Scientific African 10 (2020) e00575

Contents lists available at ScienceDirect

Scientific African
journal homepage: www.elsevier.com/locate/sciaf

The potential of pumpkin seeds as a functional food

ingredient: A review
Joachim M. Dotto a,c,∗, James S. Chacha b
a
Department of Food Biotechnology and Nutritional Sciences, The Nelson Mandela African Institution of Science and Technology, P.O. Box
447, Arusha, Tanzania
b
Department of Food Technology Nutrition and Consumer Sciences, College of Agriculture, Sokoine University of Agriculture, P.O. Box
3006, Chuo Kikuu, Morogoro, Tanzania
c
Centre for Research, Agricultural Advancement, Teaching Excellence and Sustainability in Food and Nutrition Security (CREATES-FNS),
The Nelson Mandela African Institution of Science and Technology, P.O. Box 447, Arusha, Tanzania

a r t i c l e i n f o a b s t r a c t

Article history: Pumpkin seeds may be tiny, but they are densely packed with useful nutrients and nu-
Received 19 February 2020 traceuticals such as amino acids, phytosterols, unsaturated fatty acids, phenolic com-
Revised 26 May 2020
pounds, tocopherols, cucurbitacins and valuable minerals. All these bioactive compounds
Accepted 24 September 2020
are important to a healthy life and well-being. The purpose of this review is to merge
the evidence-based information on the potential use pumpkin seeds as a functional food
Keywords: ingredient and associated biological mechanisms, collected from electronic databases (Sci-
Anthelmintic enceDirect, ResearchGate, PubMed, Scopus and Google Scholar) up to January 2020. Bioac-
Anticancer tive compounds in pumpkin seeds exhibit promising activities such as anthelmintic, an-
Cytoprotection tidiabetic, antidepressant, antioxidant, antitumor and cytoprotective. Furthermore, these
Minerals bioactives carry potential in ameliorating microbiological infections, hepatic and prostate
Phenolic compounds
disorders. As evidenced from literature, pumpkin seeds show potential to be used as both
Phytosterols
a traditional and functional food ingredient provided further animal and clinical investiga-
Prostate
tions are carried out to establish the respective molecular mechanisms and safety profile.
© 2020 The Author(s). Published by Elsevier B.V. on behalf of African Institute of
Mathematical Sciences / Next Einstein Initiative.
This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/)

Introduction

In recent years, seeds and nuts have received growing attention due to high nutraceutical and therapeutic value of their
bioactive components [1-5]. This is no exception to pumpkin seeds. Pumpkin with oily seeds belongs to the Cucurbitaceae
family. Although there are various varieties grown throughout the world, the most commercially important species are Cu-
curbita pepo (most common), C. maxima, C. moschata, C. mixta, and C. stilbo[6,7]. Pumpkins are cultivated worldwide for
many purposes varying from commercial, decorative to agricultural uses [8,9]. The popularity of pumpkin in many systems
of traditional medication has led researchers turning their attention to this crop [7,10-12]. While pumpkin seeds are largely
regarded as agro-industrial waste [8,13], they serve as powerhouses of nutrients with interesting nutraceutical properties

∗
Corresponding author.
E-mail addresses: j.dottoe@gmail.com, joachimd@nm-aist.ac.tz (J.M. Dotto).

https://doi.org/10.1016/j.sciaf.2020.e00575
2468-2276/© 2020 The Author(s). Published by Elsevier B.V. on behalf of African Institute of Mathematical Sciences / Next Einstein Initiative. This is an
open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
J.M. Dotto and J.S. Chacha Scientific African 10 (2020) e00575

Table 1
Nutritive value of pumpkin seeds (per 100 g) by different
researchers.

Nutrient Nutritional value

Amin et al. [8] Rezig et al. [2]
Dry Basis Wet Basis

Moisture (mg) 56.74 6.96

Ash (mg) 3.54 3.47
Energy (kJ) 311.54 –
Carbohydrate (mg) 5.18 –
Total sugars (mg) 9.73 1.15
Protein (mg) 21.31 40.00
Fat (mg) 23.45 35.53
Total fiber (mg) 46.65 12.89
Ascorbic acid (mg) 15.00 –
Sodium (mg) 1.35 189.81
Potassium (mg) 434.71 471.70
Iron (mg) 6.02 7.07
Calcium (mg) 4.00 44.92
Zinc (mg) 18.78 8.42
Phosphorus (mg) 0.74 1471.24
Copper (mg) 0.31 89.84
Manganese (mg) 1.35 3.93
Magnesium (mg) 4.35 527.85

‘–’ – data not available. Some data have been converted to

be expressed as mg/100 g.

