期刊论文详细信息
BMC Complementary and Alternative Medicine
Timosaponin-BII inhibits the up-regulation of BACE1 induced by Ferric Chloride in rat retina
Kun Xiong1  Hui Wang1  Chun-Ling Fan1  Dan Chen1  Shuang Chen1  Meng-Qi Zhang2  Pei Liu3  Lei Shang1  Ju-Fang Huang1 
[1] Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, 410013, China;Eight-year Clinical Medicine Doctor Program, Grade 2006, Central South University Xiangya School of Medicine, Changsha, Hunan, 410013, China;Five-year Medicine Program, Grade 2009, Central South University Xiangya School of Medicine, Changsha, Hunan, 410013, China
关键词: ;    Retina;    BACE1;    Oxidative stress;    Timosaponin-BII;   
Others  :  1231532
DOI  :  10.1186/1472-6882-12-189
 received in 2012-06-29, accepted in 2012-10-18,  发布年份 2012
【 摘 要 】

Background

Our previous studies indicated that oxidative stress up-regulated the expression of β-amyloid precursor protein cleavage enzyme-1 (BACE1) in rat retina. Pharmacological reports have shown Timosaponin-BII, a purified extract originating from Chinese medical herb Rhizoma Anemarrhenae, is characterized as an antioxidant. Our present study aimed to determine whether Timosaponin-BII affected the expression of BACE1, β-amyloid precursor protein cleavage production of Aβ1-40 and β-C-terminal fragment (β-CTF) in rat retina, which were pre-treated with the oxidizing agent (solution of FeCl3).

Results

Few distinctions of BACE1 distribution were observed among all groups (normal control group, model group, Timosaponin-BII treated and vehicle control groups). Rat retinas in model group and vehicle control group manifested an apparent up-regulation of BACE1 expression. Meanwhile, the level of malonaldehyde (MDA), Aβ1-40 and β-CTF were increased. However, when comparing with the vehicle control group, the retinas in Timosaponin-BII treated group showed significantly less BACE1 (p<0.05) and accumulated less Aβ1-40 or β-CTF (p<0.05). It also showed significantly decreased level of MDA (p<0.05) and prolonged partial thromboplastin time (p<0.05).

Conclusion

Our data suggested that Timosaponin-BII remarkably inhibited the up-regulation of BACE1 and reduced the over-production of β-CTF and Aβ in rat retina, which was induced by FeCl3. The mechanism of Timosaponin-BII on BACE1 expression may be related to its antioxidant property.

