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Improvement of Sexual Behavior in Male Rats via Dietary Supplementation with Panax ginseng Extract Standardized with Ginsenoside Rg3



Mosaad A. Abdel-Wahhab, Aziza A. El-Nekeety, Soher E. Aly, Won J. Yoon, Yong T. Kim and Myung H. Park
 
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ABSTRACT

Korean ginseng (Panax ginseng CA Meyer) is important traditional medicinal plants whose ginsenosides are generally accepted as serving to improve sexual functions, such as penile erection. The aim of the current study was to utilize panax ginseng extract standardized with ginsenoside Rg3 (PGRg3) to improve the sexual behavior in rats. Male rats were categorized on the basis of seven consecutive mating pre-tests as Sexually-Active (SA) and Sexually-Inactive (SI); and stretching-yawning, penile erection, sedation and stereotyped behavior of the same animals. The results indicated that PGRg3 at three tested doses (50, 150 and 450 mg kg-1 b.wt.) enhanced the copulatory pattern of both SI and SA rats, ejaculation mechanisms, increase the sexual drive of SI rats. The two groups of rats, exhibited different behavioral responses to PGRg3. Moreover, PGRg3 was effective in SA rats at dose as low as 50 mg kg-1 b.wt. however it was effective in SI rats at the higher doses (150 and 450 mg kg-1 b.wt.). It could be concluded that PGRg3 succeeded to enhance sexual behavior and has beneficial effects as traditional medicinal herbal plant in male with sexual dysfunction.

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Mosaad A. Abdel-Wahhab, Aziza A. El-Nekeety, Soher E. Aly, Won J. Yoon, Yong T. Kim and Myung H. Park, 2013. Improvement of Sexual Behavior in Male Rats via Dietary Supplementation with Panax ginseng Extract Standardized with Ginsenoside Rg3. Journal of Medical Sciences, 13: 337-345.

DOI: 10.3923/jms.2013.337.345

URL: https://scialert.net/abstract/?doi=jms.2013.337.345
 
Received: March 23, 2013; Accepted: April 29, 2013; Published: June 13, 2013



INTRODUCTION

The sexual dysfunction is a common disease and with an increasing incidence as a result of the longer lifespan, the increasing prevalence of degenerative diseases as well as the increase in injuries and stress associated with industrialized lifestyles. Both medical and surgical treatment modalities are available for treating sexual dysfunction. Inspite of the availability of conventional medical treatments, people are still seeking for alternative natural recourses derived from plants and herbs to improve their sexual life (Rowland and Tai, 2003). However, the efficiency of these agents in the treatments of sexual dysfunction in not clear.

In recent years, the use of dietary supplements has been increased dramatically (Ervin et al., 2004; Noonan and Noonan, 2006). Supplements are becoming more important and more commonly used by consumers in their personal healthcare regimens (Marinac et al., 2007; Timbo et al., 2006). 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 (APIs) 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 (FDA, 2007a-c, 2009; Reepmeyer et al., 2007). This practice is illegal and places consumers at risk for potentially serious side effects from these drugs such as abnormal vision, headaches, myalgia, dizziness, flushing and dyspepsia (Fink et al., 2002; Sunwoo et al., 2004). Of further concern is that these APIs may interact with prescription medications such as nitrates, erythromycin and protease inhibitors (Langtry and Markham, 1999). Interaction between PDE-5 inhibitors and nitrates, for example, can dangerously lower blood pressure. Patients treated with nitrates for medical conditions often concomitantly suffer from erectile dysfunction. Due to the potential for life-threatening drug interactions, these patients may turn to “natural” products as alternatives and unknowingly become exposed to pharmaceutical drugs (FDA, 2006).

Korean red ginseng is widely used in traditional medicine for the treatment of many disorders (Goldstein, 1975; Bahrke and Morgan, 1994). The root or root extract of P. ginseng has been demonstrated to induce vasodilation (Chen et al.,, 1984), inhibit platelet aggregation (Kimura et al., 1988; Teng et al., 1989), enhance learning and memory (Abe et al., 1994), produce anxiolytic effects (Bhattacharya and Mitra, 1991) and facilitate male rat copulatory behavior (Kim et al., 1976). Previous studies have investigated the physiological effects of ginsenoside saponins, the biologically active constituents of ginseng (Soldati and Sticher, 1980) and determined that specific ginsenosides can elicit significant effects on nitric oxide synthesis (Chen and Lee, 1995), acetylcholine induced catecholamine secretion (Tachikawa et al., 1995), maternal aggression (Yoshimura et al., 1988) and glycemic activity (Ng and Yeung, 1985). Although over 30 different ginsenosides have been identified overall (Soldati and Sticher, 1980; Tachikawa et al., 1995), the ginsenoside content between different strains of ginseng is vastly different (Bahrke and Morgan, 1994), suggesting that distinct ginseng strains may produce different physiological effects. The aim of the current study was to utilize Panax ginseng extract standardized with ginsenoside Rg3 (PGRG3) to improve the sexual behavior in active and inactive male rats.

