., 1993, 264, (4 Pt 1), C866-874.
32. Sairanen, T.; Ristimaki, A.; Karjalainen-Lindsberg, M.L.; Paetau, A.; Kaste, M.; Lindsberg, P.J. Cyclooxygenase-2 is inducedglobally in infarcted human brain. Ann. Neurol., 1998, 43(6), 738-747.
33. Tomimoto, H.; Akiguchi, I.; Wakita, H.; Lin, J.X.; Budka, H. Cyclooxygenase-2 is induced in microglia during chronic cerebralischemia in human. Acta Neuropathol., 2000, 99(1), 26-30.
34. Strauss, K.I.; Barbe, M.F.; Marshall, R.M.; Raghupathi, R.; Mehta, S.; Narayan, R.K. Prolonged cyclooxygenase-2 induction inneurons and glia following traumatic brain injury in the rat. J. Neurotrauma, 2000, 17(8), 695-711.
35. Barone FC, Feuerstein GZ. Inflammatory mediators and stroke:new opportunities for novel therapeutics. J. Cereb. Blood FlowMetab., 1999, 19(8), 819-834.
36. Hara, K.; Kong, D.L.; Sharp, F.R.; Weinstein, P.R. Effect ofselective inhibition of cyclooxygenase 2 on temporary focalcerebral ischemia in rats. Neurosci. Lett., 1998, 256(1), 53-56.
37. Dore, S.; Otsuka, T.; Mito, T.; Sugo, N.; Hand, T.; Wu, L.; Hurn, P.D.; Traystman, R.J.; Andreasson, K. Neuronal overexpression ofcyclooxygenases-2 increases cerebral infarction. Ann. Neurol., 2003, 54(2), 155-162.
38. Nakayama, M.; Uchimura, K.; Zhu, R.L.; Magayama, T.; Rose, M.;Stetler, R.A.; Isakson, P.C.; Chen, J.; Graham, S.H. Cyclooxygenase-2 inhibition prevents delayed death of CA1hippocampal neurons following global ischemia. Proc. Natl. Acad. Sci. USA., 1998, 95(18), 10954-10959.
39. Yermakova, A.; O'Banion, M.K. Cyclooxygenases in the centralnervous system: implications for treatment of neurologicaldisorders. Curr. Pharm. Des., 2000, 6(17), 1755-1776.
40. Lin, B. In: Complementary and Alternative Therapies and theAging Population: An Evidence-Based Approach, Watson, R.R. Ed. Elsevier: New York. 2009, pp. 229-275.
41. Yagami, T. Cerebral arachidonate cascade in dementia:Alzheimer's disease and vascular dementia. Curr. Neuropharm., 2006, 4, (1), 87-100.
42. Fujioka, M.; Okuchi, K.; Sakaki, T.; Hiranatsu, K.I.; Miyamoto, S.;Iwasaki, S. Specific changes in human brain following reperfusionafter cardiac arrest. Stroke, 1994, 25(10), 2091-2095.
43. Furlan, A.J.; Sila, C.A.; Chimowitz, M.I.; Jones, S.C. Neurologicalcomplications related to cardiac surgery. Neurol. Clin., 1992, 10(1), 145-166.
44. Harrison, M.J. Neurologic complications of coronary artery bypassgrafting: diffuse or focal ischemia? Ann. Thorac. Surg., 1995, 59(5), 1356-1358.
45. Lin, B.; Ginsberg, M.D.; Busto, R.; Dietrich, W. D. Sequentialanalysis of subacute and chronic neuronal, astrocytic andmicroglial alterations after transient global ischemia in rats. ActaNeuropathol., 1998, 95(5), 511-523.
46. Tatemichi, T.K.; Paik, M.; Bagiella, E.; Desmond, D.W.; Pirro, M.;Hanzawa, L.K. Dementia after stroke is a predictor of long-termsurvival. Stroke, 1994, 25(10), 1915-1919.
47. Tatemichi, T.K.; Paik, M.; Bagiella, E.; Desmond, D.W.; Stern, Y.;Sano, M.; Hauser, W.A.; Mayeux, R. Risk of dementia after strokein a hospitalized cohort: results of a longitudinal study. Neurology, 1994, 44(10), 1885-1891.
48. Wisniewski, H.M.; Maslinska, D. Beta-protein immunoreactivity inthe human brain after cardiac arrest. Folia Neuropathol., 1996, 34(2), 65-71.
49. Jendroska, K.; Poewe, W.; Daniel, S.E.; Pluess, J.; Iwerssen-Schmidt, H.; Paulsen, J.; Barthel, S.; Schelosky, L.; Cervos-Navarro, J.; DeArmond, S.J. Ischemic stress induces deposition ofamyloid beta immunoreactivity in human brain. Acta Neuropathol., 1995, 90(5), 461-466.
50. Lin, B.; Schmidt-Kastner, R.; Busto, R.; Ginsberg, M. D. Progressive parenchymal deposition of PP-amyloid precursor proteinin rat brain following global cerebral ischemia. Acta Neuropathol., 1999, 97(4), 359-368.
51. Lin, B.; Ginsberg, M.D. In: Pharmacology of cerebral ischemia2000, ed. J. Krieglstein, and S. Klumpp, Ed.; Medpharm ScientificPublishers. Stuttgart, 2000; pp. 37-52.
52. Chan, P.H. Future targets and cascades for neuroprotectivestrategies. Stroke, 2004, 35, (suppl I), 2748-2750.
53. nd,ed.; Li, Y.K. and Jiang, M. Y, Eds.; Chinese Medicine of China: Beijing, 1993; pp.48-78. (in Chinese)
54. Chen, Y.; Yang, L.; Lee, T.J. Oroxylin A inhibition oflipopolysaccharide-induced iNOS and COX-2 gene expression viasuppression of nuclear factor-kappaB activation. Biochem. Pharmacol., 2000, 59(11), 1445-1457.
55. Lim BO, Yu BP, Kim SC, Park DK. The antioxidative effect ofganhuangenin against lipid peroxidation. Phytother. Res., 1999, 13(6), 479-483.
