Aphrodisiac effects of Panax ginseng extract standardized with ginsenoside Rg3 in male rats

Abstract

Keywords Abstract Panax ginseng Sildenafil citrate Sex behavior Sexual disorders In traditional medicine, Panax ginseng has been used to treat various behavioral effects. However, a little is known about the effect of ginsenoside Rg3, the most ingredients in panax ginseng, on male copulatory and sexual behavior. The aim of the current study was to investigate the effect of panax ginseng extract standardized with ginsenoside Rg3 (PGRg3) on general mating behaviour, libido, potency and the adverse effects in normal male Sprague-Dawley rats. Four tests were carried out to evaluate different sexual parameters. Male rats were divided into different groups in each test and treated with different doses of PGRg3 (50, 250 and 500 mg/kg b.w.) and Sildenafil citrate (5 mg/kg b.w). Female rats with oestrus phase were used to analyze the mating behavior.The results indicated that PGRg3 significantly increased mounting frequency, intromission frequency, ejaculatory latency in the first and second series, erection, quick flips, long flips and aggregate of penile reflexes. Whereas, it significantly decreases mounting latency, intromission latency and post ejaculatory intervals in dose dependent manner. Moreover, PGRg3 was found to be devoid of any conspicuous gastric ulceration and any other adverse effects. PGRg3 extract at the higher dose (500 mg/kg b.w.) was comparable to the standards drug Sildenafil citrate with regards to all the tested parameters. It could be concluded that PGRg3 extract produced a significant and sustained increase in the sexual activity of normal male rats without any conspicuous gastric ulceration and adverse effects. The most important conclusion is that the resultant aphrodisiac effectively of PGRg3 extract lends support to the claims for its traditional usage in sexual disorders.

Full text

Aphrodisiac effects of Panax ginseng extract standardized with
ginsenoside Rg3 in male rats
Mosaad A. Abdel-Wahhab *
Food Toxicology & Contaminants Dept., National Research center, Dokki, Cairo, Egypt.
Olivier Joubert
Faculty of Pharmacy, Lorraine University, EA 3452 CITHEFOR, Nancy Cedex, 54001, France.
Aziza A. El-Nekeety
Food Toxicology & Contaminants Dept., National Research center, Dokki, Cairo, Egypt.
Myung H. Park
Ambo Institute, Seoul, South Korea.
Won J. Yoon
Lotte R & D Center, Lotte Group, Seoul, 150-964, South Korea.
Yong T. Kim
Lotte R & D Center, Lotte Group, Seoul, 150-964, South Korea.
Bertrand H. Rihn
Faculty of Pharmacy, Lorraine University, EA 3452 CITHEFOR, Nancy Cedex, 54001, France.
*Corresponding author: mosaad_abdelwahhab@yahoo.com
Keywords Abstract
Panax ginseng
Sildenafil citrate
Sex behavior
Sexual disorders
In traditional medicine, Panax ginseng has been used to treat various behavioral effects. However, a little is
known about the effect of ginsenoside Rg3, the most ingredients in panax ginseng, on male copulatory and
sexual behavior. The aim of the current study was to investigate the effect of panax ginseng extract
standardized with ginsenoside Rg3 (PGRg3) on general mating behaviour, libido, potency and the adverse
effects in normal male Sprague-Dawley rats. Four tests were carried out to evaluate different sexual
parameters. Male rats were divided into different groups in each test and treated with different doses of
PGRg3 (50, 250 and 500 mg/kg b.w.) and Sildenafil citrate (5 mg/kg b.w). Female rats with oestrus phase
were used to analyze the mating behavior.The results indicated that PGRg3 significantly increased mounting
frequency, intromission frequency, ejaculatory latency in the first and second series, erection, quick flips,
long flips and aggregate of penile reflexes. Whereas, it significantly decreases mounting latency,
intromission latency and post ejaculatory intervals in dose dependent manner. Moreover, PGRg3 was found
to be devoid of any conspicuous gastric ulceration and any other adverse effects. PGRg3 extract at the
higher dose (500 mg/kg b.w.) was comparable to the standards drug Sildenafil citrate with regards to all the
tested parameters. It could be concluded that PGRg3 extract produced a significant and sustained increase in
the sexual activity of normal male rats without any conspicuous gastric ulceration and adverse effects. The
most important conclusion is that the resultant aphrodisiac effectively of PGRg3 extract lends support to the
claims for its traditional usage in sexual disorders.
1. Introduction
Sexual dysfunction and/or erectile dysfunction (ED) are major challenges for an individual’s subjective well-being. It is a common problem with
increase in prevalence and etiological factors, including degenerative diseases, increase in injuries and stress associated with industrialized
lifestyles [1]. Clinically, ED is defined as the persistent inability to achieve or maintain a penile erection sufficient for satisfactory sexual
performance [2] and it is a medical problem affecting young as well as old men. The incidence of ED increases with age, reaching 20-40% in
men 60-69 yr of age and 50-100% in men in their 70s and 80s, depending on the differing definitions of ED in various studies [3]. Beyond the
aging process, other cardiovascular (CV) risk factors such as hypertension, diabetes, smoking, obesity, and dyslipidemia have been shown to be
significantly associated with ED [4][5].
