Flavones from root of scutellaria baicalensis georgi: Drugs of the future in neurodegeneration?

CNS and Neurological Disorders - Drug Targets

Volumn 10, Issue 2, 2011, Pages 184-191

  Ga̧siorowski, Kazimierz ^a   Lamer Zarawska, Eliza ^a   Leszek, Jerzy ^a   Parvathaneni, Kalpana ^b   Yendluri, Bharat Bhushan ^b   Błach Olszewska, Zofia ^c   Aliev, Gjumrakch ^d  

^a WROCLAW MEDICAL UNIVERSITY   (Poland)

^b University of San Antonio   (United States)

^c INSTITUTE OF IMMUNOLOGY AND EXPERIMENTAL THERAPY   (Poland)

^d University of Atlanta   (United States)

Author keywords

Baicalein; Neurodegeneration; Neuroprotection; Oroxylin a; Wogonin

Indexed keywords

ALPHA SYNUCLEIN; AMYLOID BETA PROTEIN; BAICALEIN; BAICALIN; FLAVONE DERIVATIVE; OROXYLIN A; SCUTELLARIA BAICALENSIS EXTRACT; WOGONIN;

AGING; ANTICONVULSANT ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; ARTICLE; COGNITION; HUMAN; NERVE CELL NECROSIS; NERVE DEGENERATION; NEUROPROTECTION; NONHUMAN; OXIDATIVE STRESS; PHARMACODYNAMICS; PLANT ROOT; SCUTELLARIA BAICALENSIS; SEDATION; TRANQUILIZING ACTIVITY;

EID: 79551669330     PISSN: 18715273     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152711794480384     Document Type: Article

References (81)

