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Chapter 8
Prosexual Effects of Lycium Barbarum
Benson Wui-Man Lau, Mason Chin-Pang Leung, Kai-Ting Po,
Raymond Chuen-Chung Chang and Kwok-Fai So
B. W.-M. Lau () · R. C.-C. Chang
LKS Faculty of Medicine, Department of Anatomy, The University of Hong Kong,
Pokfulam, Hong Kong
e-mail: benson.lau@polyu.edu.hk
B. W.-M. Lau · M. C.-P. Leung · K.-T. Po
Department of Rehabilitation Sciences, The Hong Kong Polytechnic University,
Kowloon, Hong Kong, People’s Republic of China
K.-F. So
LKS Faculty of Medicine, Department of Ophthalmology, The University of Hong Kong,
Pokfulam, Hong Kong, People’s Republic of China
R. C.-C. Chang · K.-F. So
The State Key Laboratory of Brain and Cognitive Science, The University of Hong Kong,
Pokfulam, Hong Kong, People’s Republic of China
R. C.-C. Chang · K.-F. So
LKS Faculty of Medicine, Research Centre of Heart, Brain, Hormone and Healthy Aging,
The University of Hong Kong, Pokfulam, Hong Kong, People’s Republic of China
R. C.-C. Chang · K.-F. So
GMH institute of Central nervous System Regeneration, Guangdong Key Laboratory of Brain
Function and Diseases, Jinan University, Guangzhou, People’s Republic of China
Abstract Lycium barbarum, also known as wolfberry, has been commonly used
as an oriental herb in China for a long period. Wolfberry is suggested to be antiag-
ing and used to maintain health of kidneys, liver, and the eyes. In the practice of
traditional Chinese medicine, wolfberry was also prescribed for patients who suf-
fered from dysfunctions of sexual desire. Although it has been put into application
for a long history, the underlying mechanism is still elusive. In the past decades,
increasing lines of evidence support the roles of wolfberry in promoting male sex-
ual functioning. The benefit of wolfberry was shown on different aspects includ-
ing preventing the reproductive tissues from oxidative insult, improving motility
of sperm, maintaining a testosterone level, and promoting sexual performance of
the hemicastrated rats. This chapter discusses on the recent research findings, both
from bench and bedside, which support the prosexual function of wolfberry, and
discusses the potential clinical application of wolfberry on the treatment of sexual
behavior.
© Springer Science+Business Media Dordrecht 2015
R. C-C. Chang, K-F. So (eds.), Lycium Barbarum and Human Health,
DOI 10.1007/978-94-017-9658-3_8
114 B. W.-M. Lau et al.
Keywords Wolfberry · Lycium barbarum · Sexual behaviors · Mating ·
Reproduction · Aphrodisiac
The prosexual and fertility effect of wolfberry was first described by the Chinese
herbalist Li Shizhen (Wang et al. 2002). While in traditional Chinese medicine
(TCM) practice, wolfberry is commonly prescribed for sexual dysfunction, the ben-
eficial effect of wolfberry on reproduction provided by scientific methodology has
just investigated in the past two decades.
8.1 Beneficial Effect of Wolfberry on Sexual Behavior
The first evidence which supports the prosexual effect of wolfberry polysaccharide
on live animals was reported by Luo et al. (2006). Lycium barbarum polysaccharide
(LBP) treatment for 22 days was shown to attenuate the impaired copulatory per-
formance caused by hemicastration in rats, which is shown by markedly shortened
penis erection latency, mounts latency, and increased successful mount percentage.
Interestingly, the sexual performance of rats with LBP treatment is even slightly
better than that of normal rats. In parallel to the sexual behavior, sex hormones
in plasma and the weight of accessory reproductive organ are also maintained in
hemicastrated rats treated with LBP. To elucidate the protective effect at cellular
level, the authors also tested the protective effect of LBP on testicular tissues. When
being subjected to hyperthermia, rat testis tissues were found to have decreased
weight and superoxide dismutase (SOD) activity, which is associated with a struc-
tural damage of the seminiferous tubules. Pretreatment with LBP before the heat
exposure was able to prevent the abovementioned damage on the testicular tissue.
Furthermore, treatment with LBP in vitro also prevented the deoxyribonucleic acid
(DNA) damage caused by H2O2. These findings support the traditional Chinese
viewpoint that wolfberry is an aphrodisiac agent and may facilitate fertility by sci-
entific evidence.
Apart from TCM practice, wolfberry was also adapted as a remedy to improve
sexual functioning in Korea (Sohn et al. 2008). An herbal formulation consists of
the seeds of wolfberry and other herbs were tested for its effect on penile erection.