MATERIALS AND METHODS

Chemicals and hormones: Ketamine, xylazine (Bayer, Cairo, Egypt) was freshly dissolved in saline at a concentration that allowed the administration of 1 mL kg-1, subcutaneously (s.c.) for the females. Estradiol benzoate and progesterone (Sigma Chemical Co., St. Louis, MO, U.S.A.) were dissolved in corn oil and both injected S.C. in a volume of 0.2 mL/ female rat.

Ginseng materials: The standarized Panax ginseng extract EFLA400 (Phoenix ginseng) (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 by Lotte Group R&D Center (Seoul, Korea). The content of ginsenoside Rg3 (PGRg3), a pharmacologically active ingredient of Phoenix ginseng, was 3.6 % (w/w) (Panwar et al.,, 2005) as determined by HPLC (i.e., 36 μg mg-1 P. ginseng extract). PGRG3 was dissolved just before treatment in a certain amount of saline to make 50, 150 and 450 mg mL-1 solutions. The solutions were sterilized by membrane filtration and administrated orally to the rats at a volume of 1 mL kg-1 b.wt.

Experimental animals: Three months old male and female Sprague-Dawley rats (140-150g.) were purchased from Animal House Colony, NRC, Giza, Egypt. The animals were maintained on standard lab diet (Protein: 16.04%; Fat: 3.63%; Fiber: 4.1% and metabolic energy: 0.012 MJ) and water ad libitum at the Animal House Lab., National Research Center. After an acclimation period of 2 weeks, animals were maintained on a 12-h light cycle; from 7 am to 7 p.m. The females were ovariectomized under intraperitoneally injection (i.p.) with ketamine plus xylazine anesthesia (120±2 mg kg-1 b.wt.) and were used as mating stimulus in the copulatory experiments. The experimental protocol was approved by National Research Center Review Committee for the use of human or animal Subjects.

Behavioral procedure: All the experiments were performed between 9 a.m. and 2 p.m. in a soundproof, air-conditioned room, where the animals were monitored by trained observers unaware of the experimental design. Sixty male rats were divided into four treatment groups and treated orally with only one dose day-1 of PGRg3 for a period of one month as follow: (1) the control group, (2) the group treated orally with PGRg3 at low dose (50 mg kg-1 b.wt), (3) the group treated orally with PGRg3 at medium dose (150 mg kg-1 b.wt.) and (4) the group treated orally with PGRg3 at high dose (450 mg kg-1 b.wt.).

Evaluation of male sexual behavior: Evaluation of male sexual behavior was carried out using the ovariectomized females which were brought into estrus by subcutaneously (s.c.) injection with 30 μg estradiol benzoate and after 48 h they were injected with 0.5 mg progesterone and were used 4-5 h thereafter. All females were screened with non-experimental sexually experienced males and only those exhibiting good sexual receptivity (solicitation behavior and lordosis in response to mounting) and no rejection behavior were used. The males were transferred singly to an observation cage (40x30x34 cm) and after a 3-min adaptation period, a receptive female were introduced. Male copulatory behavior was evaluated according to the method described by Dewsbury (1972) by calculating the (1) The time from the introduction of the female until the first mount and intromission [mount latency and intromission latency (ML and IL)], (2) The number of mounts and intromissions preceding ejaculation [mount and intromission frequency (MF and IF)], (3) The interval between the first intromission and ejaculation [ejaculation latency (EL)] and (4) The time between the first ejaculation and the next intromission [post-ejaculatory interval (PEI)]. After the PEI, the test was considered complete.

Tests were discontinued when IL or PEI was >15 min or EL was>30 min. Only those animals which were completed at least the last five or four mating tests out of the seven conducted at 4-day intervals were considered Sexually Active (SA) (n = 28). Whereas, those which never mounted or intromitted during the training tests were considered Sexually Inactive (SI) (n = 25). Animals which were displayed discontinuous activity were discarded (n = 7). In addition, the following parameters were evaluated in the 6 and 7th test: (1) Latency to the first contact (CL) as the time from the introduction of the female on the opposite side of the cage until the first voluntary contact by the male and (2) Total time spent in genital exploration by the male (GET), which were recorded from the introduction of the female until the first ejaculation or the end of the test in the event of its being discontinued.

