Total Flavone of Hawthorn Leaf inhibits neuronal apoptosis in brain tissue of rat models of chronic cerebral ischemia

doi:10.3969/j.issn.2095-4344.2014.49.002

Abstract

Abstract:

BACKGROUND: Cerebrovascular disease often causes dysfunction of the brain nerve, and nerve cell apoptosis is the important factor of cerebral nerve dysfunction. The excessive expression of c-fos can block the transduction of intracellular signal so that producing some apoptosis-promoting factors, which involve in nerve cell apoptosis process after ischemia injury of brain. Bcl-2 is an inhibited factor. It might to be the key to treat ischemic cerebrovascular disease by inhibiting or reducing the apoptosis of nerve cells after ischemia injury.

OBJECTIVE: To investigate the therapeutic effect and mechanism of the Total Flavone of Hawthorn Leaf on chronic cerebral ischemia rats.

METHODS: A total of 72 healthy male Sprague-Dawley rats were randomly divided into sham surgery group, model group, Total Flavone of Hawthorn Leaf group and ginkgo leaf group. Permanent bilateral carotid artery ligation was used to prepare chronic cerebral ischemia model in the model group, Total Flavone of Hawthorn Leaf group and ginkgo leaf group. Total Flavone of Hawthorn Leaf group and ginkgo leaf group respectively received 140 mg/kg Total Flavone of Hawthorn Leaf and 12.3 mg/kg ginkgo leaf intragastrically for 36 days from 36 days after model induction. Model group and sham surgery group received 3.5 mL/kg physiological saline intragastrically.

RESULTS AND CONCLUSION: Compared with the model group, the expression of c-fos protein significantly deceased in the Total Flavone of Hawthorn Leaf group (P < 0.01), Bcl-2 expression levels significantly increased (P < 0.01), and Ca²⁺ content decreased (P < 0.05). Moreover, no significant difference in above indexes was detected between Total Flavone of Hawthorn Leaf group and ginkgo leaf group (P > 0.05). These data indicated that the protective effect of Total Flavone of Hawthorn Leaf on chronic cerebral ischemia was associated with its inhibition of neuronal apoptosis. Its mechanism of anti-apoptosis might be associated with up-regulating expression of Bcl-2, down-regulating expression of c-fos and decreasing Ca²⁺ content in brain.

中国组织工程研究杂志出版内容重点：肾移植；肝移植；移植；心脏移植；组织移植；皮肤移植；皮瓣移植；血管移植；器官移植；组织工程

全文链接：

Key words: brain ischemia, flavones, crataegus, ginkgo biloba, apoptosis

CLC Number:

R318

Tan Rong-fang, Xia Ai-hua, Wu Xiao-guang, Cao Na-na, Li Meng-meng, Zhang Tian-ge, Wang Yi-ru, Yue Zhi-ling. Total Flavone of Hawthorn Leaf inhibits neuronal apoptosis in brain tissue of rat models of chronic cerebral ischemia[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(49): 7879-7883.

Figures/Tables 1

References

[1] Tu YH, Hu CL. Discussion on the early rehabilitation of stroke treatment with acute symptoms worsen. Chongqing Yixue. 2007;36(16):1666-1667.
[2] Tai WJ, Ye X, Bao XQ, et al. Study of microglia and cerebral ischemia relationship.Yaoxue Xuebao.2012;47(3): 346-353.
[3] Khodagholi F, Ashabi G. Dietary supplementation with Salvia sahendica attenuates memory deficits, modulates CREB and its down-stream molecules and decreases apoptosis in amyloid beta-injected rats. Behav Brain Res. 2013;15(241):62-69.
[4] Zhao L, Wu XG, Du LY, et al. The influence of hawthorn leaves flavonoids on vascular dementia(vd) rat hippocampul glutamate and NMDA receptor expression. Guangdong Yixue. 2014;35(3):353-356.
[5] Miao GX, Mao XX, Wu XG, et al. Impact of total flavone of hawthorn leaf on learning and memory ability and intracephalic cholinergic activity in rats with vascular dementia. Jiepou Xue Zazhi. 2014;37(2):192-196.
[6] Ni J, Ohta H, Matsumoto K, et al. Progressive cognitive impairment following chronic cerebral hypoperfusion induced by permanent occlusion of bilateral carotid arteries in rats. Brain Res. 1994;653(1-2):231-236.
[7] Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989;20(1):84-91.
[8] Shivaraju A, Yu C, Kattan MW, et al. Temporal trends in percutaneous coronary intervention-associated acute cerebrovascular accident (from the 1998 to 2008 Nationwide Inpatient Sample Database). Am J Cardiol. 2014;114(2):206-213.
[9] Killander F, Anderson H, Kjellén E, et al. Increased cardio and cerebrovascular mortality in breast cancer patients treated with postmastectomy radiotherapy-25 year follow-up of a randomised trial from the South Sweden Breast Cancer Group. Eur J Cancer. 2014. in press.
[10] Takasusuki T, Yamaguchi S, Hamaguchi S, et al. Effects of general anesthetics on substance P release and c-Fos expression in the spinal dorsal horn. Anesthesiology. 2013;119(2):433-442.
[11] Naseer MI, Ullah I, Rasool M, et al. Erratum to: Downregulation of dopamine D1 receptors and increased neuronal apoptosis upon ethanol and PTZ exposure in prenatal rat cortical and hippocampal neurons. Neurol Sci. 2014. in press.
[12] Abdelli S, Papas KK, Mueller KR, et al. Regulation of the JNK3 Signaling Pathway during Islet Isolation: JNK3 and c-fos as New Markers of Islet Quality for Transplantation. PLoS One. 2014;9(7):e99796.
[13] Sayin A, Derinöz O, Yüksel N, et al. The effects of the estrus cycle and citalopram on anxiety-like behaviors and c-fos expression in rats. Pharmacol Biochem Behav. 2014; 124C:180-187.
[14] Hendrickx A, Pierrot N, Tasiaux B, et al. Epigenetic regulations of immediate early genes expression involved in memory formation by the amyloid precursor protein of Alzheimer disease. PLoS One. 2014;9(6):e99467.
[15] Lee SY, Lee KS, Yi SH, et al. Acteoside suppresses RANKL-mediated osteoclastogenesis by inhibiting c-Fos induction and NF-κB pathway and attenuating ROS production. PLoS One. 2013;8(12):e80873.
[16] Zhang L, He Q, Wang Q, et al. Intracellular Ca2+ overload induced by extracellular Ca2+ entry plays an important role in acute heart dysfunction by tentacle extract from the Jellyfish Cyanea capillata. Cardiovasc Toxicol. 2014. in press.
[17] Liang YG, Jorgensen AG, Kaestel CG, et al. Bcl-2, Bax, and c-Fos expression correlates to RPE cell apoptosis induced by UV-light and daunorubicin. Curr Eye Res. 2000;20(1): 25-34.
[18] Ouyang YB, Giffard RG. microRNAs affect BCL-2 family proteins in the setting of cerebral ischemia. Neurochem Int. 2013. in press.