Pumpkin (Cucurbita sp.) seeds as nutraceutic: A review on status quo and scopes

Abstract

The seeds of pumpkin (Cucurbita sp.) are gen-
erally considered to be agro-industrial wastes and dis-
carded. In some parts of the world, the seeds are consumed
raw, roasted or cooked, but only at the domestic scale. With
the discovery of their richness in protein, fibres, minerals,
polyunsaturated fatty acids and phytosterols, they are being
regarded valuable for the food industry. The attention of
food technologists has resulted in their foray into the
commercial food sector. Food companies are experimenting
with their incorporation into a slew of savouries and con-
sumers are showing interest in them. Also, their beneficial
effects on blood glucose level, immunity, cholesterol, liver,
prostate gland, bladder, depression, learning disabilities and
parasite inhibition are being validated. The conversion of
these agro-wastes into value-added ingredients is likely to
be a big step towards the global sustainability efforts; thus,
it deserves more investigation. This review furnishes an
updated account of this emerging nutraceutical.

Full text

1 23
Mediterranean Journal of Nutrition
and Metabolism
Official Journal of the Italian Association
for Dietetics and Clinical Nutrition (ADI)
a member of the Italian Federation of
Nutritional Societies (FeSIN)
ISSN 1973-798X
Mediterr J Nutr Metab
DOI 10.1007/s12349-013-0131-5
Pumpkin (Cucurbita sp.) seeds as
nutraceutic: a review on status quo and
scopes
Seema Patel

1 23
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REVIEW
Pumpkin (Cucurbita sp.) seeds as nutraceutic:
a review on status quo and scopes
Seema Patel
Received: 9 March 2013 / Accepted: 13 June 2013
Ó Springer-Verlag Italia 2013
Abstract The seeds of pumpkin (Cucurbita sp.) are gen-
erally considered to be agro-industrial wastes and dis-
carded. In some parts of the world, the seeds are consumed
raw, roasted or cooked, but only at the domestic scale. With
the discovery of their richness in protein, fibres, minerals,
polyunsaturated fatty acids and phytosterols, they are being
regarded valuable for the food industry. The attention of
food technologists has resulted in their foray into the
commercial food sector. Food companies are experimenting
with their incorporation into a slew of savouries and con-
sumers are showing interest in them. Also, their beneficial
effects on blood glucose level, immunity, cholesterol, liver,
prostate gland, bladder, depression, learning disabilities and
parasite inhibition are being validated. The conversion of
these agro-wastes into value-added ingredients is likely to
be a big step towards the global sustainability efforts; thus,
it deserves more investigation. This review furnishes an
updated account of this emerging nutraceutical.
Keywords Pumpkin seed  Functional food 
Polyunsaturated fatty acid  Phytosterol  Prostate health
Introduction
Pumpkins (Cucurbit sp.) belonging to the Cucurbitaceae
family are grown widely around the world as a vegetable
(Fig. 1a). In the USA, they are vastly used for Halloween
carvings and thanksgiving feasts. Most of the crops are pro-
cessed into canned pumpkins or pie mix. However, the
plentiful flat, oval seeds are generally discarded as agricultural
residues (Fig. 1b). The seeds are uniquely flavoured with nutty
taste and are consumed asroasted, salted snack in some parts of
Canada, Mexico, USA, Europe and China. Now, grocery stores
are also selling these seeds as baked, sprouted, fermented,
pumpkin protein concentrate and pumpkin protein isolate, as
their richness in protein, iron, zinc, manganese, magnesium,
phosphorous, copper, potassium, polyunsaturated fatty acids,
carotenoids and c-tocopherol is beginning to surface.
There is a growing interest in vegetable oils of special
composition, and pumpkin seed oil is a promising candi-
date in this regard. Cold press or steam distillation is used
for oil extraction. The dark greenish-red oil is used for
cooking, as marinade or salad dressing and it has already
been touted as a contender to olive oil. It is being used in
many epicurean delights, viz. chocolate, cereal bar, bread,
cake, muffin, soup, pesto, stew and pasta garnish. Pumpkin
seed butter is considered as a great alternative to peanut
butter. Major US food stores such as Costco, Trader Joes
and Walmart sell myriad varieties of pumpkin seed-based
food products, viz. granola chunks, tortilla chips, vegetable
salad, sourdough bread, cookies and quinoa salad.