[6-8,10]. The consumption rate of pumpkin seed is increasing in many African countries and elsewhere due to their eth-
nomedical benefits [7,8]. More often than not, the seeds are consumed directly as snacks after roasting and salting. They
are also used as food additives in the baking industry [6,14].
A significant number of studies have established a relationship between natural bioactive components of foods and health
promotion and disease prevention [15-17]. The foods that qualify this diet-health relationship are known as functional foods
[13]. Plants are natural sources of bioactive compounds and are widely used as functional food ingredients. The pumpkin
seeds, like other seeds, are rich in functional components. They are high in vitamin E (tocopherols), carotenoids, provita-
mins [18], pigments, pyrazine, squalene, saponins [19], phytosterols, triterpenoids, phenolic compounds and their derivatives
[6-8,20], coumarins, unsaturated fatty acids, flavonoids and proteins [21-23]. Moreover, pumpkin seeds are good source of
magnesium, potassium, phosphorus, as well as other minor minerals such as zinc, manganese, iron, calcium, sodium, and
copper [8,24]. Some of these bioactives and minerals act simultaneously at different or identical target sites with the poten-
tial to impart physiological benefits, promote well-being and reduce the risk of non-communicable disorders such as tumors
[4,21,25], microbial infections [26-28], hyperglycemia and diabetes [15,29], oxidative stress associated complications [30-33],
prostate disorders [34-36] and urinary bladder complications [16,34,37,38]. Other therapeutic activities of pumpkin seed ex-
tract (PSE) include hepatoprotective [39,40], wound healing and hair-growth stimulating [12,41-44], anthelmintic [10,45-47],
antioxidant [6,11,28,48,49] and chemoprotective properties [4,6].
This review discusses in-depth information on functional (or nutraceutical) properties of pumpkin seeds linked to molec-
ular roles to discover its promising potential as a functional food ingredient, recognize the gaps and furnish a technical
base and direction for future studies. The available articles on pumpkin seeds from online databases (Scopus, Research-
Gate, Google Scholar, SciFinder, PubMed, ScienceDirect, and Web of Science) published in English only up to January 2020
collected using the keywords “pumpkin”, “pumpkin seed” and “Cucurbita” were used to compose this article.

Nutritional composition of pumpkin seeds

With the global production of 27 million metric tons annually [50], pumpkin is one of the well-studied disease-
preventing vegetables [15–19]. Currently, the interest of public and health professionals towards the importance of func-
tional foods in the prevention of diseases is gaining its grounds [16,37,39,40,51-53]. Pumpkin seeds are densely packed with
valuable functional nutrients. While nutrients in the pumpkin seeds serve as the principal metabolites that sustain life,
functional ingredients in the seeds play key roles in disease prevention and health promotion in human beings [13,15,54].
The nutritional composition of the pumpkin seeds is summarized in Table 1. Principal fatty acids in pumpkin seed oil
(PSO) are linoleic, oleic, stearic and palmitic that cover more than 95% of total fatty acids and about 75% of which are
unsaturated fatty acids (UFAs) [3,11,17,55]. Small concentrations of arachidic and linolenic acid have also been reported
[14,40,56,57]. Fatty acid profile of the PSO is presented in Table 2. The unsaturated fatty acids have been extensively studied
due to their protective effect against cardiovascular diseases [39,58]. They are important for healthy growth and devel-
opment of brain and nervous system, respectively; also they are reported to have health benefits in the amelioration of
coronary heart diseases, hypertension and arthritis [3,8,39,59]; not to mention inflammation, autoimmune-related disorders

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Table 2
Amino acid (g/100 g) and fatty acid (mg/100 g) profiles in pumpkin seeds.

Nutrient Nutritional value Reference

Amino acid in g/100 g

Alanine 0.74 — 6.9 [8,63,71]
Arginine 1.70 — 23.10 [8,63,71]
Aspartic acid 2.05 — 2.70 [8,71]
Cystine 0.40 — 6.40 [63,71]
Glutamic acid 3.50 — 3.73 [8,71]
Glycine 1.50 — 6.80 [8,63,71]
Histidine 0.80 — 3.00 [8,63,71]
Isoleucine 0.81 — 4.90 [8,63,71]
Leucine 2.30 — 12.20 [8,63,71]
Lysine 1.50 — 4.00 [8,63,71]
Methionine 0.30 — 2.10 [8,63,71]
Phenylalanine 1.30 — 8.20 [8,63]
Proline 1.70 — 5.00 [8,63]
Serine 0.64 — 7.40 [8,63,71]
Threonine 0.83 — 3.40 [8,63,71]
Tryptophan 0.60 [8]
Tyrosine 0.83 — 4.30 [8,63,71]
Valine 1.36 — 6.70 [8,63,71]
Fatty acid in mg/100 g
Capric acid (C10:0) 0.45 [8]
Lauric acid (C12:0) 1.34 [8]
Myristic acid (C14:0) 0.01 — 0.20 [8,57,72]
Palmitic acid (C16:0) 1.57 — 27.78 [2,3,8,17,40,56,57,72-75]
Stearic acid (C18:0) 0.78 — 13.46 [2,3,8,17,40,56,57,72-75]
Oleic acid (C18:1) 2.93 — 42.80 [2,3,8,17,40,56,57,72-74]
Linoleic acid (C18:2) 4.59 — 69.12 [2,3,8,17,40,56,57,72, 73]
Linolenic acid (C18:3) 0.20 — 2.25 [8,14,17,40,57,72]
Palmitoleic (C16:1) 0.13 — 0.20 [57,72]
Arachidic acid (C20:0) 0.30 — 2.20 [2,40,56,57,72,75]

Some data have been converted to be expressed as g/100 g and mg/100 g for
amino acids and fatty acids, respectively.

