African Journal of Microbiology Research Vol. 5(32), pp. 5796-5805, 30 December, 2011
Available online at http://www.academicjournals.org/AJMR
ISSN 1996-0808 ©2011 Academic Journals
Utility and importance of walnut, Juglans regia Linn: A
Nael Abu Taha and Mohammed A. Al-wadaan
Chair of Advanced Proteomics and Cytomics Research, Faculty of Science, King Saud University, Riyadh 11415,
Accepted 9 September, 2011
Juglans regia Linn is a medicinal plant that has been widely used in traditional medicine for a wide
array of ailments that include helminthiasis, diarrhea, sinusitis, stomachache, arthritis, asthma, eczema,
scrofula, skin disorders, and various endocrine diseases such as diabetes mellitus, anorexia, thyroid
dysfunctions, cancer and infectious diseases. The present review, attempts to provide comprehensive
information on the ethnobotanical use, pharmacology, nutritional value, preclinical and clinical studies,
toxicity, other uses and current research prospects of the Juglans regia L. Currently, there is a renewed
interest in walnut, and several investigations aimed at scientific validation of its traditional uses and a
humble scientific investigation aimed at isolation and identification of active constituents of crude
Key words: Juglans regia, nutritional value, bioactivity, clinical trial, traditional use, toxicity.
Origin and distribution
Walnut (Juglans regia L.) is the most widespread tree nut
in the world. The tree is commonly called as the Persian
walnut, white walnut, English walnut or common walnut.
It belongs to juglandaceae and has the scientific name
Juglans regia. The walnut tree species is native to the old
world. It is native in a region stretching from the Balkans
eastward to the western Himalayan chain (Fernandez-
Lopez et al., 2000) and was cultivated in Europe as early
as 1000 BC. At present, walnut is cultivated commercially
*Corresponding author. E-mail: firstname.lastname@example.org.
Abbreviations: FAs, Fatty acids; PUFAs, polyunsaturated fatty
acids; AA, amino acid; MICs, minimum inhibitory
concentrations; IC50, half maximal inhibitory concentration;
TMV, tobacco mosaic virus; DPPH, 2,2-diphenyl-1-
picrylhydrazyl; LDL, low-density lipoprotein; CCl4, carbon
tetrachloride; LDH, lactate dehydrogenase; GSH, glutathione;
GR, glutathione reductase; GOT, glutamyl oxaloacetic
transaminase; GPT, glutamyl pyruvic transaminase; TG,
triglycerides; EDV, endothelium-dependent vasodilation; CP,
throughout southern Europe, northern Africa, eastern
Asia, the USA and western South America. World
production of whole walnut was around 1.5 × 106 t in
2008 (FAO, 2008). China is the leading world producer,
followed by the USA, Iran, Turkey, Ukraine, Romania,
France and India, but production in other countries such
as Chile and Argentina has increased rapidly in recent
years (Martinez et al., 2010).
Walnut composition and nutritional value
Walnut has been used globally in human nutrition since
ancient times. The high protein and oil contents of the
kernels of Juglans regia L. (Juglandacea) make this fruit
indispensable for human nutrition. Therefore, the walnut
is classified as a strategic species for human nutrition
and is included in the FAO list of priority plants (Gandev,
2007). The seed part of the fruit (kernel) is consumed
fresh, toasted, or mixed with other confectionaries. In the
Middle East walnuts are added alone or along with
almonds, date, and raisin as a special pastry preparation
called Ma'moul. Walnuts are nutrient-rich food due to
high contents of fats, proteins, vitamins and minerals.
They are also good source of flavonoids, sterols, pectic
Table 1. Nutritional value of Juglans regia L.
Value per 100 g
Vitamins (USDA, 2010)
Fatty acids (Muradoglu et al., 2010)
Unsaturated fatty acids
Palmitoleic acid C16:1
Oleic acid C18:1
Gadoleic acid C20:1
Linoliec acid C18:2
Lineliec acid C18:3
Saturated fatty acid
Myristic acid C14:0
Palmitic acid C16:0
Stearci acid C18:0
Archidic acid C20:0
substances, phenolic acids and related polyphenols. The
nutritional contents differs from a cultivar to another
which can be influenced by genotype, cultivator, different
ecology and different soil (Caglarirmak, 2003; Crews et
al., 2005; Martinez et al., 2010; Muradoglu et al., 2010).