Evaluation of sex penile erection (PE), sedation and stereotyped behavior (SB): Stretching-Yawning (SY) and PE episodes were counted up for each animal. Sedation and Stereotyped Behavior (SB) were scored as described by Ferrari and Giuliani (1993). In brief, every 5 min, starting immediately in the test period (30 min), each rat was observed for 30 sec sedation was graded: 0 = absent, 1 = immobility of the animal for at least 25 sec with open eyes, 2 = immobility of the animal for at least 25 sec with closed eyes. SB was graded: 0 = absent, 1 = low (intermittent or continuous sniffing), 2 = high (continuous sniffing and/or intermittent or continuous licking and biting). Sedation and SB values were represented for each rat by the sum of all the scores attributed to the animal during the test period.

Experimental protocol: After having verified the consistency of the SA rats copulatory behavior in the 6 and 7th tests, twenty four animals from the selected SA rats were divided into four groups (6 rats/ group; not statistically different for any of the parameters considered), which were orally received saline, PGRg3 at 50, 150 and 450 mg kg-1 b.wt. Another twenty four of the selected SI rats were randomly divided into four groups and were treated orally as previously described. SA and SI rats were transferred in groups of three homogeneous as regards treatment and sexual typology to the glass observation cages which they were accustomed singly. The tests (Experiment 1) were started immediately after the oral treatment with PGRg3 and were lasted 30 min. During this period, SY, PE, sedation and SB were evaluated for each rat. Immediately after the completion of the recording of the above behavioral parameters, the second experiment was started and the male rats were placed singly in other cages where their sexual behavior towards a receptive female, presented 3 min later, were observed.

Statistical analysis: All data were subjected to statistical analyses using the General Linear Models (GLM) Procedure of the Statistical Analysis System (SAS, 1982). The significance of the differences among treatment groups with variable means was determined by Waller-Duncan k-ratio T test (Waller and Duncan, 1969). All statements of significance were based on a probability level of p< 0.05.

RESULTS

Experiment 1: The effects of oral administration of PGRg3 (50, 150 and 450 mg kg-1) on SY, PE, sedation and SB are depicted in (Fig. 1, 2, 3 and 4), respectively. These results indicated that SY episodes of the control animals in SA and SI groups were sporadic during the test period and did not differ significantly. Treatment with PGRg3 at 50 mg kg-1 b.wt. stimulated SY in all rats however, no significant difference was observed between the two types of animal. On the other hand, at 150 or 450 mg kg-1 b.wt., PGRg3 showed to be effective in SA rats, whereas, SI animals received PGRg3 at 450 mg kg-1 showed a significant increase in SY compared to those of control SI (Fig. 1).

The current results also indicated that PE was similar in the control SA and SI animals (Fig. 2). However, stimulation of PE was apparent after PGRg3 treatment at all doses only for SI animals in dose dependent fashion (Fig. 2).

Fig. 1: Stretching-Yawning (SY) in SI and SA rats treated orally with PGRg3 extract (n)

Fig. 2: Penile Erection (PE) in SI and SA rats treated orally with PGRg3 extract (n)

On the other hand, both SA and SI rats displayed significant increased sedation after PGRg3 treatment (Fig. 3). The comparative analysis between SI and SA rat sedation observed in the control animals and after the oral administration of PGRg3 at the three tested doses showed that sedation was significantly different in the two types of animal. Moreover, the sedation was found to be increased in SI and SA rats in a dose dependent manner although this increase was pronounced in the SI than the SA animals. A similar degree of SB was also scored in SI and SA rats only after PGRg3 administration (Fig. 4).

Experiment 2: Data presented in Table 1 revealed that all SI rats scored a higher CL (185 ±75) compared to those values for SA rats (4.3±0.9) in the 7th test. On the other hand, in the 8th test, oral treatment with PGRg3 at the three tested doses (50, 150, 450 mg kg-1 b.wt.) resulted in significant decreases in both CL (175±62, 130±22, 90±12, respectively) and GET (50±2.1, 42±3.9, 30±0.9, respectively) for SI animals.

Fig. 3: Sedation in SI and SA rats treated orally with PGRg3 extract (score)

Fig. 4: Stereotyped Behavior (SB) in SI and SA rats treated orally with PGRg3 extract (score)

Table 1: Effect of oral treatment with different doses of PGRg3 on contact latency (CL) and genital exploration (GET) of sexually inactive (SI) and active (SA) male rats
Within each column, means superscript with different letters (a, b, c, d) are significantly different (p = 0.05), CL: Contact latency; GET: Genital exploration; SA: Sexual active; SI: Sexual inactive

Table 2: Effect of oral treatment with PGRg3 extract on copulatory behavior of sexually inactive (SI) rats
Within each column, means superscript with different letters (a, b, c, d) are significantly different (p = 0.05), ML: mount latency; IL: Intromission latency, MF: Mount frequency; IF: Intromission frequency; EL: Ejaculation latency; PEI: Post-ejaculatory interval