and cancer [4,21,25,60,61]. Moreover, only two fatty acids are known to be essential for humans, linoleic and alpha-linolenic
acids, because they cannot be synthesized in the human body and must, therefore, be supplied through diet.
Pumpkin seed is high in crude protein, roughly 35%, and this translates to a significant and different amount of amino
acids [14]. Amino acids play important roles both as building units of proteins and as intermediates in metabolism. The
dietary supply of adequate quantity and quality essential amino acids is equally important for physiological functions in
human body [62,63]. The amino acid composition of pumpkin seed’s protein is given in Table 2. Studies show that protein
isolates from pumpkin seed resemble those of soybean with high values of bioavailability of amino acids [63,64]. In fact,
Yang et al. [1] and Rezig et al. [63] clarified that the globulin’s structure of pumpkin seeds’ protein is analogous to that
of legume seeds. This pose an important note because this nutritional similarity may provide an approval of the pumpkin
seed protein as a reliable ingredient in formulating nutritious food recipes, hence ameliorating the damaging effects linked
to protein malnutrition facing the susceptible communities. Furthermore, protein isolates of pumpkin seeds have promising
antioxidative and chelating properties [1,65-67].
The pumpkin seeds possess a significant amount of valuable minerals as well. Table 1 details mineral information of
pumpkin seeds. The seeds are rich in potassium (K) and relatively lower in sodium (Na), high in calcium (Ca), manganese
(Mn), phosphorus (P), and magnesium (Mg). Pumpkin seeds are also good source of trace elements such as zinc (Zn), iron
(Fe), not to mention copper (Cu). Minerals such as Zn, Cu, Mn, and Fe possess antioxidant potential hence serve as cofactors
of vital antioxidation-dependant biocatalyst [68,69]. Similarly, the low sodium and high potassium contents in the pumpkin
seeds translate to a significant clinical implication for improving cardiovascular health [70]. Zinc is essential in male repro-
duction, structural proteins and cellular protection [22]. These mineral concentrations may, therefore, make pumpkin seed a
useful ingredient for food fortification, at least for bakery products.
The pumpkin seed oil has been reported as a good source of phenolic compounds thus attracting considerable attention
to researchers due to their promising health benefits to humans [9,76-78]. Phenolic compounds form a wide group of com-
pounds synthesized as the secondary metabolic products in plants [78,79] possessing key antioxidant properties [13,15,54].
Thanks to the presence of a hydroxyl functional group that possesses radical scavenging ability making it suitable for re-
ducing the risk of some oxidation-induced degenerative diseases [77]. As presented in Table 3, studies found that domi-
nant phenolic compounds in the pumpkin seeds are tyrosol, vanillin, p-hydroxybenzoic, caffeic, ferulic, and vanillic acids;
and some small amounts of luteolin, protocatechuic, trans-p-coumaric and syringic acids. Nevertheless, the direct antioxi-
dizing potential could be compromised by their low bioavailability. This is because phenolics are susceptible to metabolic
transformation to form complexes and some other simple compounds. These complexes are less effective than the parent

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J.M. Dotto and J.S. Chacha Scientific African 10 (2020) e00575

Table 3
Phytochemical composition (in mg/kg) in pumpkin seed oil.

Phytochemical Nutraceutical value Reference

Phenolic compound
Protocatechuic acid 3.66 [81]
Luteolin 1.98 [9]
p-Hydroxybenzoic acid 15.96 [81]
Vanillic acid 0.62 — 6.66 [2,9,81]
Caffeic acid 1.01 — 12.20 [2,81]
Ferulic acid 0.18 — 7.05 [9,81]
Vanillin 2.61 [9]
Trans-p-Coumaric 1.82 [81]
Tyrosol 17.69 [9]
Syringic acid 0.36 [81]
Tocopherol isomer
α -Tocopherol 2.04 — 353.00 [19,72,83,84]
β -Tocopherol 5.4 [74]
γ -Tocopherol 97.15 — 893.00 [19,72,74,83,84]
δ -Tocopherol 2.32 — 22.5 [72,74,83]
α -Tocotrienol 15.5 [83]
γ -Tocotrienol 145 [83]
Phytosterols
Desmosterol 86.7 [85]
Campesterol 2.56 — 53.35 [2,57,72,85]
Campestanol 2.91 [2]
Brassicasterol 10.67 [2]
Stigmasterol 38.7 — 134.83 [2,57,85]
Cholesterol 7.76 — 12.88 [2,57]
24-methylenecholesterol 2.43 [2]
β -Sitosterol 12.08 — 100.00 [72,85]
Spinasterol 26.81 — 745.00 [57,72,85]
7,22,25-Stigmastatrienol 26.24 — 815.00 [57,72,85]
5-Avenasterol 1875.01 [2]
7-Avenasterol 9.70 — 437.00 [2,57,72,85]
7-Stigmastenol 479.64 — 523.32 [2,57]
5,23-Stigmastadienol 11.64 [2]
5,24- Stigmastadienol 14.55 [2]
7,25-Stigmastadienol 15.58 — 26.45 [57,72]
7- Campesterol 46.08 [2]
5-Sterols 143.84 — 261.00 [57,85]
5-Stigmasterol 1.31 [72]
7-Sterols 754.56 — 2680.00 [57,85]
7-Stigmastadienol 1.99 [72]
Clerosterol 51.41 [2]
Sitosterol 1923.51 [2]
Sitostanol 182.36 [2]

Some data have been converted to be expressed as mg/kg.

