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

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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?