56. Shieh, D.; Liu, L.; Lin, C. Antioxidant and free radical scavengingeffects of baicalein, baicalin and wogonin. Anticancer Res., 2000, 20(5A), 2861-2865.
57. You, K.M.; Jong, H.G.; Kim, H.P. Inhibition of cyclooxygenase/lipoxygenas from human platelets by polyhydroxylated/methoxylated flavonoids isolated from medicinal plants. Arch. Pharm. Res., 1999, 22(1), 18-24.
58. Wei, L.; Yuan, T. Analysis of Chinese Medication;, ShanghaiScience and Technology Publisher: Shanghai, 1997. (in Chinese)
59. Hamada, H.; Hiramatsu, M.; Edamatsu, R.; Mori, A. Free radicalscavenging action of baicalein. Arch. Biochem. Biophys., 1993, 306(1), 261-266.
60. Kim, Y.O.; Leem, K.; Park, J.; Lee, P.; Ahn, D.K.; Lee, B.C.; Park, H.K.; Suk, K.; Kim, S.Y.; Kim, H. Cytoprotective effect ofScutellaria baicalensis in CA1 hippocampal neurons of rats afterglobal cerebral ischemia. J. Ethnopharmacol., 2001, 77(2-3), 183-188.
61. Cho, J.; Lee, H. Wogonin inhibits ischemic brain injury in a ratmodel of permanent middle cerebral artery occlusion. Biol. Pharm. Bull., 2004, 27(10), 1561-1564.
62. Xue, X.; Qu, X.; Yang, Y.; Sheng, X.; Cheng, F.; Jiang, E.; Wang, J.; Bu, W.; Liu, Z. Baicalin attenuates focal cerebral ischemicreperfusion injury through inhibition of nuclear factor κB p65activation. Biochem. Biophys. Res. Commun., 2010, 403(3-4), 398-404.
63. Cui, L.; Zhang, X.; Yang, R.; Liu, L.; Wang, L.; Li, M.; Du, W. Baicalein is neuroprotective in rat MCAO model: role of 12/15-lipoxygenase, mitogen-activated protein kinase and cytosolicphospholipase A2. Pharm. Biochem. Behav., 2010, 96(4), 469-475.
64. Pallast, S.; Arai, K.; Pekcec, A.; Yigitkanli, K.; Yu, Z.; Wang, X.;Lo, E.H.; van Leyen, K. Increased nuclear apoptosis-inducingfactor after transient focal ischemia: a 12/15-lipoxygenasedependentorganelle damage pathway. J. Cereb. Blood FlowMetab., 2010, 30(6), 1157-1167.
65. Okuda, S.; Saito, H.; Katsuki, H. Arachidonic acid: toxic andtrophic effects on cultured hippocampal neurons. Neuroscience, 1994, 63(3), 691-696.
66. Gao, Z.; Huang, K.; Yang, X.; Xu, H. Protective effects offlavonoids in the roots of Scutellaria Baicalensis Georgi, againsthydrogen peroxide-induced oxidative stress in HS-SY5Y cells. Pharmacol. Res., 2001, 43(2), 173-178.
67. Hanasaki, Y.; Ogawa, S.; Fukui, S. The correlation between activeoxygen scavenging and antioxidative effects of flavonoids. FreeRadic. Biol. Med., 1994, 16(6), 845-850.
68. Morimoto, S.; Tateishi, N.; Matsuda, T.; Tanaka, H.; Taura, F.;Furuya, N.; Matsuyama, N.; Shoyama, Y. Novel hydrogen peroxidemetabolism in suspension cells of Scutellaria Baicalensis Georgi. J. Biol. Chem., 1998, 273(20), 12601-12611.
69. Gao, D.; Tawa, R.; Masaki, H.; Okano, Y.; Sakurai, H. Protectiveeffects of baicalein against cell damage by reactive oxygen species. Chem. Pharm. Bull., (Tokyo), 1998, 46(9), 1383-1387.
70. Shao, Z.;, Vanden, H. T.L.; Qin, Y.; Becker, L.B.; Schumacker, P.T.; Li CQ, Dey L, Barth E, Halpern H, Rosen GM, Yuan CS. Baicalein attenuates oxidant stress in cardiomyocytes. Am. J. Physiol. Heart. Circ. Physiol., 2002, 282(3), H999-H1006.
71. Shao, Z.; Li, C.; Vanden, H. T.L.; Becker, L.B.; Schumacker, P.T.;Wu JA, Attele AS, Yuan CS. Extract from Scutellaria baicalensisGeorgi attenuates oxidant stress in cardiomyocytes. J. Mol. CellCardiol., 1999, 31(10), 1885-1895.
72. Gao, Z.; Huang, K.; Yang, X.; Xu, H. Free radical scavenging andantioxidant activities of flavonoids extracted from the radix ofScutellaria baicalensis Georgi. Biochim. Biophys. Acta, 1999, 1472(3), 643-650.
73. Gao, D.; Sakkurai, K.; Katoh, M.; Chen, J.; Ogiso, T. Inhibition ofmicrosomal lipid peroxidation by baicalein: a possible formation ofan iron-baicalein complex. Biochem. Mol. Biol. Int., 1996, 39(2), 21-25.
74. Tezuka, Y.; Irikawa, S.; Kaneko, T.; Banskota, A.; Nagaoka, T.;Xiong Q, Hase K, Kadota S. Screening of Chinese herbal drugextracts for inhibitory activity on nitric oxide production andidentification of an active compound of Zanthoxylum bungeanum. J. Ethnopharmacol., 2001, 77(2-3), 209-217.
75. Wakabayashi, I. Inhibitory effects of baicalein and wogonin onlipopolysaccharide-induced nitric oxide production inmacrophages. Pharmacol. Toxicol., 1999, 84(6), 288-291.
76. Gabrielska, J.; Oszmianski, J.; Zylka, R.; Komorowska, M. Antioxidant activity of flavones from Scutellaria baicalensis inlecithin liposomes. Z Naturgorsch[C], 1997, 52(11-12), 817-823.
77. Yokozawa, T.; Dong, E.; Kawai, Y.; Gemba, M.; Shimizu, M. Protective effects of some flavonoids on the renal cellularmembrane. Exp. Toxicol. Pathol., 1999, 51(1), 9-14.
