Goji Berries as a Potential Natural Antioxidant Medicine: An Insight into Their Molecular Mechanisms of Action

Abstract

Goji berries (Lycium fruits) are usually found in Asia, particularly in northwest regions of China. Traditionally, dried goji berries are cooked before they are consumed. They are commonly used in Chinese soups and as herbal tea. Moreover, goji berries are used for the production of tincture, wine, and juice. Goji berries are high antioxidant potential fruits which alleviate oxidative stress to confer many health protective benefits such as preventing free radicals from damaging DNA, lipids, and proteins. Therefore, the aim of the review was to focus on the bioactive compounds and pharmacological properties of goji berries including their molecular mechanisms of action. The health benefits of goji berries include enhancing hemopoiesis, antiradiation, antiaging, anticancer, improvement of immunity, and antioxidation. There is a better protection through synergistic and additive effects in fruits and herbal products from a complex mixture of phytochemicals when compared to one single phytochemical.

Full text

Review Article
Goji Berries as a Potential Natural Antioxidant Medicine: An
Insight into Their Molecular Mechanisms of Action
Zheng Feei Ma ,
1,2
Hongxia Zhang,
3
Sue Siang Teh,
3,4
Chee Woon Wang,
5
Yutong Zhang ,
6
Frank Hayford,
7
Liuyi Wang,
1
Tong Ma,
8
Zihan Dong,
1
Yan Zhang,
1
and Yifan Zhu
1
1
Department of Health and Environmental Sciences, Xi’an Jiaotong-Liverpool University, Suzhou 215123, China
2
School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, 15200 Kelantan, Malaysia
3
Department of Food Science, University of Otago, Dunedin 9054, New Zealand
4
Department of Food Science, Faculty of Applied Sciences, Tunku Abdul Rahman University College, Kuala Lumpur 53300, Malaysia
5
Department of Biochemistry, Faculty of Medicine, MAHSA University, Bandar Saujana Putra, Jenjarom, 42610 Selangor, Malaysia
6
Jinzhou Medical University, Jinzhou 121000, China
7
Department of Nutrition and Dietetics, School of Biomedical and Allied Health Sciences, College of Health Sciences,
University of Ghana, P. O. Box KB143, Korle-Bu, Accra, Ghana
8
Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Institutes of
Integrative Medicine of Fudan University, Shanghai 200032, China
Correspondence should be addressed to Zheng Feei Ma; zhengfeeima@gmail.com
and Yutong Zhang; zhangyutong730@hotmail.com
Received 30 June 2018; Revised 1 October 2018; Accepted 17 December 2018; Published 9 January 2019
Guest Editor: Germán Gil
Copyright © 2019 Zheng Feei Ma et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Goji berries (Lycium fruits) are usually found in Asia, particularly in northwest regions of China. Traditionally, dried goji berries
are cooked before they are consumed. They are commonly used in Chinese soups and as herbal tea. Moreover, goji berries are used
for the production of tincture, wine, and juice. Goji berries are high antioxidant potential fruits which alleviate oxidative stress to
confer many health protective benefits such as preventing free radicals from damaging DNA, lipids, and proteins. Therefore, the
aim of the review was to focus on the bioactive compounds and pharmacological properties of goji berries including their
molecular mechanisms of action. The health benefits of goji berries include enhancing hemopoiesis, antiradiation, antiaging,
anticancer, improvement of immunity, and antioxidation. There is a better protection through synergistic and additive effects in
fruits and herbal products from a complex mixture of phytochemicals when compared to one single phytochemical.
1. Introduction
Goji berries (Lycium fruits) are obtained from two closely
related plants, Lycium chinense and Lycium barbarum. They
are usually found in Asia, particularly in northwest regions of
China. Lycium belongs to the Solanaceae family that yields
numerous foods, including some fruits that are yellow to
red, ranging from potatoes and tomatoes to eggplants. Both
of these Lycium species are generally marketed as goji berry
as well as wolfberry. It is a 1-2 cm long berry, bright
orange–red ellipsoid colour with a sweet and tangy flavor
[1]. After harvesting in late summer–early autumn, it is
sun-dried as a dried fruit.
