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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2015

Open Access 01-12-2015 | Research article

Neuroprotective effect of the hairy root extract of Angelica gigas NAKAI on transient focal cerebral ischemia in rats through the regulation of angiogenesis

Authors: Tae Woo Oh, Ki-Ho Park, Hyo Won Jung, Yong-Ki Park

Published in: BMC Complementary Medicine and Therapies | Issue 1/2015

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Abstract

Background

In this study, we investigated the neuroprotective effect of the hairy root extract of Angelica gigas NAKAI (Angelica Gigantis Radix) on transient focal cerebral ischemia in rats through the regulation of angiogenesis molecules.

Methods

Male Sprague-Dawley rats were induced focal cerebral ischemia by a transient middle cerebral artery occlusion (tMCAO) for 90 min, and then orally administrated with the water extract of A. gigas hairy roots (AG). After 24 h reperfusion, infarction volume and the changes of BBB permeability were measured by TTC and Evans Blue (EB) staining. The neuronal cell damage and the activation of glial cells were assessed by immunohistochemistry in the ischemic brain. The expression of angiogenesis-induced proteins such as angiopoietin-1 (Ang-1), and vascular endothelial growth factor (VEGF), inflammatory protein such as intercellular adhesion molecule-1 (CAM-1), tight junction proteins such as ZO-1, and Occludin and the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT were determined in the ischemic brains by Western blot, respectively.

Results

The treatment of AG extract significantly decreased the volumes of brain infarction, and edema in MACO-induced ischemic rats. AG extract decreased the increase of BBB permeability, and neuronal death and inhibited the activation of astrocytes and microglia in ischemic brains. AG extract also significantly increased the expression of Ang-1, Tie-2, VEGF, ZO-1 and Occludin through activation of the PI3K/Akt pathway. AG extract significantly increased the expression of ICAM-1 in ischemic brains.