After treatment for 4 weeks, the intracavernosal pressure was found to increase
markedly in medicated animals, which indicate that erection was promoted. Simul-
taneously, an expression of nNOS and eNOS (neuronal and endothelial nitric oxide
synthase, respectively), which generate nitric oxide as a vasodilator, was also found
to be upregulated by the medication. These observations suggested that the herbal
mixture may promote male copulatory function by promoting penile erection.
A study conducted by Lau et al. tested whether the LBP could counteract the
sexual-suppressing effect of high dose corticosterone (Lau et al. 2012). As several
studies suggested that neurogenesis (i.e., production of new functional neurons)
115
8 Prosexual Effects of Lycium Barbarum
may be an essential mediator of sexual behavior and newborn neurons may have an
important role in the regulation of sexual behavior (Lau et al. 2011; Leuner et al.
2010), the authors examined whether neurogenesis takes roles in the prosexual ef-
fect of LBP and the association between LBP treatment, sexual behavior, and neu-
rogenesis. The results of the study indicated that LBP facilitated male sexual behav-
ior by significantly increased copulatory efficiency (CE) and ejaculation frequency
(EF), and decreased ejaculation latency (EL). LBP at dosage of 1 mg/kg showed the
most significant effect than a higher dosage of 10 mg/kg.
Furthermore, LBP also significantly reversed the inhibited sexual behav-
ior induced by corticosterone in intromission latency (IL) and CE and reversed
suppressed neurogenesis induced by corticosterone in terms of number of BrdU-
positive cells in subventricular zone (SVZ) and hippocampus. LBP also promotes
the neuronal differentiation of neural precursor cells as shown by DCX staining.
Moreover, the study further revealed that sexual performance is correlated with
neurogenesis in SVZ and hippocampus and the direct relationship is examined by
comparing BrdU-positive cells and sexual behavior between blocking neurogenesis
in LBP treatment group and control group. After blocking neurogenesis, the rats
showed impaired sexual performance, which indicate the necessity of neurogenesis
in sexual functioning. This study demonstrated the enhancing effect of LBP on male
sexual behaviors in rats, the association between neurogenesis and the causal rela-
tionship between neurogenesis and sexual behavior. As newborn neurons may have
an important role in the regulation of sexual behavior, this study suggests that LBP
may promote sexual behavior through the regulation of neurogenesis.
A randomized controlled clinical study was conducted to investigate the effect of
a drink which was prepared from wolfberry (“Goji Juice GoChi”) on general health
of human subjects (Amagase and Nance 2008). The drink was prepared from fresh
wolfberry, with a daily serving which is equivalent to at least 150 g of fresh wolf-
berry. Questionnaires were used to evaluate subjective well-being after consuming
the drink for 14 days. In comparing to the placebo group, the subjects who had
the wolfberry drink responded with a significantly higher energy level, feeling of
health and exercise performance, and reduction in fatigue and stress. Interestingly,
more than half of the female subjects consumed the juice reported decrease in pain
during their mentrual period, and a few subjects in the treatment groups stated they
had increased sexual ability and activity. Since these aspects on reproduction were
not the main foci of the randomized controlled trial (RCT), no dedicated instrument
and analysis were used to evaluate the difference between the treatment and pla-
cebo groups. Another study reported by the same research group indicated that after
chronic consumption of the wolfberry drink for 30 days, the in vivo antioxidant
markers including SOD and glutathione peroxidase (GSH-Px) in the plasma were
upregulated (Amagase et al. 2009), which exposed the antioxidant properties of the
wolfberry drink on human. As oxidative stress may be one of the underlying mecha-
nisms of sexual inhibition and infertility, the antioxidant action of wolfberry drink
in human may be linked to the prosexual effect reported by the previous study. Nev-
ertheless, the effect on the subjective feelings on human sexual function would be
116 B. W.-M. Lau et al.
worthwhile for future RCT experiment. As increasing lines of evidence showed the
prosexual effect of wolfberry in laboratory animals, further studies on the potential
reproductive effect of wolfberry on human would be valuable for the translation of
laboratory studies to clinical applications.