Traditionally, dried goji berries are cooked before they
are consumed. They are commonly used in Chinese soups
and as herbal tea. Moreover, goji berries are used for the
production of tincture, wine, and juice [2]. Many pharmaco-
logical functions related to the eyes, kidney, and liver partic-
ularly have been promoted by the consumption of goji berry
in populations [3]. Goji berries are often incorporated into
Hindawi
Oxidative Medicine and Cellular Longevity
Volume 2019, Article ID 2437397, 9 pages
https://doi.org/10.1155/2019/2437397

herb formulas. The dose of goji berries is in the range of
6-18 g. However, if goji berries are used as a single herb rem-
edy, this dose may be insufficient. This is because the other
herbs in the specific formulation may contain same compo-
nents as goji berries such as polysaccharides and carotenoids.
Goji berries could be used as a major component in a formu-
lation or as a single herd. One of the recommended therapies
in the treatment of atrophic gastritis is to consume twice daily
with 10 g Lycium fruits each time. Besides that, 15 g of goji
berries per day is considered beneficial to supply adequate
zeaxanthin which is estimat ed at 3 mg/day as a dietary supple-
ment for eye health [4]. A 20 g Lycium fruit in a simple tea is
able to improve decreased visual perception [5]. Hence, the
dosage range of goji berry alters to 15-30 grams (2- to 5-fold
increases) when it is the main herd apart from that in the com-
plex formula where the dosage range is around 6-18 g [4].
Goji berries are gradually being regarded as a functional
food in many Asian countries as well as throughout Europe
[3]. They also have been marketed as a health food in the
western countries [6]. Goji berries recently gained a growing
popularity as a “superfruit”in North America and European
countries because of their potential health-promoting
properties. For example, goji berries have been used to
increase longevity and for the benefits to liver, kidney, and
vision since ancient times [2]. Due to the rich medical
properties and chemical composition, goji berry has been
consumed as an important food of a health-promoting diet
for hundreds of years.
2. Bioactive Compounds of Goji Berries
There are many bioactive compounds distinguished by high
antioxidant potential in goji berries. The nutrients in goji
berries are included 46% of carbohydrate, 16% of dietary
fiber, 13% of protein, and 1.5% of fat. Thus, goji berries can
be an excellent source of macronutrients. Micronutrients
which included minerals and vitamins can be found in goji
berries as well. There are studies that reported the presence
of riboflavin, thiamine, nicotinic acid, and minerals such as
copper, manganese, magnesium, and selenium in goji berries
[7]. The bioactive compounds responsible for health benefits
have been evaluated based on the macronutrients and micro-
nutrients of goji berries. The high biological activity compo-
nents in goji berries are polysaccharides, carotenoids, and
phenolics [8]. These functional components are related with
the health-promoting properties of goji berries.
The most important group of compounds present in goji
berries is polysaccharides. Polysaccharides comprise 5–8% of
dried fruits, and they are found in the water-soluble form of
highly branched L. barbarum polysaccharides [1]. These six
kinds of monosaccharides (i.e., arabinose, galactose, glucose,
rhamnose, mannose, xylose, and galacturonic acid) are found
in goji berries [5].
A group of carotenoids are the colour components of
Lycium fruit. Carotenoids are the second highly significant
group of biologically active compounds with health benefit
properties present in goji berry. The total carotenoid content
of different goji berries ranged from 0.03 to 0.5% of dried
fruits. Being responsible for the characteristic bright and
vivid orange to red colouration, the lipid soluble carotenoids
occur at extremely high levels in goji berries [2]. One of the
most common carotenoids found in goji berries is zeaxanthin
in the form of dipalmitin zeaxanthin. In ripening goji berries,
the content of zeaxanthin can reach around 77.5% of
total carotenoids. Zeaxanthin palmitate (phasalien) contains
31–56% of the total carotenoids. As for now, the best natural
source of dipalmitin zeaxanthin is goji berries. The fractions
of beta-carotene (35.9 μg/g), cryptoxanthin, and neoxanthin
(72.1 μg/g) are also detected in goji berry extracts [8].