The major components of walnut oil are triacylglycerols
(980 g/kg oil), in which monounsaturated fatty acids (FAs)
(mainly oleic acid) and polyunsaturated FAs (PUFAs;
linoleic and α-linolenic acids) are present in high amounts
in all genotypes (Table 1). Oil contents reported by
Taha and Al-wadaan 5797
Pereira et al. (2008) (78.83 to 82.4%) were higher than
those reported by other researchers (Savage, 2001;
Muradoglu et al., 2010). In general, the FA composition of
walnut oil resembles that of soybean oil, but walnut oil
contains a greater concentration of linolenic acid. In fact,
among vegetable oils, walnut oil has one of the highest
amounts of PUFAs (up to 78% of the total FA content).
Walnuts have high amount of omega-6 and omega-3
PUFA, which are essential dietary fatty acids. Clinical
studies suggest that omega-3 PUFA have significant role
in prevention of coronary heart disease (Davis et al.,
2007). Oil rich in oleic acid displays greater oxidative
stability therefore; it could be widely used as frying oil.
According to an investigation conducted by several
researchers, It was found that the average value for
protein was 18.1% (Amaral et al., 2003); Muradolu, 2005;
Mitrovic et al., 1997; Muradoglu, 2010; Savage, 2001).
They are mainly composed of glutelins (about 70% of the
total seed proteins) together with lesser amounts of
globulins (18%), albumins (7%) and prolamins (5%)
(Martinez et al., 2010). The amino acid (AA) composition
of walnut flour is dominated by the acidic AA residues of
aspartate and glutamate together with relatively high
levels of arginine. Walnut proteins contain all essential
AAs required for the needs of a human adult. The
lysine/arginine ratio in walnut proteins is lower than those
observed in other common vegetable proteins, and this
fact has been identified as a positive feature in the
reduction of atherosclerosis development (Sza-Tao et al.,
2000; Venkatachakm and Sathe; 2006; Martinez et al.,
2010). Walnut cultivars analyzed have recorded rich
mineral composition, especially potassium, magnesium,
and calcium. The minimum and maximum macro and
micro nutrient contents of walnut are presented in Table 1
(Ravai, 1992; Payne, 1985; Souci et al., 1994;
Cosmulescu et al., 2009). Walnuts contain high levels of
potassium, phosphorus and magnesium and lower
sodium. These elements play an important role for many
enzymes activity especially as cofactor.
Juglans regia leaves have been used mostly in worldwide
traditional medicines as antimicrobial, antihelmintic,
astringent, keratolytic, antidiarrhoeal, hypoglycaemic,
depurative, tonic, carminative, and for the treatment of
sinusitis, cold and stomach ache (Girzu et al., 1998;
Mouhajir et al., 2001; Vaidyaratnam, 2005). In Turkish
folk medicine, fresh leaves applied on the naked body or
forehead to reduce fever or on swelled joint to alleviate
the rheumatic pain (Fujita et al., 1995; Yesilada, 2002).
The kernel of J. regia has been used for the treatment of
inflammatory bowel disease in Iranian traditional
medicine (Kim et al., 2006). In Palestine, it is used for
treatment of diabetes and asthma (Jaradat, 2005; Kaileh
et al., 2007) and to treat prostate and vascular
disturbance (Spaccarotella et al., 2008). The plant is
5798 Afr. J. Microbiol. Res.
used as a topical remedy for dermal inflammation and
excessive perspiration of the hands and feet. It is also a
common home remedy for the treatment of chronic
eczema and scrofula. The leaves of this plant is used
topically to treat scalp itching and dandruff, sunburn and
superficial burns as well as an adjunctive emollient in skin
disorders (Gruenwald et al., 2001; Robbers et al., 1999;
Ali-Shtayeh and Abu Ghdeib, 1999; Blumenthal, 2000;
Baytop, 1999). It also has high anti-atherogenic potential
and a remarkable osteoblastic activity that adds to the
beneficial effect of a walnut enriched diet on
cardioprotection and bone loss (Papoutsi et al., 2008).