8.2 Protective Effect of Wolfberry on Reproductive
Tissues
Since wolfberry has been shown to exert its effect by its antioxidant activity, it
was hypothesized that antioxidation is a mechanism that underlies the beneficial
effect of wolfberry on reproductive function. As a by-product of intracellular res-
piration, reactive oxygen species (ROS) are reactive molecules which may damage
the reproductive tissues if in excess amount (Balaban et al. 2005). ROS species
including hydroxyl ions, superoxide, and nitric oxides are generated in the testis
during steroidogenesis and spermatogenesis (Mathur and D’Cruz 2011). While an
appropriate level of ROS is required for the normal functioning of the testis tissue
and sperms, an excessive amount of ROS is detrimental to the sperms as the sperms
are highly sensitive to peroxidation due to the rich content of polyunsaturated fatty
acids (PUFA) on the plasma membrane. A proper balance between the ROS and an-
tioxidants is thus needed to maintain the functioning of the reproductive tissues and
sperms. As antioxidants were found in various edible plants (Clément et al. 2012),
it is suggested that plant-derived feed supplements may inhibit the oxidative stress
in livestocks and may promote both fertility and reproductive functions. One of the
food supplements that received increasing attention is wolfberry.
Different studies have investigated the protective effect of wolfberry on repro-
ductive tissues by both in vivo and in vitro methods, and tried to determine whether
wolfberry exerts its effect through its antioxidant properties. The protective effect
of wolfberry polysaccharides on testicular tissue was firstly shown in a tissue cul-
ture study (Wang et al. 2002). When seminiferous epithelium was cultured for a
prolonged period and at a relatively high temperature, structural degradation was
induced in terms of increase in intercellular space and appearance of multinucleated
spermatids, which is due to the impaired spermatogenesis. Inclusion of wolfberry
polysaccharide in the culture medium reduced the structural damage caused by the
lengthened culture time and hyperthermia. The spermatozoa were also found to be
more motile when treated with LBP. The reduced structural damage is accompanied
with a decrease in apoptotic rate of epithelium cells and reduction in oxidative stress
(illustrated by ultraviolet C light induced lipid peroxidation and superoxide induced
cytochrome c reduction). The authors suggest that the protective effect of LBP may
be due to its antioxidant properties.
In another study conducted by Zhang et al. showed that LBP could protect the
spermatogenesis in testis caused by Bisphenol A (BPA) (Zhang et al. 2013). BPA is
a commonly found monomer in plastic wares and widely used in adhesive and den-
117
8 Prosexual Effects of Lycium Barbarum
tal fillings (Podlipna and Cichna-Markl 2006). Despite its wide range of applica-
tions, BPA was found to decrease the weight of testis, induce apoptosis in spermato-
genic tissues, decrease testosterone levels and increase the rate of infertility in rats
(Li et al. 2009; Podlipna and Cichna-Markl 2006; Xiao et al. 2011). Interestingly,
LBP was shown to prevent the retardation of reproductive function in rats caused
by BPA. First, LBP was shown to increase the weight of testis and epididymis in
BPA-treated rats, although not to a level comparable to the normal controls. Sec-
ond, LBP was shown to prevent the decrease in the level of sex hormones caused
by BPA. Third, the proapototic marker, Bax was found to decrease after LBP treat-
ment. Finally, oxidative stress was also suppressed by the LBP. These data suggest
that LBP would mitigate the damage of testicular tissues from BPA by suppressing
apoptosis and oxidative stress, while further exploration of the fertility of the rats
after BPA and LBP treatment would support the use of wolfberry in reproductive
function against toxic agents on reproductive system.
Another study explored whether pretreatment with LBP could ameliorate the
detrimental effect on reproductive system caused by doxorubicin (DOX), an antitu-
mor drug used in the treatment of solid and hematological tumors (Xin et al. 2012).
Aside from its side effect on cardiopulmonary and excretory system (Minotti et al.
2004), DOX also causes toxicity on testicular tissue and spermatozoa manifested
in decreasing quantity and motility of sperm, increasing the rate of abnormal sperm
production and increasing apoptosis in the spermatogenesis process. Being similar
to the abovementioned studies, the authors hypothesized that oxidative stress is
a major underlying mechanism of the disturbed reproductive function. Evidences
indicated that the weight of the testis and epididymis in DOX-treated male rats was
preserved by LBP.
Morphologically, degenerative changes including depletion of germ cells, ir-
regular seminiferous tubules and scarcity of spermatogonia were caused by DOX,
which could be prevented by LBP. While LBP does not show any effect on sperm
quantity and quality in healthy rats, it effectively prevented the decline of sperm
quantity and quality which is induced by DOX. Furthermore, the increased oxida-
tive stress in testicular tissues caused by DOX, indicated by the level of malondi-
aldehyde (by-product of lipid peroxidation) and GSH-peroxidase (a scavenger of
free radicals), was attenuated by LBP. Again, the evidence suggests that LBP may
be a potential adjunct therapy for the protection of reproductive organs through the
regulation of oxidative stress.