1. Vauzour, D.; Vafeiadou, K.; Rodriguez-Mateos, A.; Rendeiro, C.; Spencer, J.P. The neuroprotective potential of flavonoids: a multiplicity of effects. Genes Nutr., 2008, 3(3-4), 115-126.
2. Williams, R.J.; Spencer, J.P.; Rice-Evans, C. Flavonoids: antioxidants or signalling molecules? Free Radic. Biol. Med., 2004, 36(7), 838-849.
3. Spencer, J.P. The interactions of flavonoids within neuronal signalling pathways. Genes Nutr., 2007, 2(3), 257-273.
4. Schroeter, H.; Spencer, J.P.; Rice-Evans, C.; Williams, R.J. Flavonoids protect neurons from oxidized low-density-lipoproteininduced apoptosis involving c-Jun N-terminal kinase(JNK), c-Jun and caspase-3. Biochem. J., 2001, 358(Pt 3), 547-557.
5. Lau, F.C.; Bielinski, D.F.; Joseph, J.A. Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide-activated BV2 microglia. J. Neurosci. Res., 2007, 85(5), 1010-1017.
6. Chen, J.C.; Ho, F.M.; Pei-Dawn Lee, C.; Chen, C.P.; Jeng, K.C.; Hsu, H.B.; Lee, S.T.; Wen Tung, W.; Lin, W.W. Inhibition of iNOS gene expression by quercetin is mediated by the inhibition of IkappaB kinase, nuclear factor-kappa B and STAT1, and depends on heme oxygenase-1 induction in mouse BV-2 microglia. Eur. J. Pharmacol., 2005, 521(1-3), 9-20.
7. Spencer, J.P. Food for thought: the role of dietary flavonoids in enhancing human memory, learning and neuro-cognitive performance. Proc. Nutr. Soc., 2008, 67(2), 238-252.
8. Bochorakova, H.; Paulova, H.; Slanina, J.; Musil, P.; Taborska, E. Main flavonoids in the root of Scutellaria baicalensis cultivated in Europe and their comparative antiradical properties. Phytother. Res., 2003, 17(6), 640-644.
9. Ye, F.; Wang, H.; Jiang, S.; Wu, J.; Shao, J.; Cheng, X.; Tu, Y.; Zhang, D.Y. Quality evaluation of commercial extracts of Scutellaria baicalensis. Nutr. Cancer, 2004, 49(2), 217-222.
10. Chen, G.; Ying, X.Y.; Ye, J.N. Differentiation of Scutellariae Radix from Astragali Radix by capillary electrophoresis with electrochemical detection. Analyst, 2000, 125(5), 815-818.
11. Iriti, M.; Vitalini, S.; Fico, G.; Faoro, F. Neuroprotective herbs and foods from different traditional medicines and diets. Molecules, 2010, 15(5), 3517-3555.
12. Tsai, T.H.; Liu, S.C.; Tsai, P.L.; Ho, L.K.; Shum, A.Y.; Chen, C.F. The effects of the cyclosporin A, a P-glycoprotein inhibitor, on the pharmacokinetics of baicalein in the rat: a microdialysis study. Br. J. Pharmacol., 2002, 137(8), 1314-1320.
13. Lu, T.; Song, J.; Huang, F.; Deng, Y.; Xie, L.; Wang, G.; Liu, X. Comparative pharmacokinetics of baicalin after oral administration of pure baicalin, Radix scutellariae extract and Huang-Lian-Jie-Du- Tang to rats. J. Ethnopharmacol., 2007, 110(3), 412-428.
14. Srinivas, N.R. Baicalin, an emerging multi-therapeutic agent: pharmacodynamics, pharmacokinetics, and considerations from drug development perspectives. Xenobiotica, 2010, 40(5), 357-367.
15. Xing, J.; Chen, X.; Zhong, D. Absorption and enterohepatic circulation of baicalin in rats. Life Sci., 2005, 78(2), 140-146.
16. Tang, Y.; Zhu, H.; Zhang, Y.; Huang, C. Determination of human plasma protein binding of baicalin by ultrafiltration and highperformance liquid chromatography. Biomed. Chromatogr., 2006, 20(10), 1116-1119.