Conclusions

Our results indicate that the hairy root of AG has a neuroprotective effect in ischemic stroke.
Literature
1.
Jin K, Minami M, Lan JQ, Mao XO, Batteur S, Simon RP. Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc Natl Acad Sci U S A. 2001;98:4710–5.CrossRefPubMedPubMedCentral
2.
Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med. 2002;8:963–70.CrossRefPubMed
3.
Parent JM, Vexler ZS, Gong C, Derugin N, Ferriero DM. Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol. 2002;52:802–13.CrossRefPubMed
4.
Zhang R, Zhang Z, Zhang C, Zhang L, Robin A, Wang Y, et al. Stroke transiently increases subventricular zone cell division from asymmetric to symmetric and increases neuronal differentiation in the adult rat. J Neurol Sci. 2004;24:5810–5.
5.
Xiong Y, Mahmood A, Chopp M. Angiogenesis, neurogenesis and brain recovery of function following injury. Curr Opin Investig Drugs. 2010;11(3):298–308.PubMedPubMedCentral
6.
Folkman J, D’Amore PA. Blood vessel formation: what is its molecular basis? Cell. 1996;87:1153–5.CrossRefPubMed
7.
8.
Koblizek TI, Runting AS, Stacker SA, Wilks AF, Risau W, Deutsch U. Tie2 receptor expression and phosphorylation in cultured cells and mouse tissues. Eur J Biochem. 1997;244:774–9.CrossRefPubMed
9.
Sato TN, Tozawa Y, Deutsch U, Wolburg-Buchholz K, Fujiwara Y, Gendron-Maguire M, et al. Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature. 1995;376:70–4.CrossRefPubMed
10.
Wong AL, Haroon ZA, Werner S, Dewhirst MW, Greenberg CS, Peters KG. Tie2 expression and phosphorylation in angiogenic and quiescent adult tissues. Circ Res. 1997;81:567–74.CrossRefPubMed
11.
McColl BW, Rothwell NJ, Allan SM. Systemic inflammatory stimulus potentiates the acute phase and CXC chemokine responses to experimental stroke and exacerbates brain damage via interleukin-1 and neutrophil-dependent mechanisms. J Neurosci. 2007;27:4403–12.CrossRefPubMed
12.
McColl BW, Rothwell NJ, Allan SM. Systemic inflammation alters the kinetics of cerebrovascular tight junction disruption after experimental stroke in mice. J Neurosci. 2008;28:9451–62.CrossRefPubMed
13.
Ma Y, Zechariah A, Qu Y, Hermann DM. Effects of vascular endothelial growth factor ischemic stroke. J Neurosci Res. 2012;90:1873–82.CrossRefPubMed
14.
Zhang ZG, Zhang L, Tsang W, Soltanian-Zadeh H, Morris D, Zhang R, et al. Correlation of VEGF and angiopoietin expression with disruption of blood-brain barrier and angiogenesis after focal cerebral ischemia. J Cereb Blood Flow Metab. 2002;22(4):379–92.CrossRefPubMed
15.
Kim KM, Kim MJ, Kang JS. Absorption, distribution, metabolism, and excretion of decursin and decursinol angelate from Angelica gigas NAKAI. J Microbiol Biotechnol. 2009;19:1569–72.CrossRefPubMed
16.
Baek IH, Chae JW, Song GY, Kwon KI. LC-MS/MS Assay validation for a new immune modulator, JHL45, and its major metabolite in plasma: Application to pharmacokinetic studies in rats. Bull Korean Chem Soc. 2009;30:2631–6.CrossRef
17.
Song JS, Chae JW, Lee KR, Lee BH, Choi EJ, Ahn SH, et al. Pharmacokinetic characterization of decursinol derived from Angelica gigas NAKAI in rats. Xenobiotica. 2011;41:895–902.CrossRefPubMed
18.
Kang SY, Lee KY, Park MJ, Kim YC, Markelonis GJ, Oh TH, et al. Decursin from Angelica gigas mitigates amnesia induced by scopolamine in mice. Neurobiol Learn Mem. 2003;79:11–8.CrossRefPubMed
19.
Kil JS, Kim MG, Choi HM, Lim JP, Boo Y, Kim EH, et al. Inhibitory effects of Angelicae Gigantis Radix on osteoclast formation. Phytother Res. 2008;22:472–6.CrossRefPubMed
20.
Kang TC, Hwang IK, Park SK, An SJ, Yoon DK, Moon SM, et al. Chronological changes of N-methyl-D-aspartate receptors and excitatory amino acid carrier 1 immunoreactivities in CA1 area and subiculum after transient forebrain ischemia. J Neurocytol. 2001;30:945–55.CrossRefPubMed
21.
Yan JJ, Kim DH, Moon YS, Jung JS, Ahn EM, Baek NI, et al. Protection against beta-amyloid peptide-induced memory impairment with long-term administration of extract of Angelica gigas or decursinol in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28:25–30.CrossRefPubMed
22.
Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989;20:84–91.CrossRefPubMed
23.
Vakili A, Kataoka H, Plesnila N. Role of arginine vasopressin V1 and V2 receptors for brain damage after transient focal cerebral ischemia. J Cereb Blood Flow Metab. 2005;25:1012–9.CrossRefPubMed
24.
Asahi M, Wang X, Mori T, Sumii T, Jung JC, Moskowitz MA, et al. Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components after cerebral ischemia. J Neurosci. 2001;21:7724–32.PubMed
25.
Tuttolomondo A, Di Sciacca R, Di Raimondo D, Renda C, Pinto A, Licata G. Inflammation as a therapeutic target in acute ischemic stroke treatment. Curr Top Med Chem. 2009;9(14):1240–60.CrossRefPubMed
26.
Zhu Y, Shwe Y, Du R, Chen Y, Shen FX, Young WL, et al. Effects of angiopoietin-1 on vascular endothelial growth factor-induced angiogenesis in the mouse brain. Acta Neurochir Suppl. 2006;96:438–43.CrossRefPubMed
27.
Krupinski J, Kaluza J, Kumar P, Kumar S, Wang JM. Role of angiogenesis in patients with cerebral ischemic stroke. Stroke. 1994;25:1794–8.CrossRefPubMed
