Review Article
Open Access
Ginseng Berry, a Promising Anti-Aging Strategy: Recent
Opinions on the Biological Effects of a Traditional Korean
Ingredient
Juewon Kim1,2#, Si Young Cho1#, Su Hwan Kim1, Sunmi Kim1, Chan-Woong Park1,
Hyun Woo Park1, Dae Bang Seo1*, Song Seok Shin1*
1R&D Unit, Amore Pacific Corporation, Yongin-si, Gyeonggi-do 446-729, Republic of Korea, Japan
2Department of Integrated Biosciences, University of Tokyo, Chiba 277-8562, Japan
*Corresponding author: Dae Bang Seo, Beauty Food Research Institute, R&D Unit, AmorePacific Corporation, Yongin-si, Gyeonggi-do 446-729,
Republic of Korea; Tel: +82 31 280 5975; E-mail:
Song Seok Shin, Beauty Food Research Institute, R&D Center, AmorePacific Corporation, Yongin-si, Gyeonggi-do 446-729, Republic of Korea; Tel: +82 31
280 5601; E-mail:
Dae Bang Seo, Beauty Food Research Institute, R&D Unit, AmorePacific Corporation, Yongin-si, Gyeonggi-do 446-729, Republic of Korea; Tel: +82 31 280 5975; E-mail: @ Song Seok Shin, Beauty Food Research Institute, R&D Center, AmorePacific Corporation, Yongin-si, Gyeonggi-do 446-729, Republic of Korea; Tel: +82 31 280 5601; E-mail: @
Received: August 12, 2015; Accepted: December 07, 2015; Published: January 01, 2016
Citation: Kim J, Cho SY, Kim SH, Kim S, Park CW, et al. (2016) Ginseng Berry, a Promising Anti-Aging Strategy: Recent Opinions on
the Biological Effects of a Traditional Korean Ingredient. J Adv Res Biotech 1(2): 8. DOI:
Kim J, Cho SY, Kim SH, Kim S, Park CW, et al. (2016) Ginseng Berry, a Promising Anti-Aging Strategy: Recent Opinions on the Biological Effects of a Traditional Korean Ingredient. J Adv Res Biotech 1(2): 8. DOI: http://dx.doi.org/10.15226/2475-4714/1/2/00101
Abstract
A recent effort in the development of new medications and
immune modulatory agents is to search for candidates among
natural products because they have relatively low toxicities in clinical
applications. Ginseng root has been used as a traditional medicine
in Korea, Japan and China and has demonstrated efficacy against
various human diseases, such as cancer, viral infectious diseases,
diabetes, and atherosclerosis. Recent observations and clinical
studies have elevated the interest in the potential health effects
of the ginseng berry, an association that appears to be due to the
phytochemical content of this fruit. The ginseng berry has various
bioactivities, such as anti-diabetic, anti-cancer, anti-inflammation,
anti-oxidation, anti-neuro degeneration, and enhancement of sexual
function bioactivities. Moreover, the effective anti-aging component
of the ginseng berry, syringaresinol, has the ability to stimulate
longevity via gene activation. Further molecular and clinical studies
are necessary to elucidate the numerous bioactive substances in the
ginseng berry that contribute to public health.
Keywords: Ginseng Berry; Ginsenoside Re; Syringaresinol;
Panax Ginseng; Bioactive; Phyto Chemical
Introduction: Ginseng and the Ginseng berry
Ginseng (Panax ginseng) is a popular herbal medicine that
has been used in Asia for 5,000 years [1]. Ginseng is classified as
fresh, white, or red ginseng, depending on the processing method.
As a traditional herb, red ginseng is known as an adaptogen
that restores and improves normal well-being. The use of this
herbal plant has been widespread throughout the world because
of its therapeutic effects. The well-known biochemical and
pharmacological effects include anti-cancer [2], anti-fatigue [3],
and anti-diabetic effects [4], along with promoting the synthesis
of DNA, RNA and proteins [5]. The herb is used as a tea, an extract,
or raw directly from powdered root [6]. The representative
bioactive compounds are widely considered to begin senosides, which are ginseng-specific saponins [7]. Currently, more than
100 naturally occurring saponins of various types and products
of enzymatic conversion have been isolated from the roots,
stems, leaves, flowers, berries, and seeds of ginseng. The different
parts of ginseng contain distinct ginsenoside profiles, and thus,
different parts probably possess different pharmacological
effects [8].