Although a number of treatments became available in the last two decades, problems with costs, efficacy, safety and ease to administer were
experienced [6]. These treatments ranged from herbal remedies used by native healers, mostly in the Eastern countries, to the more sophisticated
designer drugs, which are based on a better understanding of the physiological mechanism of erection [2]. Dietary supplement use has
experienced tremendous growth in the past years [7]. Supplements are becoming more important and more commonly used by consumers in
their personal healthcare regimens [8] [9]. Numerous products are currently promoted for enhancing erectile function and sexual performance in
men and are marketed with the implied assumption that they are safe and natural. Yet reports of adulteration for products in this category
abound. Adulterants found in dietary supplements include, but aren’t limited to, active pharmaceutical ingredients such as the PDE-5 inhibitors
sildenafil (Viagra®), vardenafil (Levitra®), tadalafil (Cialis®) and, in an attempt to avoid detection, the unapproved analogues of these drugs
[10][11][12][13][14][[15][16].
In recent years, several studies report the benefits of functional food and herbal ingredients such as Panax ginseng C.A. Meyer in the treatment
of ED [17] [18]. For 2,000 years Panax ginseng has had a rich medicinal history [19]. Practitioners of Chinese medicine use it as a tonic and
restorative to promote health and longevity [20]. It has been prescribed to improve stamina, concentration, stress resistance, and work efficiency
General Health and Medical Sciences, Vol(1), No (1), October, 2014. pp. 3-8
TI Journals
General Health and Medical Sciences
www.tijournals.com
ISSN:
xxxx-xxxx
Copyright © 2014. All rights reserved for TI Journals.
2409-9856

in the healthy as well as to improve well-being in patients with degenerative conditions associated with old age and chronic disease [21]. The
tonic and adaptogenic activity of Panax ginseng is thought to enhance physical performance, which includes sexual stamina. The aim of the
present study was to investigate the aphrodisiac effect of Phoenix Ginseng extract standardized with ginsenoside Rg3 in detail compared with the
standard drug Sildenafil citrate (Viagra), using multiple parameters along with its probable gastric ulceration and adverse effects in sexually
normal male Sprague-Dawley rats.
2. Materials and Methods
2.1. Plant material
The standardized Panax ginseng extract EFLA400 (Batch No. 303298) of Panax ginseng C. A. Mayer was prepared according to the published
procedure (Korean patent 0425022, PCT/KR2003/000003) and was supplied from Lotte Group R & D Centre (Seoul, Korea).
2.2. Chemicals
Sildenafil citrate (Viagra) was purchased from Pfizer Inc. (Cairo, Egypt), ethinyl oestradiol, progesterone and xylocane ointment (5%) were
purchased Sigma Chemical Co. (St. Louis, USA).
2.3. Animals
Twelve weeks old male (350-400 g) and female Sprague-Dawley rats (225-275 g) were purchased from Animal House Colony, NRC, Giza,
Egypt. Animals were housed singly in separate standard cages and were maintained under standard laboratory conditions (temperature 24-28°C,
relative humidity 60-70%, 12 h light-dark cycle) with free access to standard lab diet (Protein: 16.04%; Fat: 3.63%; Fiber: 4.1%, and metabolic
energy: 0.012 MJ) and water ad libitum throughout the study except during the experiment. The study design was approved by the ethical
committee for animal care and use of the National Research Center, Dokki, Cairo, Egypt.
2.4. Drug and PGRg3 preparation
PGRg3, Sildenafil citrate and ethinyl oestradiol were suspended in distilled water using Tween 80 (1%) and were administrated orally.
Progesterone was dissolved in olive oil for subcutaneous injection. All the drug solutions were prepared just before the administration.
2.5. Mating behavior test
The test was carried out according to the methods described by Dewsbury and Davis [22] and Szechtman et al. [23] as modified by Amin et al.
[24. Fifty healthy and sexually experienced male Sprague-Dawley rats that were showing brisk sexual activity were selected for the study.