28.
Ramsauer M, Krause D, Dermietzel R. Angiogenesis of the blood–brain barrier in vitro and the function of cerebral pericytes. FASEB J. 2002;16:1274–6.PubMed
29.
Fruttiger M, Calver AR, Krüger WH, Mudhar HS, Michalovich D, Takakura N, et al. PDGF mediates a neuron–astrocyte interaction in the developing retina. Neuron. 1996;17:1117–31.CrossRefPubMed
30.
Holash J, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zagzag D, et al. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science. 1999;284:1994–8.CrossRefPubMed
31.
McCarthy MJ, Crowther M, Bell PR, Brindle NP. The endothelial receptor tyrosine kinase tie-1 is upregulated by hypoxia and vascular endothelial growth factor. FEBS Lett. 1998;423:334–8.CrossRefPubMed
32.
Krum JM, Khaibullina A. Inhibition of endogenous VEGF impedes revascularization and astroglial proliferation: roles for VEGF in brain repair. Exp Neurol. 2003;181:241–57.CrossRefPubMed
33.
Kovacs Z, Ikezaki K, Samoto K, Inamura T, Fukui M. VEGF and flt. Expression time kinetics in rat brain infarct. Stroke. 1996;27:1865–73.CrossRefPubMed
34.
Hayashi T, Abe K, Suzuki H, Itoyama Y. Rapid induction of vascular endothelial growth factor gene expression after transient middle cerebral artery occlusion in rats. Stroke. 1997;28:2039–44.CrossRefPubMed
35.
Mandriota SJ, Pepper MS. Regulation of angiopoietin-2 mRNA levels in bovine microvascular endothelial cells by cytokines and hypoxia. Circ Res. 1998;83:852–9.CrossRefPubMed
36.
Oh H, Takagi H, Suzuma K, Otani A, Matsumura M, Honda Y. Hypoxia and vascular endothelial growth factor selectively up-regulate angiopoietin- 2 in bovine microvascular endothelial cells. J Biol Chem. 1999;274:15732–9.CrossRefPubMed
37.
Beck H, Acker T, Wiessner C, Allegrini PR, Plate KH. Expression of angiopoietin-1, angiopoietin-2, and tie receptors after middle cerebral artery occlusion in the rat. Am J Pathol. 2000;157:1473–83.CrossRefPubMedPubMedCentral
38.
Stratmann A, Risau W, Plate KH. Cell type-specific expression of angiopoietin-1 and angiopoietin-2 suggests a role in glioblastoma angiogenesis. Am J Pathol. 1998;153:1459–66.CrossRefPubMedPubMedCentral
39.
Zhang ZG, Zhang L, Croll SD, Chopp M. Angiopoietin-1 reduces cerebral blood vessel leakage and ischemic lesion volume after focal cerebral embolic ischemia in mice. Neuroscience. 2002;113:683–7.CrossRefPubMed
40.
Korhonen J, Partanen J, Armstrong E, Vaahtokari A, Elenius K, Jalkanen M, et al. Enhanced expression of the tie receptor tyrosine kinase in endothelial cells during neovascularization. Blood. 1992;80:2548–55.PubMed
41.
Lin TN, Wang CK, Cheung WM, Hsu CY. Induction of angiopoietin and Tie receptor mRNA expression after cerebral ischemia-reperfusion. J Cereb Blood Flow Metab. 2000;20:387–95.CrossRefPubMed
42.
Beat AI, Michel AL. Angiogenesis and inflammation face off. Nat Med. 2006;12:171–2.CrossRef
43.
Plate KH, Beck H, Danner S, Allegrini PR, Wiessner C. Cell type specific upregulation of vascular endothelial growth factor in an MCAocclusion model of cerebral infarct. J Neuropathol Exp Neuro. 1999;58:654–66.CrossRef
44.
Chae JK, Kim I, Lim ST, Chung MJ, Kim WH, Kim HG, et al. Coadministration of angiopoietin-1 and vascular endothelial growth factor enhances collateral vascularization. Arteriosclerosis, Thrombosis, and Vascualr Biology. 2000;20:2573–8.CrossRef
45.
Kopp HG, Avecilla ST, Hooper AT, Shmelkov SV, Ramos CA, Zhang F, et al. Tie2 activation contributes to hemangiogenic regeneration after myelosuppression. Blood. 2005;106:505–13.CrossRefPubMedPubMedCentral
46.
Strbian D, Durukan A, Pitkonen M, Marinkovic I, Tatlisumak E, Pedrono E, et al. The blood–brain barrier is continuously open for several weeks following transient focal cerebral ischemia. Neurosci. 2008;153:175–81.CrossRef
47.
Wunder A, Schoknecht K, Stanimirovis DB, Prager O, Chassidim Y. Imaging blood-brain barrier dysfunction in animal disease models. Epilepsia. 2012;53(6):14–21.CrossRefPubMed
48.
Sawada N, Murata M, Kikuchi K, Osanai M, Tobioka H, Kojima T, et al. Tight junctions and human diseases. Med Electron Microsc. 2003;36:147–56.CrossRefPubMed
49.
50.
Furuse M, Itoh M, Hirase T, Nagafuchi A, Yonemura S, Tsukita S, et al. Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions. J Cell Biol. 1994;127:1617–26.CrossRefPubMed
51.
Lo EH, Dalkara T, Moskowitz MA. Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci. 2003;4:399–415.CrossRefPubMed
52.
Thurston G, Suri C, Smith K, McClain J, Sato TN, Yancopoulos GD, et al. Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science. 1999;286(5449):2511–4.CrossRefPubMed
Metadata
Title
Neuroprotective effect of the hairy root extract of Angelica gigas NAKAI on transient focal cerebral ischemia in rats through the regulation of angiogenesis
Authors
Tae Woo Oh
Ki-Ho Park
Hyo Won Jung
Yong-Ki Park
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2015
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-015-0589-4

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