Download American Ginseng Acutely Regulates Contractile Function of the Heart

American Ginseng Acutely Regulates
Contractile Function of Heart
Mao Jiang
School of Kinesiology
Faculty of Health Sciences
The University of Western Ontario
Outline
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Introduction
Hypothesis and Specific Questions
Materials and Methods
Results
Future studies
Background
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Americian ginseng (Panax quinquefolius) differs from
other types of ginseng in its active ingredient and
characteristic biological responses.
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Adaptogenic effect of ginseng on the cardiovascular
system
1) Enhanced recovery of cardiac and brain ischemia injury
2) Inhibition of thrombin-induced platelet aggregation
3) Protection by ginsenoside-induced nitric oxide release
Background
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Effect of ginseng on blood pressure and cardiac
contractile function
1) Ginsenoside-induced transient hypertensive and hypotensive
effect
2) Chronic treatment of ginseng exerts a relaxing effect (decreased
systolic blood pressure, vasodilatation, depressant action on
cardiomyocyte contraction and heart rate)
3) Underlying mechanisms are still unclear
Hypothesis
American ginseng-induced nitric oxide release
and alterations in intracellular Ca2+ transient
lead to the characteristic changes in
contractile performance in cardiac myocytes
and vascular smooth muscle
Specific questions
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Does American ginseng acutely regulate contractile
performance of the heart?
What is the molecular mechanism underlying the
alterations?
Does American ginseng regulate the contractile
function and vasculature of heart during exercise
(ergogenic effect)?
Materials and Methods
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8-week old male Sprague Dawley rats
Water soluble ginseng for gavage at 300 mg/kg
body weight
Measurement of the cardiac contractile function
1) Langendorff Isolated-perfused heart (9 ml/min/g wet wt of tissue)
2) Electrocardiogram in anesthetized rats
3) Non-invasive blood pressure measurement
Heart Rate Recorded by ECG
400
*
*
300
200
100
in
se
hr
24
1
hr
G
G
on
in
se
tr
ol
ng
ng
0
C
Heart Rate (BPM)
500
hr
g
in
se
n
G
24
hr
G
g
se
n
in
se
ng
l
tr
o
*
24
in
se
ng
0.000
G
*
1h
rG
in
0.06
hr
0.005
l
0.010
on
C
0.00
tr
o
0.05
PR Interval (s)
0.10
on
*
QT Interval (s)
g
se
n
in
0.15
C
g
in
se
n
G
24
hr
G
se
ng
RR Interval (s)
*
1
hr
0.015
24
se
ng
l
tr
o
on
C
1h
rG
in
0.020
1h
rG
in
l
tr
o
on
C
QRS Interval (s)
0.20
0.06
*
*
0.04
0.02
0.00
0.04
0.02
0.00
Hear Rate recorded by Non-invasive BPR
*
400
*
300
200
100
ng
se
G
in
hr
24
1h
rG
in
on
se
n
tr
o
l
g
0
C
Heart Rate (bpm)
500
24
hr
in
G
se
ng
se
ng
G
in
ro
l
0
on
t
se
ng
Diastolic Pressure (mmHg)
50
C
in
G
se
ng
G
in
100
hr
hr
hr
ro
l
on
t
150
1
24
1
C
Systolic Pressure (mmHg)
Developed Pressure recorded by Non-invasive BPR
100
80
60
40
20
0
Developed Pressure recorded by Langendorff Perfused Heart
Developed Force (mmHg)
0.2 S
80
60
40
20
0
Control
1 hr Ginseng
24 hr Ginseng
40
20
in
s
in
hr
G
24
ol
se
ng
en
g
0
G
in
G
G
hr
1
24
hr
in
on
tr
ol
se
ng
se
ng
0
60
1h
r
100
80
tr
200
100
on
300
C
Heart Rate (BPM)
400
C
Developed Force (mmHg)
Heart rate and Developed Pressure Recorded by Langendorff Perfused Heart
Developed Force (mmHg)
200
150
250 µg/ml ginseng
100
50
0
0
200
400
600
800
600
800
Time (s)
100
Coronary Pressure (mmHg)
Wash
80
60
40
20
0
200
400
Time (s)
Futures Studies
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Investigating the molecular mechanisms underlying the
American ginseng-induced alterations in contractile
performance in heart and its vasculature
Measurement of Ca2+ transient in isolated cardiac myocytes:
1) Patch-clamp technique (sarcolemma L-type Ca2+ channel, Ca2+dependent K+ channel )
2) High-speed fluorescence imaging system (Ca2+ sparks)
3) Isolated SR vesicles to study the SR Ca2+ release and uptake function
and its regulation by protein phosphorylation
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Investigating American ginseng-mediated alterations on
the contractile function and vasculature of heart during
exercise
Acknowledgements
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Supervisor:
Dr. E.G. Noble
Lab members: Mehrbod Estaki
Tomasz Dzialoszynski
Financial support: OGIRC and CIHR
Thank You!
