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Ginseng and male reproductive function

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Ginseng is often referred to as the King of all herbs, and is found to be a promising agent to improve general well-being. Ginseng has also been reputed as an aphrodisiac, and is used to treat sexual dysfunction as well as to enhance sexual behavior in traditional Chinese medical practices. Data from animal studies have shown a positive correlation among ginseng, libido, and copulatory performances, and these effects have been confirmed in case-control studies in human. In addition, ginseng is found to improve the sperm quality and count of healthy individuals as well as patients with treatment-related infertility. These actions are mostly attributed to ginsenosides, the major pharmacological active components of ginseng. This review compiles the current knowledge about the multifaceted effects of ginseng on male reproductive function, and also focuses on its mechanisms of action that may represent novel therapeutic strategies for the treatment of male reproductive diseases or disorders.
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REVIEW
Introduction
Infertility is a growing problem in the world. In 2010, an esti-
mated 48.5 million couples worldwide were infertile.1 In approxi-
mately 40% of these couples, the male partner has been either
the sole or a contributing cause of infertility.2,3 Herbal therapy is
increasingly popular worldwide as a way to treat infertility. In the
United States, 17% constantly visited herbal therapist in the past
18 mo out of the 29% of infertile couples who use complementary
and alternative medicine.3 In a clinic-based survey conducted in
Jordan, 44% of infertile patients use herbal medicine as part of
their infertility treatment.4 Among them, 8% went for Chinese
medication.4 In South Australia, 29% of interviewed infertile
subjects use herbal remedies, in which 4.2% uses ginseng.5
Ginseng is one of the most precious herbs in traditional
Chinese medicine. There are at least nine species of ginseng and
are mostly named by their geographical origins, such as Asian
ginseng (Panax ginseng), American ginseng (Panax quinquefo-
lium), and Japanese ginseng (Panax japonicus). The genus name
“Panax” is given to ginseng by the Russian botanist Carl A Meyer
in 1843. “Panax” means “all-healing” in Greek, and Panax gin-
seng is conventionally referred to the Asian ginseng. Ginseng has
been reported to have diverse physiological effects in multiple
systems, including cardiovascular, immune, and neuronal. It has
also been used to enhance sex performance and satisfaction. In
this review, we will summarize the effects of ginseng on male sex
performance and spermatogenesis. Recent evidences on its mech-
anisms of action that may represent novel therapeutic strategies
for the treatment of male reproductive diseases or disorders will
be discussed.
Sex Performance
Erection
Ginseng is commonly taken by itself or with an herbal for-
mula to enhance sexual performance in traditional Chinese
medical practices. The beneficial effects have been scientifically
evaluated and confirmed in meta-analyses of randomized clinical
trials.6 For example, in a double-blind, placebo-controlled study,
45 men with moderate to severe erectile dysfunction had found
improvement in their scores on erectile performance and sexual
satisfaction after treated with three times daily doses of 900 mg
Korean red ginseng for 8 wk.7 A similar study on 60 men with
erectile dysfunction also reported marked improvement in erec-
tile function including rigidity, penetration, and maintenance of
erection after taking Korean red ginseng (1000 mg) three times
daily for 12 wk.8
In animal studies, treatment with Korean red ginseng and
ginseng berry extract has been shown to significantly relax the
pre-contracted penile corpus cavernosum smooth muscles of rab-
bits in vitro, and increase the intracavernosal pressure of rats in
vivo.9,10 Data from studies on ginseng berry extract suggest that
this action is nitric oxide (NO) dependent. The pharmacologi-
cally active components of ginseng, ginsenosides, are known to
be able to induce NO synthesis in endothelial cells and perivascu-
lar nerves, and to augment vascular smooth muscle cell’s sensitiv-
ity to NO.11,12 This release of NO causes smooth muscle to relax,
thus allowing more blood to enter the erectile bodies known as
corpus cavernosum and causing erection.13 Among the ginsen-
osides, Rg1 has been found for NO production in endothelial
cells by glucocorticoid receptor (GR)-dependent, non-genomic
*Correspondence to: Alice ST Wong; Email: awong1@hku.hk
Submitted: 09/04/2013; Accepted: 09/05/2013
http://dx.doi.org/10.4161/spmg.26391
Ginseng and male reproductive function
Kar Wah Leung and Alice ST Wong*
School of Bi ological Sciences; Uni versity of Hong Kong; H ong Kong, PR China
Keywords: ginseng, ginsenosides, sexual behavior, sperm, spermatogenesis, steroid receptor
Abbreviations: ACh, acetylcholine; AR, androgen receptor; cGMP, cyclic guanosine monophosphate; CREM, cAMP-responsive
element modulator; CP, cyclophosphamide; DA, dopamine; ER, estrogen receptor; GABA, gamma-aminobutyric acid; GDNF,
glial cell-derived neurotrophic factor; GR, glucocorticoid receptor;LH, luteinizing hormone; NO, nitric oxide; NOS, nitric oxide
synthase; PR, progesterone receptor; ZEA, zearalenone
Ginseng is often referred to as the King of all herbs, and is
found to be a promising agent to improve general well-being.
Ginseng has also been reputed as an aphrodisiac, and is used
to treat sexual dysfunction as well as to enhance sexual behav-
ior in traditional Chinese medical practices. Data from animal
studies have shown a positive correlation among ginseng,
libido, and copulatory performances, and these effects have
been confirmed in case-control studies in human. In addition,
ginseng is found to improve the sperm quality and count of
healthy individuals as well as patients with treatment-related
infertility. These actions are mostly attributed to ginsenosides,
the major pharmacological active components of ginseng.