17. Lai, M.Y.; Hsiu, S.L.; Chen, C.C.; Hou, Y.C.; Chao, P.D. Urinary pharmacokinetics of baicalein, wogonin and their glycosides after orl administration of Scutellariae Radix in humans. Biol. Pharm. Bull., 2003, 26(1), 79-83.
18. Fan, L.; Wang, J.C.; Jiang, F.; Tan, Z.R.; Chen, Y.; Li, Q.; Zhang, W.; Wang, G.; Lei, H.P.; Hu, D.L.; Wang, D.; Zhou, H.H. Induction of cytochrome P450 2B6 activity by the herbal medicine baicalin as measured by bupropion hydroxylation. Eur. J. Clin. Pharmacol. 2009, 65(4), 403-409.
19. Jang, S.I.; Kim, H.J.; Hwang, K.M.; Jekal, S.J.; Pae, H.O.; Choi, B.M.; Yun, Y.G.; Kwon, T.O.; Chung, H.T.; Kim, Y.C. Hepatoprotective effect of baicalin, a major flavone from Scutellaria radix, on acetaminophen-induced liver injury in mice. Immunopharmacol. Immunotoxicol., 2003, 25(4), 585-594.
20. Tan, B.K.; Vanitha, J. Immunomodulatory and antimicrobial effects of some traditional chinese medicinal herbs: a review. Curr. Med. Chem., 2004, 11(11), 1423-1430.
21. Li-Weber, M. New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat. Rev., 2009, 35(1), 57-68.
22. Ma, Z.; Otsuyama, K.; Liu, S.; Abroun, S.; Ishikawa, H.; Tsuyama, N.; Obata, M.; Li, F.J.; Zheng, X.; Maki, Y.; Miyamoto, K.; Kawano, M.M. Baicalein, a component of Scutellaria radix from Huang-Lian-Jie-Du-Tang(HLJDT), leads to suppression of proliferation and induction of apoptosis in human myeloma cells. Blood, 2005, 105(8), 3312-3318.
23. Bonham, M.; Posakony, J.; Coleman, I.; Montgomery, B.; Simon, J.; Nelson, P.S. Characterization of chemical constituents in Scutellaria baicalensis with antiandrogenic and growth-inhibitory activities toward prostate carcinoma. Clin. Cancer Res., 2005, 11(10), 3905-3914.
24. Spencer, J.P. Flavonoids: modulators of brain function? Br. J. Nutr., 2008, 99 (E Suppl 1), ES60-ES77.
25. Dai, J.Y.; Yang, J.L.; Li, C. Transport and metabolism of flavonoids from Chinese herbal remedy Xiaochaihutang across human intestinal Caco-2 cell monolayers. Acta Pharmacol. Sin., 2008, 29(9), 1086-1093.
26. Walgren, R.A.; Lin, J.T.; Kinne, R.K.; Walle, T. Cellular uptake of dietary flavonoid quercetin 4'-beta-glucoside by sodium-dependent glucose transporter SGLT1. J. Pharmacol. Exp. Ther., 2000, 294(3), 837-843.
27. Passamonti, S.; Terdoslavich, M.; Franca, R.; Vanzo, A.; Tramer, F.; Braidot, E.; Petrussa, E.; Vianello, A. Bioavailability of flavonoids: a review of their membrane transport and the function of bilitranslocase in animal and plant organisms. Curr. Drug Metab., 2009, 10(4), 369-394.
28. Halliwell, B. Oxidative stress and neurodegeneration: where are we now? J. Neurochem., 2006, 97(6), 1634-1658.
29. Moreira, P.I.; Smith, M.A.; Zhu, X.; Nunomura, A.; Castellani, R.J.; Perry, G. Oxidative stress and neurodegeneration. Ann. NY Acad. Sci., 2005, 1043, 545-552.
30. Lin, M.T.; Beal, M.F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature, 2006, 443(7113), 787-795.
31. Migliore, L.; Coppede, F. Environmental-induced oxidative stress in neurodegenerative disorders and aging. Mutat. Res., 2009, 674(1-2), 73-84.
32. Gao, H.M.; Liu, B.; Zhang, W.; Hong, J.S. Critical role of microglial NADPH oxidase-derived free radicals in the in vitro MPTP model of Parkinson's disease. FASEB J., 2003, 17(13), 1954-1956.
33. Uttara, B.; Singh, A.V.; Zamboni, P.; Mahajan, R.T. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr. Neuropharmacol., 2009, 7(1), 65-74.