The bark, branches and exocarp of the immature green
fruit of this medicinal plant have been used to treat
gastric, liver and lung cancer a long time in China (Liu et
al., 2004; Baytop, 1999). It is used by traditional healer in
northeastern region of Mexico to protect against liver
damage (Torres-gonzalea et al., 2011). The bark is used
as miswaks for teeth cleaning (Ibrar et al., 2007). In
Nepal the bark paste is useful in arthritis, skin diseases,
toothache, and hair growth. Seed coat is used for healing
wounds (Kunwar and Adhikari, 2005). The shell of
Juglans regia is used in Calabria folk medicine to heal
malaria (Tagarelli et al., 2010).
Hot and cold solvent and aqueous extract of leaves,
barks, fruits and green husks of J. regia from different
countries revealed broad spectrum antibacterial activity
against gram-positive and gram-negative bacteria viz.
Bacillus cereus, Bacillus subtilis, Staphylococcus aureus,
Pseudomonas aeruginosa, Escherichia coli, Klebsiella
pneumoniae, Staphylococcus epidermidis, Micrococcus
luteus, Salmonella typhimurium, Enterococcus faecalis,
Bacillus thuringiensis, Protomonas extroquens, and
Proteus sp. using agar streak method, disc diffusion
method and microplate alalmar blue assay (Deshpande
et al., 2011; Poyrazolu et al., 2010; Pereira et al., 2008;
Oliveira et al., 2008; Pereira et al., 2007; Qa’dan et al.,
2005a b; Citoglu and Altanlar, 2003; Upadhyay et al.,
2010b). The antimicrobial activity against gram-negative
bacteria were selective since not all the fruit extract of J.
regia cultivator inhibited the growth of Pseudomonas
aeruginosa and E. coli. cv. Lara inhibited the growth of
K. pneumoniae (MIC of 100 mg/mL), cv. Mayette
inhibited the development of P. aeruginosa and E. coli
with minimum inhibitory concentrations (MICs) of 50 and
10 mg/mL, respectively, and cv. Mellanaise inhibited the
growth of E. coli and K. pneumoniae at concentration of
100 mg/mL (Ali-Shtayah et al., 1999). Mexican aqueous
bark and leaves extract exhibited no antimycobacterial
activity. Only the hexane and methanol extract showed
antimycobacterial activity with MIC of 100 and 125 mg/ml,
respectively using Soxhlet extractor (Cruz-Vega et al.,
2008). Over 45% of Iranian clinical isolates of
Helicobacter pylori strain were inhibited by J. regia
aqueous and equal mixture of methanol, diethyl ether and
petroleum benzene extract (Nariman et al., 2004). In a
recent study, juglone was shown to potently inhibit the
three key enzymes from Helicobacter pylori,
cystathionine γ-synthase (HpCGS), malonyl-CoAacyl
carrier protein transacylase (HpFabD), and β-
hydroxyacyl-ACP dehydratase (HpFabZ) with the half
maximal inhibitory concentration (IC50) values of 7.0±0.7,
20±1, and 30±4 μmol/L, respectively. Therefore, HpCGS,
HpFabD, and HpFabZ are considered to be the potential
targets of juglone (Kong et al., 2008). The antibacterial
activity of Jordanian J. regia leaves extract to acne
developing organism revealed that 12.5% S. epidermidis
isolates were resistant to the leaf extract where as all
Propionibacterium acnes isolates were sensitive even to
10% of the extract (Qa'dan et al., 2005b).
J. regia fruits, leaves and bark aqueous and solvents
extract exhibited antifungal activity against wide range of
fungi using disc diffusion method, agar dilution method,
agar streak dilution and Raddish method. Pereira et al.
(2008) reported that all the walnut varieties exhibited
antifungal activity against Candida albicans and
Cryptococcus neoformans when soxhleted with light
petroleum ether (b.p. 40-60°C). The higher inhibition was
observed with cv. Lara extract (MIC of 1 mg/mL).
However, C. albicans and C. neoformans were only
resistant to cv Mallanaise extract. Cold extraction of fruit,
leaves and bark inhibited the growth of Microsporum
canis, Trichophyton mentagrophytes, and Trichophyton
violaceum (Ali-Shtayah et al., 1999). On the other hand,
the aqueous extract of green husks showed no antifungal
activity against C. albicans and C. neoformans (Oliveira
et al., 2008). Methanol, acetone, chloroform and ethyl
acetate bark extract revealed antifungal activity against
A. niger, Alternaria alternata, Trihoderma viresn,
fusarium solani, Pichia guiliermondii, Pichia jadinii and all
Candida speices tested (Upadhyay et al., 2010c; Ahmad
et al., 1973).