Animals were divided into 5 groups (10 rats/group) and kept singly in separate cages during the experiment. Group (1); received 10 ml/kg
distilled water and represented the control group. Groups (2-4); received oral daily doses of PGRg3 (100, 250 and 500 mg/kg b.w, respectively)
for 7 days at 18:00 h. Group (5); served as standard and was given orally suspension of sildenafil citrate (5 mg/kg b.w), 1 h prior to the
commencement of the experiment. Since the male animals should not be tested in unfamiliar circumstances, the animals were bring to the
laboratory and exposed to dim light (in 1 w fluorescent tube in a laboratory of 14' × 14') at the stipulated time of testing daily for 6 days before
the experiment. The female animals were artificially brought into oestrus (heat) by orally administration of ethinyl oestradiol suspension (100
µg/animal) 48 h prior to the pairing plus progesterone injected subcutaneously (1 mg/animal) 6 h before the experiment [23]. The receptivity of
the female animals was confirmed before the test by exposing them to male animals, other than the control, test and standard animals. The most
receptive females were selected for the study. The experiment was carried out on the 7th day after commencement of the treatment of the male
animals at 20:00 h in the same laboratory and under the light of same intensity. One receptive female was introduced into each cages of one
male. The observation for mating behaviour was immediately commence and continue for first 2 mating series.
The test was terminated if the male failed to evince sexual interest. If the female did not show receptivity she was replaced by another artificially
warmed female. The occurrence of events and phases of mating were recorded on audio-cassette as soon as they appeared. Their disappearance
was also recorded. Later, the frequencies and phases was determined from cassette transcriptions: number of mounts before ejaculation or
mounting frequency (MF), number of intromission before ejaculation or intromission frequency (IF), time from the introduction of female into
the cage of the male up to the first mount or mounting latency (ML), time from the introduction of the female up to the first intromission by the
male or intromission latency (IL), time from the first intromission of a series up to the ejaculation or ejaculatory latency (EL), and time from the
first ejaculation up to the next intromission by the same male or post ejaculatory interval (PEI). However, in the second mating series only the
EL was recorded.
2.6. Libido test
This test was carried out by the method described by Amin et al. [24]. Another fifty sexually experienced male rats were divided into 5 groups
(10 rata/group) and were kept singly in separate cages during the experiment. Group (1); represented the control group and received oral dose of
distilled water (10 ml/kg b.w). Groups (2-4); received oral doses of PGRg3 suspension (100, 250 and 500 mg/kg b.w, respectively) once a day in
the evening (18:00 h) for 7 days. Group (5); was served as standard and given oral dose of sildenafil citrate (5 mg/kg b.w) 1 h prior to the
commencement of the experiment. The female rats were made receptive by hormonal treatment and all the animals were accustom to the testing
condition as previously mentioned in the mating behavior test. The animals were observed for the mounting frequency (MF) on the evening of
day seven at 20:00 h. The penis was exposed by retracting the sheath and 5% xylocaine ointment was applied 30, 15 and 5 min before starting
observations. Each male animal was placed individually with the receptive female in the same cage. The number of mountings was noted and the
animals were observed for intromission and ejaculation.
2.7. Potency test
The potency test was carried out according to the methods described previously [24]. Another fifty male rats were divided into 5 groups (10
rats/group) and were kept singly in separate cages during the experiment. Group (1); the control group, received oral dose of distilled water (10
ml/kg b.w). Groups (2-4); received daily oral dose of PGRg3 (100, 250 and 500 mg/kg b.w respectively) for 7 days. Group (5); received oral
dose of sildenafil citrate (5 mg/kg b.w.) 1 h before the commencement of the experiment. On the 8th day, the test for penile reflexes was carried
out by placing the animal on its back in a glass cylinder partial restraint. The preputial sheath was push behind the glans by means of thumb and
index finger and held in this manner for a period of 15 min. Such stimulation elicits a cluster of genital reflexes. The following components were
recorded: Erections (E), Quick Flips (QF) and Long Flips (LF).
4 Mosaad A. A. Abdel-Wahhab *, Olivier Joubert, Aziza A. El-Nekeety , Myung H. Park, Won J. Yoon, Yong T. Kim, Bertrand H. Rihn
General Health and Medical Sciences Vol(1), No (1), October, 2014.

2.8. Ulcerogenecity test
Another Forty male animals (350-400 g) were divided into 4 groups 10 rats/group) including the control group (received 10 ml/kg b.w of
distilled water), the groups treated daily for 7 days with oral doses of PGRg3 (100, 250 and 500 mg/kg b.w. respectively). At the 8th day, all the
animals were killed and the stomach was incised along the greater curvature and washed carefully with physiological saline and examined for
any gastric lesions immediately using a magnifying glass. The number of erosions per stomach were assessed for severity by two observers, who
were followed the same evaluation criteria, according to the score of Cioli et al. [25]: (0) absence of lesion, vasodilation or up to 3 pin point
ulcers; (1) more than 3 pin point ulcers, (2) from 1 to 5 small ulcers (< 2 mm); (3) more than 5 small ulcers (< 2 mm) and (4) 1 or more giant
ulcers.
2.9. Adverse effects
All treated rats were observed at least once daily for any overt sign of toxicity (salivation, rhinorrhoea, lachrymation, ptosis, writhing,
convulsions and tremors), stress (erection of fur and exophalmia) and changes in behaviour (such as spontaneous movement in the cage,
climbing, cleaning of face). In addition, food and water intake were noted.