Table 3: Effect of oral treatment with PGRg3 extract on copulatory behavior of sexually active (SA) rats
Within each column, means superscript with different letters (a, b, c, d, e) are significantly different (p = 0.05), ML: Mount latency; IL: Intromission latency, MF: Mount frequency; IF: Intromission frequency, EL: Ejaculation latency; PEI: Post-ejaculatory interval

This decrease was pronounced in the animals received the higher doses of PGRg3 which indicated that the PGRg3 is effective on SI rats. In SA rats, these parameters were also affected by the treatment with PGRg3 at the three tested doses and the recorded CL values were 4.2±0.9, 3.±0.9 and 2.6±0.4 for 50, 150 and 450 mg kg-1 b.wt., respectively. However, the recorded GET values for the SA rats were 3.8±1.1, 2.1 ±0.2 and 1.6±0.7 for the three tested doses, respectively. It is clear from the data presented in Table 1 that CL and GET were significantly decreased by the treatment with PGRg3 in a dose dependent manner which also indicate that PGRg3 was also effective in SA rats although these effects were pronounced in SI rats than SA group.

Daa presented in Table 2 showed the effects of PGRg3 on copulatory behavior in SI rats and indicated that PGRg3 have a significant improvement in the copulatory behavior in SI rats. The results revealed that these parameters were decreased significantly in the three tested doses and the recorded values were 200±12, 170± 22 and 98 ±14, respectively for ML; 260±29, 195±18 and 123±16, respectively for IL; 450±32, 340±26 and 204±45, respectively for EL and 430±25, 340±32 and 201±39, respectively for PEI. Whereas, MF and IF were significantly increased in this group in the 8th test compared to the same parameters in the same SI rats in the 7th pre-test and the recorded values for MF in this test were 5±1.6, 8±1.8 and 15±3.4 for the three tested doses respectively. However, the recorded V of IF were 3±0.8, 5±1.5 and 11±2.5 for the tested doses, respectively. In the same concern, data presented in Table 3 showed that PGRg3 had a significant improvement on the various parameters regarding the copulatory behavior for SA rats in a dose dependent manner. The results also suggested that PGRg3 enhanced libido and copulatory performance as indicated by the increased of IL (60 ±9, 75±8 and 116±9), MF (26±6, 32±7 and 46±3), IF (16±1, 19±3 and 22±1) and EL (430±42, 440 ±20 and 460±38) with the significant decrease in ML (14±2, 10±2 and 8±4) and PEI (411±35, 405±22 and 317±28) for the three tested doses, respectively. Moreover, there were significant differences between the data collected in the 7th per-test and those collected in the 8th test for the same SA group of rats.

DISCUSSION

Ginseng is well known herb used for the treatment of sexual dysfunction. Several studies on laboratory animals have shown that ginseng enhance libido and copulatory performance. These effects of ginseng may not be due to changes in hormone secretion, but to the direct effects of ginseng, or its ginsenoside components, on the central nervous system and gonadal tissues (Kang et al., 2002; Tsai et al., 2003). Indeed, there is good evidence that ginsenosides can facilitate penile erection by directly inducing the vasodilatation and relaxation of penile corpus cavernosum (Hong et al., 2002). Moreover, the effects of ginseng on the corpus cavernosum appear to be mediated by the release and/or modification of release of nitric oxide from endothelial cells and perivascular nerves (Murphy and Lee, 2002). Treatment with ginseng extract also affects the central nervous system and has been shown to significantly alter the activity of hypothalamic catecholamines involved in the facilitation of copulatory behavior and hormone secretion. The findings that ginseng treatment decreased prolactin secretion also suggested a direct nitric oxide-mediated effect of ginseng at the level of the anterior pituitary (Kang et al., 2002). Thus, animal studies lend growing support for the use of ginseng in the treatment of sexual dysfunction and provide increasing evidence for a role of nitric oxide in the mechanism of ginsenoside action.

The present study demonstrated that PGRg3 exerts a sexual stimulation in both SI and SA rats which seems to involve ejaculation mechanisms and sex-arousal. It has already been shown that these independent aspects of sexual behavior are variously modulated by pharmacological agents (Beach, 1956). In the current study, all sexual parameters tested including CL, GET, which reflect interest towards the female (Ferrari and Giuliani, 1995) and certain measures of copulatory pattern (mount and intromission latencies, post ejaculatory interval), which resemble human ‘libido’, were significantly affected by the PGRg3 treatment.

The modulatory effect of PGRg3 on sexual drive was further confirmed in SI rats by the enhancement effects of the extract to stimulate copulatory behavior, to modify GET or to reduce CL. Moreover, CL was significantly decreased in these animals after PGRg3 treatment at the three tested doses although these effects were pronounced in the groups received the higher doses (i.e 450 mg kg-1 b.wt.), probably as a consequence of the anti-sedative effects exerted by PGRg3 at high doses.