Recently, many health reports have recommended an
increase in fruit intake as part of a healthy dietary pattern
[9,10]. These reports allow for various forms of fruit, including
fresh, frozen, and dried, as well as juices, and recommend fruits
such as oranges, apples, bananas, grapes, raisins, and berries.
Whereas berries are known as a good source of potassium or
fiber, recent studies suggest that berry fruits are a rich source of
many phytochemicals that have a broad spectrum of bioactivity
and a positive impact on general health. Several berry fruits,
including blackberries, blueberries, cranberries, raspberries,
and strawberries, have recently received attention as a result of
their effects in vitro and their associations with lowered risks for
some chronic diseases, which were found in recent observational
research [11,12]. As a perennial herb, ginseng develops flowers
and fruits that bloom in its third and fourth year. Unlike the
widely used ginseng root, the ginseng berry is preserved for
planting and has not been used by general populations. A recent
study reported that the ginseng leaf and berry have higher levels
of ginsenosides than ginseng root, and their pharmacological
activities have also been reported [13]. In this review, we will
summarize the research on the role of dietary ginseng berries in
delaying aging, as well as evidence suggesting positive biological
effects to prevent age-related diseases.
Ginseng Berry Bioactive Content and Composition
The bioactive components of ginseng are triterpene glycosides
or saponins, which are commonly regarded as ginsenosides. It has been reported that ginsenosides are the most effective
agents in ginseng in the treatment and prevention of cancer
and the regulation of blood glucose and blood pressure [14].
Ginsenosides are divided into three major groups based on the
triterpene aglycones panaxadiol, panaxytriol, and olenolic acid
derivatives [15]. Other chemical compounds from Panax ginseng
include alkenes, alkynes, sterols, fatty acids, mono-triterpenes,
phenyl propanoids, kairomones, carbohydrates (sugars and
polysaccharides), amines, flavonoids, organic acids and vitamins.
In addition to amino acids, nucleic acids, various enzymes and
inorganic compounds are obtained from ginseng [16]. More than
60 different types of ginsenoside have been identified that are
contained in the plant roots, leaves and fruits [17,18]. Because
different parts of the plant contain distinct ginsenoside content,
the pharmacological activity of the various parts of the plant may
be different. Recent studies have demonstrated that the ginseng
berry has a different ginsenoside profile and higher ginsenoside
content than the root [19]. Interestingly, among the ginsenosides,
ginseng berry extract contains high levels of ginsenoside Re,
amounting to almost more than 30-40 times that of ginseng
root, indicating that the ginseng berry may be a superior form to
ginseng root extract for ingesting a large amount of ginsenoside
Re [20]. In addition, ginseng berry extract contains larger
amounts of vitamin E, vitamin K, folic acid, and potassium than
the raw materials (i.e., skin, flesh, juice) of ginseng. Currently,
ginseng berry extract is being evaluated in clinical and preclinical
trials because its components are more efficacious as compared
to ginseng root extract.
Chemistry and Pharmacological Effects of
Ginsenoside Re
Ginsenosides are glycosides that contain an aglycone with
a dammarane (except Ro). They are divided into two groups
based on the type of aglycone: the proto panax adiol ginsenoside
group and the proto panaxa triolginsenoside group. Ginsenosides
possess different chemical structures due to variations in the
type of sugar moiety and the number and site of attachment.
Ginsenoside Re belongs to the proto panaxatriol group and
is a major component in ginseng leaf and berry, occurring in
much higher quantities than in root [13]. Previous studies have
shown that ginsenoside Re exhibits multiple pharmacological
activities via different mechanisms both in vivo and in vitro. First,
ginsenoside Re has anti-inflammatory effects, and it ameliorates
inflammation by inhibiting macrophage activation [21,22] and
regulating auto phagy [23]. Ginsenoside also has anti-diabetic
activities. Ginsenoside Re reverses insulin resistance in the
muscles of high-fat-diet-fed rats [24], and this effect is most likely
due to the inhibition of NFκB [25]. Moreover, ginsenoside Re
lowers blood glucose and lipid levels [26,27], as well as exhibits an
anti-diabetic effect in ob/ob mice [28]. It also reduces the oxidative
stress level in pancreatic beta-cells and diabetic rats [29,30] and,
interestingly, attenuates diabetes-associated cognitive deficits in
rats [31]. Several studies have suggested that ginsenoside Re has
protective effects and beneficial functions on the cardiovascular
system, such as contractive and electromechanical alternans
[32-35], anti-arrhythmic effects [33,36] nit-ischemic activity [37- 39], angio genic regeneration [40,41], and electrophysiological
activities of cardiac cells [42-45]. Ginsenoside Re also exhibits
neuro protective effects, and the beneficial effects of ginsenoside
Re on Alzheimer’s disease [46-48], Parkinson’s disease [49], and
depression [50] have been reported. The neuro protection of
ginsenoside Re is mediated by an anti oxidative effect [38,51],
the regulation of inflammatory mediators [52], and nitric oxide
signaling [53]. Some reports have proposed that ginsenoside Re
can promote sperm capacitation [54] and motility [55] and also
has an estrogenic effect [56]. Ginsenoside Re has demonstrated
angio genic effects in in vitro [41,57] and in vivo [40,41] models.