compounds, due to blocking of the phenolic hydroxyl groups responsible for its antioxidizing role [9,80,81]. Additionally,
the lower aqueous solubility of the phenolics is reportedly contributing to their limited bioavailability [59,78,80,82]. This
problem could be solved by micro- or nano-encapsulation of the PSO or PSE to impede its functional loss. Encapsulation of
these bioactives is believed to keep their bioactivities against oxidation, metabolic influences and other destructive reactions
within the digestive system and cellular components. This effective delivery system is not only limited to the phenolics but
UFAs, tocopherols and other phytochemicals as well.
Pumpkin seeds are also a good source of vitamin E. This vitamin in the seeds includes four tocopherol and tocotrienol
isomers (α , β , γ , and δ ) [86,87]. Their only isomeric difference lies in the number and position of the methyl groups of the
chromanol ring [87,88]. Nevertheless, only one isomer (d-RRR-α -tocopherol) qualifies the criteria of being a real vitamin E
[86]. While sunlight is an effective trigger of synthesis of vitamin E in the human body, yet many plant species are good
sources of the vitamin. Pumpkin seed, for example, is rich in tocopherols with γ -tocopherol being the dominant isomer
trailed by α - and δ -tocopherols (Table 3). It also contains small amount of α -tocotrienol, β - and γ -tocotrienols. Tocopherols
and tocotrienols in pumpkin seeds are powerful antioxidants with the ability to deactivate highly-active radicals by releasing
H+ ion from its ring [29,86]. In so doing, they keep cell’s lipids from peroxidation hence reduced risk of oxidative threats
[87,89]. Tocopherols may also serve as prooxidants and decrease some quantity of transition metals in the tissues. The
mechanism for the action is, however, highly dependent on the tocopherol levels. In spite of the central role of tocopherols
in plants being that of antioxidant, non-antioxidant functions have been delineated [18,29,89,90]. As the γ -tocopherol has
been lately reported to be effective in neutralizing peroxynitrite—a potent oxidant with an extensive array of cell injuring
effects, more interest on cell signalling-related activities of tocopherols has gained its grounds [86-88]. Lately, studies have

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Table 4
Anthelmintic effects of pumpkin seed oil and extract.

Model Dosage Significance Reference

In vivo 140 Ascaridia galli infected
chickens
In vivo 40 Heligmosoides bakeri
infected mice
In vivo 90 gastrointestinal-
helminths-naturally-infected
chickens
In vivo Hymenolepis
nana-experimentally-infected
female mice
In vitro Ascaridia galli infected
chicks
2000 mg/kg per body weight (BW) Reduced A. galli mortality rate by Abdel-Aziz et al. [10]
of PSE for 48 h 66.9%
8 g/ kg of 40% PSE per BW for 25 Reduced in the worm burden of Grzybek et al. [47]
days the treated mice by 79.8%. Also,
effective in reducing the fecal egg
counts of H. bakeri
2 g of ground pumpkin seed per Showed 83.0%, 80.00% and 88.00% Acorda et al. [20]
bird per day lethal effect on Ascaridia galli,
Heterakis gallinarum and Raillietina
spp. load, respectively
500 mg/kg per BW of (PSE) for 13 Decreased the number of adult H. Alhawiti et al. [45]
days nana recovered from infected
female mice and egg production
from day 3 after treatment and
disappeared completely on day 14
75 mg/mL of PSE for 36 h The mortality rate of 85% was Abdel-Aziz et al. [10]
post-treatment noticed.

In vitro anthelmintic assays using
Heligmosoidesbakeri: egg hatching,
larva and adult worms
For eggs: 350 μg/mL of PSO at 24
°C for 48 h of incubation;
for larva: 300 μg/mL at 27 °C for 5
days;
for adult worms: 75 μg/mL for
48 h of incubation then observed
microscopically.
The ethanolic extract egg hatching Grzybek et al. [47]
arrest 79.8% (p = 0.013);
larval inhibition was 89.3%
(p = 0.013);
while adult motility was
significantly reduced compared to
the control after 24 h.

revealed that tocotrienols possess considerable anticholesterolemic potential—unique to tocotrienols, not to mention their
neuroprotective, cardioprotective, and antitumor properties [11,29,86]. Tocotrienols share several functional features of iso-
lated tocopherols in vitro and they are measurable in plasma in the human and animal subjects [90], but so far there is
limited information of their bioaccumulation in human tissues.
Pumpkin seeds and PSO are valuable source of phytosterols [91]. Although there are more than 100 different types
of phytosterols identified in plant species, the dominant phytosterols reported in PSO are 7-sterols, contrary to most
vegetable oils [91-93]. This dominancy is succeeded by sitosterol, 7,22,25-stigmastatrienol, 7-stigmastenol, spinasterol
[39,85,94,95], just to mention a few. Table 3 provides a full list of phytosterols in pumpkin seed oil identified so far. Phytos-
terols have been intensively and extensively studied for their lowering effects of blood low-density-lipoprotein cholesterols
[92,96,97], which then translate to a reduced risk of cardiovascular threats. Moreover, a number of studies have concluded
that phytosterols lower the risk of some forms of cancers [36,98], and ameliorate the treatment of prostate complications
[34-36]. This level of phytosterols in the pumpkin seed make it a suitable alternative nutraceutical in the management of
some non-communicable diseases in human [42,43].