A previous study showed that CL and GET are useful indicators of rat copulatory activity (Ferrari and Giuliani, 1995). But while it seems obvious that CL will be different in SA and SI rats, one would hardly expect a similarly low GET in the two types of rat. However, it has been demonstrated that, after repeated copulatory training tests, low GET reflects opposite situations in SI and SA rats, namely, sexual indifference in the former and high sexual drive culminating in copulation in the latter (Ferrari and Giuliani, 1995). The second significant finding which emerges from the current study was that the animals categorized as SA and SI on the basis of their sexual behavior were also markedly different in their behavioral response to the same doses of the PGRg3. In the SA rats, treatment with PGRg3 induced a moderate sedation that was significantly lower than that induced in SI rats. Moreover, PGRg3 stimulated PE and SY to a great extent. As regards SY, an impressive effect was seen in SI animals not only at the low dose but also at the high dose.

It is well documented that SY is stimulated by certain receptors including the dopamine receptors. If SY is evoked by a selective stimulation of a particular dopamine receptor subtype, namely the DA D2 autoreceptor (Ferrari, 1985) or alternatively the DA D3 receptor (Kostrzewa and Brus, 1991), it may be hypothesized that this kind of receptor is particularly sensitive in SI rats. Although, any interpretation regarding the underlying mechanisms is at present highly speculative, several possibilities can be proposed. The first possibility is that there are basic, a priori, behavioral and biochemical differences between the animals classified as SA and SI. The second possibility is that in SA rats the sensitivity of DA receptors is changed by repeated copulatory tests because of the release of DA into certain brain area during the copulation (Damsma et al.,, 1992).

The sexual-stimulant properties of PGRg3 are not surprising, as one of the major actions of the extract may be the block of the reuptake of dopamine (DA) and so increase its synaptic availability (Oh et al., 1997; Nah et al., 2009; Hwang and Jeong, 2010). The key role of DA in sexual behavior is well documented (Ferrari and Giuliani, 1995; Lee et al., 2008). Other mechanisms for the sexual properties enhancement of the PGRg3 may be involved the improvement of the testicular function and the increase of testosterone secretion as well as increase the sperm counts (Kim et al., 1999; Hassan et al., 2006; Qinna et al., 2009). In this regards, Hwang et al. (2004) reported that ginseng improves the survival rate and sperm quality in guinea pigs exposed to TCDD and stimulates the spermatogenesis (Yamamoto et al., 1977). This action may be attributed to the increase in LH secretion which acts directly on the pituitary gland (Tsai et al., 2003). Furthermore, the current study revealed that treatment with PGRg3 resulted in a significant decrease in mount and intromission latency (ML and IL). These results were in agreement with those reported by other investigators (Murphy et al., 1998). Similar to these findings, Hong et al. (2002) reported that erectile function scores were significantly higher in patients treated with Korean red ginseng than in those who received placebo. Moreover, Wang et al., (2010) proved that ginsenoside Rg1 from panax ginseng could be a promising new drug for erectile dysfunction and low libido.

Although, ginseng’s exact mechanism of action remains elusive, its physiological effects are thought to be due to the presence of tetracyclic triterpenoid saponins known as ginsenosides in the Panax species (Murphy and Lee, 2002). These ginsenosides appear to have an effect both on the neurotransmitters involved in sexual arousal and on the NO/cGMP pathways involved in erection (Park et al., 2006; Lin et al., 2007). Although there is also a possible impact on the Hypothalamus-Pituitary-Adrenal (HPA) axis with a corresponding impact on cortisteroid and prolactin levels (Kim et al., 1976).

The big question is does ginseng live up to its reputation as a male sexual tonic? From the obtained data, the answer appears to be a qualified yes, but dosage and length of administration appear to be important (Choi et al., 1995). In a sixteen week, double-blind study using three grams of ginseng per day versus a placebo in men suffering from erectile dysfunction, the ginseng treatment offered significant improvement in erectile quality over placebo (Hong et al., 2002). Another study also found a significant improvement over placebo only after several weeks of administration (Choi et al., 1999). The same study also found no changes in sexual response after acute, short-term ginseng administration. Moreover, Shamloul (2010) recommended ginseng as an effective aphrodisiac.

It would appear; therefore, that PGRg3 has the potential to be useful as a sexual enhancer in SA rats at dose as low as 50 mg kg-1 b.wt. However, in SI rats the dose should be increased to at least 150 mg kg-1 to induce a significant sexual enhancement. Similar to the current observations were reported by Ellis and Reddy (2002) and Coleman et al. (2003) however, they recommended a higher dose reached 1 g per day for a period of several weeks.

CONCLUSION

From the current study, we can conclude that PGRg3 succeeded to improve male sexual behavior in both active and inactive rats. Moreover, these results demonstrated that PGRg3 significantly facilitates male copulatory behavior and lend growing support for the use of PGRg3 extract as traditional medicinal in the treatment of male sexual dysfunction.

