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Effects of American Ginseng on Erectile Function and Sexual Behaviour. Matthew Barnes Supervisor: Lique Coolen The University of Western Ontario. Introduction: Erectile dysfunction. There is a growing demand for phosphodiesterase 5 (PDE5) inhibiters ( Wessells et al 2001) - PowerPoint PPT Presentation
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MATTHEW BARNESSUPERVISOR: LIQUE COOLEN
THE UNIVERSITY OF WESTERN ONTARIO
Effects of American Ginseng on Erectile Function and Sexual Behaviour
Introduction: Erectile dysfunction
There is a growing demand for phosphodiesterase 5 (PDE5) inhibiters (Wessells et al 2001)
Furthermore, men with type 2 diabetes have a 28% prevalence of erectile dysfunction (Feldman et al 1994)
HOWEVER, 46% of men with type 2 diabetes don’t respond to PDE5 inhibitors (Rendell et al 1999)
Finally, after a year of treatment, men with type 2 diabetes who respond positively to treatment may revert back to pretreatment conditions (Penson et al 2003)
Prevalence of Erectile Dysfunction in Older Men
Finlan
d
Ecuad
or, C
olumbia
, Ven
ezue
laUSA
Singap
ore
Brasil
UK, Neth
erlan
ds
Franc
e
German
yIta
ly0
10
20
30
40
50
60
70
80
Perc
ent
(%)
Ginseng improves erectile function
Ginseng (North American and Korean Red) Facilitates sexual behavior in
rats (Murphy et al 1998)
Korean Red Ginseng: Causes vasodilation in
erectile tissue: corpus cavernosum (rabbit, canine) (Kang et al 2005, Chen and Lee 1995)
Ginsenoside effects on erectile physiology
Ginseng and Diabetes
Decreased eNOS mRNA and expression (Xie et al 2007)
Increase eNOS phosphorylation Yu et all 2007)
Decreased VEGF expression and mRNA (Musicki et al 2004)
Increase VEGF expression via glucocorticoid receptor activation (Leung et al 2006)
Hyperglycemia → ROS → lipid peroxidation and upregulated cytokines and adhesion molecules → vascular damage (Yan et al 2008)
Antioxidant (Cho et al 2006)
Increase glutathione and decrease markers for lipid peroxidation (Ryu et al 2005)
Decreasing glucose levels in blood (Ji and Gong 2007)
Overview Research Goals
Test the hypothesis that North American (Ontario) Ginseng facilitates erectile function and sexual behavior:1. In healthy male rats
2. In diabetic male rats
Objectives – Current study
Investigate the effects of Ontario ginseng on sexual behavior and erectile function in healthy, adult male rats
Determine the effects of ginseng on anxiety and other non-sexual effects in healthy male rats.
Determine if ginseng acts centrally, peripherally, or both.
Animal Model
Rat Long Evans
Hooded rat: will also be used for diabetic model (Zucker Fatty rat)
Show more psychogenic erections than albino rats
Ontario ginseng
Composite from 5 Ontario farms
Tested for heavy metal and herbicide levels, as well as adulteration
Delivery: Oral by gavage daily 2 – 4 hours after lights off.
Dosages: aqueous extract (125 or 250 mg/kg) or saline ethanol extract (125 or 250 mg/kg) or saline
Timeline
Start Injection
s
Reward/Aversion• Conditioned Place Preference
Anxiety Tests
• Elevated Plus Maze
• Open Field
Sexual Behavio
ur• Sexual
Motivation
Erection Tests
• Non-Contact Erections
Week 3 Week 6Week 5Week 4
Saline Low High38
40
42
44
46
48
50 Pre-testPost-test
Pref
eren
ce S
core
(%)
Reward/Aversion
Aqueous extract was not rewarding or aversiveConditioned Place Preference
Saline Low High0
10
20
30
40
50
60
Pref
eren
ce S
core
(%
)
*
Ethanol extract is rewarding
Aqueous n = 8, Ethanol n = 10
AnxietyAqueous or ethanol extracts did not cause or reduce anxiety
Saline Low High0
20
40
60
80 Closed ArmsOpen Arms
Perc
ent
of T
ime
(%)
Saline Low High0
20406080
100120140
Tim
e (s
ecs)
Elevated Plus Maze
Open Field Test
Aqueous n = 8
Overview
NA ginseng does not cause aversion nor anxiety
Therefore: any effects on sexual behaviour will not be secondary to these influences.
Sexual Behavior
Aqueous extract slightly increased erectile function
# of Mounts # of Intromission02468
10121416
ControlLowHigh*
Aqueous n = 8
Control Low High0
10
20
30
40
50
60
70
80
90
Copulation Efficiency
Perc
ent
(%)
*
Sexual Behavior
# Mounts # Intromissions0
2
4
6
8
10
12
14ControlLowHigh
Ethanol extract did not affect erectile function but increased motivation.
Control Low High0
10
20
30
40
50
60
70
80 Copulation Efficiency
Perc
ent
(%)
Mount Latency
Intromission Latency
0
50
100
150
200
250
ControlLowHigh
Tim
e (s
econ
ds)
* *
Ethanol n = 10
Non-contact ErectionsAqueous extract did not affect non-contact erections (psychogenic erections)
Saline Low High0.0
1.0
2.0
3.0
Num
ber
of E
rect
ions
Saline Low High0
100200300400500600700800900
1000
Tim
e un
til F
irst
Er
ecti
on (
secs
)
Ethanol extract also had no effect
Saline Low High0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
Num
ber
of
Erec
tion
s
Saline Low High0
100200300400500600700800
Tim
e un
til F
irst
Er
ecti
on (
secs
)
Aqueous n = 8, Ethanol n = 10
Conclusions – Healthy ratsAqueous extract: increase copulation
efficiency; suggestive of increased erectile function during mating.
Ethanol extract: decreases mount and intromission latency; suggestive of increased sexual arousal. A trend exists of decreased mount frequency.
No effects on any other parameter of sexual behaviour or erectile function induced by distal cues.
Ongoing studies
Determine sites of action: central or peripheralPeripheral:
Erectile tissues (quantitative PCR, NO activity assays)
Central Nervous System: Neural activity mapping to visualize neurons
activated by ginseng following acute and chronic administration
Future studies
Determine effects of Ginseng on sexual/erectile function in rat model of diabetes
Zucker rats have a mutated leptin geneMost are diabetic displaying phenotypes
similar to type 2 diabetes patients: Obesity Insulin resistance Impaired vasodilation Hypertension
(Kasiske et al 1992)
Future Studies
Test effects of both extracts on erectile function in Zucker Fatty rats:
Sexual behaviour Intercavernous pressure recordings
Thank you!_____________________________________________________________________________________________________
Dr. Coolen, Dr. Lui, Dr. Hammond, Dr. FengOntario Ministry of Research and Innovation
HAVE YOU HAD YOUR GINSENG TODAY?
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