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Bioactive Compounds of Cucurbitaceae Seed Oils as Nutraceuticals and Health-Promoting Substances
Table 2a. Tocopherol and tocotrienol composition of Citrullus lanatus seed oils (mg/kg).
Sample Origin
Citrullus
lanatus (Thunb.)
Matsum. &
Nakai
Citrullus
lanatus (Thunb.)
Matsum. &
Nakai
Kalahari melon
(Citrullus
lanatus)
Citrullus lanatus
var. Sugar Baby
Citrullus lanatus
var. Q-F-12
Citrullus lanatus
var. D-W-H-21
Citrullus lanatus
var. Red Circle
- 1885
Citrullus
colocynthoides
Brazil
Latvia
Namibia
Pakistan
Sudan
Extraction
procedure
n-hexane
Expeller
n-hexane-
ethyl acetate
(9:1; v/v)
Soxhlet
extractor
(Petroleum
ether)
Soxhlet
extractor
(n-hexane)
Soxhlet
extractor
(Petroleum
ether)
α-T β-T γ-T δ-T α-T3 β-T3 γ-T3 δ-T3 Reference
1.68 ±
0.29
1.43 ±
0.38
12.9 ± 3.0
259.4 ±
26.8
195.6 ±
12.2
164.3 ±
5.6
122.0 ±
7.1
120.6 ±
10.25
0.6 ±
32.7 ±
- - 359 ± 2.1 10 ± 1.0 ND ND ND ND
62.83 ±
-
10.12
71.07 ±
-
11.15
313 ±
0.1
3.0
10.2
705.6 ±
6.6
- - 12.3 ± 0.9 ND ND ND ND
- - 58.3 ± 1.2 ND ND ND ND
- - 9.1 ± 0.5 ND ND ND ND
- - 20 ± 1.1 ND ND ND ND
0.69 ±
0.05
0.69 ±
0.07
7.2 ± 0.5
93.3 ± 9.3 ND ND ND ND
ND ND ND ND
ND ND ND ND
0.4 ±
0.1
0.5 ±
-
0.1
-
T: Tocopherol; T3: Tocotrienol; Values are means ± SD of three determinations; SD: standard deviation; ND: Not Determined.
de Conto et al.
(2011)
Górnaś et al.
(2014)
Nyam et al.
(2009)
Raziq et al.
(2012)
Mariod et al.
(2009)
melon (Cucumis melo) seed oils, respectively. The results are obviously lower than those reported by
Mallek-Ayadi et al. (2018) in melon seeds (87.52 mg QE/100g). Another research discovered that the
total flavonoid content of watermelon seeds was 3.06 mg catechin per milligram (Mehra et al., 2015).
Carotenoids
Carotenoids are lipophilic compounds found in seed oils. These bioactive chemicals have antioxidant
characteristics because they are effective singlet oxygen quenchers and chain-breaking antioxidants,
protecting cells and other bodily components from free radical damage (Murkovic et al., 2002). Carotenoids have also been linked to several health advantages, including the prevention of cardiovascular
disease, prostate cancer, and macular degeneration (Silva et al., 2018; Stahl & Sies, 2005). In terms of
nutrition, these pigments are said to be high in vitamin A, in addition to their antioxidant characteristics
(Mallek-Ayadi et al., 2019).
Total carotenoid content in cold pressed pumpkin seed oil (Cucurbita pepo L.) was estimated to be
between 69 mg/Kg and 228 mg/Kg by Özbek & Ergönül (2020). According to Tuberoso et al. (2007),
cold pressed pumpkin seed oil had more -carotene than flaxseed, grapeseed, maize, peanut, rapeseed,
soybean, and sunflower cold pressed oils, but less than virgin olive oil. The carotenoid content of Cu-
cumis melo has been observed to range between 2.43 and 38.5 mg/kg. This amount was comparable to
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Bioactive Compounds of Cucurbitaceae Seed Oils as Nutraceuticals and Health-Promoting Substances
Table 2b. Tocopherol and tocotrienol composition of Cucumis melo L. seed oils (mg/100g).
Sample Origin α-T β-T (β+ γ)-T (β+ δ)- T γ-T δ-T α-T3 β-T3 γ-T3 δ-T3 Reference
Cucumis melo Var.
‘Maazoun’
Cucumis melo var.
‘flexuosus’
Cucumis melo var.
‘agrestis’
Cucumis melo var.
‘Inodorus’
Canary melon
(Cucumis melo L.)
Yellow melon
Cucumis melo var.
‘inodorus Naudin’
Cucumis melo var.
‘tibish’
Cucumis melo var.
‘agrestis’
Cucumis melo var.
‘agrestis’
ND: not determined.