34. Huang, W.H.; Lee, A.R.; Yang, C.H. Antioxidative and anti-inflammatory activities of polyhydroxyflavonoids of Scutellaria bacalensis GEORGI. Biosci. Biotechnol. Biochem., 2006, 70(10), 2371-2380.
35. Gao, Z.; Yang, X.; Huang, K.; Xu, H. Free-radical scavenging and mechanism study of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Appl. Magn. Reson., 2000, 19(1), 35-44.
36. Gao, Z.H.; Huang, K.X.; Yang, X.L.; Xu, H.B. Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. BBA-Gen. Subjects, 1999, 1472(3), 643-650.
37. Shao, Z.H.; Vanden Hoek, T.L.; Qin, Y.M.; Becker, L.B.; Schumacker, P.T.; Li, C.Q.; Dey, L.; Barth, E.; Halpern, H.; Rosen, G.M.; Yuan, C.S. Baicalein attenuates oxidant stress in cardiomyocytes. Am. J. Physiol-Heart C., 2002, 282(3), H999-H1006.
38. Perez, C.A.; Wei, Y.B.; Guo, M.L. Iron-binding and anti-Fenton properties of baicalein and baicalin. J. Inorg. Biochem., 2009, 103(3), 326-332.
39. Shieh, D.E.; Liu, L.T.; Lin, C.C. Antioxidant and free radical scavenging effects of baicalein, baicalin and wogonin. Anticancer Res., 2000, 20(5A), 2861-2865.
40. Liang, R.; Han, R.M.; Fu, L.M.; Ai, X.C.; Zhang, J.P.; Skibsted, L.H. Baicalin in radical scavenging and its synergistic effect with beta-carotene in antilipoxidation. J. Agric. Food Chem., 2009, 57(15), 7118-7124.
41. Woo, A.Y.H.; Cheng, C.H.K.; Waye, M.M.Y. Baicalein protects rat cardiomyocytes from hypoxia/reoxygenation damage via a prooxidant mechanism. Cardiovasc. Res., 2005, 65(1), 244-253.
42. Tai, M.C.; Tsang, S.Y.; Chang, L.Y.F.; Xue, H. Therapeutic potential of wogonin: A naturally occurring flavonoid. CNS Drug Rev., 2005, 11(2), 141-150.
43. Chen, Y.; Yang, L.; Lee, T.J. Oroxylin A inhibition of lipopolysaccharide-induced iNOS and COX-2 gene expression via suppression of nuclear factor-kappaB activation. Biochem. Pharmacol., 2000, 59(11), 1445-1457.
44. Lin, C.M.; Chen, C.S.; Chen, C.T.; Liang, Y.C.; Lin, J.K. Molecular modeling of flavonoids that inhibits xanthine oxidase. Biochem. Biophys. Res. Commun., 2002, 294(1), 167-172.
45. Lin, H.Y.; Shen, S.C.; Lin, C.W.; Yang, L.Y.; Chen, Y.C. Baicalein inhibition of hydrogen peroxide-induced apoptosis via ROS-dependent heme oxygenase 1 gene expression. BBA-Mol. Cell Res., 2007, 1773(7), 1073-1086.
46. Chou, C.C.; Pan, S.L.; Teng, C.M.; Guh, J.H. Pharmacological evaluation of several major ingredients of Chinese herbal medicines in human hepatoma Hep3B cells. Eur. J. Pharm. Sci., 2003, 19(5), 403-412.
47. Suk, K. Regulation of neuroinflammation by herbal medicine and its implications for neurodegenerative diseases - A focus on traditional medicines and flavonoids. Neurosignals, 2005, 14(1-2), 23-33.
48. Krause, D.L.; Muller, N. Neuroinflammation, microglia and implications for anti-inflammatory treatment in Alzheimer's disease. Int. J. Alzheimers Dis., 2010, 2010, Article ID: 732806.
49. Gao, H.M.; Hong, J.S. Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol., 2008, 29(8), 357-365.
50. Kim, D.H.; Kim, H.K.; Park, S.; Kim, J.Y.; Zou, Y.; Cho, K.H.; Kim, Y.S.; Yu, B.P.; Choi, J.S.; Chung, H.Y. Short-term feeding of baicalin inhibits age-associated NF-kappaB activation. Mech. Ageing Dev., 2006, 127(9), 719-725.
51. Lamer-Zarawska, E.; Wisniewska, A.; Błach-Olszewska, Z. Anticancer properties of Scutellaria baicalensis root in aspect of innate immunity. Adv. Clin. Exp. Med., 2010, 19, 419-428.