Background
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Americian ginseng (Panax quinquefolius) differs from other types of ginseng in its active ingredient and characteristic biological
responses.
Adaptogenic effect of ginseng on the cardiovascular system (enhanced
recovery of cardiac and brain ischemia
injury, inhibition of thrombin凝血酶 -induced platelet aggregation (antiatherosclerotic Action), protection by
ginsenoside-induced nitric oxide release)
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Intravenous administration of ginseng to anesthetized dogs resulted in reduction, followed by an increase in blood pressure, and transient
vasodilatation (79)
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Depressant action of Panax and Korean ginseng on cardiomyocyte contraction of rat (Scott, et al. 2001), rabbit (Lei, et al. 1986) and dog (Lee, et al.
1981), which may be mediated in part through increased NO production (Scott, et al. 2001) or Nitric oxide-dependent modulation of the delayed
rectifier K+ current and the L-type Ca2+ current by ginsenoside Re, an ingredient of Panax ginseng, in guinea-pig cardiomyocytes (Bai et al.
2004).
Ginsenoside Re enhances the slowly activating component of the delayed rectifier K+ current (IKs) and suppresses the L-type Ca2+ current, These
results indicate that ginsenoside Re-induced IKs enhancement and I(Ca,L) suppression involve NO actions. Direct S-nitrosylation of channel protein
appears to be the main mechanism for IKs enhancement, while a cGMP-dependent pathway is responsible for I(Ca,L) inhibition
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Total ginsenosides increase coronary perfusion flow in isolated rat hearts through activation of PI3K/Akt-eNOS signaling.(Yi, et al. 2010)
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Li et al. reported that ginsenoside-induced vasorelaxation also involves Ca2+ activated K+ channels in vascular smooth muscle cells
Korean red ginseng can improve the vascular endothelial dysfunction in patients with hypertension possibly through increasing NO
Single channel analysis on calcium channel blockade action of panaxadiol and panaxatriol saponins (Rb1, Rb2, Rb3, Rc, and Rd) on
cultured rat ventricular myocytes (Zhong et al, 1994, 1995); Ca2+ channel blocking effect of panaxadiol saponins and panaxatriol
saponins of cultured cardiac cells (Jiang, 1992)
Rg1 (purified saponin of Panax notoginseng) should not be a Ca2+ channel antagonist :from Effects of Rg1 on calcium channel of guinea
pig ventricular myocytes (Zhang et al. 1999), although it is reported that Rg1 prolonged ventricular refractoriness and repolarization, and
increased ventricular fibrillation threshold (VFT). It was indicated that cardiac electrophysiological effects of Rg1 were similar to those of
amiodarone(胺碘酮). (Wu et al. 1995)
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Panax ginseng:Ginsenoside Re suppresses electromechanical alternans(交替)in cat and human
cardiomyocytes (wang et al. 2008) Electromechanical alternans (EMA) is a proarrhythmic cardiac abnormality that results from disturbances of intracellular
Ca(2+) homeostasis ginsenoside Re suppresses EMA in cat atrial and ventricular myocytes, cat ventricular muscle, and human atrial myocytes. The effects of Re are not mediated via actions on
sarcolemmal ion channels or action potential configuration. Re acts via a subcellular mechanism to enhance the opening of RyRs and thereby overcome the impaired SR Ca(2+) release
underlying EMA.
Background
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Effect of red ginseng on blood pressure in patients with essential
hypertension and white coat hypertension (Han et al, 1998)
Inhibitory effect of (the root of Panax ginseng ) ginsenoside Rb1 on
cardiac hypertrophy induced by monocrotaline (野百合)in rat (Jiang et al.
2007), which may be involved in its inhibitory effects on CaN signal
transduction
The myocardial protective effects of trilinolein, isolated from the
Chinese herb Sanchi (Panax notoginseng), may be related to its
antioxidant effects. In the present study, we investigated the effects of
trilinolein on angiotensin II-induced cardiomyocyte hypertrophy.
Chronic pretreatment with American ginseng berry and its polyphenolic
constituents attenuate oxidant stress in cardiomyocytes.(Mehendale et
al. 2006), The results suggest that pretreatment with AGBE upregulates
peroxide detoxifying mechanisms, which could affect intracellular
oxidant dynamics in cardiomyocytes.
Background
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Anti-stress. Proof of the mysterious efficacy of ginseng:
basic and clinical trials: clinical effects of medical ginseng,
korean red ginseng: specifically, its anti-stress action for
prevention of disease. We studied and considered the action of
medical ginseng on living organisms that were exposed to
various stresses such as cold environment and industrial work.
Furthermore, we confirmed the preventive effects of medical
ginseng on the common cold symptom complex, including flu, by
clinical observation. ( Kaneko et al. 2004)
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