2.10. Statistical analysis
All data were statistically analyzed using the General Linear Models Procedure of the Statistical Analysis System [26]. The significance of the
differences among treatment groups was determined by Waller-Duncan k-ratio [27] . All statements of significance were based on probability of
P < 0.01.
3. Results
3.1. Mating behavior test
The current results (Table 1) indicated that PGRg3 at the three tested doses increased significantly the mounting frequency (MF), intermission
frequency (IF), ejaculatory latency in the first series (EL1) and ejaculatory latency in the second series (EL2) in a dose dependent manner
compared with the control animals. Whereas; the extract at the same doses decreased significantly the mounting latency, intromission latency
and post ejaculatory interval. The same data clearly indicated that administration of the standard drug Sildenafil citrate at 5 mg/kg b.w resulted in
a significant increase in MF, IF, EL1 and EL2 accompanied by a significant decrease in ML, IL and PEI. It is of interest to mention that there is
no significant difference between PGRg3 at the higher dose (500 mg/kg b.w.) and the standard drug regarding all the tested parameters although
animals treated with PGRg3 at the higher dose showed an increase in the number of mount before ejaculation (MF) and the time from the first
ejaculation up to the next intromission than the standard drug. On the other hand, EL2 recorded the same values in the animals received PGRg3
at 500 mg/kg b.w. and those in the standard drug group. However, the other parameters showed insignificant decrease compared to the standard
drug.
3.2. Test for libido
The test for libido showed that administration of PGRg3 increased the mounting frequency (MF) at the three tested doses (Table 2). The extract
at 100 and 250 mg/kg b.w. significantly increased MF compared to the control group although there was a significant difference between these
groups and the group received the extract at the higher dose (500 mg/kg b.w.) and those received the standard drug sildenafil. On the other hand,
there was no significant difference in MF between the higher dose group (500 mg/kg b.w.) and the group received sildenafil. The number of
intromission before ejaculation or intromission frequency (IF) and ejaculation were found to be absent in the entire treatment group including the
standard drug group (Table 2).
3.3. Test for potency
The current results for potency test (Table 3) indicated that the three tested doses of PGRg3 and the standard drug significantly increased
erection (E), quick flips (QF), long flips as well as the aggregate of these penile reflexes (TPR) compared to the control group. Although there
was a significant difference in all the test for potency parameters between the groups treated with PGRg3 at 50 and 100 mg/kg b.w. and the
sildenafil group, the group received the higher dose of PGRg3 (500 mg/kg b.w) was comparable to the sildenafil group in all the tested
parameters.
3.4. Test for ulcerogenecity
The current study revealed that treatment with PGRg3 for 7 days at the three tested doses did not result in any ulceration in gastric mucosa of
male Sprague-Dawley rats (Fig. 1). Moreover, there were neither treatment related defects nor overt clinical signs of toxicity (salivation,
rhinorrhoea, lachrymation, ptosis, writhing, convulsions and tremors), stress (erection of fur and exophalmia) and changes in behaviour (such as
spontaneous movement in the cage, climbing, cleaning of face) and appearance evident. The food and water intake of all groups of rats treated
with the three tested doses of PGRg3 and the standard drug remained similar to those of the control group.
Table 1: Effect of PGRg3 mating behavior in male rats
Parameter control PGRg3
(100 mg) PGRg3
(250 mg) PGRg3
(500 mg) Sildenafil
citrate*
Mounting Frequency (MF) 12.5 ± 0.43a 15.3 ± 0.5b 18.3 ± 0.76c 37.7 ± 1.23d 37.5 ± 1.4d
Intromission Frequency (IF) 11.3 ± 1.05a 14.3 ± 0.7b 18.3 ± 1.1c 26.5 ± 0.7d 26.8 ± 0.6d
Mounting Latency (ML, sec) 22.3 ± 0.8a 18.8 ± 0.6b 15.5 ± 0.8c 10.5 ± 0.4c 10.17 ± 0.48c
Intromission Latency (IL, sec) 46.17 ± 1.8a 42.3 ± 2.14b 39 ±1.65c 34.8 ± 1.01d 37.33 ± 1.45e
Ejaculatory Latency in first series (EL 1, sec) 68 ± 1.67a 74.16 ± 2.18b 84 ± 2.62c 117 ± 3.37d 119 ± 3.25d
Ejaculatory Latency in second series (EL 2 , sec) 90 ± 2.65a 110.8 ± 3.86b 134.3 ± 2.25c 148.5 ± 2.4d 148.5 ± 2.2d
Post Ejaculatory Interval (PEI, sec) 519.7 ± 16.4a 444.5 ± 10.6b 405.7 ± 11.1c 299.7 ± 3.6d 295.5 ± 7.02d
*Sildenafil citrate was used at 5 mg/kg b.w
Within each raw, means superscript with different letters are significantly different (P≤ 0.01).