Mei-zhi et al. (2007) reported that 95% ethanol and ethyl
acetate leaves extract of J. regia, inhibited tobacco
mosaic virus (TMV). The methanol extract of J. regia
inhibited Sindbis virus at a minimum concentration of 1.5
µg/ml (Mouhajir et al., 2001).
The antioxidant potential of ethyl acetate, butanol, meta-
nol, ether and aqueous methanol extract of walnut
kernels, husks and leaves were measured by different
methods such as reducing power, scavenging activity on
2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and lipid
oxidation inhibition by β-carotene linoleate system. All the
extracts showed strong antioxidant activity (Qamar and
Sultana, 2011; Carvalho et al., 2010; Abbasi et al., 2010;
Rahimipanah et al., 2010; Zhang et al., 2009b; Almeida
et al., 2008; Oliveira et al., 2008; Pereira et al., 2008;
Pereira et al., 2007; Fukuda et al., 2003). Bullo et al.
(2010) reported a decrease in the antioxidant burden
observed in enzymatic and non-enzymatic antioxidant
systems after the consumption of a whole-walnut or a
walnut-skin diet in C57BL/6 mice. The same author also
reported that consumption of walnuts and walnut skins
have no deleterious effect on low-density lipoprotein
(LDL) oxidizing capability, despite their higher contents of
omega-6 PUFAs. Several phenolic compounds isolated
from J. regia such as pyrogallol, p-hydroxybenzoic acid,
vanillic acid, ethyl gallate, protocatechuic acid, gallic acid,
3,4,8,9,10-pentahydroxydibenzo pyran-6-one, tannins,
glansrins, adenosine, adenine, etc, could provide a
chemical basis for some of the health benefits claimed for
J. regia in foods and folk medicine (Zhang et al., 2009a;
Fukuda et al., 2003).
Fukuda et al. (2004) demonstrated a strong inhibitory
activity of walnut polyphenols and the polyphenolic
components like Casuarictin, tellimagradin II and
Tellimagradin I on different enzymes like glycosidase,
sucrose, maltase and amylase. In addition to the above
findings, researchers also noticed that walnut polyphenol-
rich fraction has triglyceride lowering effect and urine
peroxide lowering effect in genetically inherited Type II
diabetes mellitus (db/db) mice at the dose of
200mg/kg/day. The consumption of walnut leaf pellets in
alloxan induced diabetic rats at the dose of 185 mg/kg
reduced fasting blood sugar significantly and the
histomorphometric study of pancreas showed a sign of
regeneration of β-cells in the treated group (Jelodar et al.,
2007). J. regia leaves methanolic extract at dose of 250
mg/kg decreases the postprandinal plasma blood glucose
levels in both short and long term models. The plant
extract significantly inhibited α-glucosidase activity in vitro
for both maltase and sucrase enzymes and showed no
changes in the insulin and glut-4 genes expression. The
author attributed the inhibitory action of the plant extract
to gallic acid and caffeoylquinic acid in the leaves
(Teimori et al., 2010).
Kale et al. (2011) reported that stem park of J. regia
Taha and Al-wadaan 5799
acetone extract exhibited significant activity at all dilution
tested when compared to the Albendazole standard
against Eicinia feotida. The benzene, methanol and
ethanol soxhlet extracts of J. regia stem bark on adult
Indian earthworm, Pheretima posthuma exhibited
significant anthelmintic activity as comparable to that of
standard drug Piperazine citrate (Upadhyay et al.,
2010a). The 95% ethanol, petroleum ether and ethyl
acetate extract of green walnut hull have obvious anti-
feeding effect on armyworm and the small vegetable-
moth. The research group indicated that anti-feeding rate,
death rates as well as growth inhibition rate of armyworm
have correspondingly changed in dose dependant
manner (Me-zhi et al., 2006).