Phenolic acids and flavonoids are examples of the pheno-
lic compounds found in goji berries. Some phenolic com-
pounds in goji berries are caffeic acid (3.73 μg/g),
caffeoylquinic acid (0.34 μg/g), chlorogenic acid (12.4 μg/g),
p-coumaric acid (6.06 μg/g), quercetin-diglucoside
(66.0 μg/g), kaempferol-3-O-rutinoside (11.3 μg/g), and rutin
(42.0 μg/g) [8]. These phenolic compounds have a very high
antioxidant capacity [8]. Table 1 summarises some chemical
compounds found in goji berries [9].
3. Pharmacological Properties of Goji Berries
Goji berries have become popular over the years due to its
public acceptance as a “superfood”with highly advantageous
antioxidant and nutritive properties. A superfood is a
“nutrient-rich”food considered to be especially beneficial
for health or well-being. The carotenoid content of goji
berries had been drawn a lot of attention due to its beneficial
effects including antioxidant property on vision, retinopathy,
and macular degeneration.
In very recent years, interest of consumers about the
health benefits of different berry-type fruits, their resultant
juices, and their capsules has quickly increased [10]. Berry
fruits are rich in antioxidant phytochemicals [11, 12], and
these antioxidants are capable of performing a number of
functions. The present interest about the properties of several
kinds of berries is also shown by the numerous scientific arti-
cles published in journals in the last few years. The biennial
International Berry Health Benefits Symposium started in
2005 and in their latest research also focused on berry con-
sumption in relation to human health as a key component
of their symposium [13, 14]. The most extensively consumed
Table 1: Some chemical compounds of goji berries.
Composition
Moisture (%) 10.3
Crude protein (%) 8.9
Crude oil (%) 4.1
Fiber (%) 7.3
Total phenol (mg GAE/100 mL) 3.4
Antioxidant activity (%) 20.8
Myristic acid (%) 0.1
Stearic acid (%) 2.9
Palmitic acid (%) 8.2
Arachidic acid (%) 1.8
Oleic acid (%) 21.7
2 Oxidative Medicine and Cellular Longevity

berry-type products are derived from goji (Lycium
barbarum), chia (Salvia hispanica), açaí (Euterpe oleracea
Martius), jujuba (Ziziphus jujuba), pomegranate (Punica
granatum), and mangosteen (Garcinia mangostana) [10].
The dietary intake of berry fruits has been shown to have a
positive impact on human health, performance, and dis-
ease [15–24]. All these fruits support the immune system
and are rich in nutrients. Overall, they have a significant
concentration of phytosterols, monounsaturated fats, anti-
oxidants, essential amino acids, trace minerals, dietary
fiber, and fat- and water-soluble vitamins [25].
Goji berry polysaccharides, for instance, are a
well-known traditional Chinese medicine and tonic food
for many years. In connection with it health benefits, Lycium
barbarum polysaccharides (LBPs) are one of the most
valuable functional components [5, 26]. In recent years, L.
barbarum is being used not only in China but also worldwide
as a health dietary supplement in several forms including
juice and tea [27]. Consuming products made from L.
barbarum might help to decrease blood lipid concentration,
promote fertility, and improve immunity [17, 19, 27–29].
3.1. Vision-Protective Effect. The mixture of highly branched
polysaccharides and proteoglycans in LBPs has been
reported to exert ocular neuroprotective effects [30, 31]. Goji
berries, which contain a specific profile of carotenoid species
[2, 32], have high carotenoid metabolites, with zeaxanthin
making up almost 60% of the total carotenoids in the fruit
[33]. Carotenoids are main natural pigments accountable
for the yellow, red, and orange colours of many types of fruits
and vegetables [34]. They also have many biological actions
including the pro-vitamin A’s antioxidant activity.
LBPs are the active components which may improve
visual function. Chu et al. [28] reported an animal study
investigating the effects of LBPs (1 mg/kg) on localised
changes of rats’retinal function in a partial optic nerve tran-
section (PONT) model. The multifocal electroretinograms
(mfERG) were obtained from Sprague-Dawley rats. One
week later, a substantial decrease of major positive compo-
nent (P1) and photopic negative response (PhNR) ampli-
tudes of mfERG were detected in all retinal regions.