Anthelmintic effect

Gastrointestinal parasites are serious pathogens in humans and animals. Intestinal helminths, in particular, are known to
be highly rampant in global populations, with more than 3.5 billion people being infected annually [20,45,99]. Helminthic
infections are widely distributed in East Asia, the Americas, China, and sub-Saharan Africa. In fact, about 32 African coun-
tries had high-risk areas with a prevalence of over 50% [99]. The helminth problem may impose huge health and socioe-
conomic burden in the community. While there is low and selective deworming coverage for prevention of geohelminthes
using available synthetic anthelmintics in the developing countries, studies report a growing resistance to these drugs in
helminths in both humans and animals [99]. Effective anthelmintics are then necessary to combat this deadly pandemic
health problem. To resolve the problem, significant efforts are being put to exploit the naturally-occurring compounds that
are produced by plants in helminths’ metabolic pathways [10,47]. There is increasing evidence that pumpkin seeds possess
anthelminthic properties on various gastrointestinal nematodes. Table 4 summarizes the in vivo and in vitro anthelminthic
effects of pumpkin seeds. Pumpkin seed extracts demonstrated lethal activity in Heligmosoides bakeri in infected mice by 80%
[47]; Ascaridia galli in chicken over 65% [10,20]; Heterakis gallinarum, and Raillietina spp. by 80% and 88%, respectively [20];
adult Hymenolepis nana infemale mice [45]. Pumpkin seed extract induced a significant suppression on the number of adult
H. nana worms and their egg production [45]. Li et al. [100] reported that the extract of combined or uncombined pumpkin
seeds and areca nut has demonstrated ability to exterminate Taeniasaginata and Taeniasolium. Same researchers stated that
the effectiveness of pumpkin seed alone was relatively far better than areca nut alone, although the combined extract was
more effective. In another comparative study, pumpkin and papaya seed extracts were evaluated for anthelmintic activity on
Pheretima posthuman—earthworms resembling intestinal roundworms. Both extracts showed anthelmintic effect, but papaya
seed extract paralyzed and killed the worms slowly relative to PSE [101].

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From literature, it is evident that PSE exhibit the promising anthelminthic effect. However, only handful studies have
explored the mode of actions of pumpkin seed’s bioactive compounds against helminths. We, therefore, recommend further
studies should be geared to this direction, the comprehension of which could improve the value of pumpkin seed as a
functional food ingredient.

Anticarcinogenic effect

Tumor is one of the main health concerns threatening people worldwide and responsible for 12% of the world’s mortality
[102]. It results due to abnormal tissue mass growth caused by imbalance and uncontrolled cell division and cell death
[25,103]. The antioxidant potential of an individual cell is reported to be one of the risk factors that determine the abnormal
growth. The imbalance between free radicals and antioxidant defenses within cells, in favor of the former, may result in
oxidative stress, which may end up in the development of tumor or cancer cells [95,104]. Treatments include chemotherapy,
surgery and radiotherapy. However, chemotherapy suffers limitations of drug resistance, toxicity, side-effects and lacking
specificity toward tumor cells. Therefore, there is a strong interest in the use of plants as a reliable source of more efficient
anticancer medications.
Chari et al. [4] conducted an in vivo study to observe the appraisal of ethanolic pumpkin seed extract in 1,2-
dimethylhydrazine induced colon cancer in Wistar rats and found that apoptosis was induced when cells were treated with
200 mg/kg extract. The study further described that the extract is cytotoxic for cancerous cells and good for the treatment of
tumors. In another study, it has been reported that hydro-alcoholic extracts of pumpkin seeds could block the proliferation
of human hepatocarcinoma (HepG2) and colon carcinoma (CT26) tumor cell lines [104]. Furthermore, Jayaprakasam et al.
[25] reported the antiproliferative activity in breast, colon and lung cancer cell lines while Ren et al. [36] demonstrated a
dose-dependent inhibitory effect of cucurbitacin (a pumpkin seed isolate) against the proliferation of prostate cancer (PCa)
cell lines. The study also indicated that cucurbitacin induced cell cycle arrest, cytokinesis failure, and amplified levels of
apoptosis.
While some researchers believe that the anticarcinogenic potential of pumpkin seeds stems from their flavonoids and
cucurbitacin concentrations [4,25,36], others argue that the anticarcinogenic effect is not because of cucurbitacin—one of the
active constituent in pumpkin seed extract [4]. This particular evidence goes without fail, that there are other mechanisms
responsible for anticarcinogenic effects. This provides a room for further isolation and analytical studies to prove otherwise.
It is also equally important to note that the antitumor effect of the same compound on a given cancer cell vary simply due
to differences in experimental conditions, passage number of cells and culture media.

Antidepressant effect

Depression is a common illness that involves episodes of suppressed psychosocial functioning and diminishes quality
of life with such symptoms as disturbed sleep and appetite, reduced concentration, excessive guilt and sometimes suicidal
thoughts [105,106]. Practically, detection, diagnosis, and management of depression usually pose some notable challenges
to psychotherapists due to its unpredictable presentations, prognosis, and variable response to treatment. In 2001, over
4 million people reportedly had depression-related problems; and in 2008, depression was ranked as the third cause of
global burden of disease and is now projected to rank first by 2030 [106-110]. Unless effective and immediate measures are
taken, depression would claim many lives. Some plants have been reported to possess antidepressant compounds [111-116].
Recently, LaChance and Ramsey [114] profiled the antidepressant foods and reported that pumpkin seeds had an antidepres-
sant food score (AFS) of 47%. This means that the pumpkin seeds possess antidepressant potential. Another study examined
the activity of pumpkin seed extracts (PSE) through forced-swimming and tail-suspension tests compared with imipriamine-
standard drug in rats. The study concluded that pumpkin seeds possess significant antidepressive potential [117]. Though the
mode of action of PSE is still blurred, Hibbeln [118] and Eby and Eby [119] linked the antidepressant effect to tryptophan
(an essential amino acid) and 5-hydroxytryptophan (a tryptophan intermediate metabolite in the formation of the neuro-
transmitter serotonin), both being promoted as remedy for depression [120,121]. Furthermore, researches focusing on animal
and clinical trials are needed to reveal and affirm the ameliorative effect of pumpkin seed on depression. There is a limited
source of information on the potential of pumpkin seed in this area.