This review compiles the current knowledge about the multi-
faceted effects of ginseng on male reproductive function, and
also focuses on its mechanisms of action that may represent
novel therapeutic strategies for the treatment of male repro-
ductive diseases or disorders.
e26391-2 Spermatogenesis Volume 3 Issue 3
mechanisms,14 and administration of Rg1 (10 mg/kg) signifi-
cantly enhances NO release and cyclic GMP (cGMP) accumula-
tion in corpus cavernosum of mice.15
Libido
Studies on rodents reveal that both Asian ginseng (Panax
ginseng)16 and American ginseng (Panax quinquefolium)17 can
facilitate copulatory behavior. Daily treatment of Asian ginseng
(25–100 mg/kg) or ginsenoside Rg1 (2.5–10 mg/kg) demon-
strates a dose-dependent increase in mounting, intromission, and
penis licking in mice which are exposed to estrous females.18 Such
effects are not observed in mice treated with ginsenoside Rb1,
Rb2, and Ro.
Sex drive in higher mammals involves a complex coordina-
tion between the hormonal and neuronal components. The male
sex steroid, testosterone, is synthesized in the Leydig cell under
the control of luteinizing hormone (LH), which is produced by
the anterior pituitary.19 Testosterone levels are strongly correlated
with libido and testosterone is therefore one of the main forms of
prescription given to men with reduced sex drive.20 Interestingly,
rats fed with 5% Panax ginseng in their diet for 60 d have shown
significantly increased blood testosterone levels, whereas treat-
ment with 1% Panax ginseng had no effect.21 Ginsenoside Rg1
(10 mg/kg), the major active constituent in Panax ginseng,
is responsible for the increase of serum testosterone levels and
improvement of copulatory behavior observed.15 Ginsenoside
Rb1 (10 µg/kg), a key ginsenoside found in American ginseng,
is found to increase the secretion of LH by acting directly on
the anterior pituitary gland.22 In a clinical study that involves 66
participants, the use of Asian ginseng extract has been shown to
significantly increase the levels of plasma total and free testos-
terone, follicle stimulating hormone, and LH.23 However, oral
administration of American ginseng (10–100 mg/kg) for 28 d
does not seem to alter testosterone and LH levels in rats,18 sug-
gesting that type of ginseng and treatment duration could make
a difference in the libido-enhancing ability.
Several neurotransmitters have been implicated in libido, such
as dopamine (DA) for desire, acetylcholine (ACh) for arousal,
and (GABA) for orgasm. Ginsenoside Re has been shown to
increase extracellular DA and ACh levels in rat brain.24 The
action of ginsenoside Rb1 on ACh release is associated with an
increase of choline uptake into nerve endings.25 American gin-
seng extracts were shown to modulate GABAgeric neurotrans-
mission in rat brainstem neurons.26 Receptor-ligand binding
assays have demonstrated that ginsenosides Rb1, Rb2, Rc, Re,
Rf, and Rg1 are agonists of GABA(A) receptor, and Rc is also
an agonist for GABA(B) receptor.27 These findings suggest that
ginseng may regulate the pituitary-testis axis at both hormonal
and neuronal levels.
Sperm Production and Quality
Researches over the past 20 y have shown sperm counts
declining in many countries across the world. For instance, a
study on 26000 French males has shown a continuous decrease
in sperm concentration over a 17-y period.28 A 32% reduction is
found when comparing the average sperm level of a 35-y-old man
between 1989 and 2005.28 The reasons are not fully known, but
the reduction in fertility worldwide could indicate a general dete-
rioration of male’s well-being, which is becoming a major health
concern. Thus, there is a need to further understand the causes
and to establish measures to prevent it.
Sperm count and motility
The initial evidence that ginseng may have positive effects on
spermatogenesis was first published in 1977. Here it was demon-
strated that the stimulatory effect of ginseng extracts on DNA
and protein syntheses in rat testes.29 Later studies in both rodents
and humans have shown that ginseng can increase sperm count.
Ginseng-treated rats have demonstrated an increased rate of sper-
matogenesis via glial cell-derived neurotrophic factor (GDNF)
expression elevation in Sertoli cells,30 and activation of testicu-
lar cAMP-responsive element modulator (CR EM).31 GDNF is a
possible regulator of the survival and cell fate decision of undif-
ferentiated spermatogonial cells,32,33 and CREM is essential for
spermatid maturation.34 Men with little or no CREM protein/
mRNA show specific arrest of round spermatids, which could be
a possible cause of infertility.35 Both oligoastenospermic patients
and age-matched healthy counterpart showed an increase in sper-
matozoa density and motility after the use of Panax ginseng.23
Asthenospermia patients treated with ginseng also showed a sig-
nificant increase in progressive sperm motility.36 The aqueous,
organic, and polysaccharide fractions of Panax notoginseng have
been shown to enhance the directional motility of human sperms
in 60–120 min.37 Similarly, ginsenosides Rc and Rb2 (0.01 mg/
ml) have been shown to enhance sperm progression in vitro.38
To pinpoint on specific active components for this action, these
effects are found to be mediated through induction of nitric oxide
synthase (NOS) activities and NO production.39 NO is also
closely related to sperm function. Ginsenoside Re (1–100 µM)
has been shown to facilitate human sperm capacitation and acro-
some reaction through enhancing intracellular NO production.40
Sperm preservation
Ginseng is also found to help preserve the ejaculated sperms.