5Aphrodisiac effects of Panax ginseng extract standardized with ginsenoside Rg3 in male rats
General Health and Medical Sciences Vol(1), No (1), October, 2014.

Table 2: Effect of PGRg3 on Mounting Frequency (test for libido) in male rats
Groups Mounting Frequency (MF) Intromission Frequency (IF) Ejaculation (EJ)
control 16.8 ± 1.5a Nil Absent
PGRg3 (100 mg) 25.5 ± 1.4b Nil Absent
PGRg3 (250 mg) 38.5 ± 1.1c Nil Absent
PGRg3 (500 mg) 56 ± 3.2d Nil Absent
Sildenafil citrate* 56.5 ± 2.6d Nil Absent
*Sildenafil citrate was used at 5 mg/kg b.w
Means superscript with different letters are significantly different (P≤ 0.01).
Table 3: Effect of PGRg3 on Penile reflexes (test for potency)
Groups Erections (E) Quick Flips (QF) Long Flips (LF) Total Penile Reflexes (TPR)
Control 7.17 ± 0.5a 5.5 ± 0.43a 2.3 ± 0.42a 15.5 ± 0.43a
PGRg3 (100 mg) 10.17 ± 0.5b 7 ± 0.37b 4.2 ± 0.5b 16.8 ± 0.54a
PGRg3 (250 mg) 15 ± 0.9c 8.5 ± 0.67c 8.8 ± 0.47c 18.5 ± 0.43b
PGRg3 (500 mg) 28.17 ± 1.14d 10 ± 0.51d 29.3 ± 1.12d 29.3 ± 1.12c
Sildenafil citrate* 29.5± 1.18d 10 ± 0.58d 31.16 ± 1.08d 31.16 ± 1.08c
*Sildenafil citrate was used at 5 mg/kg b.w
Within each column, means superscript with different letters are significantly different (P≤ 0.01).
Fig. 1: Photograph of gastric mucosa of male Sprague-Dawley showing that
no ulceration was found in any of PGRg3-treated rats at the three tested doses.
4. Discussion
Ginseng, the root of Panax ginseng C.A. Meyer, is a traditional folk medicine that is reported to have many beneficial effects. In Asian
countries, ginseng has been used by both patients and healthy individuals to restore and enhance vital energy [28]. Several studies and clinical
trials have investigated the pharmaceutical effects, efficacies, and active components of ginseng [29]. In addition, studies have proposed that
ginseng reduces physical, chemical, and biological stress, while increasing general vitality and immune function, including physical and mental
capacity [30][31]. The chemical constituents of ginseng have been identified and approximately 40 active ingredients, including ginsenosides,
polyacetylenes, sesquiterpenes, polysaccharides, and peptidoglycans, have been isolated [32]. Ginsenosides are well characterized and known to
have a four-ring steroid-like structure with sugar moieties attached and exert their diverse effects in central and peripheral nervous systems [33].
Within the ginsenoside fraction of ginseng, particular attention was focused on ginsenoside Rg3, as it had been ascribed potent vasodilator
properties in animal models and is thought to be a significant contributor to ginseng-mediated vasoactivity [34][35]. Jang et al. [36] evaluated
the evidence regarding the effectiveness of red ginseng for treating ED and suggested a significant effect of red ginseng for the treatment of ED.
In the current study, we evaluated the effect of panax ginseng extract standardized with ginsenoside Rg3 (PGRg3) on general mating behaviour,
libido, potency and the adverse effects in normal male Sprague-Dawley rats. The results indicated that PGRg3 possesses a significant sexual
function enhancing activity as observed in sexual behaviour tests. PGRg3 significantly increased MF, IF, EL1 and EL2 accompanied with a
significant reduction in ML and IL which indicated a sexual function improving effect and proved that PGRg3 is endowed with sexual function
improving activity. This is in consonance with our earlier results which showed a sexual function improving effect of PGRg3 in male mice
[37][38]. Although the established drug (Sildenafil citrate) exhibited, as expected, tremendous activity. The increase of MF and IF in PGRg3-
treated rats (indicating the sexual motivation and efficiency of erection and penile orientation) and increasing of the libido might be the result of
increase in the several hormones that are secreted from pituitary [39].
On the other hand, PGRg3 significantly increased the frequency of all the components of penile reflexes (E, QF and LF) in the tested animals as
compared to control group but comparatively lesser than the standard drug. The aggregate of penile reflexes was also found to be increased in
the animals treated with PGRg3 and sildenafil citrate however, there was no significant difference between the groups received the extract at the
low dose (100 mg/kg b.w.) and those in the control group. Therefore, the current results revealed that PGRg3 produced a marked increase in
potency at the doses as low as 250 mg/kg b.w. It was suggested that PGRg3-induced changes in neurotransmitter levels or their action at cellular
levels [40] could change sexual behaviour [41]. Hence, the increased sexual function could be also due to the nervous stimulant action of PGRg3
6 Mosaad A. A. Abdel-Wahhab *, Olivier Joubert, Aziza A. El-Nekeety , Myung H. Park, Won J. Yoon, Yong T. Kim, Bertrand H. Rihn
General Health and Medical Sciences Vol(1), No (1), October, 2014.

