Ginseng Berry, a Promising Anti-Aging Strategy: Recent Opinions on the Biological Effects of a Traditional Korean Ingredient

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.

Rate this post

Viết một bình luận