It has been shown that the sperm count of ejaculated sperms that
were incubated with ginseng extract was significantly higher
than those treated with vehicle.41 Treatment with ginsenoside
Rg1 (50 µg/ml) significantly increases sperm motility and mem-
brane integrity of post-thawed sperms as compared with fresh
and untreated thawed sperms.42 These findings suggest that the
addition of ginseng extract to the cryogen for sperm storage could
en h a nc e fertility.
Effects of Ginseng on Spermatogenesis
During Disease States
It is known that conventional cancer treatments often lead to
various degrees of reproduction impairment, and that these effects
could be either temporary or permanent. Cyclophosphamide
(CP) is an alkylating agent that shows cytostatic effects by form-
ing covalent DNA adducts. Since CP targets rapidly dividing
cells, it is extensively used to suppress tumor malignancy, and
as an immunosuppressant for organ transplantation patients.
However, this drug often leads to gonadal toxicity, and infertility
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as a consequence discourages many patients from choosing CP
treatment. It has been shown that intake of American ginseng
(500 mg/kg/day) can protect sperms, in particular by increasing
the sperm count, reducing sperm death and abnormalities, and
resuming sperm motility from CP insult in adult male Wistar
rats as compared with CP treatment alone.43 Furthermore, treat-
ment of protopanazatriol saponin is shown to markedly reduce
the chemotherapeutic agent (busulfan)-induced structural defect
of the testis in mice, suggesting that ginseng may have applica-
tions in the recovery of male infertility after cancer treatments.44
Radiation therapy is sometimes given to patients as part of
the cancer therapy. However, the unselective action of radiation
therapy can also damage normal cells, leading to side effects.
Amifostine (WR-2721) is one of the radioprotectants that is
registered for human use, but its usage leads to many negative
side effects, such as hypertension, nausea, and vomiting.45 This
compound is also cytotoxic to stem spermatogonia, thus limit-
ing its clinical use.46 It is interesting to note that intraperitone-
ally injection of Panax ginseng extract (10 mg/kg) given to adult
male Swiss albino mice for 4 d can protect germ cell popula-
tion and function against γ-radiation, and dramatically reduce
γ-radiation-associated sickness, including anorexia, diarrhea,
weight loss, lethargy, and epilation.47
Zearalenone (ZEA) is an estrogenic mycotoxin that commonly
contaminates the environment as its presence in the crops, which
causes reproductive disorders in farm animals. The consumption
of Korean red ginseng (300 mg/kg) for 4 wk every other day has
been shown to be able to prevent ZEA-induced spermatogenesis
impairment in rats via modulating Fas/Fas-L expression.48
Males with non-insulin-dependent diabetes mellitus (type 2
diabetes) often suffer from sexual dysfunction.49 Studies have
found the benefits of ginseng intake. For example, the admin-
istration of standardized ginseng extract (100 mg/kg) daily for
90 d in streptozotocin-induced diabetic rats has been shown to
result in a significant improvement of fertility parameters and
decrease in testicular pathological signs, such as degenerative
changes of the seminiferous tubules.50 Furthermore, the con-
sumption of Korean red ginseng (30 mg/kg, three times a week
for 1 mo) can help streptozotocin-induced type 2 diabetic male
rats to improve on libido and sexual performance.51 In addition,
ginseng has been shown to be able to stabilize diabetes disease
progression. In a double-blinded, placebo-controlled study, it has
been shown that daily ginseng intake (100 or 200 mg) among
type-2 diabetic patients demonstrated significant reduction in
fasting blood glucose and body weight, and improvement in gly-
cated hemoglobin, serum N-terminal propeptide concentration,
psychological performance, and physical activities.52 Si m i l a rly,
Korean red ginseng has been shown to be able to enhance cGMP
levels of the corpus cavernosum in rats with metabolic syndrome
and may therefore improve erectile function.53
A continuous exposure to environmental toxins is considered
to be a cause of fertility decline. Ginseng has been demonstrated
to have a cytoprotective effects against these toxins, in which
administration of Panax ginseng extract is reported to signifi-
cantly reduce the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced
pathological and genotoxical damages in rat testes.54 In addition,
treatment of Panax ginseng is found to protect Sertoli cells from
the cytotoxic effects of bisphenol A.55
Mechanisms of Action on Spermatids
Ginsenosides are triterpenoid saponins that structurally
resemble the steroid hormones. Thus, it is tempting to spec-
ulate that the effects of ginsenosides on sexual function and
spermatogenesis are a result of activation of steroid receptors.
Androgens are sex steroids that are essential for the develop-
ment and maintenance of male sexual characteristics, and
regulate normal spermatogenesis. Androgen receptor (AR) is
abundantly expressed in male genital tissues and in spermato-
zoa,56 and its expression is significantly decreased in infertile
men.57 Ginsenoside Rb1 and Re have been reported to be AR
agonists, through which these ginsenosides stimulate NO pro-
duction via the activation of NOS.58,59 Ginseng berry extract
GB0710, of which ginsenoside Re is the key ingredient, could
improve erectile dysfunction in rats by inducing NO produc-
tion.10 Re-induced NO production in sperm has also been
shown to be involved in capacitation and acrosome reaction,
and that these effects could be a result of the non-genomic
activities of the Re-AR interaction.40
Estrogen is another hormone with profound effects on sexual
function of both male and female. Estrogen supplements have
been shown to improve sexual function of testosterone defi-
ciency men.60 In this regard, although estrogen receptor (ER)
α-knockout mice have undisrupted reproductive tract develop-
ment, these mice display less masculine sexual behavior61 and
have a much lower fertility rate.62 Several ginsenosides, including
Rb1, Re, Rg1, Rg3, and Rh1, are agonists of ERα that have been
shown to elicit both receptor-dependent transcriptional and non-
transcriptional estrogenic actions in multiple cell types.58,63-66 In
this regard, ER has been reported on human spermatozoa and
that it is located mainly on the plasma membrane,67-70 suggesting
that ginsenosides may modulate male sexual function through
non-genomic interactions of ER.