The ethanolic extracts of J. regia leaves exhibited potent
anti-inflammatory activity as potent as indomethacin
against carrageenan-induced hind paw edema model in
mice without inducing any gastric damage (Erdemoglu et
al., 2003). Mokhtari et al. (2008) stated that the alcohol
extract of walnut leaves in dose of 1.5 mg/kg caused a
significant nociception decrease in acute phase of
formalin test where as the aqueous (2.87 and 1.64 g/kg)
and ethanolic (2.044 and 1.17 g/kg) extracts of leaves
showed antinociceptive activity in hotplate test
suggesting a promising analgesic and anti-inflammatory
agents against diseases such as rheumatoid arthritis. On
the basis of Qamar and Sultana (2011) result, a
protective role of methanolic J. regia extract against CSE-
induced acute lung toxicity in Wistar rats was suggested.
The extract significantly decreased the levels of Lactate
dehydrogenase (LDH), total cell count, total protein and
increased the glutathione (GSH) level in bronchoalveolar
lavage fluid. It also significantly restored the levels of
Glutathione reductase (GR), catalase and reduced the
xanthine oxidase (XO) activity in lung tissue.
The macerated hexane extract of J. regia fruit produced
significant antidepressant activity at both doses of 100
and 150 mg/kg body weight when compared with
standard drug fluoxetine on male Wistar rats. The
antidepressant activity was evaluated by forced
swimming and tail suspension test (Rath and Pradhan,
Ozer et al. (2007) suggested that gel formulation
containing ellagic acid and plant leaves extract of J. regia
is effective in treating uneven skin pigmentation. The
ethanolic leaves extract could be suggested as new
5800 Afr. J. Microbiol. Res.
sources of skin-whitening agents. Aitani and Shimoda
(2005) reported that melanin formation was inhibited at
concentration 1 to 30 μg/ml in Pre-cultured B16
melanoma cells incubated with medium containing walnut
polyphenols and their result indicated that walnut
polyphenols is more superior to the popular skin-
lightening agent, ascorbic acid and arbutin upon data
Orally fed Walnut polyphenols prepared from the
kernelpellicle demonstrated a dose dependent lowering
effect in glutamyl oxaloacetic transaminase (GOT) and
glutamyl pyruvic transaminase (GPT) in carbon
tetrachloride (CCl4) induced liver damage in mice model
after a single oral administration (200 g/kg). Result
indicated that walnut polyphenols is more superior to
Curcumin, a commonly used hepatoprotective agent. The
effect of each active component of in vitro evaluation of
walnut polyphenols on CCl4-induced cytotoxicity in
primary cultured rat hepatocytes showed that
tellimagrandin I, casuarictin, tellimagrandin II, and rugosin
C (Figure 1) are inhibitory on CCl4-induced cytotoxicity in
primary cultured rat hepatocytes however, tellimagrandin
I of walnut polyphenols is believed to be the most
important active compound responsible for
hepatoprotective effect (Hiroshi et al., 2008). The same
author, Hiroshi et al. (2006) reported that 50% EtOH
extract from endocarps of walnuts on mice liver injury
models induced by carbon tetrachloride at the dose of
100 and 200 mg/kg significantly suppressed GOT and
GPT deviations. Polyphenolic constituents,
tellimagrandins I and II, rugosin C and casuarictin were
found to be principal constituents with hepatoprotective
activity against oxidative damage.
Oral administration of a polyphenol-rich extract (WP) from
walnuts (100 and 200 mg/kg) in high fat diet fed mice
significantly reduced liver weight and serum triglycerides
(TG) where as hepatic β-oxidation in cytosol, including
peroxisome, was enhanced by WP (50-200 mg/kg). A
polyphenol-rich extract was found to possess
hypotriglyceridemic activity via enhancement of
peroxisomal fatty acid β-oxidation in the liver. These
results suggest that tellimagrandin I is involved in the
hypotriglyceridemic mechanism (Shimoda et al., 2009).