78. DeGeorge, J.J.; Walenga, R.; Carbonetto, S. Nerve growth factorrapidly stimulates arachidonate metabolism in PC12 cells: potentialinvolvement in nerve fiber growth. J. Neurosci. Res., 1988, 21(2-4), 323-332.
79. 2+,elevation by reducing phospholipaseC activity in C6 rat glioma cell. J. Pharm. Pharmacol., 1998, 50(10), 1179-1182.
80. Chen, Y.; Shen, S.; Chen, L.; Lee, T.; Yang, L. Wogonin, baicalin, and baicalein inhibition of inducible nitric oxide synthase andcyclooxygenase-2 gene expressions induced by nitric oxidesynthase inhibitors and lipopolysaccharide. Bioch. Pharmacol., 2001, 61(11), 1417-1427.
81. Tu, X.; Yang, W.; Shi, S.; Chen, Y.; Wang, C.; Chen, C.; Chen, Z. Baicalin Inhibits TLR2/4 Signaling Pathway in Rat BrainFollowing Permanent Cerebral Ischemia. Inflammation, publishedonline, 22 September 2010
82. Tu, X.; Yang, W.; Shi, S.; Wang, C.; Chen, C. Neuroprotectiveeffect of baicalin in a rat model of permanent focal cerebralischemia. Neurochem. Res., 2009, 34(9), 1626-1634.
83. Shaw, S.; Naegeli, P.; Etter, J.D.; Weidmann, P. Role ofintracellular signaling pathways in hydrogen peroxide-inducedinjury to rat glomerular mesangial cells. Clin. Exp. Pharmacol. Physiol., 1995, 22(12), 924-33.
84. Nakamura, N.; Hayasaka, S.; Zhang, X.; Nagaki, Y.; Matsumoto, M.; Hayasaka, Y.; Terasawa, K. Effects of baicalin, baicalein, andwogonin on interkeukin-6 and interleukin-8 expression and nuclearfactor-kappa B binding activities induced by interleukin-1 β inhuman retinal pigment epithelial cell line. Exp. Eye Res., 2003, 77(2), 195-202.
85. Piao, H.; Jin, S.; Chun, H.; Lee, J.; Kim, W. Neuroprotective effectof wogonin: potential roles of inflammatory cytokines. Arch. Pharm. Res., 2004, 27(9), 930-936.
86. Lee, H.; Kim, Y.O.; Kim, H.; Kim, S.; Noh, H.; Kang, S.; Cho, G.;Choi, W.; Suk, K. Flavonoid wogonin from medicinal herb isneuroprotective by inhibiting inflammatory activation of microglia. FASEB. J., 2003, 17(13), 1943-1944.
87. Son D, Lee P, Lee J, Kim H, Kim SY. Neuroprotective effect ofwogonin in hippocampal slice culture exposed to oxygen andglucose deprivation. Eur. J. Pharmacol., 2004, 493(1-3), 99-102.
88. Lee, H.; Yang, L.; Wang, C.; Hu, S.; Chang, S.; Lee, Y. Differential effects of natural polyphenols on neuronal survival inprimary cultured central neurons against glutamate-and glucosedeprivation-induced neuronal death. Brain Res., 2003, 986, (1-2), 103-13.
89. Xue, X.; Qu, X.; Yang, Y.; Sheng, X.; Cheng, F.; Jiang, E.; Wang, J.; Bu, W.; Liu, Z. Baicalin attenuates focal cerebral ischemicreperfusion injury through inhibition of nuclear factor κB p65activation. Biochem. Biophys. Res. Commun., 2010, 403(3-4), 398-404.
90. Hwang, Y.; Shin, C.; Huh, Y.; Ryu, J. Hwangryun-Hae-Dok-Tang(Huanglian-Jie-du-Tang) extract and its constituents reduceischemia-reperfusion brain injury and neutrophil infiltration in rats. Life Sci., 2002, 71(18), 2105-2117.
91. Zhu, M.; Rajamani, S.; Kaylor, J.; Han, S.; Zhou, F.; Fink, A. Theflavonoid baicalein inhibits fibrillation of α-synuclein anddisaggregates existing fibrils. J. Bio. Chem., 2004, 279(26), 26846-26857.
92. Lin, C.; Shieh, D. The anti-inflammatory activity of Scutellariarivularis extracts and its active components, baicalin, baicalein andwogonin. Am. J. Chin. Med., 1996, 24(1), 31-36.
93. Li, B.; Fu, T.; Gong, W.; Dunlop, N.; Kung, H.; Yan, Y.; Kang, J.;Wang, J. The flavonoid baicalin exhibits anti-inflammatory activityby binding to chemokines. Immunopharmacology, 2000, 49(3), 295-306.
94. Krakauer, T.; Li, B.; Young, H. The flavonoid baicalin inhibitssuperantigen-induced inflammatory cytokines and chemokines. FEBS Lett., 2001, 500(1-2), 52-55.
95. Nakahata, N.; Kutsuwa, M.; Kyo, R.; Kubo, M.; Hayashi, K.;Ohizumi, Y. Analysis of inhibitory effects of scutellariae radix andbaicalein on prostaglandin E2 production in rat C6 glioma cells. Am. J. Chin. Med., 1998, 26(3-4), 311-323.
96. Kimura, Y.; Matsushita, N.; Yokoi-Hayashi, K.; Okuda, H. Effectsof baicalein isolated from Scutellaria baicalensis Radix on adhesionmolecule expression induced by thrombi and thrombin receptoragonist peptide in cultured human umbilical vein endothelial cells. Planta Med., 2001, 67(4), 331-334.
97. Kimura, Y.; Matsushita, N.; Okuda, H. Effects of baicalein isolatedfrom Scutellaria baicalensis on interleukin 1 beta-and tumornecrosis factor alpha-induced adhesion molecule expression incultured human umbilical vein endothelial cells. J. Ethnopharmacol., 1997, 57(1), 63-67.
98. Kimura, Y.; Okuda, H.; Ogita, Z. Effects of flavonoids isolatedfrom scutellariae radix on fibrinolytic system induced by trypsin inhuman umbilical vein endothelial cells. J. Nat. Prod., 1997, 60(6), 598-601.