Feeding with LBPs prior to PONT preserved the functions
of retina. All mfERG responses were reported to be within
the normal range in the superior retina, and most of the infe-
rior retinal responses were considerably increased at week 4.
The retina ventral part had secondary degeneration which
affected the ganglion cell layer and outer retina. LBPs caused
alterations to the functional reduction caused by PONT by
regulating the signal from the outer retina. Zhu et al. reported
that LBPs inhibited the N-methyl-N-nitrosourea-induced rat
photoreceptor cell apoptosis [35]. In addition, LBPs also pro-
tected the retinal structure by regulating the expressions of
caspase and PARP [35].
The protective characteristics of goji berry extracts on
retina cells have been shown in the early stage of the retina
degeneration in both human and animal studies [1].
Consumption of dietary L. barbarum has been shown to be
retinoprotective. A study by Yu et al. in 2013 showed that
1% (kcal) wolfberry upregulated carotenoid metabolic genes
of zeaxanthin and luteolin and also improved the biogenesis
of mitochondria in the retina of db/db diabetic mice [36]. It
has been suggested that inhibited expression of these zeaxan-
thin and luteolin-metabolizing genes can cause hyperglycae-
mia, which increases the risk of retinopathy [1].
Using Royal College of Surgeons (RCS) rats as a
hereditary retinal dystrophy model, Ni et al. examined
the potential neuroprotective effects of aqueous extract of
dried L. barbarum [37]. The results indicated that the
aqueous extract of dried L. barbarum might possess a neu-
roprotective activity on the retinal tissue of RCS rats at the
initial stage by hindering apoptosis involving caspase-2
protein and protecting photoreceptors [37]. Prior studies
had established that apoptosis is the dominant mechanism
of photoreceptor degeneration in RCS rats [38, 39]. The
contribution of polysaccharide fractions of L. barbarum
to the prevention of glaucoma was further demonstrated
on the retinal ganglion cells (RGC) in rats with high intra-
ocular pressure (IOP), indicating the neuroprotective effect
of L. barbarum [40]. Further research work by Tang et al.
[41] and Hu et al. [42] also established the protective
effect of L. barbarum on diabetic retinal injury.
Goji berries have also been shown to exhibit macular
benefits in a randomized controlled study of healthy elderly
participants [43]. It was observed that after 90 days of daily
dietary supplementation with 13.7 g lacto-wolfberry (LWB)
(a proprietary milk-based formulation of goji berry) elevated
plasma antioxidant and zeaxanthin levels group, by 26% and
57%, respectively, in supplemented subjects [43]. It is also
suggested that taurine, a nonessential free amino acid in goji
extracts, may hinder the diabetic retinopathy progress
through elevated cAMP levels and enhanced PPAR-γactivity
in retinal cells [44]. Taurine is found abundantly in goji. Goji
powder extracted with methanol contains 10 7±0 1% tau-
rine (w/w). Elevated cAMP levels have been known as pro-
tective against the dysfunction of the endothelial barrier
[45, 46]. Results from Pavan et al. [47] strongly suggested
that in high glucose-treated cells, elevated cAMP concentra-
tions mediate the impairment of the epithelial barrier and
goji berries could be used to achieve their reversal. The pro-
tective property of L. barbarum extract was also confirmed
by Shen et al. using human retina neuron cells [48].
3.2. Lipid-Lowering Effect. The lipid-lowering health benefit
of LBP and its purified constituents have been demonstrated
in animals with limited clinical studies in humans. Besides
having antioxidant activity in vitro [8, 49, 50] and in vivo
[49, 51], they have also shown to have the ability to lower
the blood lipid concentrations of alloxan-induced diabetic
rabbits [7] and mice fed by high-fat diet (HFD) [52]. Ming
et al.’s research showed that abnormal lipid peroxidation
parameters were returned to near normal level and lipid per-
oxidation accumulation was inhibited after administrating
LPS to mice fed on HFD. This suggests that LBP seems to
play an imperative role in lipid metabolism [52]. The results
were consistent with previous findings, where mice and rats
fed with polysaccharide fractions supplemented with HFD
were characterized by lowered concentration of total choles-
terol, LDL-cholesterol, and triglycerides and increased
3Oxidative Medicine and Cellular Longevity

concentration of HDL-cholesterol compared to mice and rats
on high-fat diets without polysaccharide fractions [53–55].