Different lines of evidence showed that ionizing irradiation has damaging effects
in male reproductive system (Bonde 2010) and testicular spermatogenic cells were
highly sensitive to ionizing irradiation. Cancer patients receiving radiotherapy or
people working with radioactive substances often had infertility and sexual dys-
function (Hasegawa et al. 1997). A study attempted to elucidate whether LBP could
protect the reproductive tissues from ionizing irradiation-induced reproductive cell
damage (Luo et al. 2011). Male rats were exposed to various levels of ionizing ir-
radiation and then cotreated with LBP. After the experiment, sperm count, their mo-
tility, erection latency, sexual behavior, serum hormone, DNA damage in testicular
118 B. W.-M. Lau et al.
cells, and protein content of testicular tissues were tested. The result showed that in
irradiated animals, sperm count and their motility were significantly reduced. More-
over, erection latency, mounting, and ejaculation latencies were extended, serum
testosterone levels was lower and DNA damage in testicular cells were observed
after exposing to ionizing irradiation. The longer the exposure to ionizing irradia-
tion, the greater the deleterious effect will be found. Cotreatment with LBP was
shown to significantly alleviate the detrimental effect on the reproductive tissues.
The author suggested that LBP could repair the damage in testicular cells caused
by ionizing irradiation, regulate the serum testosterone level, and protect testicu-
lar cells against deleterious effects of free radicals caused by ionizing irradiation.
A subsequent study conducted by the same group showed that LBP upregulates
the expression of antiapoptotic protein Bcl-2, downregulated proapoptotic Bax
and maintain the mitochondrial membrane potential of testicular tissues (Luo et al.
2014), which suggests that LBP may have antiapoptotic effects against irradiation.
Owing to the traditional viewpoint that wolfberry is aphrodisiac and its availabil-
ity is at low cost, the potential profertility effect of wolfberry in female has drawn
the attention of research groups as early as the 1970s (Suzuki et al. 1972). In a study
conducted by Suzuki and coworkers, intravenous injection of crude water-soluble
extract of Lycium Chinense, another species of wolfberry or goji berry, induced
ovulation in rabbits (Suzuki et al. 1972). However, due to the lack of an appropriate
control group in the abovementioned study, whether the ovulation is induced by the
wolfberry extract or due to other confounds remains to be determined.
Huang et al. studied the effect of LBP on in vitro maturation of the female gam-
ete (Huang et al. 2008). Interestingly, when frozen oocyte with cryoprotection was
thawed and treated with LBP in culture conditions, the maturation rate was signifi-
cantly higher than the traditional sucrose medium. However, while the maturation-
promoting action was attributed to the influence on solution viscosity and osmolal-
ity, it is unknown of whether the effect is specific to the wolfberry.
In a case study, concentrated herbal extracts (Zuo-gui-wan), which contains
cooked wolfberry and other herbs such as dogwood fruit and cyathula root, was
used to treat a woman with premature ovarian failure and secondary amenorrhea
(Chao et al. 2003). After 3 months of therapy, ovulation return and the woman con-
ceived successfully.
Interestingly, wolfberry was found to benefit not only the adult animals but also
offsprings when they are exposed to it during the gestation period (Feng et al. 2010).
It was found that prenatal stress resulted in a significant decrease in cognitive func-
tion in female offspring, which could be prevented significantly by pretreatment
of mother rats with milk-based wolfberry. After the pretreatment with wolfberry
polysaccharide for 2 weeks, female rats were allowed to mate. Then, the pregnant
female subjects were restrained by a transparent plastic tube on days 14–20 of preg-
nancy three times daily from 45 min to 1 h. The female offspring were subsequently
tested at 1 month of age. Morris Water Maze was used to test the spatial memo-
ry and the offspring rats were sacrificed to test the oxidative brain mitochondrial
119
8 Prosexual Effects of Lycium Barbarum
damage. The result showed that prenatal restraint stress induced memory and learn-
ing deficiency of female offspring, but not in male offspring, while middle and high
doses wolfberry pretreatment significantly reduced the impairment. In vitro studies
by the authors showed that wolfberry dose dependently scavenged hydroxyl and
superoxide radicals and inhibited ascorbic acid-induced dysfunction in brain tissue
and tissue mitochondria.
When comparing to male, the effect of wolfberry on female reproductive func-
tion and offspring remains unclear and only a few limited reports studied the ef-
fect. There is a lack of supportive scientific evidence on the effect of wolfberry on
female sexual behavior and reproduction. However, as it was shown that wolfberry
could increase the levels of plasma sex hormones and protect the male gametes, it is
likely that female reproductive system may be benefited by the herb. The support-
ing evidence from empirical studies will definitely strengthen the clinical usage of
wolfberry in practice, and even as a food supplement.