Antidiabetic and hypoglycemic effects

Diabetes is a serious global metabolic disorder characterized by elevated blood glucose levels resulting from the failure
of cells to use glucose. Diabetes occurs due to the inability of the pancreas to produce adequate insulin, the resistance
of cellular tissues to insulin activity, or both [122-124]. Diabetes caused roughly 1.5 million deaths in 2012 where more
than 80% occurring in low- and middle-income countries [125,126]. It was estimated that 422 million adults were living
with diabetes in 2014, compared with 108 million in 1980 globally [126]. This translates to increased socio-economic issues
at family and national level as well. While the emerging incidence of this metabolic disease can be slowly reduced with
different lifestyle choices such as physical exercises, abstinence from cigarette smoking and consumption of appropriate diet,
pumpkin seed, like many other seeds, could contribute to the modulation of this disease largely by promoting hypoglycemic
activity [53,123,127,128].

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In an in vivo study that involved the induced mild and severely diabetic Wistar rats, the PSE showed to lower the
elevated blood glucose levels by 26.15% and 39.33%, respectively at an effective dose of 200 mg/kg body weight (BW). Fur-
thermore, the study described that extract of pumpkin seed induces the hypoglycemic and antidiabetic activity through
stimulating insulin release from pancreatic β -cells [123]. Likewise, in a randomized, single-blinded, placebo-controlled study
involving normoglycemic adults supplied with 65 g of pumpkin seeds, and there was a remarkable alleviation of postpran-
dial [129]. In another study, Gutierrez and Martha [102] evaluated the hypoglycemic and antioxidant effects of flax and
pumpkin seeds mixture in the kidney of alloxan-induced diabetic rats. The mixture ameliorated the antioxidant enzymes
activities observed in diabetic rats and decreased plasma and kidney malondialdehyde levels. This suggests that the mixture
possesses substantial hypoglycemic and antioxidant activities. Researchers, in this particular study, believed that antidia-
betic activity of the seeds’ mixture stems from their protective role in quenching free radicals hence ensuring the survival
of pancreatic β -cells. Again, in recent studies, Marbun et al. [130] and Bayat et al. [131] reported that increased intake of
pumpkin extract has a positive effect on glycemic control, lipid profile and pancreatic β cells. The activity being attested
to the effect of bioactive compounds including flavonoids, triterponoids, steroids, and polyphenolic components. In another
in-vivo experiment against PX-407-induced diabetes in rats, results provided pharmacological evidence of pumpkin seeds as
a hypoglycemic agent; mediated by the interaction of various botanicals with multiple targets operating in diabetes mellitus.
The presence of tocopherols has been reported to be responsible for this activity [29]. Moreover, Aboelnaga [132] observed
some improvement signs in diabetic-obese rats after treating them with pumpkin seeds, husk tomato and their combination.
Gu and Li [133] also claimed that polysaccharides in ungerminated pumpkin seeds and proteins from germinated pumpkin
seeds also had the hypoglycemic effect. Some studies mention that pumpkin powder with sugar-removed and common
pumpkin powder both showed a significant increase in plasma insulin and reduction in blood glucose [134]. Pumpkin seed
is rich in pectin, a type of dietary fiber [14, 72], which regulates blood glycemic levels and reduce the need for insulin when
fiber-rich foods are consumed by diabetic patients [15,135].
It is apparent that a significant number of studies on the antidiabetic and hypoglycemic potential of pumpkin seeds have
been reported. Nevertheless, authors insist that more animal and clinical trials are needed to firmly establish molecular
mechanisms of actions, evaluate activities and associated health benefits of pumpkin seeds in the prevention of diabetes in
humans.

Antihyperplastic effect on prostate gland

Benign prostatic hyperplasia (BPH) is a non-cancerous enlargement of the prostate gland caused by the proliferation of
both stromal and epithelial cells. Benign prostatic hyperplasia develops after the age of 40 and has high morbidity and low
mortality rate. Herbal medicines have been used for the treatment of numerous chronic and severe diseases [136]. Table 5
presents in vivo activities of pumpkin seed against BPH. Pumpkin seed showed ameliorative activity on testosterone-induced
hyperplasia in the rat prostate [35] and citral-induced hyperplasia of the prostate in Wistar male mice [137]. Furthermore,
oil-free hydroethanolic PSE alleviated International Prostate Symptom Score (IPSS) of 14.8 in sixty men patients by 30% [138].
Hong et al. [139] conducted a clinical trial on 47 men with BPH symptoms, patients received a mixture of pumpkin seed
and saw palmetto oil. The oil mixture administration reduced IPSS significantly within 3 months. In another 12-month, ran-
domized, placebo-controlled, parallel-group trial enrolled 1,431 men (of average 65 years old) with BPH. The group treated
with PSE led to a clinically relevant reduction in IPSS compared with the placebo group [140]. Only preliminary studies were
carried out on PSO and PSE on its potential to treat BPH. Therefore, additional researches are emphasized to further inves-
tigate and reveal some functional bioactive compounds and the respective underlying molecular mechanisms to establish
their potential in the treatment of benign prostatic hyperplasia.