Pumpkin seeds and derived oil comprise a multi-million
dollar industry in Europe. Most of the oil is manufactured
in Austria, Slovenia, Serbia and Hungary. Its popularity is
at the nascent phase in other regions of the globe, which
slowly but surely is gathering momentum. This review
strives to provide an updated account of the established and
putative benefits, bottlenecks and scopes for broader uses.
Nutrients
The phytochemical composition renders the seeds valuable
for nutritional purposes. Stevenson et al. [1] studied several
S. Patel (&)
Bioinformatics and Medical Informatics Research Center,
San Diego State University, 5500 Campanile Dr,
San Diego, CA 92182, USA
e-mail: seemabiotech83@gmail.com
123
Mediterr J Nutr Metab
DOI 10.1007/s12349-013-0131-5
Author's personal copy

pumpkin cultivars (Cucurbita maxima D.), for their seed oil
content, fatty acid composition and tocopherol content. The
oil content ranged from 11 to 31 %. Total unsaturated fatty
acid content ranged from 73 to 81 %. The predominance of
linoleic, oleic, palmitic and stearic acids was observed. The
a-tocopherol content of the oils ranged from 27 to 75 mg/g,
while c-tocopherol ranged from 75 to 493 mg/g. Ryan et al.
[2] determined the levels of phytosterols, squalene and
tocopherols in pumpkin seeds. The method comprised acid
hydrolysis and lipid extraction followed by alkaline
saponification, prior to analysis by HPLC. Beta-sitosterol
was the most prevalent phytosterol, ranging in concentra-
tion from 24.9 mg/100 g seed. Squalene was particularly
abundant (89 mg/100 g) and the total oil content amounted
to 42.3 % (w/w) in pumpkin seeds. Veronezi and Jorge [3]
reported variation in total phenolic compounds in the lipid
fractions of different cultivars of pumpkins (Mini Paulista
and Nova Caravela showed highest). Kim et al. [4] reported
that the major fatty acids in the pumpkin seeds were pal-
mitic, stearic, oleic and linoleic acids. C. pepo and C. mos-
chata seeds had significantly more c-tocopherol than C.
maxima, whose seeds had the highest b-carotene content. C.
pepo seeds had significantly more b-sitosterol than the
others. Among 11 types of nuts and seeds profiled for their
nutritional abundance, pumpkin seeds scored highest for
iron content (95.85 ± 33.01 ppm) [5]. The nutrient distri-
bution in pumpkin seed is presented in Table 1.
Antioxidant activity
Andjelkovic et al. [6] measured the total phenolics content
in the pumpkin seed oil, which ranged from 25 to 51/mg
GAE/kg of oil. The individual phenolics were tyrosol,
vanillic acid, vanillin, luteolin and sinapic acid. The max-
imum antioxidant capacity measured by the reduction of
the DPPH radical was 62 %. Ardabili et al. [7] reported
that the addition of pumpkin seed oil improved the frying
Fig. 1 a A ripe pumpkin in
vine. b The seeds
Table 1 Bioactive components and their percentages in pumpkin
seed (nutrient value per 100 g)
Components Nutrient value Percentage of
RDA
Energy 559 kcal 28
Carbohydrates 10.71 g 8
Protein 30.23 g 54
Total fat 49.05 g 164
Cholesterol 0 mg 0
Dietary fibre 6 g 16
Vitamins
Folate 58 lg15
Niacin 4.987 mg 31
Pantothenic acid 0.750 mg 15
Pyridoxine 0.143 mg 11
Riboflavin 0.153 mg 12
Thiamine 0.27 mg 23
Vitamin A 16 IU 0.5
Vitamin C 1.9 lg3
Vitamin E 35.10 mg 237
Electrolytes
Sodium 7 mg 0.5
Potassium 809 mg 17
Minerals
Calcium 46 mg 4.5
Copper 1.343 mg 159
Iron 8.82 mg 110
Magnesium 592 mg 148
Manganese 4.543 mg 198
Phosphorus 1,233 mg 176
Selenium 9.4 lg17
Zinc 7.81 mg 71
Phytonutrients
Carotene-b 9 lg–
Cryptoxanthin-b 1 lg–
Lutein–zeaxanthin 74 lg–
Courtesy: USDA National Nutrient Database
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stability of canola oil. The better antioxidative effect of the
former was attributed to its phenolic composition.