52. Shen, Y.C.; Chiou, W.F.; Chou, Y.C.; Chen, C.F. Mechanisms in mediating the anti-inflammatory effects of baicalin and baicalein in human leukocytes. Eur. J. Pharmacol., 2003, 465(1-2), 171-181.
53. Suk, K.; Lee, H.; Kang, S.S.; Cho, G.J.; Choi, W.S. Flavonoid baicalein attenuates activation-induced cell death of brain microglia. J. Pharmacol. Exp. Therap., 2003, 305(2), 638-645.
54. Chen, C.J.; Raung, S.L.; Liao, S.L.; Chen, S.Y. Inhibition of inducible nitric oxide synthase expression by baicalein in endotoxin/cytokine-stimulated microglia. Biochem. Pharmacol., 2004, 67(5), 957-965.
55. Chen, Y.C.; Shen, S.C.; Chen, L.G.; Lee, T.J.; Yang, L.L. Wogonin, baicalin, and baicalein inhibition of inducible nitric oxide synthase and cyclooxygenase-2 gene expressions induced by nitric oxide synthase inhibitors and lipopolysaccharide. Biochem. Pharmacol., 2001, 61(11), 1417-1427.
56. van Praag, H.; Lucero, M.J.; Yeo, G.W.; Stecker, K.; Heivand, N.; Zhao, C.; Yip, E.; Afanador, M.; Schroeter, H.; Hammerstone, J.; Gage, F.H. Plant-derived flavanol(-)epicatechin enhances angiogenesis and retention of spatial memory in mice. J. Neurosci., 2007, 27(22), 5869-5878.
57. Maher, P.; Akaishi, T.; Abe, K. Flavonoid fisetin promotes ERKdependent long-term potentiation and enhances memory. Proc. Natl. Acad. Sci. USA, 2006, 103(44), 16568-16573.
58. Spencer, J.P.; Vauzour, D.; Rendeiro, C. Flavonoids and cognition: the molecular mechanisms underlying their behavioural effects. Arch. Biochem. Biophys., 2009, 492(1-2), 1-9.
59. Spencer, J.P. The impact of fruit flavonoids on memory and cognition. Br. J. Nutr., 2010, 104(Suppl 3), S40-S47.
60. Shang, Y.; Cheng, J.; Qi, J.; Miao, H. Scutellaria flavonoid reduced memory dysfunction and neuronal injury caused by permanent global ischemia in rats. Pharmacol. Biochem. Behav., 2005, 82(1), 67-73.
61. Shang, Y.Z.; Gong, M.Y.; Zhou, X.X.; Li, S.T.; Wang, B.Y. Improving effects of SSF on memory deficits and pathological changes of neural and immunological systems in senescent mice. Acta Pharmacol. Sin., 2001, 22(12), 1078-1083.
62. Kim, D.H.; Jeon, S.J.; Son, K.H.; Jung, J.W.; Lee, S.; Yoon, B.H.; Choi, J.W.; Cheong, J.H.; Ko, K.H.; Ryu, J.H. Effect of the flavonoid, oroxylin A, on transient cerebral hypoperfusion-induced memory impairment in mice. Pharmacol. Biochem. Behav., 2006, 85(3), 658-668.
63. Liu, C.; Wu, J.; Gu, J.; Xiong, Z.; Wang, F.; Wang, J.; Wang, W.; Chen, J. Baicalein improves cognitive deficits induced by chronic cerebral hypoperfusion in rats. Pharmacol. Biochem. Behav., 2007, 86(3), 423-430.
64. Lee, H.H.; Yang, L.L.; Wang, C.C.; Hu, S.Y.; Chang, S.F.; Lee, Y.H. Differential effects of natural polyphenols on neuronal survival in primary cultured central neurons against glutamate- and glucose deprivation-induced neuronal death. Brain Res., 2003, 986(1-2), 103-113.
65. Piao, H.Z.; Jin, S.A.; Chun, H.S.; Lee, J.C.; Kim, W.K. Neuroprotective effect of wogonin: potential roles of inflammatory cytokines. Arch. Pharm. Res., 2004, 27(9), 930-936.
66. Lim, J.S.; Yoo, M.; Kwon, H.J.; Kim, H.; Kwon, Y.K. Wogonin induces differentiation and neurite outgrowth of neural precursor cells. Biochem. Biophys. Res. Commun., 2010, 402(1), 42-47.