Cytoprotective effect

Some chemical compounds possess the ability to protect a cell from the deadly metabolic attacks caused by toxic
molecules, a phenomenon known as cytoprotection [103]. A good example of cytoprotection is that demonstrated by
prostaglandins. Prostaglandins prevent gastric ulcers not by inhibiting gastric acid release but by increasing mucosal pro-
tection. In a similar fashion, in vivo studies have showed that there are some properties of PSE that protect cells against
toxic cellular attacks from an array of harmful compounds [143,144]. The cytoprotective activities of pumpkin seed oil and
extract is presented in Table 6. Pumpkin seed extract (PSE) suppressed the emamectin-induced lethal effects such as DNA
disintegration, oxidative stress, and apoptosis in mice [6,77]; ameliorated the cyclophosphamide-induced reproductive toxi-
city in male rats [22]; exhibited hepatoprotective activities against acetoaminophen-induced liver damage in rats [66]; and
lowered the rate of lipid peroxidation in hepatic cells induced by carbon tetrachloride (CCl4 ). Furthermore, PSE increased the
superoxide dismutase, enzymes antioxidant which are technically related to ameliorative actions of CCl4 -induced liver injury
[66]. The PSE has also been reported to reduce liver steatosis and fibrosis as well [145]. In several studies, PSE demonstrated
potent hepatoprotective activities even at lower doses, and it was a potent inhibitor of 1,2-dimethylhydrazine metabolism,
making it an effective chemoprotective agent [4]. Since baseline studies on the cytoprotective potential of pumpkin seed
exhibit promising results, there is an opportunity for further investigations to ascertain the cytoprotective effects in valid
animal models before progress to clinical trials.

7
J.M. Dotto and J.S. Chacha
Table 5
Antihyperplastic activities demonstrated by pumpkin seed oil and pumpkin extract on prostate.
Model
In vivo testosterone-induced
hyperplasia of mice’s prostate.
In vivo citral-induced hyperplasia
of the prostate in 30 Wistar male
mice.
Sixty men of the average age of 61
with the International Prostate
Symptom Score (IPSS) of 14.8
involved in the research.
A one-year, randomized,
partially-blinded,
placebo-controlled, parallel-group
trial enrolled 1,431 men (50 − 80
years) with BPH.
A randomized clinical trial study
involved 100 BPH male patients.
A randomized, double-blind,
placebo-controlled clinical trial
included 57 males aged 40–80
years.
A randomized, double-blind,
placebo-controlled clinical trial
performed to 47 men with BPH.
Table 6
Cytoprotective activities of pumpkin seed oil and extract.
Model
In vivo emamectin-induced
oxidative stress in mice
In vivo bisphenol A-induced
toxicity in mice
In vivo cyclophosphamide-induced
reproductive toxicity in adult male
rats.
In vivo acetoaminophen-induced
liver injury in Sprague-Dawley
rats.
In vivo CCl4 -induced liver damage
in low-protein fed 52 rats was
studied.
In vivo hepatic macrovesicular
steatosis and inflammation
induced in high-fat diet fed to
20-Wistar rat.
Dosage
2.0 and 4.0 mg/100 g of PSO for
20 days.
Supplied with a normal diet, 5 -
10% of which was pumpkin seeds.
Ingested the oil-free
hydroethanolic
PSE once per day for 12 weeks.
500 mg twice a day for 52 weeks.
Received PSO for 24 weeks
Ingested PSE for 12 weeks
Subjects received a mixture of
pumpkin seed oil and saw
palmetto oil for 12 weeks.
Dosage
4 ml/kg pumpkin seed oil (PSO).
1 mL/kg BW of PSO per day for 28
days.
300 mg/kg BW of PSE for 6 weeks.
1 mL/kg BW of the pumpkin seed
protein isolate
1 mL/kg BW of the pumpkin seed
protein isolate.
50 g/kg BW of PSO for 422 days.
8
Scientific African 10 (2020) e00575
Significance Reference
Impeded testosterone-induced Gossell-Williams et al. [35]
prostate hyperplasia.
Relieved the symptom of benign Abdel-Rahman [137]
prostatic hyperplasia. Ameliorated
citral-induced abnormal growth of
the prostate in a dose-dependent
fashion.
Alleviated IPSS symptom by 30% Leibbrand et al. [138]
(95% CI). Symptom reduction
significantly influenced the quality
of life (p = 0.0001) after 3 weeks
of intervention.
Demonstrated a notable decrease Vahlensieck et al. [140]
in IPSS, but the prostate size
remains unchanged in the treated
group relative to the control
group.
IPSS had significant differences at Shirvan et al. [141]
baseline and 24 weeks after the
co-administration. Quality of life
was also better in all tested
groups.
Reduced in IPSS in the treated Coulson et al. [142]
group notably compared to the
control group.
Co-treatment of the seed oil and Hong et al. [139]
saw palmetto oil are safe and
effective as matching medicinal
combination to treat BPH.
Significance Reference
Induced ameliorative actions to Abou-Zeid et al. [6]
cellular lethal activities such as
DNA disintegration, oxidative
stress, programmed cell death and
gene expression.
Co-administration of PSO impeded Fawzy et al. [77]
DNA fragmentation and
suppressed the histopathological
modifications in testis and hepatic
cells.
Increased the level of total Aghaei et al. [22]
antioxidant capacity and
ameliorated the toxicity.
Demonstrated significant Nkosi et al. [66]
hepatoprotective activity.
Reversed the levels of lipid Nkosi et al. [65]
peroxidation in hepatic
homogenate, increased the
superoxide dismutase, enzymes
antioxidant such as catalase as
well as glutathione peroxidase
which are technically related with
ameliorative actions of
CCl4 -induced liver damage.
Attenuated hepatic fibrosis and Zhao et al. [145]
infiltration around portal section.
J.M. Dotto and J.S. Chacha Scientific African 10 (2020) e00575