Nkosi et al. [8] investigated the antioxidative effects of
pumpkin seed protein isolate on rats kept on a low-protein
diet for 5 days. The rats were subjected to acetaminophen
intoxication and then given pumpkin protein isolate. The
rats were killed at 24, 48 and 72 h after their respective
treatments. The isolate exhibited about 80 % radical scav-
enging activity, chelating activity of approximately 64 %
on Fe
2?
ions and an inhibition of approximately 10 % of
xanthine oxidase. CCl
4
-induced liver injury was alleviated
by pumpkin protein isolate as evidenced from the improved
antioxidant level and lowered levels of lipid peroxidation.
El-Boghdady [9] reported that pumpkin seed oil protected
the small intestine of rats from methotrexate-induced
damage through antioxidant and anti-inflammatory effects.
Oral gavage of the oil alone or with ellagic acid for 5 days
prior to methotrexate treatment decreased the intestinal
damage, serum prostaglandin E2, tissue malondialdehyde,
nitric oxide, myeloperoxidase, xanthine oxidase and aden-
osine deaminase activities and increased GSH level.
Functional food and technical developments
and hurdles
Naghii and Mofid [10] studied the effect of consumption of
iron-fortified ready-to-eat cereal (30 g providing 7.1 mg
iron/day) and pumpkin seed kernels (30 g providing
4.0 mg iron/day) for 4 weeks. Indices of iron status such as
reticulocyte count, haemoglobin, haematocrit, serum fer-
ritin, iron, total iron-binding capacity and transferrin per-
cent were determined. Better response for iron status as
indicated by higher serum iron was observed after the
consumption period. Young children, adolescents, women
of reproductive ages and pregnant women who are often
prone to iron deficiency-caused anaemia may be benefitted.
Norfezah et al. [11] investigated the effect of incorporation
of flour from the three different fractions (peel, flesh and
seed) of Crown pumpkin (C. maxima). The flour was
incorporated into an extruded snack formulation at various
levels and processed in a twin-screw extruder to make ten
expanded snack products. Inclusion of the peels and seeds
at 10 % yielded extruded products with similar expansion
and density characteristics to the control sample; however,
an inclusion of greater than 10 % led to hardness of the
product. Radocaj et al. [12] developed a stable spread rich
in x-3 and x-6 fatty acids using a hull-less pumpkin seed
oil press cake. Response surface methodology (RSM) was
employed to optimize the spreads. The spread resembled
commercial peanut butter, in appearance, texture as well as
spreadability. The product contained x-3 fatty acids and
showed no visual oil separation even after 1 month of
storage. An optimum spread was produced using 1.25 %
(w/w) of stabilizer and 80 % of hemp oil (w/w of the total
added oil) which had 0.97 g of x-3 fatty acids per serving
size and oil separation of 9.2 % after 3 months of storage.
Ward and Ainsworth [13] developed an inexpensive
weaning food with adequate dietary energy, protein and fat
for malnourished infants in Kenya. The porridge was
cooked, dried and blended with ground pumpkin seeds
followed by heat treatment and storage at ambient tem-
perature for 8 weeks. The in vitro protein digestibility was
82.5 %, confirming a high-quality protein food. HPLC
analysis detected no free-floating water-soluble amino
acids, indicating food stability. A low peroxide value was
found, confirming the absence of rancidity, and viscometer
analysis approved the consistency for infant feeding, though
flavour got a less favourable score. El-Soukkary [14]
determined the effect of incorporation of pumpkin seed into
wheat flour and dough properties. The results indicated that
pumpkin seed products could be added to wheat flour up to a
17 % protein level for raw, roasted and autoclaved pumpkin
meal, 19 % level for germinated, fermented and pumpkin
protein concentrate and 21 % level for pumpkin protein
isolate without a detrimental effect on dough or loaf quality.
On the other hand, the addition of pumpkin seed proteins
resulted in increasing protein, lysine and mineral contents
compared to the control. In vitro protein digestibility
improved when the pumpkin seed proteins were added.