ACKNOWLEDGMENT

This work was full supported by Lotte R and D Center, Lotte Group, Seoul, 150-964, South Korea.

REFERENCES
Abe, K., S.I. Cho, I. Kitagawa, N. Nishiyama and H. Saito, 1994. Differential effects of ginsenoside Rb1 and malonylginsenoside Rb1 on longterm potentiation in the dentate gyrus of rats. Brain Res., 649: 7-11.
CrossRef  |  Direct Link  |  

Bahrke, M.S. and W.P. Morgan, 1994. Evaluation of the ergogenic properties of ginseng. Sports Med., 18: 229-248.
CrossRef  |  Direct Link  |  

Beach, F.A., 1956. Characteristics of Masculine Sex Drive. In: Nebraska Symposium on Motivation, Jones, M.R. (Ed.). University of Nebraska Press, Lincoln, Nebraska, pp: 1-32.

Bhattacharya, S.K. and S.K. Mitra, 1991. Anxiolytic activity of panax ginseng roots: An experimental study. J. Ethnopharmacol., 34: 87-92.
CrossRef  |  

Chen, X. and T.J.F. Lee, 1995. Ginsenosides-induced a nitric oxide-mediated relaxation of the rabbit corpus cavernosum. Br. J. Pharmacol., 115: 15-18.
CrossRef  |  Direct Link  |  

Chen, X., C.N. Gillis and R. Maolli, 1984. Vascular effects of ginsenosides In vitro. Br. J. Pharmacol., 82: 485-491.
Direct Link  |  

Choi, H.K., D.H. Seong and K.H. Rha, 1995. Clinical efficacy of Korean red ginseng for erectile dysfunction. Int. J. Impotence Res., 7: 181-186.
PubMed  |  Direct Link  |  

Choi, Y.D., K.H.O. Rha and H.K.I. Choi, 1999. In vitro and in vivo experimental effect of Korean red ginseng on erection. J. Urol., 162: 1508-1511.
CrossRef  |  Direct Link  |  

Coleman, C.I., J.H. Hebert and P. Reddy, 2003. Effects of Panax ginseng on quality of life. J. Clin. Pharm. Therap., 28: 5-15.
CrossRef  |  PubMed  |  Direct Link  |  

Damsma, G., J.G. Pfaus, D. Wenksten, A.G. Phillips and H.C. Fibiger, 1992. Sexual behavior increases dopamine transmission in the nucleus accumbens and striatum of male rats: Comparison with novelty and locomotion. Behav. Neurosci., 106: 181-191.
PubMed  |  Direct Link  |  

Dewsbury, D.A., 1972. Effects of tetrabenazine on the copulatory behaviour of male rats. Eur. J. Pharmacol., 17: 221-226.
CrossRef  |  Direct Link  |  

Ellis, J.M. and P. Reddy, 2002. Effects of Panax ginseng on quality of life. Ann. Pharmacotherapy, 36: 375-379.
PubMed  |  Direct Link  |  

Ervin, R.B., J.D. Wright and D. Reed-Gillette, 2004. Prevalence of leading types of dietary supplements used in the third national health and nutrition examination survey, 1988-94. Adv. Data, 349: 1-7.
PubMed  |  Direct Link  |  

FDA, 2006. FDA warns consumers about dangerous ingredients in dietary supplements promoted for sexual enhancement. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108690.htm.

FDA, 2007. FDA requests recall of true man sexual energy, energy max dietary supplements. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm109020.htm.

FDA, 2007. 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). http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm109049.htm.

FDA, 2007. Final rule for current good manufacturing practices (CGMPs) for dietary supplements. http://www.fda.gov/Food/GuidanceRegulation/CGMP/ucm079496.htm.

FDA, 2009. Safety alerts for human medical products: Stamina-Rx. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm168017.htm.

Ferrari, F. and D. Giuliani, 1993. Influence of idazoxan on the dopamine D2 receptor agonist-induced behavioural effects in rats. Eur. J. Pharmacol., 250: 51-57.
CrossRef  |  Direct Link  |  

Ferrari, F. and D. Giuliani, 1995. Sexual attraction and copulation in male rats: Effects of the dopamine agonist SND 919. Pharmacol. Biochem. Behav., 50: 29-34.
CrossRef  |  Direct Link  |  

Ferrari, F., 1985. Sexual excitement and stretching-yawning induced by B-HT 920. Pharmacol. Res. Comm., 17: 557-563.
PubMed  |  Direct Link  |  

Fink, H.A., R. Mac Donald, I.R. Rutks, D.B. Nelson and T.J. Wilt, 2002. Sildenafil for male erectile dysfunction: A systematic review and meta-analysis. Arch. Internal Med., 162: 1349-1360.
CrossRef  |  PubMed  |  Direct Link  |  

Goldstein, B., 1975. Ginseng: Its history, dispersion and folk tradition. Am. J. Chin. Med., 3: 223-234.
CrossRef  |  Direct Link  |  

Hassan, A.M., S. Abbes, M.H. Park, Y.T. Kim, W.J. Yoon and M.A. Abdel-Wahhab, 2006. Panax ginseng extract standardized with ginsenoside Rg3 counteracts the reproduction disturbance in male rats received Zearalenone mycotoxin. Proceedingsw of the 9th International Symposium on Ginseng, September 25-28, 2006, Geumsan, Korea -.