The multitude of pharmacological activities of ginsenoside Re
can be obtained by dietary ingestion of the ginseng berry. Oral
ingestion of ginseng berry extract results in significantly higher
absorption (0.33-0.75%) compared to the low oral bioavailability
of ginsenoside Re from ginseng root (0.19-0.28%) [20]. In
herbal or alternative medicine, a whole herbal extract might be
advantageous compared to isolated natural ingredients.
Ginseng Berry: Preventive and Therapeutic Roles
Because the ginseng berry has more abundant ginsenoside
content than the root parts [58] (Table 1), the ginseng berry not
only exhibits ginseng root-like effects but also has many other
specific biological activities. Moreover, in addition to ginsenoside
Re, the ginseng berry contains other bioactive components that
can be efficiently absorbed from dietary ginseng berry extract
[20] .Here, we review the pharmacological activities of a whole
extract of the ginseng berry as well as evidence suggesting the
potential of a novel anti-aging compound.
Anti-Diabetic Activity
Ginseng has received increasing attention as a complementary
and alternative medicine for the treatment of diabetes. Ginseng
extract treatment has been reported to have hypoglycemic
effects in animal models of type 1 and 2 diabetes [4,59]. A
previous study reported that ginseng berry extract exhibited
greater hypoglycemic activity as compared to the same dosage of
a root extract [60]. And the consumption of ginseng berry extract
increased insulin secretion and ameliorated hyperglycemia in
diabetic mice [61,62]. The anti-diabetic effects of the ginseng
berry that have been discussed focus on effective components
[63], reduced blood glucose levels [64-67] and administration
[68,69]. A recent study revealed that ginseng berry extract
improved insulin sensitivity in aged mice by increasing protein
levels of tyrosine phosphorylated insulin receptor substrate-1
and insulin resistance-related protein AKT [70]. According to
these results, the ginseng berry may ameliorate age-related
metabolic disorders, such as diabetes.
Anti-Cancer Activity
The reports from early studies demonstrated that ginseng has
strong immune-stimulatory properties, such as macrophage and
dendritic cell activation, proliferation, and viability of spleen cells
[71,72]. Recent studies have reported that the ginseng berry also
exhibits anti-cancer activity in in vitro [2,73-77] and in vivo [2,
78,79], as well as the ability to attenuate chemotherapy-induced side effects [80,81]; these effects result from the promotion of
dendrite cell maturation. Interestingly, the ginseng berry induced
a higher degree of co-stimulatory molecule up regulation than
the root extract at the same concentrations [82].These studies
indicate that the ginseng berry is an intense tumor therapeutic
vaccine adjuvant that can be used in investigations and clinical
research.
Anti-Inflammation and Anti-Oxidative Activity
Recent studies have reported that anti-inflammatory
compounds prevent the progression of atherosclerosis without
altering the blood lipid profiles in hyper lipidemic mice [83,84],
indicating that anti-inflammatory compounds may be used as
therapeutic agents for the treatment of inflammatory diseases.
The ginseng berry has been shown to suppress reactive
oxygen species production [85,86], NF-κB activation [19] and
inflammatory gene expression [87] in vitro and in vivo. The
ginseng berry suppressed atherosclerotic lesion development
by inhibiting NF-κB-mediated atherogenic inflammatory gene
expression through the induction of antioxidant enzymes
without lowering serum lipid levels in a hyper lipidemic mouse
model [19]. Moreover, chronic pretreatment with ginseng berry
attenuated oxidative stress in cardio myocytes [88] and up
regulated human umbilical vein endothelial cell proliferation and
migration [89]. These studies provide insight into the therapeutic
potential of the ginseng berry for the treatment of oxidative
stress and inflammation-related diseases.