99. Kimura, Y.; Yokoi, K.; Matsushita, N.; Okuda, H. Effects offlavonoids isolated from scutellariae radix on the production oftissue-type plasminogen activator and plasminogen activatorinhibitor-1 induced by thrombin and thrombin receptor agonistpeptide in cultured human umbilical vein endothelial cells. J. Pharm. Pharmacol,., 1997, 49(8), 816-822.
100. Higashitani, A.; Tabata, S.; Hayashi, T.; Hotta, Y. Plant saponinscan affect DNA recombination in cultured mammalian cells. CellStruct. Funct., 1989, 14(5), 617-624.
101. Ohtsuka, M.; Fukuda, K.; Yano, H.; Kojiro, M. Effects of nineactive ingredients in Chinese herbal medicine sho-saiko-to on 2-[2-furyl]-3-[5-nitro-2-furyl] acrylamide mutagenicity. Jpn J CancerRes, 1995, 86(12), 1131-1135.
102. Chen, X.; Nishida, H.; Konishi, T. Baicalin promoted the repair ofDNA single strand breakage caused by H2O2 in cultured NIH3T3fibroblasts. Biol. Pharm. Bull., 2003, 26(2), 282-284.
103. Stanke-Labesque, F.; Devillier, P.; Bedouch, P.; Cracowski, J.L.;Chavanon, O.; Bessard, G. Angiotensin II-induced contractions inhuman internal mammary artery: effects of cyclooxygenase andlipoxygenase inhibition. Cardiovasc Res, 2000, 47(2):376-383.
104. Liu, C.; Wu, J.; Gu, J.; Xiong, Z.; Wang, F.; Wang, J.; Wang, W.;Chen, J. Baicalein improves cognitive deficits induced by chroniccerebral hypoperfusion in rats. Pharmacol. Biochem. Behav., 2007, 86(3), 423-430.
105. Heo, H.; Kim, D.; Choi, S.; Shin, D.; Lee, C. Potent inhibitoryeffect of flavonoids in Scutellaria baicalensis on amyloid betaproteins-induced neurotoxicity. J. Agric. Food Chem., 2004, 52(13), 4128-4132.
106. Lebeau, A.; Esclaire, F.; Rostene, W.; Pelaprat, D. Baicaleinprotects cortical neurons from oooamyloid (25-35) induced toxicity. Neuroreport,; 2001, 12(10), 2199-2202.
107. Skovronsky, D.M.; Lee, V. M.; Pratico, D. Amyloid precursorprotein and amyloid ppppeptide in human platelets. J. Bio. Chem., 2001, 276(20), 17036-17043.
108. Di Luca, M.; Colciaghi, F.; Pastorino, L.; Borroni, B.; Padovani, A.; Cattabeni, F. Platelets as a peripheral district where to studypathogenetic mechanisms of Alzheimer disease: the case ofamyloid precursor protein. Eur. J. Pharmacol., 2000, 405(1-3), 277-283.
109. Cotman, C.W.; Tenner, A.J.; Cummings, B.J. α-amyloid convertsan acute phase injury response to chronic injury responses. Neurobiol. Aging, 1996, 17(5), 723-731.
110. Li, F.; Wang, Z.; Liu, P.; Hong, J. Inhibition of microglialactivation by the herbal flavonoid baicalein attenuatesinflammation-mediated degeneration of dopaminergic neurons. J. Neural. Transm., 2005, 112(3), 331-347.
111. Lim, J.S.; Yoo, M.; Kwon, H.J.; Kim, H.; Kwon, Y.K. Wogonininduces differentiation and neurite outgrowth of neural precursorcells. Biochem. Biophys. Res. Commun., 2010, 402(1), 42-47.
112. Zhang, Z.; W, R.; Li, P.; Liu, f.; Zhang, W.; Zhang, P.; Li, P.;Wang, Y. Baicalin administration is effective in positive regulationof twenty-four ischemia/reperfusion-related proteins identified by aproteomic study. Neuroche. Int., 2009, 54(8), 488-496.
113. Gasiorowski, K.; Lamer-Zarawska, E.; Leszek, J.; Parvathaneni, K.; Yendluri, B.B.; Bach-Olszewska, Z.; Aliev, G. Flavones fromRoot of Scutellaria Baicalensis Georgi: Drugs of the Future inNeurodegeneration? CNS Neurol. Disord. Drug Targets., 2011, Jan11.
114. Akao, T.; Kawabata, K.; Yanagisawa, E.; Ishihara, K.; Mizuhar, Y.; Wakui, Y.; Sakashita, Y.; Kobashi, K. Baicalin, thepredominant flavone glucuronide of scutellariae radix, is absorbedfrom the rat gastrointestinal tract as the aglycone and restored to itsoriginal form. J. Pharm. Pharmacol., 2000, 52(12), 1563-1568.
115. Tsai, T.; Liu, S.; Tsai, P.; Ho, L.; Shum, A.Y.C.; Chen, C. Theeffects of the cyclosporin A, a P-glycoprotein inhibitor, on thepharmacokinetics of baicalein in the rat: a microdialysis study. Br.J. Pharmacol., 2002, 137(8), 1314-1320.
116. Lai, M.; Hsiu, S.; Chen, C.; Hou, Y.; Chao, P. Urinarypharmacokinetics of baicalein, wogonin and their glycosides afteroral administration of scutellariae radix in human. Biol. Pharm. Bull., 2003, 26(1), 79-83.
117. Homma, M.; Oka, K.; Taniguchi, C.; Nitsuma, T.; Hayashi, T. Systematic analysis of post-administrative Saiboku-To urine byliquid chromatography to determine pharmacokinetics of traditionalChinese Medicine. Biomed. Chromatogr., 1997, 11(3), 125-131.
118. Moto, R.; Motozuka, T.; Nakano, M.; Tatsumi, Y.; Sakamoto, F.;Kasaka, N. The chemical structure of new substance as themetabolite of baicalin and time profiles for the plasmaconcentration after oral administration of sho-saiko-to in human. Yakugaku Zasshi, 1998, 118(3), 79-87.