【 授权许可】

   
2012 Huang et al.; licensee BioMed Central Ltd.

附件列表
Files Size Format View
Figure 5. 43KB Image download
Figure 4. 47KB Image download
Figure 3. 45KB Image download
Figure 2. 93KB Image download
Figure 1. 43KB Image download
Figure 5. 43KB Image download
Figure 4. 47KB Image download
Figure 3. 45KB Image download
Figure 2. 93KB Image download
Figure 1. 43KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】
  • [1]Attems J, Yamaguchi H, Saido TC, Thal DR: Capillary CAA and perivascular Abeta-deposition: two distinct features of Alzheimer's disease pathology. J Neurol Sci 2010, 299(1–2):155-162.
  • [2]Gotz J, Eckert A, Matamales M, Ittner LM, Liu X: Modes of Abeta toxicity in Alzheimer's disease. Cellular and molecular life sciences: CMLS 2011, 68(20):3359-3375.
  • [3]Selkoe DJ: Toward a comprehensive theory for Alzheimer's disease. Hypothesis: Alzheimer's disease is caused by the cerebral accumulation and cytotoxicity of amyloid beta-protein. Ann N Y Acad Sci 2000, 924:17-25.
  • [4]Selkoe DJ: Alzheimer's disease: genes, proteins, and therapy. Physiol Rev 2001, 81(2):741-766.
  • [5]Blasko I, Beer R, Bigl M, Apelt J, Franz G, Rudzki D, Ransmayr G, Kampfl A, Schliebs R: Experimental traumatic brain injury in rats stimulates the expression, production and activity of Alzheimer's disease beta-secretase (BACE-1). J Neural Transm 2004, 111(4):523-536.
  • [6]Wen Y, Onyewuchi O, Yang S, Liu R, Simpkins JW: Increased beta-secretase activity and expression in rats following transient cerebral ischemia. Brain Res 2004, 1009(1–2):1-8.
  • [7]Tong Y, Zhou W, Fung V, Christensen MA, Qing H, Sun X, Song W: Oxidative stress potentiates BACE1 gene expression and Abeta generation. J Neural Transm 2005, 112(3):455-469.
  • [8]Velliquette RA, O'Connor T, Vassar R: Energy inhibition elevates beta-secretase levels and activity and is potentially amyloidogenic in APP transgenic mice: possible early events in Alzheimer's disease pathogenesis. J Neurosci 2005, 25(47):10874-10883.
  • [9]Sun X, He G, Qing H, Zhou W, Dobie F, Cai F, Staufenbiel M, Huang LE, Song W: Hypoxia facilitates Alzheimer's disease pathogenesis by up-regulating BACE1 gene expression. Proc Natl Acad Sci U S A 2006, 103(49):18727-18732.
  • [10]Yan XX, Xiong K, Luo XG, Struble RG, Clough RW: beta-Secretase expression in normal and functionally deprived rat olfactory bulbs: inverse correlation with oxidative metabolic activity. J Comp Neurol 2007, 501(1):52-69.
  • [11]Huang JF, Huang K, Shang L, Wang H, Yan XX, Xiong K: Beta-amyloid precursor protein cleavage enzyme-1 expression in adult rat retinal neurons in the early period after lead exposure. Neural Regen Res 2011, 6(14):1045-1051.
  • [12]Xiong K, Cai H, Luo XG, Struble RG, Clough RW, Yan XX: Mitochondrial respiratory inhibition and oxidative stress elevate beta-secretase (BACE1) proteins and activity in vivo in the rat retina. Exp Brain Res 2007, 181(3):435-446.
  • [13]Misonou H, Morishima-Kawashima M, Ihara Y: Oxidative stress induces intracellular accumulation of amyloid beta-protein (Abeta) in human neuroblastoma cells. Biochemistry 2000, 39(23):6951-6959.
  • [14]Paola D, Domenicotti C, Nitti M, Vitali A, Borghi R, Cottalasso D, Zaccheo D, Odetti P, Strocchi P, Marinari UM, et al.: Oxidative stress induces increase in intracellular amyloid beta-protein production and selective activation of betaI and betaII PKCs in NT2 cells. Biochem Biophys Res Commun 2000, 268(2):642-646.
  • [15]Tamagno E, Bardini P, Obbili A, Vitali A, Borghi R, Zaccheo D, Pronzato MA, Danni O, Smith MA, Perry G, et al.: Oxidative stress increases expression and activity of BACE in NT2 neurons. Neurobiol Dis 2002, 10(3):279-288.
  • [16]Fukumoto H, Cheung BS, Hyman BT, Irizarry MC: Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease. Arch Neurol 2002, 59(9):1381-1389.
  • [17]Li R, Lindholm K, Yang LB, Yue X, Citron M, Yan R, Beach T, Sue L, Sabbagh M, Cai H, et al.: Amyloid beta peptide load is correlated with increased beta-secretase activity in sporadic Alzheimer's disease patients. Proc Natl Acad Sci U S A 2004, 101(10):3632-3637.