Antimicrobial effect

Statistics estimates that antimicrobial resistance will escalate mortality rate to 10 million lives annually by 2050—which
is somewhat intimidating as the current figure estimates 70 0,0 0 0 deaths annually [26]. The main challenge associated with
the emergence of antimicrobial resistance includes inappropriate use of prescribed antibiotics, a mutation in microorganisms
and the lack of new antibiotics available for the treatment of resistant microorganisms [26,27, 146]. The worrying figure
is rather avertible if novel, safe, and potent compounds that can fight off the resistant microbe strains are discovered or
developed.
Cell culture studies have indicated promising antimicrobial activity of pumpkin seed extract on various strains of mi-
croorganism. The seed extract has effective antibacterial activity against Staphylococcusaureus, Bacillus subtilis, Staphylococcus
werneri, Pseudomonas putida, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumonia and Escherichia coli[23,27,147].
Furthermore, cucurmoschin, a pumpkin seed protein isolate, inhibits mycelial growth in the fungi Botrytis cinerea, Fusar-
ium oxysporum, Mycosphaerella arachidicola and Mycosphaerella oxysporum. It is likely that the translation-inhibiting activity
of antifungal proteins accounts for, at least partially, their antifungal effect [146,148]. From the findings, it is obvious that
the pumpkin seed protein is seemingly effective against the tested gram-positive bacteria and has less effect against gram-
negative bacteria. El-Aziz et al. [27] reported that gram –ve bacteria are more resistant to protein and oil antimicrobial
effect than gram +ve because of their cell wall lipopolysaccharides which may prevent these active compounds to reach the
cytoplasmic membrane of gram-negative bacteria.
There are only preliminary studies conducted regarding evaluation of the antimicrobial effectiveness of PSE and the find-
ings from these studies look promising. Further investigation is important to profile the responsible functional compounds
and identify their molecular mechanisms in reversing the microbial resistance. This could be followed by testing efficiency
in both multi-antimicrobial resistant gram +ve and gram –ve microorganisms in the accepted experimental setup.

Other nutraceutical roles of pumpkin seeds

In addition to thematic nutraceutical functions discussed above, the PSO and PSE showed to possess ameliorative effect
on hepato-inflammation and lipotoxicity [145,146]; healing wounds [51]; high-fat-diet-induced obesity in animal models
[149]; and recurrent aphthous stomatitis (RAS) in clinical trials. Although the mode of action of PSO in treatment of RAS
is still unclear, the probable mechanism of action is thought to be through its anti-inflammatory and antioxidant activities
[150]. Furthermore, Ramak and Mahboubi [93] recorded that PSO had significant anti-androgenic (hair growth promoting)
effect than the placebo group they examined while the self-rated improvement score was significantly higher than the
placebo group. The inhibitory effect of pumpkin seed oil on androgen in rats is reportedly grounded to its phytosterol
and phenolic content [42,44,151,152]. Only a few experimental evidences have provided conclusive statements on the anti-
inflammation, healing, anti-RAS, anti-androgenetic and anti-obese activities of PSO and PSE. Therefore, further studies in
these directions are warranted to test and affirm the activity of PSO and PSE in reliable experimental models.

Conclusion and future directions

In general, many researchers across the world have been working on pumpkin seeds to explore the potential bioactivities
of PSE or PSO and reported them to possess anthelmintic, antidiabetic, hypoglycemic, antihyperplastic, antitumor, cytopro-
tective, and antimicrobial properties. Meanwhile, some research gaps were identified in the existing literature on pumpkin
seeds to prove its biological activities and confirm its value as a potential functional food ingredient.
Very limited work was reported in the literature on pharmacokinetics of PSE bioactives and identification and character-
ization of functional compounds. Further research should be carried out to correlate PSE’s pharmacodynamics to pharma-
cokinetics. Moreover, there were no reports on attempts made to develop formulations to avoid metabolic oxidation, and
this creates an opportunity for further research in this direction.
Regardless of the notable progress made in pumpkin seed’s research over the years, studies on the effectiveness in an-
imal models, mechanism of action, and safety profile were scarce. Further research is necessary to fill the gap in existing
knowledge on the safety of pumpkin seeds as functional food ingredient.
Herein, an attempt was made to present an overview of the bioactivities of pumpkin seeds that would be valuable for
scholars to further investigate pumpkin seeds’ potential as a functional food ingredient.

Declaration of Competing Interest

The authors solemnly declare no conflict of interest

Ethical Statement

Neither human nor animal subjects were involved in the development of this review article

9
J.M. Dotto and J.S. Chacha Scientific African 10 (2020) e00575

Acknowledgement

Not applicable

Authors’ contributions

Joachim M. Dotto conceived the literature review concept, conducted a literature search, compiled and interpreted all the
data, and wrote the entire manuscript. James S. Chacha, on the other hand, contributed with the ideas and knowledge for
this investigation, conducted a literature search, analyzed all the data and reviewed the manuscript. All authors read and
approved the final manuscript.

Funding

This review article did not receive grant from any funding agencies in the public, commercial, or nonprofit sectors.

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