Panax notoginseng saponins (PNS) are known as clinical anti-stroke herbal medicines. The aim of this study is to describe the impact of PNS on ischemia-reperfusion-induced cerebral microvasculature barrier dysfunction which has not been investigated yet. Mice were subjected to transient middle cerebral artery occlusion and PNS were administrated to mice 3 days before and 2 days after surgery. Leukocyte adhesion, albumin leakage, tight junctions and other parameters in the cortex were measured. The PNS 45 mg/kg intervention alleviated leukocyte adhesion, inhibited endothelial barrier alterations evidenced by reduced albumin leakage and tight junction degradations, and ultimately ameliorated infarct volumes and neurological deficits subsequent to ischemia-reperfusion. Taken together, P. notoginseng saponins are able to attenuate leukocyte-mediated microvascular disturbance at the onset of ischemic stroke.

1.
Prabhakaran
S
,
Ruff
I
,
Bernstein
RA
.
Acute stroke intervention: a systematic review
.
JAMA
.
2015
Apr
;
313
(
14
):
1451
62
.
[PubMed]
0098-7484
2.
Molina
CA
.
Reperfusion therapies for acute ischemic stroke: current pharmacological and mechanical approaches
.
Stroke
.
2011
Jan
;
42
(
1
Suppl
):
S16
9
.
[PubMed]
0039-2499
3.
Dalkara
T
,
Arsava
EM
.
Can restoring incomplete microcirculatory reperfusion improve stroke outcome after thrombolysis?
J Cereb Blood Flow Metab
.
2012
Dec
;
32
(
12
):
2091
9
.
[PubMed]
0271-678X
4.
Kloner
RA
,
King
KS
,
Harrington
M
:
No-reflow Phenomenon in Heart and Brain.
American Journal of Physiology-Heart and Circulatory Physiology
2018
;0:null.
5.
Sweeney
MD
,
Sagare
AP
,
Zlokovic
BV
.
Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders
.
Nat Rev Neurol
.
2018
Mar
;
14
(
3
):
133
50
.
[PubMed]
1759-4758
6.
Sandoval
KE
,
Witt
KA
.
Blood-brain barrier tight junction permeability and ischemic stroke
.
Neurobiol Dis
.
2008
Nov
;
32
(
2
):
200
19
.
[PubMed]
0969-9961
7.
Lawrence
MB
,
Springer
TA
.
Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins
.
Cell
.
1991
May
;
65
(
5
):
859
73
.
[PubMed]
0092-8674
8.
Yadav
R
,
Larbi
KY
,
Young
RE
,
Nourshargh
S
.
Migration of leukocytes through the vessel wall and beyond
.
Thromb Haemost
.
2003
Oct
;
90
(
4
):
598
606
.
[PubMed]
0340-6245
9.
Li
H
,
Qiang
L
,
Zhang
C
,
Wang
C
,
Mu
Z
,
Jiang
L
.
Publication trends in studies examining radix notoginseng as a treatment for ischemic brain injury
.
Neural Regen Res
.
2014
Sep
;
9
(
17
):
1635
42
.
[PubMed]
1673-5374
10.
Shi
X
,
Yu
W
,
Liu
L
,
Liu
W
,
Zhang
X
,
Yang
T
, et al.
Panax notoginseng saponins administration modulates pro- /anti-inflammatory factor expression and improves neurologic outcome following permanent MCAO in rats
.
Metab Brain Dis
.
2017
Feb
;
32
(
1
):
221
33
.
[PubMed]
0885-7490
11.
Son
HY
,
Han
HS
,
Jung
HW
,
Park
YK
.
Panax notoginseng attenuates the infarct volume in rat ischemic brain and the inflammatory response of microglia
.
J Pharmacol Sci
.
2009
Mar
;
109
(
3
):
368
79
.
[PubMed]
1347-8613
12.
Zeng
XS
,
Zhou
XS
,
Luo
FC
,
Jia
JJ
,
Qi
L
,
Yang
ZX
, et al.
Comparative analysis of the neuroprotective effects of ginsenosides Rg1 and Rb1 extracted from Panax notoginseng against cerebral ischemia
.