Juglone has been reported to inhibit intestinal
carcinogenesis induced by azoxymethane in rats and
might be a promising chemopreventive agent in human
intestinal neoplasia (Sugie et al., 1998). Juglone was also
proven to be a potent cytotoxic agent in vitro in human
tumor cell lines, including human colon carcinoma (HCT-
15) cells, human leukemia (HL-60) cells and doxorubicin-
resistant human leukemia (HL-60R) cells (Kamei et al.,
1998; Segura-Aguilaretal, 1992). In a recent study,
Juglone inhibited the growth and induce apoptosis of
sarcoma and 180 SGC-7901 cells in vivo. The
mechanism is mediated by the activation of the
mitochondrial death pathway, which requires the
generation of reactive oxygen species (ROS), down-
regulation of Bcl-2 protein expression and up-regulation
of Bax protein expression (Ji et al., 2011). Walnut
methanolic extracts obtained from J. regia seed, green
husk and leaf showed concentration dependent growth
inhibition against human renal cancer cell lines A-498,
769-P and the colon cancer cell line Caco-2. Concerning
A-498 renal cancer cells, all extracts exhibited similar
growth inhibition activity (IC50 values between 0.226 and
0.291 mg/mL), while 769-P renal and Caco-2 colon
cancer cells, walnut leaf extract showed a higher
antiproliferative efficiency (IC50 values of 0.352 and 0.229
mg/mL, respectively) than green husk or seed extracts
(Carvalho et al., 2010). The tested dried fine powder of J.
regia light petroleum seed extract in cancer induced in
Swiss albino mice with the help of 7,12-
Dimethylbenz(a)anthracene (DMBA) and croton oil
showed the petroleum extract was significant in reducing
the cancer cells (Kumudhavalli et al., 2010).
Other medicinal uses
Willis et al. (2009) examined the effects of walnut diet on
motor and cognitive ability in aged rats for 8 weeks. The
three treated groups (2, 6 and 9%) revealed that the 2%
walnut diet improved performance on rod walking, while
the 6% walnut diet improved performance on the medium
plank walk; the higher dose of the 9% walnut diet
impaired reference memory, however the researcher
attributed this to the number of polyphenolic compounds
that could be negatively effecting reference memory at a
higher dose. A 2004 study by the NYS Institute for Basic
Research in Developmental Disabilities (OMRDD)
revealed that methanolic extract of walnut was able to
inhibit and defibrillize fibrillar amyloid β- protein (the
principal component of amyloid plaques in the brains of
patients with Alzheimer's). It is proposed that
polyphenolic compounds present in walnuts may be
responsible for its anti-amyloidogenic activity (Chauhan
et al., 2004). Similarly, it was found that two of its major
components in walnuts, gallic and ellagic acid, act as
"dual-inhibitors" of the enzyme acetylcholinesterase
which, in association with amyloid inhibits protein
aggregation, and inhibit the site of acetylcholinesterase
responsible for the breakdown of acetylcholine. These
results suggest that walnuts may reduce the risk or delay
Taha and Al-wadaan 5801
Strictinin (Shimoda et al., 2009)
Juglone (Kong et al., 2008)
Juglanin (C )
(Liu et al.,
Juglanin B (Liu et al., 2008)
Figure 1. Chemical structures of compounds isolated from Juglans regia L.
Figure 1 contd.
5802 Afr. J. Microbiol. Res.
the onset of Alzheimer's disease by maintaining amyloid-
protein in the soluble form and prevent the breakdown of
acetylcholine (Society for Neuroscience, 2007).
A daily intake of 43 to 57g of walnuts incorporated into
Japanese diet for 4 weeks to 40 healthy Japanese men
and women lowered blood cholesterol, particularly in
women (Iwamoto et al., 2000). In double-blind case with
either plasma triglyceride (TG) concentration more that
350 mg/dl or total cholesterol concentration more that
250 mg/dl were randomized into two groups, group A
subject were administered 6 capsules, each filled with
500 mg of the extracted walnut oil, per day for 45 days,
group B individual serve as control and received placebo
for 45 days. The result of this lowered plasma triglyceride
level by 19 to 33% (Zibaeenezhad et al., 2003). Ros et al.
(2004) reported that substituting walnuts for
monounsaturated fat in a Mediterranean diet improves
endothelium-dependent vasodilation (EDV) in
hypercholesterolemic subjects. A daily intake of 8-13
walnuts for 4 weeks significantly improves the EDV of 21
hypercholesterolemic males and females.
On the other hand, walnut-enriched meals effectively
prevented post prandial lipidemia where triacylglycerol
was significantly reduced (Bellido et al., 2004).