[31][42]. On the other hand, several reports revealed that ginsenosides inhibit voltage-gated Ca2+ channels in the dorsal root ganglion
nociceptive neurons and adrenal chromaffin cells [43] and also inhibit brain voltage-gated Na+ channels [43][44][45]. Moreover, the resultant
aphrodisiac affectivity of PGRg3 extract might also be increasing the release of nitric oxide [46][47] although there is also a possible impact on
the hypothalamus-pituitary-adrenal (HPA) axis with a corresponding impact on cortisteroid and prolactin levels.
In a previous work, we reported that PGRg3 administration increased testosterone secretion [38]. The increase in the levels of testosterone in
adult males resulted in a moderate but significant increase in sexual desire and libido [48] which may be responsible for the enhanced sexual
behaviour in the animals [49] and probably raise the level of luteinizing hormones (LH) [41][50][51]. The prolonged of ejaculatory latency in the
PGRg3-treated rats indicating an increase of ejaculatory threshold [51]. Moreover, the steroidal saponins such as PGRg3 increase LH and FSH
levels that in turn increase testosterone. These hormones are found at high concentrations in rat testis and seminal fluids [39]. Testosterone also
enhances sexual desire, index of libido, motivation and sexual performance.
Different herbs are reported to produce an increase in gastric acid secretion by a cholinergic mechanism [52], thus, their use for sexual
invigoration may cause gastric ulceration and other adverse effects. Therefore, ulcerogenic and other adverse effects of PGRg3 were also
evaluated. The results of this evaluation were negative. This suggests that the short term use of PGRg3 for this purpose is apparently safe.
5. Conclusion
The results indicated that the traditional folk medicine, panax ginseng via its higher content of PGRg3 can produced a significant and sustained
increase in the sexual activity of normal male rats, without any conspicuous gastric ulceration and adverse effects. Thus, the resultant
aphrodisiac effectivity of the extract lends support to the claims for its traditional usage in sexual disorders. The mechanism by which PGRg3
may induce its action may be hormonal and/or nervous stimulant.
Acknowledgments
This work was full supported by Lotte R & D Center, Lotte Group, Seoul, 150-964, South Korea.
References
[1] Suresh S, Prithiviraj E, Prakash S Dose- and time-dependent effects of ethanolic extract of Mucuna pruriens Linn. seed on sexual behaviour of normal
male rats. J Ethnopharmacol 2009; (122): 497-501.
[2] Guirguis WR Oral treatment of erectile dysfunction: from herbal remedies to designer drugs. J Sex Marital Ther 1998; (24): 69-73.
[3] Lewis RW, Fugl-Meyer KS, Corona G, Hayes RD, Laumann EO, Moreira ED, Rellini AH, Segraves T Definitions/epidemiology/risk factors for sexual
dysfunction. J Sex Med 2010; (7): 1598-1607.
[4] Feldman HA, Johannes CB, Derby CA, Kleinman KP, Mohr BA, Araujo AB, McKinlay JB Erectile dysfunction and coronary risk factors: prospective
results from the Massachusetts male aging study. Prev Med 2000; (30): 328-338.
[5] Fung MM, Bettencourt R, Barrett-Connor E Heart disease risk factors predict erectile dysfunction 25 years later: the Rancho Bernardo Study. J Am Coll
Cardiol 2004; (43): 1405-1411.
[6] Rakuambo NC, Meyer JJM, Hussein A, Huyser C, Mdlalose SP, Raidani TG In vitro effect of medicinal plants used to treat erectile dysfunction on
smooth muscle relaxation and human sperm. J Ethnopharmacol 2006; (105): 84-88.
[7] Noonan C, Noonan PW Marketing dietary supplements in the United States: a review of the requirements for new dietary ingredients. Toxicology 2006; (
221): 4-8.
[8] Timbo BB, Ross MP, McCarthy PV, Lin CT Dietary supplements in a national survey: Prevalence of use and reports of adverse events. J Am Diet Assoc
2006; 106(12): 1966-1974.
[9] Marinac JS, Buchinger CL, Godfrey LA, Wooten JM, Sun C, Willsie SK Herbal products and dietary supplements: a survey of use, attitudes, and
knowledge among older adults. J Am Osteopath Assoc 2007; 107(1): 13-20.
[10] United States Food and Drug Administration, 2007a. FDA Requests Recall of ‘True Man Sexual Energy,’ ‘Energy Max’ Dietary Supplements. Available
from: <http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm109020.htm> (accessed 16.07.09).