Procida et al. [15] investigated the carotenoid (lutein and
zeaxanthin), vitamin E (a- and c-tocopherol) and fatty acid
contents of 12 samples of pumpkin seed oils along with the
volatile fraction resulting from the roasting process. The
roasting temperature played a crucial role in the concen-
trations of volatile substances originating from Strecker
degradation, lipid peroxidation and Maillard reaction. The
findings suggest that high-temperature roasting leads to the
production of an oil with intense aromatic characteristics,
while mild conditions lead to a product with a minor
characteristic pumpkin seed oil aroma. The nutraceutical
properties of the product are confirmed by the high content
of a- and c-tocopherol and carotenoids.
Adulteration is a major risk in deriving the optimal
therapeutic benefits of pumpkin seeds and oil. Butinar et al.
[16] employed a set of HPLC triacylglycerol determina-
tions for the evaluation of the novelty of pumpkin seed oil
from Slovenia. Vujasinovic et al. [17] optimized the
roasting condition for hull-less pumpkin seeds using RSM,
for maximum yield of the bioactives and antioxidants from
the virgin pumpkin oils. The optimum conditions for
roasting the seeds were 120 °C for 49 min, which resulted
in oil with phospholipids 0.29 %, total phenols 23.06 mg/
kg, a-tocopherol 5.74 mg/100 g, c-tocopherol 24.41 mg/
100 g and antioxidant activity of 27.18 mg oil/mg DPPH.
Bowman and Barringer [18] determined the dominant
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volatiles in raw and roasted pumpkin seeds. Also, the effect
of seed coat, moisture content, fatty acid ratio, total lipids,
reducing sugars and harvest year on volatile formation was
assessed. Hull-less seeds contained higher volatile lipid
aldehydes and Strecker aldehydes. Seeds dehydrated to a
moisture content of 6.5 % before roasting had higher initial
and final volatile concentrations than seeds starting at 50 %
moisture. Sensory analyses showed that hull-less seeds
were preferred significantly than hulled seeds.
Pumpkin seeds and health
Substantial amount of research findings have accumulated
in recent times that endorse the health benefits of pumpkin
seeds and vouch for their use in dietary intervention.
Hypolipidaemic effect
Makni et al. [19] evaluated the effect of flax and pumpkin
seed mixture intake in rats fed with a 1 % cholesterol diet.
In the seed-fed group, significant increase in poly- and
monounsaturated fatty acids was observed. Plummeted
malondialdehyde level and bolstered antioxidant defence
system indicated the anti-atherogenic potential of the seed
mixture. Gossell-Williams et al. [20] examined the effect
of pumpkin seed oil supplementation on the total choles-
terol, and low-density and high-density lipoprotein cho-
lesterol, and systolic and diastolic blood pressure in rats.
Both non-ovariectomized and ovariectomized rats were
supplemented with corn oil or pumpkin seed oil for 5 days/
week for 12 weeks (40 mg/kg given orally). Blood analysis
showed healthy lipid level in the pumpkin seed oil-sup-
plemented group. Barakat and Mahmoud [21] examined
the efficacy of pumpkin seed used along with flax or
purslane seed on hyperlipidaemia in high cholesterol diet-
fed rats. A 2 % cholesterol administration caused a
significant increase in total cholesterol, total lipids and
triacylglycerol in both serum and liver. The consumption of
flax/pumpkin or purslane/pumpkin seed mixtures resulted
in a significant decrease in lipid parameters suggesting the
anti-atherogenic potential of the seed mixture.
Antihypertensive and cardioprotective effect
Pumpkin seeds play an important role in relaxing vessels
and lowering blood pressure. El-Mosallamy et al. [22]
determined the effects of pumpkin seed oil treatment
on chemical-induced hypertension in rats. The oil
(40–100 mg/kg), was given once daily for 6 weeks. Intake
of the oil significantly reduced the abnormal increase in
blood pressure caused by the chemical and normalized the
electrocardiogram changes. Also, it decreased the elevated
levels of MDA and reversed the decreased levels of NO
metabolites to normalcy. The results showed the protective
effect of pumpkin seed oil against pathological alterations
in the heart and aorta, the mechanism of which was attrib-
uted to the generation of NO. NO production is attributed to
amino acid
L-arginine. Also, the high magnesium content is
credited to reducing the risks of heart attack. The seed
supplements have shown comparable efficiency to the cal-
cium channel blocker prescription drug amlodipine.