Can J Physiol Pharmacol
.
2014
Feb
;
92
(
2
):
102
8
.
[PubMed]
0008-4212
13.
Li
H
,
Deng
CQ
,
Chen
BY
,
Zhang
SP
,
Liang
Y
,
Luo
XG
.
Total saponins of Panax notoginseng modulate the expression of caspases and attenuate apoptosis in rats following focal cerebral ischemia-reperfusion
.
J Ethnopharmacol
.
2009
Jan
;
121
(
3
):
412
8
.
[PubMed]
0378-8741
14.
Huang
XP
,
Tan
H
,
Chen
BY
,
Deng
CQ
.
Combination of total Astragalus extract and total Panax notoginseng saponins strengthened the protective effects on brain damage through improving energy metabolism and inhibiting apoptosis after cerebral ischemia-reperfusion in mice
.
Chin J Integr Med
.
2017
Jun
;
23
(
6
):
445
52
.
[PubMed]
1672-0415
15.
Wu
T
,
Sun
J
,
Kagota
S
,
Maruyama
K
,
Wakuda
H
,
Shinozuka
K
.
Panax notoginseng saponins ameliorate impaired arterial vasodilation in SHRSP.Z-Lepr(fa) /lzmDmcr rats with metabolic syndrome
.
Clin Exp Pharmacol Physiol
.
2016
Apr
;
43
(
4
):
459
67
.
[PubMed]
0305-1870
16.
Mao
XW
,
Pan
CS
,
Huang
P
,
Liu
YY
,
Wang
CS
,
Yan
L
, et al.
Levo-tetrahydropalmatine attenuates mouse blood-brain barrier injury induced by focal cerebral ischemia and reperfusion: involvement of Src kinase
.
Sci Rep
.
2015
Jun
;
5
(
1
):
11155
.
[PubMed]
2045-2322
17.
Li
X
,
Blizzard
KK
,
Zeng
Z
,
DeVries
AC
,
Hurn
PD
,
McCullough
LD
.
Chronic behavioral testing after focal ischemia in the mouse: functional recovery and the effects of gender
.
Exp Neurol
.
2004
May
;
187
(
1
):
94
104
.
[PubMed]
0014-4886
18.
Rosenberg
GA
,
Yang
Y
.
Vasogenic edema due to tight junction disruption by matrix metalloproteinases in cerebral ischemia
.
Neurosurg Focus
.
2007
May
;
22
(
5
):
E4
.
[PubMed]
1092-0684
19.
Yang
Y
,
Estrada
EY
,
Thompson
JF
,
Liu
W
,
Rosenberg
GA
.
Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat
.
J Cereb Blood Flow Metab
.
2007
Apr
;
27
(
4
):
697
709
.
[PubMed]
0271-678X
20.
Carlos
TM
,
Harlan
JM
.
Leukocyte-endothelial adhesion molecules
.
Blood
.
1994
Oct
;
84
(
7
):
2068
101
.
[PubMed]
0006-4971
21.
Gidday
JM
,
Gasche
YG
,
Copin
JC
,
Shah
AR
,
Perez
RS
,
Shapiro
SD
, et al.
Leukocyte-derived matrix metalloproteinase-9 mediates blood-brain barrier breakdown and is proinflammatory after transient focal cerebral ischemia
.
Am J Physiol Heart Circ Physiol
.
2005
Aug
;
289
(
2
):
H558
68
.
[PubMed]
0363-6135
22.
Fan
J
,
Liu
D
,
He
C
,
Li
X
,
He
F
.
Inhibiting adhesion events by Panax notoginseng saponins and Ginsenoside Rb1 protecting arteries via activation of Nrf2 and suppression of p38 - VCAM-1 signal pathway
.
J Ethnopharmacol
.
2016
Nov
;
192
:
423
30
.
[PubMed]
0378-8741
23.
Kniesel
U
,
Wolburg
H
.
Tight junctions of the blood-brain barrier
.
Cell Mol Neurobiol
.
2000
Feb
;
20
(
1
):
57
76
.
[PubMed]
0272-4340
24.