In conclusion, evidence of L. barbarum’s prosexual effect has been found at
different levels of organisms, namely: molecular level, biochemistry level, cellular
level, tissue level, behavior level. Also, it improves the general well-being of hu-
mans. We have summarized all these effects in Table 8.1.
Conclusion
Apart from protecting the DNA and alleviating the reproductive tissue damage due
to hypothermia, oxidative stress, and radiation, the fruit also protects testis from
damage by environment pollutant like BPA. Female fertility is also restored by a
herbal medicine containing wolfberry. The fruit also shows protective effect to the
cognitive function of offspring with prenatal stress. Different pieces of evidence
have shown that L. barbarum would be an all-round aphrodisiac agent that not
only improves the sexual function of male individual and the fertility of female,
but also the general health of both male and female. These beneficial effects imply
L. barbarum would be a potent functional food. Nevertheless, the drug interaction
between the fruit and common drugs, especially drugs for chronic diseases, still
need to be clarified, in order to utilize wolfberry as an adjunctive therapy for sexual
dysfunctions. Yet, further studies may be needed to determine the therapeutic dos-
age of wolfberry as the quality control of the fruit and the active components are
still being elusive.
120 B. W.-M. Lau et al.
Sex of
subjects
Reproductive
stages
Species or experimen-
tal model
Effect of wolfberry component Reference
Male ♂ Mating Rats, hemicastrated Shortened penis erection latency, mounts latency Luo et al. 2006
Increased successful mount percentage
Rats Promote penile erection Sohn et al. 2008
Penile expression level of eNOS/nNOS increased
Rats, treated with high
dose corticosterone
Increase CE and ejaculation frequency Lau et al. 2012
Decrease ejaculation latency
Reverse suppressed neurogenesis in subventricular zone and hippocampus
Rats, hemicastrated Improve CE of hemicastracted rats Luo et al. 2006
Mouse testicular tissue
Prevent the structural damage of the seminiferous tubules
Prevent DNA damage caused by H2O2
Mouse seminiferous
epithelium
Reduced structural damage of seminiferous epithelium Wang et al. 2002
More motile spermatozoa
Rats, with BPA
treatment
Prevent detrimental effect caused by BPA in terms of: increase the weight of
testis and epididymis
Zhang et al. 2013
Prevent the decrease in the level of sex hormones
Decreased level of proapototic marker, e.g., Bax
Suppressed oxidative stress
Rats, treated with
DOX
Prevents detrimental effect caused by DOX in terms of: preserved weight of the
testis and epididymis—prevent degenerative changes (depletion of germ cells,
irregular seminiferous tubules and scarcity of spermatogonia)
Xin et al. 2012
Prevent the decline of sperm quantity and quality
Attenuate the increased oxidative stress in testicular tissues
Table 8.1 Summary of the prosexual effect of Wolfberry
121
8 Prosexual Effects of Lycium Barbarum
Sex of
subjects
Reproductive
stages
Species or experimen-
tal model
Effect of wolfberry component Reference
Rats, exposed to ion-
izing radiation
Prevents detrimental effect caused by ionizing radiation in terms of: repair the
damage in testicular cells
Luo et al. 2011
Regulate the serum testosterone level and
Maintain histological integrity of testicular tissue
May have antiapoptotic effects against irradiation Luo et al. 2014
Female♀ Mating Rabbits Induce ovulation after injection of crude extract of wolfberry Suzuki et al. 1972
Mating Frozen porcine oocyte Increase maturation rate Huang et al. 2008
Gestation Human, single case A woman with premature ovarian failure and secondary amenorrhea had ovu-
lation returned and conceived after 3 months of therapy
Chao et al. 2003
Offspring Rats, offspring Reduce the impairment in memory and learning deficiency of female offspring
which were subjected to prenatal stress
Feng et al. 2010
Both
sexes
Mating Normal human Drinking wolfberry juice showed Amagase and
Nance 2008, 2009
Subjective report of increased sexual ability and activity
Elevated level of in vivo antioxidant markers including SOD and GSH-Px in
plasma
eNOS endothelial nitric oxide synthase, nNOS neuronal nitric oxide synthase, CE copulatory efficiency, DNA deoxyribonucleic acid, B PA bisphenol A, DOX
doxorubicin, SOD superoxide dismutase, GSH-Px glutathione peroxidase
Table 8.1 (continued)
122 B. W.-M. Lau et al.
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