Anti-Sexual Dysfunction
Sexual dysfunction has a severe impact on the quality of
life of affected individuals. Previous studies reported that more
than half of the male population has some degree of erectile
dysfunction [90] and one-third of the global male population,
across all ages, has some degree of premature ejaculation [91]. To
treat these symptoms, PDE5 inhibitors and selective serotonin
reuptake inhibitors are used; however, these drugs can produce
negative side effects, including headache, gastrointestinal
disorder, muscle pain and blurred vision and may have dangerous
interactions with other medications [92,93]. To avoid the risks
of side effects, people often turn to dietary ingredients, such as
ginseng. Ginsenosides have been shown to enhance nitric oxide
production by inducing nitric oxide synthase activity [94,95].
Recently, ginsenoside Rg1, which is abundantly present in the
ginseng berry, was also shown to improve male copulation
behavior via the nitric oxide/cGMP pathway [96]. Clinical
observation of patients after 8 week oral treatment indicated
that ginseng berry improved all domains of sexual function
including erectile dysfunction and premature ejaculation [97].
The ginseng berry had a greater relaxation effect on rabbit
corpus cavernosum smooth muscle than did ginseng root extract
and increased intra cavernosal pressure in a rat model in both a
dose- and duration-dependent manner. This relaxing effect might
be mediated by nitric oxide production [98]. According to these
studies, the ginseng berry can be used as an alternative medicine
for men with sexual dysfunction.
Anti-neuro Degeneration Activity
Continued research indicates the occurrence of neuronal
and behavioral deficits during aging, even in the absence of
neurodegenerative diseases such as Alzheimer’s diseases and
Parkinson’s diseases. There has been a growing interest in a
number of pharmacological approaches to help slow the rate
of both cognitive and functional declines associated with aging.
Recently, several dietary supplements with either straw berry
or blue berry extracts have been reported to reduce some
neurological deficits in animal models of aging [99,100]. Fruits
are beneficial in both forestalling and reversing the deleterious
effects of aging on neuronal communication and behavior [101].
Some of the actions reported to be elicited by ginseng include
an ability to induce effects within the central nervous system
that control functions related to stamina, fatigue, physical
stress, and the functions of memory, learning, and behavior
[102].A number of different cognitive tests have indicated
that ginseng exerts potential positive effects on memory and
learning performance in a variety of animal species [103-105].
In addition, herbal mixtures that contain ginseng have been
proven to improve cognitive performance [106].The neuro
active effects of free amino acids in ginseng seed and berries
have also been proposed [107].It has been suggested that one
potential mechanism by which the ginseng berry improves
various neurological functions is via an interaction with the
cholinergic and serotoninergic neurotransmitter systems. The suggestion of this pathway is supported by reports that
have shown that selective damage to serotonergic neurons
affects certain aspects of memory functions, specifically, spatial
working memory [108,109]. Moreover, one of the behavioral
paradigms found to be improved by ginseng and ginseng berry
supplementation was that of electroconvulsive shock, which is
known to modulate the cholinergic neurotransmitter system,
especially within brain areas, such as the hippocampus [110-
112]. It has also been proposed that ginseng and the ginseng
berry enhance the components of cholinergic systems, such as
choline acetyl transferase, which is also thought to be important
in the formation of memory [113-115]. Although there have
been a number of studies emphasizing the potential helpful
effects of ginseng on cognitive performance in animal models,
few epidemiological reports have been performed. In fact, a
comprehensive investigation of the literature found few studies
exploring the effects of ginseng on human cognitive performance,
in which significant improvement in mental arithmetic and
abstraction tests were reported [116-118].
Exploring other Bioactive Constituents in the
Ginseng Berry and Syringaresinol
Because of its numerous potent biological activities, there
have been many efforts to discover other useful components in
the ginseng berry besides ginsenoside. The ginseng berry has
many unique bioactive constituents compared to the generally
used ginseng root. Through various assays [13,119-122], a new
triterpenoid saponin, isoginsenoside-Rh3 [123], alkaloid ginsenine
[124] and a dammarane-type triterpene ketone, panaxadione [125,126], were isolated. Interestingly, ginsenoside-freemolecules promote ethanol metabolism [127]. Recently, a lignin compound, syringaresinol(4,4’-(1S,3aR,4S,6aR)-tetrahydro-1H,3H-furo[3,4-c]furan-a,4-diylbis(2,6-dimethoxyphenol)), was isolated from panax ginseng pulp and found to activate SIRT1
gene expression, leading to delayed cellular senescence and
improved endothelial cell function in endothelial cells [128].