119. Zeng, F.; Pan, L.; Zhu, H.; Zhang, Q.; Guo, L. Comparativepharmacokinetics of baicalin in plasma after oral administration ofHuang-Lian-Jie-du-Tang or pure baicalin in MCAo and shamoperatedrats. Fitoterapia, 2010, 81(6), 490-496.
120. Zhang, L.; Xing, D.; Wang, W.; Wang, R.; Du, L. Kineticdifference of baicalin in rat blood and cerebral nuclei afterintravenous administration of scutellariae radix extract. J. Ethnopharmacol., 2006, 103(1), 120-125.
121. Choi, B.M.; Kim, H.J.; Oh, G.S.; Pae, H.O.; Oh, H.; Jeong, S.;Kwon, T.O.; Kim, Y.M.; Chung, H.T. 1, 2, 3, 4, 6-Penta-O-galloylbeta-D-glucose protects rat neuronal cells (Neuro 2A) fromhydrogen peroxide-mediated cell death via, the induction of hemeoxyenase-1. Neurosci. Lett., 2002, 328(2), 185-189.
122. Prieto, J.M.; Recio, M.C.; Giner, R.M.; Manez, S.; Giner-Larza, E.M.; Rios JL. Influence of traditional Chinese anti-inflammatorymedicinal plants on leukocyte and platelet functions. J. Pharm. Pharmacol., 2003, 55(9), 1375-1282.
123. Goto, H.; Shimada, Y.; Tanaka, N.; Tanigawa, K.; Itoh, T.;Terasawa, K. Effect of extract prepared from the roots of Paeonialactiflora on endothelium-dependent relaxation and antioxidantenzyme activity in rats administered high-fat diet. Phytother. Res., 1999, 13(6), 526-528.
124. Tsuda, T.; Sugaya, A.; Ohguchi, H.; Kishida, N.; Sugaya, E. Protective effects of peony root extract and its components onneuron damage in the hippocampus induced by the cobalt focusepilepsy model. Exp. Neurol., 1997, 146(2), 518-525.
125. Ohta, H.; Ni, J.W.; Matsumoto, K.; Watanabe, H.; Shimizu, M. Peony and its major constituent, paeoniflorin, improve radial mazeperformance impaired by scopolamine in rats. Pharmacol. Biochem. Behav., 1993, 45(3), 719-723.
126. Fujiwara, H.;, Tabuchi M, Yamaguchi T, Iwasaki K, Furukawa K, Sekiguchi K, Ikarashi Y, Kudo Y, Higuchi M, Saido TC, Maeda S, Takashima A, Hara M, Yaegashi N, Kase Y, Arai H. A traditionalmedicinal herb Paeonia suffruticosa, and its active constituent1, 2, 3, 4, 6-penta-O-galloyl-α-D-glucopyranose have potent antiaggregationeffects on Alzheimer's amyloid α proteins in vitro, andin vivo. J. Neurochem., 2009, 109(6), 1648-57.
127. Hsieh, C.; Cheng, C.; Tsai, T.; Lin, I.; Liu, C.; Chiang, S.; Lin, J.;Lao, C.; Tang, N. Paeonol reduced cerebral infarction involving thesuperoxide anion and microglia activation in ischemia-reperfusioninjured rats. J. Ethnopharmacol., 2006, 106(2), 208-215.
128. Zhang, G.; Hao, X.; Chen, S.; Zhou, P.; Cheng, H.; Wu, C. Blockade of paeoniflorin on sodium current in mouse hippocampalCA1 neurons. Acta Pharmacol. Sinica., 2003, 24(12), 1248-1252.
129. Yan, D.; Saito, K.; Ohmi, Y.; Fujie, N.; Ohtsuka, K. Paeoniflorin, anovel heat shock protein-inducing compound. Cell StressChaperones, 2004, 9(4), 378-389.
130. Liu, D.; Xie, K.; Ji, X.; Ye, Y.; Jiang, C.; Zhu, X. Neuroprotectiveeffect of paeoniflorin on cerebral ischemic rat by activatingadenosine A1 receptor in a manner different from its classicalagonists. Br. J. Pharmacol., 2005, 146(4), 604-11.
131. Tang, N.; Liu, C.; Hsieh, C.; Hsieh, C-L. The anti-inflammatoryeffect of paeoniflorin on cerebral infarction induced by ischemiareperfusioninjury in Sprague-Dawley rats. Am. J. Chin. Med., 2010, 38(1), 51-64.
132. Liu J, Jin DZ, Xiao L, Zhu XZ. Paeoniflorin attenuates chroniccerebral hypoperfusion-induced learning dysfunction and braindamage in rats. Brain Res., 2006, 1089(1), 162-170.
133. Zhong, S.Z.; Ge, Q.H.; Li, Q.; Qu, R.; Ma, S.P. Peoniflorinattenuated Abeta (1-42)-mediated neurotoxicity by regulatingcalcium homeostasis and ameliorating oxidative stress inhippocampus of rats. J. Neurol. Sci., 2009, 280(1-2), 71-78.
134. Liu, D.; Zhu, J.; Jin, D.; Zhang, L.; Ji, X.; Ye, Y.; Tang, C.; Zhu, X. Behavioral recovery following sub-chronic paeoniflorinadministration in the striatal 6-OHDA lesion rodent model ofParkinson's disease. J Ethnopharmacol., 2007, 112(2), 327-332.
135. Lee, S.J.; Lee, I.S.; Mar, W. Inhibition of inducible nitric oxidesynthase and cyclooxygenase-2 activity by 1, 2, 3, 4, 6-penta-Ogalloyl-beta-D-glucose in murine macrophage cells. Arch. Pharm. Res., 2003; 26(10), 832-839.
136. Kang, D.G.; Moon, M.K.; Choi, D.H.; Lee, J.K.; Kwon, T.O.; Lee, H.S. Vasodilatory and anti-inflammatory effects of the 1, 2, 3, 4, 6-penta-O-galloyl-beta-D-glucose (PGG) via, a nitric oxide-cGMPpathway. Eur. J. Pharmacol., 2005, 524(1-3), 111-119.