  • [18]Ji X, Feng YF: Advances in studies on saponins in Anemarrhena asphodeloides. Chinese Traditional and Herbal Drugs 2010, 41(4):S12-S15.
  • [19]Hu Y, Xia Z, Sun Q, Orsi A, Rees D: A new approach to the pharmacological regulation of memory: Sarsasapogenin improves memory by elevating the low muscarinic acetylcholine receptor density in brains of memory-deficit rat models. Brain Res 2005, 1060(1–2):26-39.
  • [20]Li TJ, Qiu Y, Yang PY, Rui YC, Chen WS: Timosaponin B-II improves memory and learning dysfunction induced by cerebral ischemia in rats. Neurosci Lett 2007, 421(2):147-151.
  • [21]Lu WQ, Qiu Y, Li TJ, Tao X, Sun LN, Chen WS: Timosaponin B-II inhibits pro-inflammatory cytokine induction by lipopolysaccharide in BV2 cells. Arch Pharm Res 2009, 32(9):1301-1308.
  • [22]Ouyang S, Sun LS, Guo SL, Liu X, Xu JP: Effects of timosaponins on learning and memory abilities of rats with dementia induced by lateral cerebral ventricular injection of amyloid beta- peptide. Di Yi Jun Yi Da Xue Xue Bao 2005, 25(2):121-126.
  • [23]Cai F, Sun L, Gao S, Yang Y, Yang Q, Chen W: A rapid and sensitive liquid chromatography-tandem mass spectrometric method for the determination of timosaponin B-II in blood plasma and a study of the pharmacokinetics of saponin in the rat. J Pharm Biomed Anal 2008, 48(5):1411-1416.
  • [24]Lu WQ, Qiu Y, Li TJ, Tao X, Sun LN, Chen WS: Antiplatelet and antithrombotic activities of timosaponin B-II, an extract of Anemarrhena asphodeloides. Clin Exp Pharmacol Physiol 2011, 38(7):430-434.
  • [25]Forstl H, Kurz A: Clinical features of Alzheimer's disease. Eur Arch Psychiatry Clin Neurosci 1999, 249(6):288-290.
  • [26]Backman L, Jones S, Berger AK, Laukka EJ, Small BJ: Multiple cognitive deficits during the transition to Alzheimer's disease. J Intern Med 2004, 256(3):195-204.
  • [27]Frost S, Martins RN, Kanagasingam Y: Ocular biomarkers for early detection of Alzheimer's disease. J Alzheimers Dis 2010, 22(1):1-16.
  • [28]Koronyo-Hamaoui M, Koronyo Y, Ljubimov AV, Miller CA, Ko MK, Black KL, Schwartz M, Farkas DL: Identification of amyloid plaques in retinas from Alzheimer's patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model. NeuroImage 2011, 54(Suppl 1):S204-S217.
  • [29]Chiu K, Chan TF, Wu A, Leung IY, So KF, Chang RC: Neurodegeneration of the retina in mouse models of Alzheimer's disease: what can we learn from the retina? Age (Dordr) 2012, 34(3):633-649.
  • [30]Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, Jones PK, Ghanbari H, Wataya T, Shimohama S, et al.: Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 2001, 60(8):759-767.
  • [31]Reed TT, Pierce WM, Markesbery WR, Butterfield DA: Proteomic identification of HNE-bound proteins in early Alzheimer disease: Insights into the role of lipid peroxidation in the progression of AD. Brain Res 2009, 1274:66-76.
  • [32]Smith MA, Zhu X, Tabaton M, Liu G, McKeel DW Jr, Cohen ML, Wang X, Siedlak SL, Dwyer BE, Hayashi T, et al.: Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment. J Alzheimer's Disease: JAD 2010, 19(1):363-372.
  • [33]Lee HP, Pancholi N, Esposito L, Previll LA, Wang X, Zhu X, Smith MA, Lee HG: Early induction of oxidative stress in mouse model of Alzheimer disease with reduced mitochondrial superoxide dismutase activity. PLoS One 2012, 7(1):e28033.
  • [34]Butterfield DA, Sultana R: Methionine-35 of abeta(1–42): importance for oxidative stress in Alzheimer disease. J Amino Acids 2011, 2011:198430.
  • [35]Ma B, Xu Q, Zhao Y, Xiong C, Tan D: Use of timosaponin Bll in the preparation of a medicament or product for the prevention and treatment of stroke. Google Patents 2011.
  • [36]Yun D, Bai-ping M, Yu-wen C, Yu-xian S, Jing-jing Z, Yu-jun S: Protective effects of timosaponin BII on primary neurons against beta amyloid peptide 25–35. Chin Pharmacol Bull 2009, 25(2):244-247.
  文献评价指标  
  下载次数:72次 浏览次数:35次