Anti-diabetic effect
While diabetes patients are barred from consuming
pumpkin for its obvious carbohydrate richness, the seeds
pose no threats. Makni et al. [23] investigated the hypo-
glycaemic and antioxidant effects of flax and pumpkin seed
mixture on the kidney of alloxan-induced diabetic rats. The
characteristic histopathological changes were less pro-
nounced as the supplement ameliorated the antioxidant
enzymes CAT, SOD and GSH and decreased MDA levels.
The increases in glucose, total lipid, total cholesterol and
triglycerides in plasma were significantly subdued. Further,
Makni et al. [24] observed that a pumpkin seed oil diet
attenuated the increased levels of the plasma enzymes
aspartate aminotransferase and alanine aminotransferase
that pose a risk of diabetes. Its use in regular food may be
effective in the prevention of diabetes and its complica-
tions. Teugwa et al. evaluated the hypoglycaemic activity
of proteins derived from several species of Cucurbitaceae,
including C. moschata. The result of the oral glucose
tolerance test performed on rats revealed that globulin was
the most abundant storage protein which measured
295.11 mg/g dry matter and capable of causing significant
drop in blood sugar (88–137.80 %) [25]. However, sup-
plemental work must be undertaken to lend further cre-
dence to the above findings.
Cancer management
Pumpkin seed consumption has shown considerable bene-
fits in benign prostatic hypertrophy (enlarged prostate
gland). Gossell-Williams et al. [26] examined the effect of
pumpkin seed oil on testosterone-induced hyperplasia of
the prostate in rats. During the course of hyperplasia
induction, oral administration of either pumpkin seed oil or
corn oil (vehicle) was given for 20 days. On day 21, rats
were killed and the prostate was weighed. The induced
increase in prostate size was inhibited in rats fed with
pumpkin seed oil (2 mg/100 g). The protective effect of
pumpkin seed oil was significant at the higher dose. The
result builds hope for management of benign prostatic
hyperplasia. Hong et al. [27] conducted a randomized,
double-blind, placebo-controlled trial on benign prostatic
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hyperplasia patients. Continuation for 3 months resulted in
reduction in cancer symptoms and improved overall quality
of life. After 12 months, the hyperplasia-caused urination
and bladder problems subsided and conspicuous progress
in urinary flow was observed. Jiang et al. [28] showed that
ProstaCaid
TM
treatment (a polyherbal preparation with
pumpkin seed as an ingredient) resulted in the inhibition of
cell proliferation of the highly invasive human hormone-
independent prostate cancer PC-3 cells in a dose- and time-
dependent manner. DNA-microarray analysis demonstrated
that it inhibited the proliferation of cancerous cells through
the modulation in expression of CCND1, CDK4,
CDKN1A, E2F1, MAPK6 and PCNA genes. The formu-
lation suppressed the metastatic behaviour of cancer cells
by the inhibition of cell adhesion, cell migration and cell
invasion, which was associated with the down-regulation
of expression of CAV1, IGF2, NR2F1 and PLAU genes.
Also, it controlled the secretion of the urokinase plasmin-
ogen activator from PC-3 cells. Zaineddin et al. [29]
administered a food-frequency questionnaire to a vulnera-
ble group of women. It was found that the consumption of
sunflower and pumpkin seeds was associated with signifi-
cantly reduced postmenopausal breast cancer risk.
Gynaecological effect
Phytoestrogens are plant metabolites with structural and
functional similarity to 17b-estradiol, recognized to lower
the risk of osteoporosis, heart disease, breast cancer and
menopausal symptoms [29]. Pumpkin seed oil has been
discovered to be as rich in phytoestrogens as other plant
sources as soy foods, flaxseed, sunflower seed, sesame, etc.
Gossell-Williams et al. [30] evaluated the probable bene-
ficial effects of pumpkin seed oil on postmenopausal
women. The randomized, double-blinded and placebo-
controlled study involved 35 women who had undergone
menopause naturally or due to surgery. The subjects
receiving pumpkin seed oil showed a significant increase in
high-density lipoprotein and decrease in diastolic blood
pressure. A decrease in the severity of hot flushes, less
frequent headaches and less joint pains were reported in the
pumpkin seed oil-administered group. The placebo group
dispensed with wheat germ oil complained of more
depression and emotional insecurity. The positive response
warrants further probing into the menopause remedial
effects of pumpkin seeds.