137. Chen, L.C.; Chou, M.H.; Lin, M.F.; Yang, L. L. Pharmacokineticsof paeoniflorin after oral administration of Shao-yao-Gan-chaoTang in mice. Jpn. J. Pharmacol., 2002, 88(3), 250-255.
138. Yasuda, T.; Kon, R.; Nakazawa, T.; Ohsawa, K. Metabolism ofpaeonol in rats. J. Nat. Prod., 1999, 62(8), 1142-1144.
139. He, X.; Xing, D.; Ding, Y.; Li, Y.; Xu, L.; Du, L. Effects ofcerebral ischemia-reperfusion on pharmacokinetic fate ofpaeoniflorin after intravenous administration of Paeoniae, Radixextract in rats. J. Ethnopharmacol., 2004, 94(2-3), 339-944.
140. He, X.; Xing, D.; Ding, Y.; Li, Y.; Xiang, L.; Wang, W.; Du, L. Determination of paeoniflorin in rat hippocampus by highperformanceliquid chromatography after intravenousadministration of Paeoniae Radix extract. J. Chromatogr. B Analyt. Techno. l Biomed. Life Sci., 2004, 802(2), 277-281.
141. Xuejiang, W.; Ichikawa, H.; Konishi, T. Antioxidant potential ofqizhu tang, a Chinese herbal medicine, and the effect on cerebraloxidative damage after ischemia reperfusion rats. Biol. Pharm. Bull., 2001, 24(5), 558-563.
142. He, X.; Li, C.; Yu, S. Protective effects of radix astragali againstanoxic damages to in vitro, cultured neurons. J. Tongii Med. Univ., 2000, 20, (2) 126-127.
143. Shon, Y.; Nam, K. Protective effect of astragali radix extract oninterleukin 1 beta induced inflammation in human amnion. Phytother. Res., 2003, 17(9), 1016-1020.
144. Gui, S.; Wei, W.; Wang, H.; Wu, L.; Sun, W.; Chen, W.; Wu, C. Effects and mechanisms of crude astragalosides fraction on liverfibrosis in rats. J. Ethnopharmacol., 2006, 103(2), 154-9.
145. Zhang, W.; Wojta, J.; Binder, B.R. Regulation of the fibrinolyticpotential of cultured human umbilical vein endothelial cells;astragaloside IV downregulates plasminogen activator inhibitor-1and upregulates tissue-type plasminogen activatior expression. J. Vasc. Res., 1997, 34(4), 273-280.
146. Qu, Y.Z.; Li, M.; Zhao, Y.L.; Zhao, Z.W.; Wei, X.Y.; Liu, J.P.;Gao, L.; Gao, G.D. Astragaloside IV attenuates cerebral ischemiareperfusion-induced increase in permeability of the blood-brainbarrier in rats. Eur. J. Pharmacol., 2009, 606(1-3), 137-141.
147. Song, Z.; Ji, Z.; Lo, C.; Dong, T.; Zhao, K.; Li, O.; Haines, C.J.;Kung, S.; Tsim, K.W. Chemical and biological assessment of atraditional Chinese herbal decoction prepared from Radix Astragaliand Radix Angelicae Sinensis: orthogonal array design to optimizethe extraction of chemical constituents. Planta Med., 2004, 70(12), 1222-1227.
148. Lei, Y.; Wang, J.; Chen, K. Comparative study on angiogenesiseffect of Astragalus membrainaceus and Angelica Sinensis in chickembryo choriollantoic membrane. Zhongguo Zhong Yao Za Zhi, 2003, 28(9), 876-878.
149. Supporting Nomination for Toxicological Evaluation by theNational Toxicology Program. Chemical information reviewdocument for Dong quai[Cas Nos. 308068-61-3 (root) and299184-76-2 (extract)]. National Toxicology Program, 2008, NTP, National Institute of Environmental Health Science, NIH, U. SDepartment of Health and Human Services: Research TrianglePark, NC
150. Yang, J.W.; Ouyang, J.P.; Liao, W.J.; Liu, Y.M.; Wang, B.H.; Li, K. The effects of Chinese herb Angelica in focal cerebral ischemiainjury in the rat. Clin. Hemorheol. Microcirc., 2005, 32(3), 209-215.
151. Rhyu, M.R.; Kim, J.H.; Kim, E.Y. Radix angelica elicits both nitricoxide-dependent and calcium influx-mediated relaxation in rataorta. J. Cardiovasc. Pharmacol., 2005, 46(1), 99-104.
152. Xiaohong, Y.; Jing-Ping, O.Y.; Shuzheng, T. Angelica protects thehuman vascular endothelial cell from the effects of oxidized lowdensitylipoprotein in vitro. Clin. Hemorheol. Microcire., 2000, 22(4), 317-323.
153. Ozaki, Y. Anti-inflammatory effect of tetramethylpyrazine andferulic acid. Chem. Pharm. Bull., (Tokyo) 1992, 40(4), 954-956.
154. Cheng, C.Y.; Ho, T.Y.; Lee, E.J.; Su, S.Y.; Tang, N.Y.; Hsieh, C.L. Ferulic acid reduces cerebral infarct through its antioxidative andanti-inflammatory effects following transient focal cerebralischemia in rats. Am. J. Chin. Med., 2008, 36(6), 1105-1119.
155. Cheng, C.Y.; Su, S.Y.; Tang, N.Y.; Ho, T.Y.; Chiang, S.Y.; Hsieh, C.L. Ferulic acid provides neuroprotection against oxidative stressrelatedapoptosis after cerebral ischemia/reperfusion injury byinhibiting ICAM-1 mRNA expression in rats. Brain Res., 2008May, 1209, 136-150.
156. Cheng, C.Y.; Su, S.Y.; Tang, N.Y.; Ho, T.Y.; Lo, W.Y.; Hsieh, C.L. Ferulic acid inhibits nitric oxide-induced apoptosis byenhancing GABA (B1) receptor expression in transient focalcerebral ischemia in rats. Acta Pharmaco. l Sin., 2010, 31(8), 889-899.
157. Yabe T, Hirahara H, Harada N, Ito N, Nagai T, Sanagi T, YamadaH. Ferulic acid induces neural progenitor cell proliferation in vitro and in vivo. Neuroscience, 2010, 165(2), 515-524.