The evaluation of the lipid profile of diabetic mice and rats
fed on goji extract also showed the same results compared
with the diabetic controls [1, 7]. However, clinical studies
on the lipid-lowering properties of goji berries were limited
and almost exclusively performed in China. More so, orig-
inal data are hardly accessible, and studies were mostly
small-sized and may not have been adequately controlled.
A study of 25 Chinese subjects aged 64-80 years had their
blood lipid peroxides significantly decreased by 65% after
10 days of ingestion of 50 g/d dry goji berries [56, 57].
However, the small size of the study (N=25) and the
subjectivity of most parameters must be critically pointed
out. An in vivo investigation of the effects of serum
LBP-standardized L. barbarum preparation (GoChi) in a
randomized, double-blind, placebo-controlled clinical
study involving 50 Chinese healthy adults aged 55-72 years
showed a significant decrease in lipid peroxidation (shown
by lower concentrations of malondialdehyde (MDA)) by
8.7% and 6.0% pre-intervention and post-intervention in
the GoChi group compared with the placebo group,
respectively. This was after they were given GoChi or
placebo (120 mL/d) for 30 days [26].
3.3. Hypoglycaemic Effect. Diabetes mellitus is characterized
by abnormally high levels of blood glucose, and it is also
known as hyperglycaemia [58]. Due to the high cost and
adverse side effects of many oral hypoglycaemic agents, the
exploration and discovery of safer and more effective substi-
tutes have become very important and significant. This has
led to the investigation for hypoglycaemic activity in other
more traditionally edible food sources such as goji berries
which have been shown to have a hypoglycaemic effect in cell
and animal studies [1]. A cell experiment on hypoglycaemic
effects for instance proved that LBP3b (an extraction from
L. barbarum fruit) showed a concentration-dependent effect
on glucose uptake [59]. Male Wistar HFD-STZ-induced dia-
betic rats administered with immunoglobulin (Ig) LBP and
LBP-IV once daily for 4 continuous weeks and treated with
LBP (100 mg/kg) and LBP-IV (200, 100, and 50 mg/kg) after
showed significantly decreased concentrations of HbA1 and
blood glucose of diabetic rats compared to the diabetic
control group [60]. Alloxan-induced diabetic rabbits fed
with crude LBP and purified polysaccharide fraction
(LBP-X) from L. barbarum for 10 days also showed a
significant reduction in blood glucose level [7, 61]. Similar
results were observed after a 28-day treatment in
alloxan-induced diabetic mice with LBP [62–64]. This
was consistent with Zou et al.’s [65] findings where the
rat insulinoma cell line was used. Very limited or no
clinical human studies exist, however.
3.4. Allergic and Anaphylactic Reactions. Monzon-Ballarin
et al. [66] described two clinical cases who reported allergic
symptoms after goji berry ingestion. The patients had a pos-
itive skin prick test and a detection of specific immunoglob-
ulin (Ig) E to goji berry. An analysis of the allergenic profile
of the two patients showed a 9 kDa band, suggesting that
the corresponding protein might be related to lipid transfer
proteins (LTPs). Larramendi et al. [67] further reported a
study involving 31 subjects in Spain. The subjects included
five patients reporting allergenic symptoms on intake of
goji berries, six tolerating the berries, and 20 never having
eaten goji berries. All subjects underwent skin prick tests
with goji berries, as well as with peach peel and plant food
panallergens as biomarkers of cross-reactivity between
unrelated foods. They reported that the skin tests to goji
berries were positive in 24 subjects (77%). Positivity to goji
berries was related with positivity to peach peel and to the
panallergen-nonspecific LTPs.