[11] United States Food and Drug Administration, 2007b. FDA Warns Consumers Not to Use Super Shangai, Strong Testis, Shangai Ultra, Shangai Ultra X,
Lady Shangai, and Shangai Regular (also known as Shangai Chaojimengnan). Available from:
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm109049.htm. Accessed July 16, 2009.
[12] United States Food and Drug Administration, 2007c. Final Rule for Current Good Manufacturing Practices (CGMPs) for Dietary Supplements. Available
from: http://edocket.access.gpo.gov/2007/07-3039.htm. Accessed July 30, 2008.
[13] United States Food and Drug Administration, 2009a. Safety Alerts for Human Medical Products: Libipower Plus. Available from: http://www.fda.gov/
Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm171914.htm. Accessed July 16, 2009.
[14] United States Food and Drug Administration, 2009b. Safety Alerts for Human Medical Products: Stamina-Rx. Available from:
http://www.fda.gov/Safety/MedWatch/ SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm168017.htm. Accessed July 16, 2009.
[15] Reepmeyer JC, Woodruff JT, d'Avignon DA Structure elucidation of a novel analogue of sildenafil detected as an adulterant in an herbal dietary
supplement. J Pharm Biomed Anal 2007; 43(5): 1615-1621.
[16] Gratz SR, Flurer CL, Wolnik KA Analysis of undeclared synthetic phosphodiesterase-5 inhibitors in dietary supplements and herbal matrices by LC-ESI-
MS and LC-UV. J Pharm Biomed Anal 2004; 36(3): 525-533.
[17] Ho CC, Tan HM Rise of herbal and traditional medicine in erectile dysfunction management. Curr Urol Rep 2011; (12): 470-478.
[18] Ernst E, Posadzki P, Lee MS Complementary and alternative medicine (CAM) for sexual dysfunction and erectile dysfunction in older men and women:
an overview of systematic reviews. Maturitas 2011; (70): 37-41.
[19] Shergis JL, Zhang AL, Zhou W, Xue CC Panax ginseng in randomised controlled trials: a systematic review. Phytother Res 2013; (27): 949-965.
[20] MacKay DND Nutrients and botanicals for erectile dysfunction: Examining the evidence. Altern Med Rev 2004; 9(1): 1-16.
[21] Nocerino E, Amato M, Izzo AA The aphrodisiac and adaptogenic properties of ginseng. Fitoterapia 2000; (71): S1-S5.
[22] Dewsbury DA, Davis HN Jr Effect of reserpine on the copulatory behavior of male rats. Physiol Behav 1970; (5): 1331-1333.
[23] Szechtman H, Moshe H, Rabi S Sexual behaviour Pain sensitivity and stimulates endogenous opioid in male rats. Eur J Pharmacol 1981; (70): 279-285.
[24] Amin KMY, Khan MN, Rahman SZ, Khan NA Sexual function improving effect of Mucuna pruriens in sexually normal male rats. Fitoterapia 1996; (67):
53-58.
[25] Cioli V, Silvestrini B, Dordoni, F Evaluation of potential of gastric ulceration after administration of certain drugs. Exp Mol Pathol 1967; (6): 68-75.
[26] SAS Institute SAS User’s Guide: Statistics. SAS Institute Inc., Cary, NC; 1982.
[27] Waller RA, Duncan DB A Bayes rule for the symmetric multiple comparison problems. J Am Static Assoc 1969; (64): 1484-1503.
[28] Chong SK, Oberholzer VG Ginseng: is there a use in clinical medicine? Postgrad Med J 1988; (64): 841-846.
[29] Kiefer D, Pantuso T Panax ginseng. Am Fam Physician 2003; (68): 1539-1542.
7Aphrodisiac effects of Panax ginseng extract standardized with ginsenoside Rg3 in male rats
General Health and Medical Sciences Vol(1), No (1), October, 2014.

[30] Kaneko H, Nakanishi K 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. J Pharmacol Sci 2004; (95): 158-162.
[31] Coleman CI, Hebert JH, Reddy P The effects of Panax ginseng on quality of life. J Clin Pharm Ther 2003; 28(1): 5-15.
[32] Angelova N, Kong HW, van der Heijden R, Yang SY, Choi YH, Kim HK, Wang M, Hankemeier T, van der Greef J, Xu G, Verpoorte R Recent
methodology in the phytochemical analysis of ginseng. Phytochem Anal 2008; (19): 2-16.
[33] Nah SY, Kim DH, Rhim H Ginsenosides: are any of them candidates for drugs acting on the central nervous system? CNS Drug Reviews 2007; (13): 381-
404.
[34] Kim ND, Kang SY, Park JH, Schini-Kerth VB. Ginsenoside Rg3 mediates endothelium-dependent relaxation in response to ginsenosides in rat aorta: role
of K channels. Eur J Pharmacol 1999; 367(1): 41-49.
[35] Kim ND, Kim EM, Kang KW, Cho MK, Choi SY, Kim SG Ginsenoside Rg3 inhibits phenylephrineinduced vascular contraction through induction of
nitric oxide synthase. Br J Pharmacol 2003; 140(4): 661-670.