67. Ryu, J.H.; Tan-Lee, B.G.; Jung, J.W.; Ahh, N.Y.; Lee, S.; Yu, G.Y.; Han, S.; Lee, J.H.; Lee, G.S.; Cheong, J.H. Anti-stress effect of Scutellaria baicalensis in SD rats and ICR mice. J. Appl. Pharmacol., 2004, 12, 34-42.
68. Park, H.G.; Yoon, S.Y.; Choi, J.Y.; Lee, G.S.; Choi, J.H.; Shin, C.Y.; Son, K.H.; Lee, Y.S.; Kim, W.K.; Ryu, J.H.; Ko, K.H.; Cheong, J.H. Anticonvulsant effect of wogonin isolated from Scutellaria baicalensis. Eur. J. Pharmacol., 2007, 574(2-3), 112-119.
69. Hui, K.M.; Wang, X.H.; Xue, H. Interaction of flavones from the roots of Scutellaria baicalensis with the benzodiazepine site. Planta Med., 2000, 66(1), 91-93.
70. Park, H.G.; Choi, J.Y.; Lee, G.S.; Choi, J.H.; Son, K.H.; Yoon, S.Y.; Ko, H.S.; Ko, K.H.; Ryu, J.H.; Cheong, J.H. Different effects of flavonoids in Scutellaria baicalensis on anxious and sedative behaviors. J. Appl. Pharmacol., 2006, 14, 83-89.
71. Hui, K.M.; Huen, M.S.; Wang, H.Y.; Zheng, H.; Sigel, E.; Baur, R.; Ren, H.; Li, Z.W.; Wong, J.T.; Xue, H. Anxiolytic effect of wogonin, a benzodiazepine receptor ligand isolated from Scutellaria baicalensis Georgi. Biochem. Pharmacol., 2002, 64(9), 1415-1424.
72. Huen, M.S.Y.; Hui, K.M.; Leung, J.W.C.; Sigel, E.; Baur, R.; Wong, J.T.F.; Xue, H. Naturally occurring 2'-hydroxyl-substituted flavonoids as high-affinity benzodiazepine site ligands. Biochem. Pharmacol., 2007, 66, 2397-2407.
73. Uversky, V.N. Neuropathology, biochemistry, and biophysics of alpha-synuclein aggregation. J. Neurochem., 2007, 103(1), 17-37.
74. Meng, X.; Munishkina, L.A.; Fink, A.L.; Uversky, V.N. Effects of Various Flavonoids on the alpha-Synuclein Fibrillation Process. Parkinsons Dis., 2010, doi: 10.4061/PD, ID: 650794.
75. Masuda, M.; Suzuki, N.; Taniguchi, S.; Oikawa, T.; Nonaka, T.; Iwatsubo, T.; Hisanaga, S.; Goedert, M.; Hasegawa, M. Small molecule inhibitors of alpha-synuclein filament assembly. Biochemistry, 2006, 45(19), 6085-6094.
76. Zhu, M.; Rajamani, S.; Kaylor, J.; Han, S.; Zhou, F.; Fink, A.L. The flavonoid baicalein inhibits fibrillation of alpha-synuclein and disaggregates existing fibrils. J. Biol. Chem., 2004, 279(26), 26846-26857.
77. Jiang, M.; Porat-Shliom, Y.; Pei, Z.; Cheng, Y.; Xiang, L.; Sommers, K.; Li, Q.; Gillardon, F.; Hengerer, B.; Berlinicke, C.; Smith, W.W.; Zack, D.J.; Poirier, M.A.; Ross, C.A.; Duan, W. Baicalein reduces E46K alpha-synuclein aggregation in vitro and protects cells against E46K alpha-synuclein toxicity in cell models of familiar Parkinsonism. J. Neurochem., 2010, 114(2), 419-429.
78. Lebeau, A.; Esclaire, F.; Rostene, W.; Pelaprat, D. Baicalein protects cortical neurons from beta-amyloid(25-35) induced toxicity. Neuroreport, 2001, 12(10), 2199-2202.
79. Heo, H.J.; Kim, D.O.; Choi, S.J.; Shin, D.H.; Lee, C.Y. Potent Inhibitory effect of flavonoids in Scutellaria baicalensis on amyloid beta protein-induced neurotoxicity. J. Agric. Food Chem., 2004, 52(13), 4128-4132.
80. Wang, S.Y.; Wang, H.H.; Chi, C.W.; Chen, C.F.; Liao, J.F. Effects of baicalein on beta-amyloid peptide-(25-35)-induced amnesia in mice. Eur. J. Pharmacol., 2004, 506(1), 55-61.
81. Kim, D.H.; Kim, S.; Jeon, S.J.; Son, K.H.; Lee, S.; Yoon, B.H.; Cheong, J.H.; Ko, K.H.; Ryu, J.H. The effects of acute and repeated oroxylin A treatments on Abeta(25-35)-induced memory impairment in mice. Neuropharmacology, 2008, 55(5), 639-647.