Expression of progesterone receptor (PR) was observed on
human sperms, and a strong correlation between PR expres-
sion and sperm function has been demonstrated.71 Intriguingly,
unlike estrogens, progesterone promotes the capacitated sperm
to undergo acrosomal reaction.72,73 In concordance, a handful of
in vitro studies have demonstrated an inhibitory action of pro-
gesterone on estrogens and vice versa. For example, the estro-
gen-induced forward movement of human spermatozoa into the
oviduct could be effectively suppressed by progesterone.74-7 7 In
addition, it was shown that progesterone, which was secreted by
the culumus cells surrounding the oocyte to induce sperm hyper-
activation, was inhibited in the presence of estrogen.78 On the
other hand, estrogen and progesterone may cooperate to opti-
mize their effects on fertilization.79,80 Ginseng extracts contain a
mixture of ginsenosides that can activate either or both ER and/
or PR, and, hence, may modulate different aspects of sperm func-
tion. The ginsenoside Re-induced motility enhancement effect in
spermatozoa could be related to the findings that Re is found to
be both ER and PR agonists.58
e26391-4 Spermatogenesis Volume 3 Issue 3
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Concluding Remarks and Future Perspectives
Ginseng is a vital constituent of traditional Chinese medi-
cine and has been used to treat various physical conditions for
thousands of years, importantly as an aphrodisiac and is used to
treat sexual dysfunction as well as to enhance sexual behavior
and gonada l functions (Fig. 1). Therefore, use of ginseng appears
to be important for the development of novel therapeutics or to
increase the effectiveness of the current treatment strategies for
male reproductive diseases or disorders. However, its molecu-
lar mechanisms of action remain elusive. Research in this area
should be carried further. A versatile assay for high-throughput
expression profiling will prove useful to reveal the molecular
functions of different ginsenosides and how the different signal
networks are orchestrated. Further evaluations are also needed
to validate some of the medicinal benefits using modern analyt-
ical tools and technology-based analyses. Different approaches
to synthesize and/or modify natural ginsenosides can also be
considered to increase the efficacy/potency, metabolic stability,
and oral bioavailability for clinical applications.
Disclosure of Potential Conflicts of Interest
No potential conf licts of interest were disclosed.
Funding
This work was supported by the Health and Medical
Research Fund 11121191, Hong Kong Jockey Club Charities
Trust (HKJCCT), HKU Strategic Research Theme on
Drug, and Croucher Senior Research Fellowship to Alice ST
Wong.
Figure 1. Summary of the ginseng’s effects on male sexual function.
Ginseng enhances sexual per formance, improves male fertility through
modulating the neuronal and hormonal systems, promotes spermato-
genesis, and acts directly on sperms via steroid receptors. Ginseng also
preserves male fertility during disease states.
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REP-11- 03 26
... PG is a term that is commonly used to refer to the Asian ginseng. 44,45 PG can boost sexual activities and contentment, as indicated by research in human and animals. The effects of PG therapy on libido and copulatory performance, as well as on sexual satisfaction, have been documented in these investigations. ...
... To boost sexual performance, PG is a traditional Chinese medicine that can be used in conjunction with a herbal mix or consumed on its own. 44,46 Ginseng medication has been shown to have favorable benefits on male reproductive functioning in randomized clinical trials, according to meta-analyses of these studies. Via a double-blinded placebo-controlled-study, researchers suggested that Ginseng may improve the conditions of erectile dysfunction and increase sexual contentment in 45 male individuals. ...
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Male infertility is referred to as the lack of ability of the male to impregnate his fertile female partner even after 12 months of unprotected, frequent sexual contact. It affects anywhere from 9 percent to 15.8percent of the general population. Male infertility can be treated with a variety of conventional methods, but the effectiveness of this therapy is still under research. Complementary and alternative medicine is frequently sought by those suffering from infertility issues. In many cases, herbal medicine, for example maca, dang gui, or ginseng are applied try to ameliorate male fertility, libido, and sexual functions. Ginseng, as a cyclic adenosine monophosphate-responsive element modulator, has been shown in several preclinical investigations to stimulate spermatogenesis, as well as to improve testicular functions, sperm quality, and motility.
... Moreover, one study mentioned, the beneficial effect of KRG on erection in men with erectile dysfunction has been identified in meta-analyses of randomized controlled trials [37,25]. In another study, performed in rats treated with cyclophosphamide and ginseng, more over study under disease conditions such as cancer and diabetes, and in the post-radiation period, ginseng showed improvement of sperms profiles after treatment of animals exposed to varying degrees of radiation [38] suggesting a future positive role for ginseng in this area. ...