Syringaresinol treatment induced the binding of FOXO3 to the
SIRT1 promoter in a sequence-specific manner, leading to the
induction of SIRT1 expression. Syringaresinol exists either
exclusively as one enantiomer or as enantiomeric mixtures in
plant foods. Recent studies revealed that (+)-syringaresinol,
but not (-)-syringaresinol, up regulates SIRT1 gene expression;
thus, the ginseng berry, with a predominantly high content of
(+)-syringaresinol, exhibits higher activity in inducing SIRT1
gene expression. Syringaresinol has enantio selective effects
upon biological activity [129]. Syringaresinol also has protective
effects against hypoxia/re oxygenation-induced injury.
Syringaresinol caused the destabilization of hypoxia-inducible
factor 1 following hypoxia/re oxygenation and then protected
cellular damage and death in a FOXO3-dependent mechanism
[130]. These findings strongly suggest that the ginseng berry has
potential as an effective anti-aging reagent.
Concluding Remarks
The ginseng berry is a rich source of dietary bioactivities and
has various biological activities in addition to that of the ginseng
root. It possesses higher ginsenoside content than its root, which
has been traditionally used in herbal medicine for many human
diseases and age-related attenuates. In this study, we reviewed
the biological and pharmacological activities of the ginseng berry,
including anti-diabetic, anti-cancer, anti-inflammation, antineuro
degeneration, and also sexual function effects. In addition,
an anti-aging component of the ginseng berry, syringaresinol,
has the potential for activating the longevity genes sirt1 and
foxo. According to numerous reports, the ginseng berry has the
potential to be widely used as an anti-aging reagent for many agerelated
human diseases and to increase vitality. Basic research has
suggested a number of potential mechanisms of action for ginseng
berry bioactive substances, although further molecular research
is necessary. Furthermore, the optimal dose of ginseng berry
bioactive substances has not been determined for urinary tractor
cardiovascular health. Another major deficiency concerning the
evaluation of existing clinical reports is the lack of quantification
of ginseng berry bioactive substances or assessment of their
concentration in blood or urine. There is potent experimental
evidence that ginseng berry bioactive substances have favorable
effects on blood glucose metabolism, blood pressure, oxidative
stress, inflammation, cancer, and endothelial function. As noted,
the average daily fruit consumption is substantially less than
what is recommended. In part, encouraging consumption of a
greater proportion of plant foods, including fruit, to achieve a
healthy dietary pattern will help to attain the recommended
dietary intake of micronutrients. Although reference intake
values have yet to be developed for phytochemicals, there is a
growing consensus that their bioactivities importantly contribute
Figure 1: The different constitutions and contents of ginseng berryand
root. Ginseng berry comprises approximately 20% ginsenoside
compared to 6% ginsenoside of root part. Especially, ginseng berry has
more than 30 to 40 times amount of ginsenoside Re than root (0.1%)
whereas root contains 1% of ginsenoside Rg1 and Rb1. Moreover ginseng
berry contains 2-3 times content of crude saponin and 20-30 times
of ginsenoside than root part. In addition, ginseng berry contains many
of vitamins, minerals, and polyphenols as well.
Table 1: Amount and contents of ginsenoside in ginseng berry, leaf and
root part.
Part
Ginsenoside (mg/g)
PPD
PPT
PPT/PPD
Rb1
Rb2
Rc
Rd
Re
Rg1
Rg2
Berry
8
20
21
18
100
19
9
1.9
Leaf
5
3
2
4
42
8
4
3.8
Root
9
3
10
3
4
5
1
0.4
Ginsenoside contents and amount of ginseng berry, leaf and root [58].
PPD: protopanaxadiol; PPT: protopanaxatriol.
to promoting public health and reducing the risk of chronic
diseases. Berry fruit, including the ginseng berry, represents an
especially rich source of many phenolic acids and flavonoids that
have been associated with these benefits. Additional research
that clarifies specific dietary guidance with regard to the type of
berry should help elevate our intake of these bioactive moieties.
Acknowledgements
All authors read and approved the final manuscript. I thank all
lab members for the discussions. In addition to their contribution
to the writing, D.B.S, S.S.S, and S.Y.C. outlined and co-edited this
article. S.H.K., S.K., C.P., and H.W.P depicted the Figure data of the
ginseng berry and Table 1.