3.5. Anticancer, Antitumour, Immunostimulatory, and
Modulatory Effects. Goji berries have been utilised in tradi-
tional Chinese medicine to prevent the onset and progression
of cancer for so many years, due to its rich phytochemical
and antioxidant composition [1]. Some of its ingredients
might have a better therapeutic effect on cancer than other
foods. Hsu et al. [68] have reported that the L. barbarum
carotenoid nanoemulsion was more effective in inhibiting
HT-29 cancer cells as compared to that of the carotenoid
extract. Furthermore, both nanoemulsion and extract
could upregulate p53 and p21 expression and downregu-
late CDK1, CDK2, cyclin A, and cyclin B expression and
arrest the cell cycle at G2/M. Moreover, attributing to
most of the biological effects of the fruits including anti-
cancer, antitumour, and immunomodulatory and proper-
ties, goji berries are unusually rich in water-soluble
peptide-conjugated polysaccharides (i.e., LBPs) [69–71].
They have the ability to enhance or potentiate the host
defence mechanisms in a way to inhibit tumour growth
without harming the host. Research work conducted by
Tang et al. [41] and Gan et al. [69] established that com-
pounds in goji berries have proapoptotic and antiprolifer-
ative activity against cancer cells.
3.6. Neurological Protective Effect. The neurological protec-
tive effect of goji berries has been demonstrated in an exper-
imental study including human clinical trial. Glutamate has
been shown to be excitotoxic and is being implicated in many
neurodegenerative diseases including Parkinson’s disease
and Alzheimer’s disease [61, 72]. Thus, reduction of gluta-
mate toxicity is considered a therapeutic strategy for those
neurodegenerative diseases.
A study by Yang et al. [73] showed that LBP pretreatment
significantly improved neurological deficits by decreasing the
infarct size, hemispheric swelling, and water content in an
experimental stroke model C57BL/6N male mice fed with
either vehicle (PBS) or LBP (1 or 10 mg/kg) daily for 7 days,
indicating the neuroprotective effect of LBP. LBP again
improved the survival rate and promoted the growth of
mixed cultured retinal ganglion cells, from neonatal
Sprague-Dawley rats [74]. The first double-blind randomized
control study performed outside China to assess the general
effects of goji juice (GoChi™) in young healthy adults con-
cluded that consumption of GoChi™for 14 days improved
neurological performance generally [75]. It should be noted
4 Oxidative Medicine and Cellular Longevity

however that assessment of most parameters was subjective
and the sample size was small in this study (N=34).
3.7. Cardiovascular Protective Effect. In an experiment to
investigate the role of LBP in the reduction of myocardial
injury in ischemia/reperfusion among rats, the rat heart
LBP significantly reduced the myocardium Bax-positive rate;
also, through dose-dependent methods, the apoptosis of
myocardial cell and increase in Bcl-2 positive rate suggest
that LBP can prevent further development and deterioration
of CVD [76]. Regarding the effects on renal vascular tension
of LBP, Jia et al. [77] tested the one-clip hypertension model
among rats with hypertension. It was observed that
compared to rats not treated for hypertension, in isolated
aortic rings of LBP-treated rats, the reduced phenylephrine
contraction was observed, causing that LBP-treated rats were
significantly prevented from elevated blood pressure.
Another experiment was that rats with hyperlipidemia were
administered to take different concentrations (1 g/kg to
4 g/kg) of L. barbarum decoction for 10 consecutive days by
gastric perfusion. The authors reported that in the serum
and liver of rats, total cholesterol and triglyceride levels were
reduced; also, the level of serum low-density lipoprotein-
(LDL-) C was decreased [5, 78]. A similar result was observed
in a study by Luo et al. [7]. LBPs lowered serum total choles-
terol and triglyceride levels; meanwhile, the high-density
lipoprotein (HDL) cholesterol level was increased after a
10-day treatment among rabbits.
3.8. Antiaging Effects. In a recent review, Gao et al. [79] have
discussed the various components contributing to the antiag-
ing properties of L. barbarum. These notable components are
LBPs, betaine, β-carotene, zeaxanthin, 2-O-β-D-glucopyra-
nosyl-L-ascorbic acid (AA-2βG), and flavanoids [79]. L. bar-
barum contains betaine (a natural amino-acid). The Lycium
Chinese Miller fruit extract containing betaine has been
shown to mitigate carbon tetrachloride- (CCl4-) induced
hepatic injury by increasing antioxidative activity and lower-
ing inflammatory mediators such as COX-1/COX-2 and
iNOS. Histopathological examination was employed to con-
firm the ameliorative effects of the extract and betaine [80].