Spaccarotella et al. (2008) assessed the effect of walnuts
on markers of prostate cancer between 45 and 75 years
of age. Results suggest that walnuts improved serum γ-T
and α-T: γ-T, two biomarkers that are important in
prostate and vascular health. Total bilirubin, total protein,
albumin, aspartate aminotransferase (AST), alanine
aminotransferase (ALT), lactate dehydrogenase (LDH),
leucine aminopeptidase (LAP), gamma-
glutamyltranspeptidase (γ-GTP), cholinesterase,
amylase, lipase, Lecithin: cholesterol acyltransferase (L-
CAT), LDL-cholesterol, total cholesterol, triglyceride,
phospholipid, free fatty acid (FFA), high-density
lipoprotein (HDL)-cholesterol, Na, K, serum Fe, total iron
binding capacity (TIBC), unsaturated iron binding
capacity (UIBC), urea nitrogen, uric acid, glucose,
hemocytes revealed no abnormal reading for four male
volunteers were given oral walnut polyphenols at the
dose of 50 mg/day for 4 weeks (Oryza, 2007).
A review of the literature showed that juglone can cause
irritant reactions as well as skin hyper pigmentation but,
although it has been found to be a strong sensitizer in
guinea pigs, contact allergy is considered a very rare
event in man (Wood and Calnan, 1976; Hausen, 1981).
However, a case report of 65- year-old woman
complaints of skin hyper pigmentation and large tense
blisters involving the palms and fingers caused by the
cumulative effect of 15 kilos of walnuts shelled in the 3
days was reported by Bonamonte et al. (2001). Haque et
al. (2003) investigated the modulatory effects of walnut
aqueous extract on the toxicity of an anticancer drug,
cyclophosphamide (CP) with special reference to
protection against disruption of drug metabolizing and
antioxidant enzymes during the chemotherapy. The
extract showed a significant increase in the activity and
level of glutathione and glutathione peroxidase in both
liver and kidney tissues and catalase in liver only. While
the extract CP treated group showed a significant
decrease in the lipid peroxidation in liver and kidneys
when compared with the CP-treated group. Aqueous
extract from J. regia leaves reduced 3-(4,5-Dimethyl
thiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT)
formation by about 60% at concentration of 500 µl/ml on
HepG2 cell. Additionally, the co-culture of HepG2 with
THP1 revealed no sign of any negative effect at all
concentration tested after exposure to the extract. The
investigator also reported no significant changes of LDH
and albumin levels on the culture medium after 24 h of
exposure to the extract (Saad et al., 2006).
Hosseinzadeh et al. (2011) calculated the half-maximal
lethal dose (LD50) values of intraperitoneal injection of J.
regia aqueous and ethanolic leaves extract and found it
to be 5.5 and 3.3 g/kg, respectively. Acute dermal toxicity
studies showed that petroleum ether extract of J. regia
gives lethal effect at 2000 mg/kg (Kumudhavalli et al.,
The seeds contain unusual fatty acids which are
industrially important, as they are used in protective
coatings, dispersants, pharmaceuticals, cosmetics, soaps
and a variety of synthetic intermediates as stabilizers in
plastic formulations (Hosamani et al., 2000; Eganathan et
al., 2006). The wood is of very high quality, and is used to
make furniture, and gunstocks. The dye is used as a
coloring and tonic for dark hair (Brwon, 1995). The unripe
fruits are pickled in vinegar (Facciola, 1990).
The present review article documents the publications on
walnut and its constituents in the recent and last few
years. The paper highlights the traditional use of this
plant and some scientific validation of the claimed
biological activity in vivo as well as in vitro. To best of our
knowledge and internet survey only one case of contact
dermatitis was reported after shelling 15 kilos of walnuts.
The toxicological studies of various secondary
metabolites which contribute to its medicinal value are
still in its infancy and are becoming an important limiting
factor for utilizing the metabolites as therapeutic agent.
Besides, isolation and characterization of active
secondary metabolites responsible for various biological
activities have not yet been structurally elucidated, mode
of action, target organ of toxicity and molecular
mechanism also need to be investigated. Further trials in
humans are required to determine the efficacy of walnut
extract or one or more of its constituents and to establish
what, if any, adverse effects are observed.
The authors extend their appreciation to the Deanship of
Scientific Research at king Saud Univer-sity for funding
the work through the research group pro-ject No. RGP-
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