158. Watanabe, H. Candidates for cognitive enhancer extracted frommedicinal plants: paeoniflorin and tetramethylpyrazine. Behav. Brain Res., 1997, 83(1-2), 135-141.
159. rd,ed.; Ye, X. Ed.; Shanghai ChineseMedicine School Publisher: Shanghai, 1993; pp.377-379. (inChinese)
160. Wu, W.; Qiu, F. Experimental study on ischemia and reperfusioninjury of rat liver and effects of ligustrazine and salvia, compound. Chin. Med. Sci. J., 1994, 9(3), 162-166.
161. Hua, J.; En-tan, G. Effect of postoperative treatment with acombination of Chuan Xiong and electret on functional recovery ofmuscle grafts: an experimental study in the dog. Plast ReconstrSurg., 1996, 98(5), 851-855.
162. Li, S.; Wang, J.H.; Chen, S.L. Inhibitory effect of ligustrazine onproliferation of rabbit vascular smooth muscle cells after arterialinjury. Zhonguo Yao Li Xue Bao, 1999, 20(10), 917-922.
163. Cao, W.; Zeng, Z.; Zhu, Y.J.; Luo, W.; Demura, H.; Naruse, M.;Shi, Y. Effects of tetramethylpyrazine, a Chinese medicine, onplasma endothelin-1 levels during acute pulmonary hypoxia inanesthetized dogs. J. Cardiovasc. Pharmacol., 1998, 31, (Suppl 1), S456-459.
164. Zheng, Z.; Zhu, W.; Zhou, X.; Jin, Z.; Liu, H.; Chen, X.; Pan, J.;Demura, H.; Naruse, M.; Shi, Y. Tetramethylpyrazine, a Chinesedrug, blocks coronary vasoconstriction by endothelin-1 anddecreases plasma endothelin-1 levels in experimental animals. J. Cardiovasc. Pharmacol., 1998, 31, (Suppl1), S313-316.
165. 2 in the hypoxic isolated rat heart. Mol. Cell Biochem., 1997, 167(1-2), 153-158.
166. Peng, W.; Hucks, D.; Priest, R.M.; Kan, Y.M.; Ward, J.P. Ligustrazine-induced endothelium-dependent relaxation inpulmonary arteries via, a NO-mediated and exogenous L-argininedependentmechanism. Br. J. Pharmacol., 1996, 119(5), 1063-1071.
167. Sheu, J.R.; Hsiao, G.; Lee, Y.M.; Yen, M.H. Antithrombotic effectsof tetramethylpyrazine in vivo, experiments. Int. J. Hematol., 2001, 73(3), 393-398.
168. Sheu, J.R.; Kan, Y.C.; Hung, W.C.; Lin, C.H.; Yen, M.H. Theantiplatelet activity of tetramethylpyrazine is mediated throughactivation of NO synthase. Life Sci., 2000, 67(8), 937-947.
169. Sheu, J.R.; Kan, Y.C.; Hung, W.C.; Ko, W.C.; Yen, M.H. Mechanisms involved in the antiplatelet activity oftetramethlpyrazine in human platelets. Thromb. Res., 1997, 88(3), 259-270.
170. Zhang, Z.; Wei, T.; Hou, J.; Li, G.; Yu, S.; Xin, W. Iron-inducedoxidative damage and apoptosis in cerebellar granule cells:attenuation by tetramethylpyrazine and ferulic acid. Eur. J. Pharmacol., 2003, 467(1-3), 41-47.
171. Hsiao, G.; Chen, Y.C.; Lin, J.H.; Lin, K.H.; Chou, D.S.; Lin, C.H.;Sheu, J.R. Inhibitory mechanisms of tetramethylpyrazine in middlecerebral artery occlusion (MCAO)-induced focal cerebral ischemiain rats. Planta Med., 2006, 72(5), 411-417.
172. Pang, P.K.; Shan, J.J.; Chiu, K.W. Tetramethylpyrazine, a calciumantagonist. Planta Med., 1996, 62(5), 431-435.
173. Hsiao, G.; Chen, Y.C.; Lin, J.H.; Lin, K.H.; Chou, D.S.; Lin, C.H.;Sheu, J. R. Inhibitory mechanisms of tetramethylpyrazine in middlecerebral artery occlusion (MCAO)-induced focal cerebral ischemiain rats. Planta Med., 2006, 72(5), 411-7.
174. Kao, T.K.; Ou, Y.C.; Kuo, J.S.; Chen, W.Y.; Liao, S.L.; Wu, C.W.;Chen, C.J.; Ling, N.N.; Zhang, Y.H.; Peng, W.H. Neuroprotectionby tetramethylpyrazine against ischemic brain injury in rats. Neurochem. Int., 2006, 48(3), 166-76.
175. Li, S.Y.; Jia, Y.H.; Sun, W.G.; Tang, Y.; An, G.S.; Ni, J.H.; Jia, H.T. Stabilization of mitochondrial function by tetramethylpyrazineprotects against kainate-induced oxidative lesions in the rathippocampus. Free Radic. Biol. Med., 2010, 48(4), 597-608.
176. Tian, Y.; Liu, Y.; Chen, X.; Zhang, H.; Shi, Q.; Zhang, J.; Yang, P. Tetramethylpyrazine promotes proliferation and differentiation ofneural stem cells from rat brain in hypoxic condition via, mitogenactivatedprotein kinases pathway in vitro. Neurosci. Lett., 2010, 474(1), 26-31.
177. Chen, K.J.; Chen, K. Ischemic stroke treated with Ligusticumchuanxiong. Chin. Med. J. (Engl)., 1992, 105(10), 870-873.
178. Liang, C.C.; Hong, C.Y.; Chen, C.F.; Tsai, T.H. Measurement andpharmacokinetic study of tetramethylpyrazine in rat blood and itsregional brain tissue by high-performance liquid chromatography. J. Chromotogr. B. Biomed. Sci. Appl., 1999, 724(2), 303-309.
179. Tsai, T.H.; Liang, C. Pharmacokinetics of tetramethylpyrazine inrat blood and brain using microdialysis. Int. J. Pharm., 2001, 216(1-2), 61-66.