Anthelmintic effect
In many cultures throughout the world, pumpkin seeds are
used as a natural treatment for parasites. Several Native
American tribes used it to get rid of internal worms. Tae-
niasis refers to the infection with adult tapeworms of Taenia
spp. in the upper small intestine of humans. Exposure to
eggs of Taenia spp. leads to tissue infection, cysticercosis.
The conventional chemical drugs often cause induction of
epileptic seizures or convulsions in carriers with asymp-
tomatic concurrent neurocysticercosis. Li et al. [31] asses-
sed the curative effect of pumpkin seed/areca nut extract
treatment on 115 suspected taeniasis cases. The mean time
period for complete elimination of tapeworms in the studied
cases was 2 h. Though both plant extracts showed tapeworm
elimination, a synergistic effect was observed accounting
for 89 % efficacy. The seeds were found to be beneficial in
cases of acute schistosomiasis, a type of parasite contracted
from freshwater snails that causes fever, chills, headache,
fatigue and intense gastrointestinal discomfort. Cucurbitine,
an amino acid and carboxypyrrolidine (structural similarity
with proline) found in the seed was found to be the active
anti-worming agent. When cucurbitane extracted from
C. moschata seeds was given at a daily dose of 350–400 mg/kg
for 28 days to mice, Schistosoma japonicum development
was retarded. Shrinkage of size, atrophy of uterus and
reductions in the number of ova led to fall in the worm
population to about 44–69 %.
Safety issues
Despite the litany of health benefits, consumption of
pumpkin seeds are not entirely free from risks. Ingestion of
whole pumpkin seeds results in minor stomachache in
some consumers. Rectal seed bezoars commonly occur due
to seeds, especially in children living in countries south of
the Mediterranean and in the Middle-East. Inadequate
chewing or hasty eating of dried pumpkin seeds without
removing the hull may lead to their impaction as bezoars,
which may require manual removal under general anaes-
thesia [32]. Manne et al. [33] reported a case of a 62-year-
old man with a rectal bezoar composed of pumpkin seeds
which necessitated manual disimpaction and colonoscopy.
Rodriguez-jimenez et al. [34] reported a case of allergy to
pumpkin seed in which an IgE-mediated hypersensitivity
mechanism was demonstrated both in vivo and in vitro. A
protein of approximately 12 kDa seemed responsible for
the allergy. Roasted seeds contain trans-fat that may
deposit plaque in the arteries. Saucedo-Hernandez et al.
[35] reported that the quality control of pumpkin seed oils
is important because the cultivar types are the determinants
of their pharmaceutical properties. Willis et al. [36] con-
ducted a study on contamination of several edible seeds in
the UK, out of which Escherichia coli was detected in 9 %
of samples. Also, mycotoxins have been found to be a
threat. These findings highlight the importance of impurity-
free pumpkin seeds, good hygiene practices and rigorous
decontamination procedures.
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Conclusion and future perspective
The findings above confirm that pumpkin seed not only
serves as delicious food, but also possesses therapeutic
values. There are several cultivars of pumpkins, but so far
only C. pepo, C. maxima and C. moschata have been
studied. Nutritional assessment of other seed varieties and
breeding of the high-yield varieties can open up new food
formulation opportunities. With sufficient investigative
focus, it may emerge as a substitute to sunflower seed or a
complement to flaxseed. Pumpkin seed oil could be an
alternative to the expensive olive oil. The optimal use of this
nutrition-dense seeds must be given due attention, for it
could address the food security issue to a significant degree.
The popularization of innovative nutraceuticals for mass
nourishment is being given a fast-track status, and in this
regard this review discusses a highly relevant candidate.
Apart from the validated medicinal properties, pumpkin
seeds hold other health-restorative prospects. They are
anticipated to avoid kidney stones, treat incontinence, drive
away depression, prevent osteoporosis, promote ocular
health, nourish skin etc.; however, there are insufficient
studies in these directions. Microbial fermentation for
subduing the anti-nutritional components and value addi-
tion could be explored. Its blending with other beneficial
botanicals could result in desirable supplements. Genetic as
well as environmental factors may influence the seed
nutrient contents, so this aspect could be delved into [37].
More clinical trials are required to appreciate and utilize
the optimal nutritional potential of pumpkin seeds.
Conflict of interest There is no conflict of interest in submitting
this work to this journal.
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