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The study aimed to investigate the effect of Panax ginseng powdered supplemented 2and 5 gram as a diet on testosterone, SSH and ICSH levels, on the other hand, Panax ginseng effect on some physical parameters of sperms, histological testis traits, and testicular size in and out of season in adultrams.This study was conducted at the laboratories of Theriogenology, Department of Surgery and Obstetrics, College of Veterinary Medicine, Basrah University. The experimental study extended from May 2019 to the end of December 2020. Twenty adult rams (18-24 month old) were divided randomly into 3 groups; The 1st group 8 adult rams were subdivided into 4 rams fed 2 gram standard administered containing Panax ginseng, while the other 4 adult rams fed 5 gram standard administered containing Panax ginseng once a day for 90 days during the breeding season. The 2nd group 8 adult rams were subdivided also into 4 rams fed 2 gram standard administered containing Panax ginseng, while the other 4 rams fed 5 gram standard administered containing Panax ginseng once a day for 90 days out of season. The 3rd group 4 adult rams were used as the control group two times (in and out of season).The results illustrated the testosterone ,SSH and ICSH were high significant (P<0.05) values between treated groups of ginseng supplemented 2and 5 gram as a diet compared with control group in and out of season .The physical parameters of sperms evaluation (total sperms count, sperms motility, and progressive movement) of this study showed superiority improving of above parameters ,while the total immotile sperms andnon-progressive sperms movement showedlow significant (P<0.05) values in treated groups of ginseng supplemented 2 and 5 gram as a diet compared with control group in and out of season.The angiogenesis of the seminiferous tubules were increased and the incensement of the numbers of spermatogonia, primary and secondary spermatocytes were observed in the Panax ginseng groups through a microscopic examination during and out of season.Values of testicular diameter showed a highly significant difference (P<0.05) at (75 and 90) days in treated groups of ginseng supplemented 2 and 5 gram as a diet compared with control group in and out of season. From the above mentioned results, we conclusion that Panax ginseng may affect the morphology and motility of sperms, the important factor in male fertility, and its antioxidant status in rams.
... Making strides the rabbit generation industry in Nigeria, which has been respected as emanant or simple [30]. It is conceivable that Panax ginseng may upgrade regenerative capacities of rabbit bucks as detailed in mice and rodents treated with Panax ginseng [31]. Earlier studies on Panax ginseng with rabbits recorded significant increases in serum levels of follicle stimulating hormone (FSH), testosterone (T), triiodothyronine (T3), and tetraiodothyronine (T4) of treated rabbit bucks, whereas drain abdicate was altogether diminished in rabbit does managed Panax ginseng extricates [30,32]. ...
... The testicular protection property of Ge was explained by the presence of ginsenosides (Saw et al. 2012), which were considered as powerful antioxidants reducing oxidative stress and delaying aging (Filho et al. 2013). Moreover, Leung and Wong (2013) suggested that the possible gonado-protective effects and antioxidant role of Ge might be related to a Ge-induced decrease of reactive oxygen species. Similarly, with the testis histological findings obtained herein, Choi et al. (2004) reported that P. ginseng might have an important factor in the spermatogenesis of the treated male rats. ...
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Ginseng (Ge) is one of the most famous and precious consumed herbal medicines around the world. Ge plant roots have many advantages regarded as important in increasing fish production. Thus, the present study was conducted to investigate the possibility of using different levels (0.0, 100, and 200 mg/kg diet) of Ge as a reproductive enhancer agent for African catfish, Clarias gariepinus males. Results revealed that fish fed 200 mg Ge/kg diet significantly (P ˂ 0.05) increased growth performance, feed efficiency, gonado-somatic index, hematological parameters, serum follicle-stimulating hormone, total antioxidant capacity, sperm quality parameters, and ultrastructure of spermatozoa, as well as led to positively improved of the histological structure of the testes tissue compared to other treatments. Based on the obtained findings, it could be concluded that the effective use of dietary Ge at a level of 200 mg/kg as a promising reproductive agent for adult African catfish males consequently led to the sustainability of aquaculture for African catfish.
... These products are often used by women with sexual dysfunction in traditional medical systems from various countries and cultures (Chauhan et al., 2014). For example, Tribulus terrestris has been used to treat infertility and impotence (Chhatre et al., 2014), as well as eye ailments, among various other usages (Commission, 2015), while Panax ginseng has diverse bio-physio-psychological effects on multiple systems, including immune, cardiovascular, neuronal, and sexual effects (Leung and Wong, 2013), especially in the enhancement and restorative of sexual function (Chauhan et al., 2014;Chung et al., 2015;Rao et al., 2018). They are often viewed as more relevant, useful, authentic, culturally approved, economically acceptable, and with fewer side effects (George, 2011). ...
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Background : Female sexual dysfunction (FSD) includes female orgasmic disorder, female sexual interest or arousal disorder, and genito-pelvic pain or penetration disorder. FSD affects 40% of women worldwide, but it is understudied and likely undertreated. Natural products are frequently used by women to treat FSD, but scientific evidence of their efficacy is lacking. Objective : This systematic review and meta-analysis focused on the study of the efficacy of natural products on FSD. Study design : Systematic review and meta-analysis of existing studies on natural products in the treatment of FSD. Methods : The literature search included MEDLINE, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trial databases for studies published from January 2000 to February 2020. The quality and the level of evidence of the studies were assessed. The association between natural products and FSD was summarized using standardized mean differences (SMD) with a 95% confidence interval (CI). Results : A total of 536 studies were identified, with 20 of them meeting the criteria. According to this meta-analysis, Tribulus terrestris showed a significant positive effect in improving overall female sexual function (SMD = 1.12, 95% CI = 0.46 - 1.79, p = 0.001) and individual sexual arousal (SMD = 1.03, 95% CI = 0.22 - 1.84, p = 0.013), sexual desire (SMD = 1.08, 95% CI = 0.52 - 1.63, p = <0.001) and sexual orgasm (SMD = 0.51, 95% CI = 0.02 - 1.00, p = 0.040) domains compared to placebo. Panax ginseng was found to be effective in treating sexual arousal (SMD = 0.54, 95% CI = 0.11 - 0.97, p = 0.014) and sexual desire (SMD = 0.59, 95% CI = 0.27 - 0.90, p < 0.001) compared to placebo. Meanwhile, other natural products reviewed in this study, such as Trifolium pretense, did not differ significantly from placebo in terms of improving FSD. Conclusion : Preliminary evidence suggests that Tribulus terrestris and Panax ginseng may be effective as alternative treatments for FSD in a clinical setting.