180. Guo, J.; Duan, J.A.; Shang, E.X.; Tang, Y.; Qian, D. Determinationof ligustilide in rat brain after nasal administration of essential oilfrom Rhizoma Chuanxiong. Fitoterapia., 2009, 80(3), 168-72.
181. Zhang, H.L.; Nagatsu, A.; Watanabe, T.; Sakakibara, J.; Okuyama, H. Antioxidative compounds isolated from safflower (Carthamustinctorius L.) oil cake. Chem. Pharm. Bull., (Tokyo), 1997, 45(12), 1910-1914.
182. Leung, A.W.; Mo, Z.X.; Zheng, Y.S. Reduction of cellular damageinduced by cerebral ischemia in rats. Neurochem. Res., 1991, 16(6), 687-692.
183. Romano, C.; Price, M.; Bai, H.Y.; Olney, J.W. Neuroprotectants inHonghua: glucose attenuates retinal ischemic damage. Invest. Ophthalmol. Vis. Sci., 1993, 34(1), 72-80.
184. Zhu, H.; Wang, Z.; Ma, C.; Tian, J.; Fu, F.; Li, C.; Guo, D.;Roeder, E.; Liu, K. Neuroprotective effects of hydroxyl saffloweryellow a: in vivo, and in vitro, studies. Plant Med., 2003, 69(5), 429-433.
185. Cheng, YD.; Al-Khoury, L.; Zivin, J.A. Neuroprotection forischemic stroke: Two decades of success and failure. NeuroRx., 2004, 1(1), 36-45.
186. Lo, E.H.; Broderick, J.P.; Moskowitz, M.A. tPA and proteolysis inthe neurovascular unit. Stroke, 2004, 35(2), 354-356.
187. Lo, E.H.; Dalkara, T.; Moskowitz, M.A. Mechanisms, challengesand opportunities in stroke. Nature Reviews Neuroscience, 2003, 4(5), 399-414.
188. Moskowitz, M.A.; Lo, E.H. Neurogenesis and apoptotic cell death. Stroke, 2003, 34(2), 324-326.
189. Block, F.; Bozdag, I.; Nolden-Koch, M. Inflammation contributesto the postponed ischemic neuronal damage following treatmentwith a glutamate antagost in rats. Neurosci. Lett., 2001, 298(2), 103-106.
190. Coimbra, C.; Drake, M.; Boris-Moller, F.; Wieloch, T. Longlastingneuroprotective effect of postischemic hypothermia andtreatment with an anti-inflammatory/antipyretic drug. Evidence forchronic encephalopathic processes following ischemia. Stroke, 1996, 27(9), 1578-1585.
191. Davis, S.; Helfaer, M.A.; Traystman, R.J.; Hurn, P.D. Parallelantioxidant and antiexcitotoxic therapy improves outcome afterincomplete global cerebral ischemia in dogs. Stroke, 1997, 28(1), 198-204.
192. Chen, L.; Lee, M.; Chou, M.; Lin, M.; Yang, L. Pharmacokineticstudy of paeoniflorin in mice after oral administration of paeoniaeradix extract. J. Chromatogr. B Biomed. Sci. Appl., 1999, 735(1), 33-40.
193. Krupinski, J.; Kaluza, J.; Kumar, P.; Kumar, S.; Wang, J. Role ofangiogenesis in patients with cerebral ischemic stroke. Stroke, 1994, 25(9), 1794-1798.
194. Gao, D.; Song, J.; Hu, J.; Lin, J.; Zheng, L.; Cai, J.; Du, J.; Chen, K. Angiogenesis promoting effects of Chinese herbal medicine foractivating blood circulation to remove stasis on chick embryochorio-allantoic membrane. Zhong Xi Jie He Za Zhi, 2005, 25(10), 912-915.
195. Joseph, J.A.; Nadeau, D.A.; Underwood, A. The color code, arevolutionary eating plan for optimum health, Joseph JA, NadeauDA, Underwood A, Eds.; Hyperion: New York, 2000.
196. Liu, X.; Wang, C. Chemistry of Natural Products., ChemicalIndustry Publisher: Beijing, 2005. (in Chins)
197. Hayakawa, K.; Mishima, K.; Nozako, M.; Hazekawa, M.; Aoyama, Y.; Ogata, A.; Harada, K.; Jujioka, M.; Abe, K.; Egashira, N.;Iwasaki, K.; Fujiwara, M. High-cholesteral feeding aggravatescerebral infarction via, decreasing the CB1 receptor. Neurosci. Lett., 2007, 414(2), 183-187.
198. Ni, J.W.; Matsumoto, K.; Watanabe, H. Tetramethylpyrazineimproves spatial cognitive impairment induced by permanentocclusion of bilateral common carotid arteries or scopolamine inrats. Jpn. J. Pharmacol., 1995, 67(2), 137-141.
199. Lindvall, O.; Kokaia, Z. Recovery and rehabilitation in stroke. Stroke, 2004, 35, (Suppl I), 2691-2694.
200. Lin, B.; Busto, R.; Li, L. Natural herbal therapy attenuatessecondary injury after global ischemia in rat brain. J. Cereb. BloodFlow Metab., 2001, 21, (Suppl), S496.
201. Kong, J.; Goh, N.; Chia, L.; Chia, T. Recent advances in traditionalplant drugs and orchids. Acta. Pharmacol. Sin., 2003, 24(1), 7-21.
202. Nearing, M. The green pharmacy. Herbal medicines in modernusage. IDCR Rep., 1985, 14(1), 10-11.
203. Rates, S.M.K. Plants as source of drugs. Toxicon, 2001, 39(5) 603-613.
204. Zuo, F.; Zhou, Z.M.; Liu, M.L. Determination of 14 chemicalconstituents in the traditional Chinese medicinal preparationHuangqin-Tang by high performance liquid chromatography. Biol. Pharm. Bull., 2001, 24(6), 693-697.
205. Hachinski, V. Stoke and vascular cognitive impairment. Atransdisciplinary, translational and transactional approach. Stroke, 2007, 38(4) 1396-1430.