Flavonoids from Scutellaria baicalensis Georgi are effective to treat cerebral ischemia/reperfusion

doi:10.3969/j.issn.1673-5374.2013.06.004

Abstract

Abstract:

Based on previous studies that have shown flavonoids from the stems and leaves of Scutellaria baicalensis Georgi are neuroprotective agents in a naturally senile, D-galactose, aging in vivo model, as well as an in vitro model of oxidative/hypoxic injury, we established a cerebral ischemia/reperfusion model in rats by middle cerebral artery occlusion. The light/electron microscopic observations found significant neuropathological changes including neuron loss or swelling and rough endoplasmic reticulum injury. Moreover, the activities of lactate dehydrogenase, Na+-K+-ATPase, Ca2+-ATPase and superoxide dismutase were significantly lowered, and the levels of malonaldehyde increased. In addition, the memory of rats worsened. However, treatment with flavonoids from Scutellaria baicalensis Georgi (35, 70 and 140 mg/kg) for 13 days dramatically improved the above abnormal changes. These results suggest that the ability of flavonoids from Scutellaria baicalensis Georgi in attenuating cerebral functional and morphological consequences after cerebral ischemia/reperfusion may be beneficial for the treatment of ischemic brain disease.

Key words: neural regeneration, traditional Chinese medicine, brain injury, Scutellaria baicalensis Georgi, cerebral ischemia/reperfusion, cognitive impairment, neuronal damage, lactate dehydrogenase, Na+-K+-ATPase, Ca2+-ATPase, superoxide dismutase, malonaldehyde, grants-supported paper, photographs-containing paper, neuroregeneration

Yazhen Shang, Hong Zhang, Jianjun Cheng, Hong Miao, Yongping Liu, Kai Cao, Hui Wang. Flavonoids from Scutellaria baicalensis Georgi are effective to treat cerebral ischemia/reperfusion[J]. Neural Regeneration Research, 2013, 8(6): 514-522.

References

[1] Pennisi G, Ferri R, Cantone M, et al. A review of transcranial magnetic stimulation in vascular dementia. Dement Geriatr Cogn Disord. 2011;31(1):71-80.

[2] Vaibhav K, Shrivastava P, Javed H, et al. Piperine suppresses cerebral ischemia-reperfusion-induced inflammation through the repression of COX-2, NOS-2, and NF-κB in middle cerebral artery occlusion rat model. Mol Cell Biochem. 2012;367(1-2):73-84.

[3] Car H, Zendzian-Piotrowska M, Fiedorowicz A, et al. The role of ceramides in selected brain pathologies: ischemia/ hypoxia, Alzheimer disease. Postepy Hig Med Dosw (Online). 2012;66:295-303.

[4] Shang YZ, Miao H, Cheng JJ, et al. Effects of SSF on memory deficits in aluminum toxic mice. Zhongguo Yaoli Xue Tongbao. 2005;21(3):361-365.

[5] Song HR, Cheng JJ, Miao H, et al. Scutellaria flavonoid supplementation reverses ageing-related cognitive impairment and neuronal changes in aged rats. Brain Inj. 2009;23(2):146-153.

[6] Shang YZ, Gong MY, Zhou XX, et al. 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.

[7] Shang YZ, Qin BW, Cheng JJ, et al. Effect of Scutellaria flavonoids on KCN-induced damages in rat pheochromocytoma PC12 cells. Indian J Med Res. 2008; 127(6):610-615.

[8] Pu F, Motohashi K, Kaneko T, et al. Neuroprotective effects of Kangen-karyu on spatial memory impairment in an 8-arm radial maze and neuronal death in the hippocampal CA1 region induced by repeated cerebral ischemia in rats. J Pharmacol Sci. 2009;109(3):424-430.

[9] Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods. 1984;11(1):47-60.

[10] Yu J, Liu C, Zhang X, et al. Acupuncture improved cognitive impairment caused by multi-infarct dementia in rats. Physiol Behav. 2005;86(4):434-441.

[11] Takagi N. Pathology and strategies for the treatment of ischemic brain injury. Yakugaku Zasshi. 2009;129(10): 1215-1219.

[12] Nakano S, Kato H, Kogure K. Neuronal damage in the rat hippocampus in a new model of repeated reversible transient cerebral ischemia. Brain Res. 1989;490(1): 178-180.

[13] Wishart T, McCrea S, Ijaz S, et al. Comparisons of repetitive-and single-insult ischaemia: effects on regional brain damage and behaviour. Neuroreport. 1994;5(12): 1541-1454.

[14] Wattanathorn J, Jittiwat J, Tongun T, et al. Zingiber officinale mitigates brain damage and improves memory impairment in focal cerebral ischemic rat. Evid Based Complement Alternat Med. 2011;2011:429505.

[15] Ames A 3rd. CNS energy metabolism as related to function. Brain Res Brain Res Rev. 2000;34(1-2):42-68.

[16] Obrenovitch TP, Garofalo O, Harris RJ, et al. Brain tissue concentrations of ATP, phosphocreatine, lactate, and tissue pH in relation to reduced cerebral blood flow following experimental acute middle cerebral artery occlusion. J Cereb Blood Flow Metab. 1988;8(6):866-874.

[17] Wang Y, Zhu HY, Guo Y, et al. The influence of puerarin on the brain edema and the activity of Na+-K+-ATPase, Ca2+ -ATPase in neuron of ischemia-reperfusion rats. Zhongguo Zhongyi Jizheng. 2007;16(1):70-71.

[18] Allen CL, Bayraktutan U. Oxidative stress and its role in the pathogenesis of ischaemic stroke. Int J Stroke. 2009; 4(6):461-470.

[19] Mansoorali KP, Prakash T, Kotresha D, et al. Cerebroprotective effect of Eclipta alba against global model of cerebral ischemia induced oxidative stress in rats. Phytomedicine. 2012;19(12):1108-1116.

[20] Wang D, Yuan X, Liu T, et al. Neuroprotective activity of lavender oil on transient focal cerebral ischemia in mice. Molecules. 2012;17(8):9803-9817.

[21] Gutierrez-Merino C, Lopez-Sanchez C, Lagoa R, et al. Neuroprotective actions of flavonoids. Curr Med Chem. 2011;18(8):1195-1212.

[22] The Ministry of Science and Technology of the People’s Republic of China. Guidance Suggestions for the Care and Use of Laboratory Animals. 2006-09-30.

[23] Shang Y, Cheng J, Qi J, et al. Scutellaria flavonoid reduced memory dysfunction and neuronal injury caused by permanent global ischemia in rats. Pharmacol Biochem Behav. 2005;82(1):67-73.

[24] He W, Liu YM, Chen H, et al. Effect of breviscapine on brain edema and neutrophilinfiltration induced by focal cerebral ischemia and reperfusion in rats. Zhongguo Yaoli Xue yu Duli Xue Zazhi. 2004;18(3):161-165.

[25] Zhu CG. Neuroanatomy. Beijing: People’s Medical Publishing House. 2002.

[26] Rosenberg JC, Rush BF. An enzymatic- spectrophotometric determination of pyruvic and lactic acid in blood. Methodologic aspects. Clin Chem. 1966;12(5):299-307.

[27] He YZ, Li M, Feng GL, et al. Inhibition of pyrethroid insecticides on nerve Na+-K+-ATPase in house flies (musca domestica). Kunchong Xuebao. 1999;42(1): 19-24.

[28] Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351-358.

[29] McCord JM, Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969;244(22):6049-6055.