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Introduction, The aim of this systematic review was to evaluate the current evidence for the effectiveness of ginseng, Rutin and Moringa for treating erectile dysfunction. Methods, A broad search of the Scopus, PubMed, Cochrane and Web of Science databases was performed in complicance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The following criteria were required for articles to be included in the review: English language; observational studies (cohort studies, case control/comparative studies, single-arm studies); randomized controlled trials; non-randomized comparative studies; case series; number of participants: ≥5 for case series or ≥5 patients per group for comparative studies. The Cochrane risk of bias (RoB) assessment tool for RCTs was used to assess the risk of bias of included studies. Results, Seven full-text articles were included in this review. All studies were randomized controlled trials. No studies on Rutin and Moringa alone matched the inclusion criteria. The methodological quality of the RCTs was variable. In all studies, the group treated with ginseng reported an improvement of erectile function (EF) compared to the control groups. IIEF and IIEF-5 were used to evaluate erectile function in six studies and in four of them, the improvement of the scores in the group treated with ginseng over the control group reached the statistical significance. Conclusion, This review suggests a positive effect of ginseng on EF in men. The association of ginseng along with other nutritional components with potential beneficial effects on ED appears promising and deserves further investigation in large randomized controlled trials.
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Ethnopharmacological relevance Roots of Argyreia nervosa (Burm.f.) Bojer is used traditionally as an aphrodisiac and mentioned in the indigenous system of medicine as spermatogenic. The roots of the plant are also used as bitter, tonic, and alternative. Aim of the study To study the effect of n-butanol fraction (BTF) and ethyl acetate fraction (ETF) of methanol extract prepared from the roots of Argyreia nervosa and scopoletin isolated from ETF on testosterone biosynthesis in testis and spermatogenesis using rats. Materials and methods The effect of BTF, ETF, and scopoletin on the testosterone biosynthesis was evaluated by determining the alteration in expression of mRNA corresponding to steroidogenic enzymes and concentration of testosterone using TM-3 cell line. The ability of BTF and ETF in altering the level of testicular cholesterol and testosterone along with mRNA expression corresponding to 3β-Hydroxy-Δ⁵-steroid dehydrogenase (3β-HSD) and Acute Steroid Regulatory Protein (StAR) was evaluated using rats as experimental animals. The sperm concentration in the seminal fluid was determined, and histological studies of testicular tissues were also carried out. Results Test solutions containing BTF, ETF, and scopoletin showed a dose-dependent and statistically significant increase in the testosterone content when incubated with TM-3 cells. The test solutions also increased the fold expression of mRNA corresponding to StAR and 3β-HSD enzymes from TM-3 cells. BTF and ETF elevated testicular testosterone levels by 3.57 and 3.84-fold as compared to control animals, while the fractions showed 9.04 and 10.41-fold alteration in expression of mRNA corresponding to StAR, respectively. BTF and ETF altered the expression of mRNA corresponding to 3β-HSD by 13.43 and 15.04-fold in testicular tissues; moreover, they elevated the activity of 3β-HSD by 7.11 and 7.73 fold, respectively. The animals treated with BTF and ETF showed increased sperm concentration. Histological observations showed that the lumen of seminiferous tubules was densely populated with spermatozoa and Leydig cells were intensely stained. Extract prepared from fruits of Tribulus terrestris Linn and testosterone served as positive controls. Conclusion BTF, ETF, and scopoletin could promote testosterone biosynthesis by elevating mRNA expression corresponding to StAR, 3β-HSD, and by increasing 3β-HSD activity in the testicular tissues. Elevated testosterone concentration in testis promoted spermatogenesis. The studies provided the probable mechanism through which the roots of A. nervosa act as spermatogenic.
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Rationale: Panax ginseng (PG) and American ginseng (AMG) are both medicinal plants of the Panax genus in the Acanthopanax family. Although the chemical components of PG and AMG are similar, there are many differences of their bioactivities. In this study, the biochemical mechanisms of different bioactivities of PG and AMG were explored by researching the differential metabolites in plasma after administrations of PG and AMG, respectively. Methods: In order to explore the material basis of differential bioactivities, two groups of mice were administrated orally with PG and AMG, and the method of metabonomics was used to identify the differential metabolites in the plasma. Then the network pharmacology based on the differential metabolites was processed. Afterward, the metabolite-target-pathway network of PG and AMG was constructed, thus the pathways related to different bioactivities were analyzed. Results: Through the analysis of PCA and OPLS-DA, there were 10 differential metabolites identified in the PG group, and 8 differential metabolites identified in the AMG group. Based on the network pharmacology, the differential metabolites were classified and related to differential bioactivities of PG and AMG. In the PG group, there were 6 metabolites related to the effects of aphrodisiac and exiting the nerve, and 5 metabolites associated to raise blood pressure. In the AMG group, 5 metabolites were classified to the effect of inhibiting the nerve center, and 6 metabolites were related to antihypertensive. Conclusions: This study explored the material basis of the differential biological activity between PG and AMG, which was significantly to research PG and AMG used and promote human health.