Hong, B., Y.H. Ji, J.H. Hong, K.I.Y. Nam and T.Y. Ahn, 2002. A double-blind crossover study evaluating the efficacy of korean red ginseng in patients with erectile dysfunction: A preliminary report. J. Urol., 168: 2070-2073.
CrossRef  |  Direct Link  |  

Hwang, S.Y., W.J.J.J. Wee, J.S. Choi and S.K. Kim, 2004. Panax ginseng improves survival and sperm quality in guinea pigs exposed to 2,3,7,8-tetrachlorodibenzo- p-dioxin. BJU Int., 94: 663-668.

Hwang, Y.P. and H.G. Jeong, 2010. Ginsenoside Rb1 protects against 6-hydroxydopamine-induced oxidative stress by increasing hemeoxygenase-1 expression through an estrogen receptor-related PI3K/Akt/Nrf2-dependent pathway in human dopaminergic cells. Toxicol. Applied Pharmacol., 242: 18-28.
CrossRef  |  

Kang, H.Y., S.H. Kim, W.J. Lee and H.K. Byrne, 2002. Effects of ginseng ingestion on growth hormone, testosterone, cortisol and insulin-like growth factor 1 responses to acute resistance exercise. J. Strength Condit. Res., 16: 179-183.
Direct Link  |  

Kim, C., H. Choi, C.C. Kim, J.K. Kim and M.S. Kim, 1976. Influence of ginseng on mating behavior of male rats. Am. J. Chin. Med. (Gard City N. Y.), 4: 163-168.
PubMed  |  

Kim, W., S. Hwang, H. Lee, H. Song and S. Kim, 1999. Panax ginseng protects the testis against 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin induced testicular damage in guinea pigs. BJU Int., 83: 842-849.
CrossRef  |  Direct Link  |  

Kimura, Y., H. Okuda and S. Arichi, 1988. Effects of various ginseng saponins on 5‐hydroxytryptamine release and aggregation in human platelets. J. Pharm. Pharmacol., 40: 838-843.
CrossRef  |  

Kostrzewa, R.M. and R. Brus, 1991. Is dopamine-agonist induced yawning behavior a D3 mediated event? Life Sci., Vol. 48.

Langtry, H.D. and A. Markham, 1999. Sildenafil: A review of its use in erectile dysfunction. Drugs, 57: 967-989.
PubMed  |  

Lee, B., C.H. Yang, D.H. Hahm, H.J. Lee, S.M. Han, K.S. Kim and I. Shim, 2008. Inhibitory effects of ginseng total saponins on behavioral sensitization and dopamine release induced by cocaine. Biol. Pharm. Bull., 31: 436-441.
CrossRef  |  

Lin, W.M., Y.M. Zhang and R. Moldzio, 2007. Ginsenoside Rd Attenuates Neuroinflammation of Dopaminergic Cells in Culture. In: Neuropsychiatric Disorders an Integrative Approach, Gerlach, M., J. Deckert, K. Double and E. Koutsilieri (Eds.). Springer, Vienna, Austria, ISBN-13: 9783211735732, pp: 105-112.

Marinac, J.S., C.L. Buchinger, L.A. Godfrey, J.M. Wooten, C. Sun and S.K. Willsie, 2007. Herbal products and dietary supplements: A survey of use, attitudes and knowledge among older adults. J. Am. Osteop. Assoc., 107: 13-23.
Direct Link  |  

Murphy, L.L. and T.J.F. Lee, 2002. Ginseng, sex behavior and nitric oxide. Ann. N. Y. Acad. Sci., 962: 372-377.
CrossRef  |  

Murphy, L.L., R.S. Cadena, D. Chavez and J.S. Ferraro, 1998. Effect of American ginseng (Panax quinquefolium) on male copulatory behavior in the rat. Physiol. Behav., 64: 445-450.
CrossRef  |  

Nah, S.Y., K.S. Bhatia, J. Lyles, E.H. Ellinwood and T.H. Lee, 2009. Effects of ginseng saponin on acute cocaine-induced alterations in evoked dopamine release and uptake in rat brain nucleus accumbens. Brain Res., 1248: 184-190.
CrossRef  |  