[36] Jang DJ, Lee MS, Shin BC, Lee YC, Ernst E Red ginseng for treating erectile dysfunction: a systematic review. Br J Clin Pharmacol 2008; 66(4):444-
450.
[37] Abdel-Wahhab MA, El-Nekeety AA, Aly SE, Yoon WJ, Kim YT, Park MH Improvement of sexual behavior in male rats via dietary supplementation
with Panax ginseng extract standardized with ginsenoside Rg3. J Med Sci 2013; 13(5): 337-345.
[38] Abdel-Wahhab MA, El-Kady AA, Joubert O, El-Nekeety AA, Kim YT, Yoon WJ, Park MH, Rihn BH Pharmacological effect of panax ginseng extract
standardized with ginsenoside Rg3 on mating behavior of male rats treated with dopamine antagonists. Br J Pharm Res 2014; 4(19): 1228-1241.
[39] Abedi A, Parviz M, Karimian SM, Rodsari HR. The Effect of aqueous extract of Phoenix Dactylifera Pollen Grain on sexual behavior of male rats. J
Physiol Pharmacol Adv 2012; 2(6): 235-242.
[40] Mannaa FA, Abdel-Wahhab MA, Ahmed HH, Park MH Protective role of Panax ginseng extract standardized with ginsenoside Rg3 against acrylamide-
induced neurotoxicity in rats. J Appl Toxicol 2006; 26(3): 198-206.
[41] Suresh Kumar PK, Subramoniam A, Pushpangadan P Aphrodiasiac activity of Vanda tessellata (ROXB.) HOOK. EXDON. extract in male mice. Ind J
Pharmacol 2000; (32): 300-304.
[42] Ellis JM, Reddy P Effects of Panax ginseng on quality of life. Ann Pharmacother 2002; 36(3): 375-379.
[43] Lee JH, Jeong SM, Kim JH, Lee BH, Yoon IS, Lee JH, Choi SH, Lee SM, Park YS, Kim SS, Kim HC, Lee BY, Nah SY Effects of ginsenosides and their
metabolites on voltage-dependent Ca2+ channel subtypes. Mol Cell 2006; (21): 52-62.
[44] Kang DI, Lee J Y, Yang JY, Jeong SM, Lee JH, Nah SY, Kim Y Evidence that the tertiary structure of 20(S)-ginsenoside Rg3 with tight hydrophobic
packing near the chiral center is important for Na+ channel regulation. Biochem Biophys Res Commun 2005; (333): 1194-1201.
[45] Lee JH, Jeong SM, Kim JH, Lee BH, Yoon IS, Lee JH, Choi SH, Kim DH, Rhim H, Kim SS, Kim JI, Jang CG, Song JH, Nah SY Characteristics of
ginsenoside Rg3-mediated brain Na+ current inhibition. Mol Pharmacol 2005; (68): 1114-1126.
[46] Choi HK, Choi YD, Adaikan G, Jiang Y. Effectiveness of Korea red ginseng in erectile dysfunction-multi-national approach. J Ginseng Res 1999a; (23)
247-256.
[47] Choi YD, Rha KH, Choi HK In vitro and in vivo experimental effect of Korean red ginseng on erection. J Urol 1999b; 162 (4): 1058-10511.
[48] Giuliano F, Rampin O, Schiar A, Jardin A, Rousseau JP Autonomic control of penile erection: modulation by testosterone in the rat. J Neuroendocrinol
1993; (9): 141-150.
[49] Majewska MD, Bellino FL, Davies RA, Hornsby PJ, Lavrin DH, Nestler JE Neuronal activities of dehydroepiandrosterone, in dehydroepiandrosterone
(DHEA) and aging. Ann New York Acad Sci 1995; (774): 111-120.
[50] Yakubu MT, Akanji MA, Oladiji AT Aphrodisiac potentials of the aqueous extract of Fadogia agrestis (Schweinf Ex Hiern) stem in male albino rats.
Asian J Androl 2005; 7(4): 399-404.
[51] Yakubu MT, Akanji MA, Oladiji AT, Adesokan AA Androgenic potentials of aqueous extract of Massularia acuminata (G. Don) Bullock ex Hoyl. Stem
in male Wister rats. J Ethnopharmacol 2008; 118 (3): 508-513.
[52] Vasudevan K, Vembar S, Veeraraghavan K, Haranath PS Influence of intragastric perfusion of aqueous spice extracts on acid secretion in anaesthetized
albino rats. Indian Journal of Gastroenterology 2000; (19): 53-56.
8 Mosaad A. A. Abdel-Wahhab *, Olivier Joubert, Aziza A. El-Nekeety , Myung H. Park, Won J. Yoon, Yong T. Kim, Bertrand H. Rihn
General Health and Medical Sciences Vol(1), No (1), October, 2014.