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A component from ginseng in which sugars and proteins are covalently bound is named Panax ginseng glycoproteins (PGG). The contents of neutral carbohydrate, acid carbohydrate, and protein were 45.4%, 4.3% and 51.1%. The average molecular weight was 12,690 Da. The structure analysis showed that PGG had more than 1100 glycoproteins with molecular weight between 308.13 Da and 9991.52 Da, it was divided into two parts: long chain structure and short chain structure. These two parts were compared in molecular mass, number of amino acids, theoretical pI, instability index, aliphatic index and GRAVY. The in vivo distribution test of mice showed that PGG was enriched in mice testis, testicular tissue sections showed strong fluorescence signal expression on the surface of seminiferous tubules. We used cyclophosphamide (CP) to establish a mice model of oligoasthenozoospermia to investigate the anti-oligoasthenozoospermic effect of PGG. The results showed that PGG increased the levels of sex hormones T, FSH, PRL and sperm quality. Histopathology demonstrated that PGG promoted the differentiation process. The organ coefficient indicated that PGG had no obvious toxic and side effects. And the mechanism may be to affect the expression of protein levels such as p-ERK/ERK, p-AKT/AKT, Caspase-3, Bcl-2 and Bax. Therefore, PGG has the potential to develop into drugs for improving spermatogenic disorders.
Chapter
Since ancient times, humans across diverse cultures have shown keen interest in traditional herbal products which enhance sexual abilities, pleasure and libido, and improve sexual functions and potency. Herbal aphrodisiacs have been claimed to possess antistress as well as adaptogenic properties that assist in combating disease-associated stress and improving physical strength ultimately helping to alleviate the anxiety linked with lack of sexual desire and performance. Even in the modern era, particularly due to social or cultural reasons, some men still prefer the use of traditional herbal aphrodisiac products to counter sexual and/or reproductive dysfunctions. Important herbal aphrodisiacs—such as Panax ginseng, Tribulus terrestris, Eurycoma longifolia, Chlorophytum borivilianum, Ginkgo biloba, and Turnera diffusa var. aphrodisiaca have been discussed in this chapter in accordance with their effects and the potent molecules/compounds that manifest their activity. In fact, the constituent biomolecules present as the active principles of the herbal preparations behind their noticeable effects. However, there can be various pathways through which they may affect the sexual and reproductive functions, ranging from enhancement of spermatogenesis; modulation of hormonal levels (particularly testosterone) and steroidogenesis; erectogenic properties including improvement in sexual motivation, copulatory behavior, and modulation of neurotransmitters; to reduction of oxidative stress. For their potential incorporation into the clinical management of male reproductive and/or sexual disorders such as erectile dysfunction or male infertility in future, these herbal aphrodisiac biomolecules have to pass through stringent confirmatory studies including proper assessment of their safety and regulatory issues together with any side effect and associated toxicity for safe human administration.
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OBJECTIVE - To investigate the effect of ginseng on newly diagnosed noninsulin-dependent diabetes mellitus (NIDDM) patients. RESEARCH DESIGN AND METHODS - In this double-blind placebo-controlled study, 36 NIDDM patients were treated for 8 weeks with ginseng (100 or 200 mg) or placebo. Efficacy was evaluated with psychophysical tests and measurements of glucose balance, serum lipids, aminoterminalpropeptide (PIIINP) concentration, and body weight. RESULTS - Ginseng therapy elevated mood, improved psychophysical performance, and reduced fasting blood glucose (FBG) and body weight. The 200-mg dose of ginseng improved glycated hemoglobin, serum PIIINP, and physical activity. Placebo reduced body weight and altered the serum lipid profile but did not alter FBG. CONCLUSIONS - Ginseng may be a useful therapeutic adjunct in the management of NIDDM.
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The binding of steroids to human ejaculated spermatozoa and the effect of steroids bound to spermatozoa on sperm migration and motility in vitro was examined. A correlation between progestogens that bind to steroid-binding sites on human spermatozoa and progestogens that inhibit sperm migration was established. The results indicated that there is a direct and specific steroid effect on human spermatozoa, as some steroids such as progesterone, lynestrenol, and norethynodrel markedly inhibited sperm migration and motility, whereas other steroids such as estrone had no detectable effect on sperm migration and motility. The significance of these findings was discussed in relation to the contraceptive action of steroids applied directly to the lumen of the female genital tract.
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The effects of steroid hormones on motility and selective migration of X- and Y-bearing human spermatozoa were studied. Speed of migration was measured in a modified Kremer tube. To a 50 mcl sample of ejeculate physiologic levels of sex steroid hormones (17betaestradiol; estriol .5 ng/ml; testosterone; progesterone; lynestrenol; and norgestrel 5 ng/ml) or 200-fold higher concentrations were added and the maximal distance of migration was evaluated after 15 30 and 60 minutes. Estrogens and testosterone accelerated spermatozoal migration while gestagens had an inhibitory effect. 17-beta-estradiol was most effective (p less than .0005) in stimulating the motility of human sperm atozoa while norgestrel caused the strongest inhibition of forward movem ent (p less than .005 at 15 minutes and p less than .0005 at 30 and 60 minutes). Migration of X- and Y-bearing spermatozoa was most altered after longer distances of migration shown by an increase in the percentage of Y-bearing spermatozoa from 43.7% to 63.3% at a distance of 90 mm. Prolongation of migration time to 36 hours caused a reduction in the percentage of Y-bearing spermatozoa at the 90-mm distance from 63.3% to 46%. Specific differential effects of hormones on the pattern of spe rmatozoa were not observed.