Betaine has been shown to be an anti-inflammation agent
associated with colon carcinogenesis. It also has been shown
to possess a tumour-preventing effect on colitis-associated
cancer in mice induced by azoxymethane. Administration
with betaine significantly lowered the incidence of tumour
formation with downregulation of inflammation. Treatment
with betaine also inhibited the production of the ROS and
GSSG level in colonic mucosa and inhibited inflammatory
cytokines including IL-6, iNOS, TNF-α, and COX-2 [81].
Betaine has been shown to have preventive effects on ultravi-
olet B (UVB) irradiation-induced skin damage in mice. UVB
is a common kind of free radical that can cause extrinsic
aging, such as skin aging. Betaine has been proved to reduce
photodamage caused by UVB irradiation. Betaine can be
used to suppress the formation of UVB-induced wrinkle
and collagen damage by inhibiting the extracellular
signal-regulated kinase (ERK), protein kinase (MEK), and
matrix metalloproteinase 9 (MMP-9) [82].
3.9. Adverse Effects of Goji Berries. Apart from the allergic
and anaphylactic reactions, other side effects that consumers
should be aware of are to be mentioned. These include the
presence of organic toxic substances and risk of interactions
with other prescriptions besides allergy. Atropine, a toxic
alkaloid, is naturally present in goji berry. The content was
reported to be at toxic level. In a further work by Adam
and co-workers, the atropine concentration in eight samples
of goji berries using HPLC-MS was found to be maximally
19 ppb (w/w). Therefore, its content is far below toxic levels
(Adam et al., 2006).
Patients who experienced interactions between goji
berries and warfarin have been described in three published
case reports. Warfarin is prescribed as a common anticoagu-
lation therapy. The international normalized ratio (INR) was
observed to elevate in patients after drinking goji tea [83].
Increased bleeding from the rectum and nose was observed
in another patient who drank goji berry juice [84]. Most
recently, a study by Zhang et al. reported that an elderly
man taking a prolonged maintenance dose of warfarin after
drinking goji berry wine experienced an increased interna-
tional normalized ratio (INR) with associated bleeding [85].
Other possible interactions between goji berries and pre-
scription medications are still unknown. It is important to
take into consideration the possible risks of taking goji
berries in individuals taking medications with a narrow
therapeutic index.
Arroyo-Martinez et al. described a case report of toxic
hepatitis related to the use of goji. The symptoms reported
included nonbloody diarrhea, asthenia, and colic abdominal
pain. The patient had a mild mucocutaneous jaundice and
a generalized erythematous and pruriginous maculopapular
rash. The patient consumed goji berry tea 3 times a day
[86]. The liver function tests were elevated. Goji berries have
been shown to modulate the expression of CYP2C9 and
CYP2E1 and have an immunomodulatory property [2].
However, another possible change in goji composition is
contamination, during its production and post-marketing.
Thus, the toxic side effects of post-marketing surveillance
are another area of concern.
4. Conclusion
Similar to other plants [87–91], goji berries are a high antiox-
idant potential fruits which alleviate oxidative stress to confer
many health protective benefits such as preventing free
radicals from damaging DNA, lipids, and proteins. There is
a better protection through synergistic and additive effects
in fruits and herbal products from a complex mixture of phy-
tochemicals than from a single phytochemical. The health
benefits of goji berries include enhancing hemopoiesis, anti-
radiation, antiaging, anticancer, improvement of immunity,
and antioxidation.
Conflicts of Interest
The authors declare that they have no conflicts of interest.
5Oxidative Medicine and Cellular Longevity

Acknowledgments
Zheng Feei Ma would like to thank Siew Poh Tan, Peng
Keong Ma, Zheng Xiong Ma, Siew Huah Tan, and Feng Yuan
Lau for their active encouragement and support of this work.
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