Wang
M
,
Zhang
XJ
,
Liu
F
,
Hu
Y
,
He
C
,
Li
P
, et al.
Saponins isolated from the leaves of Panax notoginseng protect against alcoholic liver injury via inhibiting ethanol-induced oxidative stress and gut-derived endotoxin-mediated inflammation
.
J Funct Foods
.
2015
;
19
:
214
24
. 1756-4646
25.
Panés
J
,
Granger
DN
.
Leukocyte-endothelial cell interactions: molecular mechanisms and implications in gastrointestinal disease
.
Gastroenterology
.
1998
May
;
114
(
5
):
1066
90
.
[PubMed]
0016-5085
26.
Ishikawa
M
,
Cooper
D
,
Arumugam
TV
,
Zhang
JH
,
Nanda
A
,
Granger
DN
.
Platelet-leukocyte-endothelial cell interactions after middle cerebral artery occlusion and reperfusion
.
J Cereb Blood Flow Metab
.
2004
Aug
;
24
(
8
):
907
15
.
[PubMed]
0271-678X
27.
Bauer
AT
,
Bürgers
HF
,
Rabie
T
,
Marti
HH
.
Matrix metalloproteinase-9 mediates hypoxia-induced vascular leakage in the brain via tight junction rearrangement
.
J Cereb Blood Flow Metab
.
2010
Apr
;
30
(
4
):
837
48
.
[PubMed]
0271-678X
28.
Barr
TL
,
Latour
LL
,
Lee
KY
,
Schaewe
TJ
,
Luby
M
,
Chang
GS
, et al.
Blood-brain barrier disruption in humans is independently associated with increased matrix metalloproteinase-9
.
Stroke
.
2010
Mar
;
41
(
3
):
e123
8
.
[PubMed]
0039-2499
29.
Huang
X
,
Tan
H
,
Chen
B
,
Deng
C
.
[Influence of astragalosides and Panax notoginseng saponins compatibility on MMP-9 and TIMP-1 after cerebral ischemia-reperfusion in mice]
.
Zhongguo Zhong Yao Za Zhi
.
2010
Aug
;
35
(
16
):
2187
91
.
[PubMed]
1001-5302
30.
Liu
G
,
Wang
B
,
Zhang
J
,
Jiang
H
,
Liu
F
.
Total panax notoginsenosides prevent atherosclerosis in apolipoprotein E-knockout mice: role of downregulation of CD40 and MMP-9 expression
.
J Ethnopharmacol
.
2009
Nov
;
126
(
2
):
350
4
.
[PubMed]
0378-8741
31.
Liu
KZ
,
Li
JB
,
Lu
HL
,
Wen
JK
,
Han
M
.
[Effects of Astragalus and saponins of Panax notoginseng on MMP-9 in patients with type 2 diabetic macroangiopathy]
.
Zhongguo Zhong Yao Za Zhi
.
2004
Mar
;
29
(
3
):
264
6
.
[PubMed]
1001-5302
32.
Ofosu-Appiah
W
,
Sfeir
G
,
Smith
D
,
Richard
T
.
Neutrophil-mediated damage to vascular endothelium in the spontaneously hypertensive rat
.
Clin Immunol Immunopathol
.
1997
Jun
;
83
(
3
):
293
301
.
[PubMed]
0090-1229
33.
Joussen
AM
,
Murata
T
,
Tsujikawa
A
,
Kirchhof
B
,
Bursell
SE
,
Adamis
AP
.
Leukocyte-mediated endothelial cell injury and death in the diabetic retina
.
Am J Pathol
.
2001
Jan
;
158
(
1
):
147
52
.
[PubMed]
0002-9440
34.
Limaye
V
,
Li
X
,
Hahn
C
,
Xia
P
,
Berndt
MC
,
Vadas
MA
, et al.
Sphingosine kinase-1 enhances endothelial cell survival through a PECAM-1-dependent activation of PI-3K/Akt and regulation of Bcl-2 family members
.
Blood
.
2005
Apr
;
105
(
8
):
3169
77
.
[PubMed]
0006-4971
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.