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Expression of progesterone receptor (PR) localization on spermatozoa was determined in men with normal and abnormal spermiograms. Studies were also carried out to evaluate the potential of PR as a marker of sperm function. Progesterone receptor expression on spermatozoa from men with normozoospermia (n = 8), oligozoospermia (n = 7), asthenozoospermia (n = 8), oligoasthenozoospermia (n = 7), and teratozoospermia (n = 11) was analyzed using an immunocytochemical method with monoclonal antibodies against PR, and flow cytometry using a cell-impermeable fluorescein-tagged progesterone coupled to BSA complex (P-FITC-BSA). Both methods revealed significantly fewer (P < 0.05) PR-positive spermatozoa in men with oligozoospermia, asthenozoospermia, oligoasthenozoospermia, and teratozoospermia compared with men with normozoospermia, thereby suggesting that down-regulation of PR expression in spermatozoa may be one of the causes of male infertility. Spermatozoa from men with normozoospermia (n = 12), oligozoospermia (n = 12), asthenozoospermia (n = 12), oligoasthenozoospermia (n = 9), and teratozoospermia (n = 10) were exposed to low osmotic conditions in the hypoosmotic swelling (HOS) test and then analyzed for PR expression using P-FITC-BSA complex. A significantly higher percentage (P < 0.05) of spermatozoa with physiologically active plasma membrane (HOS+) lacked PR expression (HOS+PR−) in all categories of men with infertility, thereby suggesting that compared to the HOS test, PR expression is a better indicator of sperm function. Furthermore, PR expression in spermatozoa showed a strong (P < 0.05) positive correlation with their ability to undergo an in vitro acrosome reaction. This was observed in all study groups (i.e., normozoospermia, r = 0.8545; oligozoospermia, r = 0.8711; asthenozoospermia, r = 0.7645; oligoasthenozoospermia, r = 0.9003; and teratozoospermia, r = 0.8676). This suggests a potential role for PR in the events leading to the acrosome reaction in sperm.
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The cAMP-responsive element modulator (CREM) is involved in regulating gene expression in haploid spermatids. Transcriptional activity of the CREM protein is thought to be regulated by activator of CREM in the testis (ACT). Applying RT‐PCR and in situ hybridization, cell-specific gene expression of ACT was demonstrated in man, cynomolgus monkey and mouse. During normal spermatogenesis, RT‐PCR revealed a strong signal in all three species. We sequenced monkey ACT cDNA and demonstrated that the putative amino acid sequence is highly conserved between these species. In situ hybridization demonstrated ACT mRNA in mid and late pachytene spermatocytes and in round spermatids. Among four infertile men with round spermatid maturation arrest (RSMA), only one patient revealed a strong signal for ACT, while three patients displayed a weak signal for both RT‐PCR and in situ hybridization, although germ cells normally expressing ACT were present in these patients. In addition, CREM knockout mice known to be infertile due to RSMA also exhibited only a weak amplification product for ACT cDNA. ACT mRNA was barely detectable in some round spermatids, but was completely absent in pachytene spermatocytes. Database search revealed two and one CRE within the putative human and mouse ACT promoters respectively. Our findings indicate a conserved function of ACT during the evolution of mammalian spermatogenesis and suggest a role for CREM in ACT transcriptional regulation.
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In Brief Erectile dysfunction is one of the most common complications of diabetes and also one of the most underdiagnosed. Providers need to understand the pathophysiology of this condition in their diabetic patients and make an effort to diagnose and treat it. By doing so, they will improve their patients' quality of life.
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In this study, we used flow a cytometric assay to evaluate plasma membrane integrity and mitochondrial activityin post-thawed sperm that was supplemented with ginsenoside-Rg 1. Varying concentrations of ginsenoside-Rg 1 (0, 25,50 and 100 μM/ml) were used in the extender during cryopreservation to protect the DNA of thawed sperm, therebyincreasing the viability and motility rate as evaluated using a computer-assisted sperm analysis (CASA) method. Theresults derived from CASA were used to compare the fresh, control, and ginsenoside-Rg 1 groups. Sperm motility andthe number of progressively motile sperm were significantly (p<0.05) higher in the 50 μM/ml ginsenoside-Rg 1 group(61.0±4.65%) than in the control (46.6±7.02%), 25 μM/ml (46.2±4.76%), and 100 μM/ml ginsenoside-Rg 1 (52.0±1.90%) groups. However, the velocity distribution of post-thawed sperm did not differ significantly. Membraneintegrity and MMP staining as revealed using flow cytometry were significantly (p<0.05) higher (91.6±0.82%) in the50 μM/ml ginsenoside-Rg 1 group than in the other groups. Here, we report that ginsenoside-Rg 1 affects the motility and viability of boar spermatozoa. Moreover, ginsenoside-Rg 1 can be used as a protective additive for the suppression of intracellular mitochondrial oxidative stress causedby cryopreservation.
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The purpose of the study was to investigate the effects of two constituents of Panax notoginseng flower extract, Ginsenoside Rb2 and Rc, on human sperm motility and proression in vitro. Semen samples were collected from 20 patients with sperm motility between 20% and 40% of normal. All samples had sperm counts of over 20 million per milliliter, in accordance with the World Health Organization standard. Sperm were separated by a Percoll discontinuous gradient technique, and divided into a Percoll sperm control group, and three Ginsenoside Rb2 experimental groups (0.1, 0.01 and 0.001 mg/ml) and three Ginsenoside Rc experimental groups (0.1, 0.01 and 0.001 mg/ml). The results showed that at concentrations of 0.01 mg/ml and 0.001 mg/ml, Ginsenoxide Rc enhanced both sperm motility and sperm progression significantly at the end of the 1st and 2nd hour. However, the three concentrations of Ginsenoside Rb2 did not increase sperm motility at the 1st or 2nd hour, but promoted sperm progression at the 2nd hour, when compared to the Percoll group.