Ng, T.B. and H.W. Yeung, 1985. Hypoglycemic constituents of Panax ginseng. Gen. Pharmacol., 16: 549-552.
PubMed  |  

Noonan, C. and W.P. Noonan, 2006. Marketing dietary supplements in the United States: A review of the requirements for new dietary ingredients. Toxicology, 221: 4-8.
CrossRef  |  

Oh, K.W., H.S. Kim and G.C. Wagner, 1997. Inhibitory effects of ginseng total saponin on methamphetamine-induced striatal dopamine increase in mice. Arch. Pharm. Res., 20: 516-518.
CrossRef  |  

Panwar, M., M. Kumar, R. Samarth and A. Kumar, 2005. Evaluation of chemopreventive action and antimutagenic effect of the standardized panax ginseng extract, EFLA400, in Swiss albino mice. Phytother. Res., 19: 65-71.
CrossRef  |  

Park, S.W., C.H. Lee, D.H. Shin, N.S. Bang and S.M. Lee, 2006. Effect of SA1, a herbal formulation, on sexual behavior and penile erection. Biol. Pharm. Bull., 29: 1383-1386.
CrossRef  |  

Qinna, N., H. Taha, K.Z. Matalka and A.A. Badwan, 2009. A new herbal combination, Etana, for enhancing erectile function: An efficacy and safety study in animals. Int. J. Impotence Res., 21: 315-320.
CrossRef  |  

Reepmeyer, J.C., J.T. Woodruff and D.A. D'Avignon, 2007. Structure elucidation of a novel analogue of sildenafil detected as an adulterant in an herbal dietary supplement. J. Pharm. Biomed. Anal., 43: 1615-1621.
CrossRef  |  

Rowland, D.L. and W. Tai, 2003. A review of plant-derived and herbal approaches to the treatment of sexual dysfunctions. J. Sex Marital Ther., 29: 185-205.
CrossRef  |  

SAS, 1982. SAS User's Guide: Statistics. SAS Institute Inc., Cary, NC., USA.

Shamloul, R., 2010. Natural aphrodisiacs. J. Sex. Med., 7: 39-49.
CrossRef  |  PubMed  |  

Soldati, F. and O. Sticher, 1980. HPLC separation and quantitative determination of ginsenosides from Panax ginseng, Panax quinquefolium and from ginseng drug preparations. Planta Med., 39: 348-357.
CrossRef  |  

Sunwoo, S., Y.S. Kim, B.L. Cho, K.S. Cheon and H.G. Seo et al., 2004. Post-marketing surveillance study of the safety and efficacy of sildenafil prescribed in primary care to erectile dysfunction patients. Int. J. Impotence Res., 17: 71-75.
CrossRef  |  

Tachikawa, E., K. Kudo, T. Kashimoto and E. Takahashi, 1995. Ginseng saponins reduce acetylcholine-evoked Na+ influx and catecholamine secretion in bovine adrenal chromaffin cells. J. Pharmacol. Exp. Therap., 273: 629-636.
Direct Link  |  

Teng, C.M., S.C. Kuo, F.N. Ko, J.C. Lee, L.G. Lee, S.C. Chen and T.F. Huang, 1989. Antiplatelet actions of panaxynol and ginsenosides isolated from ginseng. Biochim. Biophys. Acta, 990: 315-320.
CrossRef  |  

Timbo, B.B., M.P. Ross, P.V. McCarthy and C.T.J. Lin, 2006. Dietary supplements in a national survey: Prevalence of use and reports of adverse events. J. Am. Diet. Assoc., 106: 1966-1974.
Direct Link  |  

Tsai, S.C., Y.C. Chiao, C.C. Lu and P.S. Wang, 2003. Stimulation of the secretion of luteinizing hormone by ginsenoside-Rb1 in male rats. Chin. J. Physiol., 46: 1-7.
Direct Link  |  

Waller, R.A. and D.B. Duncan, 1969. A bayes rule for the symmetric multiple comparisons problem. J. Am. Stat. Assoc., 64: 1484-1503.
CrossRef  |  Direct Link  |  

Wang, X., S. Chu, T. Qian, J. Chen and J. Zhang, 2010. Ginsenoside Rg1 improves male copulatory behavior via nitric oxide/cyclic guanosine monophosphate pathway. J. Sexual Med., 7: 743-750.
CrossRef  |  Direct Link  |  

Yamamoto, M., A. Kumagai and Y. Yamamura, 1977. Stimulatory effect of Panax ginseng principles on DNA and protein synthesis in rat testes. Arzneimittelforschung, 27: 1404-1405.
PubMed  |  Direct Link  |  

Yoshimura, H., K. Watanabe and N. Ogawa, 1988. Acute and chronic effects of ginseng saponins on maternal aggression in mice. Eur. J. Pharmacol., 150: 319-324.
CrossRef  |  

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