Tunisia
Sudan
Brazil
Spain
Brazil
Sudan
Sudan
(Ghibaish)
Sudan
(Gezira)
2.85
±
0.17
0.4 ±
0.05
- - - - 29.1± 0.6 -
3.98
±
0.02
6.88
±
0.61
2.05
±
0.03
2.7 ±
0.17
7.21
± 0.1
8.21
± 01
18.13 ±
-
0.41
- - -
- - -
- - -
- - -
- - -
- - -
- - -
6.09 ±
0.53
33.5 ±
0.26
46.77±
0.04
63.08 ±
0.75
24.96 ±
0.00
13.1 ±
0.41
32.2 ±
0.1
30.2 ±
0.2
- ND ND ND ND
0.8 ± 0.05
ND ND ND ND Mariod et al. (2009)
ND ND ND ND ND
0.77 ± 0.03
ND ND ND ND ND
27.4 ± 0.53 ND ND ND ND Azhari et al. (2014)
0.17 ± 0.03 -
0.2 ± 0.1 -
0.47 ±
0.02
-
0.33
± 0.2
0.3 ±
0.05
0.9 ±
0.03
- -
- -
Mallek-Ayadi et al.
(2018)
Veronezi & Jorge
(2018)
- Górnaś et al. (2015)
da Silva & Jorge
(2014)
Mariod & Matthäus
(2008)
Mariod & Matthäus
(2008)
that of watermelon seed oil (Citrullus lanatus), which had a carotenoid level ranging from 6.3 to 39.1
mg/kg (de Conto et al., 2011; Szydlowska-Czerniak et al., 2011; da Silva & Jorge, 2014).
Chlorophylls
One of the most common pigments in edible oils, chlorophylls, may operate as an antioxidant in lipid
auto-oxidation while also acting as a sensitizer and producing singlet oxygen molecules in the presence
of light (Choe, 2017). Cold pressed pumpkin seed oil has chlorophyll levels equivalent to virgin olive
oil (30.8 mg/kg and 33.9 mg/kg, respectively) (Tuberoso et al., 2007). Mallek-Ayadi et al. (2019) found
a total concentration of 5.70 mg/kg of chlorophyll in melon seed oil.
BIOLOGICAL ACTIVITIES OF CUCURBITACEAE SEED OILS
Antioxidant activities
According to Silva et al. (2018), the presence of certain chemicals, such as phenolics and flavonoids, is
primarily responsible for seed oil’s antioxidant activity. Other research has shown that certain fatty acids
and trace components, such as linoleic acid, are relevant in terms of oil antioxidant action (Ramaprasad
et al., 2006). The hydrogen-donating antioxidants model’s antiradical activity is commonly utilized to
test antioxidant characteristics in a relatively short period. The DPPH free radical scavenging test is
often used to measure this capacity. In this context, IC
scavenge 50% of DPPH radicals. Thus, a low IC
refers to the sample concentration necessary to
50
corresponds to a strong scavenging capability, and
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299

Bioactive Compounds of Cucurbitaceae Seed Oils as Nutraceuticals and Health-Promoting Substances
it is evaluated by graphing percentage inhibition against various oil concentrations (Guergouri et al.,
2017). Cold pressed Cucurbitaceae seed oils were tested for antiradical activity by Rezig et al. (2019).
Cucumis melo var. ‘Ananas,’ Citrullus lanatus var. ‘Crimson,’ and Cucurbita pepo var. ‘Essahli’ all had
values of 52.55 ± 5.08 g/g, 159.64 ± 15.47 g/g, and 64.71 ± 6.07 g/g, respectively. Furthermore,
IC
50
Azhari et al. (2014) showed Seinat (Cucumis melo var. “tibish”) seed oil to have stronger antioxidant
activity than Rezig et al. (2019), with an IC
of 25.2 mg/mL. When compared to cold pressed ‘Essahli’
50
Cucurbita pepo L. and ‘Crimson’ Citrullus lanatus seed oils, Cucumis melo var. ‘Ananas’ seed oil had
the best antioxidant activity. Casoni et al. (2019) classified PSO (IC
DPPH radical scavenging activity oil,” along with oils of chia seed (IC
= 38.8 percent), sunflower seed (IC50 = 25.7 percent -39.3 percent), linseed (IC50 = 32.7 percent),
(IC
50
argan seed (IC
seed (IC
seed (IC
50
50
= 31.5 percent), mustard seed (IC50 = 34.6%), red grape seed (IC50 = 33.7%), almond
50
= 25.3%), rapeseed (IC50 = 35.1%), walnut (IC50 = 36.2%), negrilic (IC50 = 33%), and sesame
= 36.9%). The DPPH radical scavenging activity of these seed oils was mostly determined by
the content of tocochromanols. Górnaś et al. (2015) discovered a substantial association (R
= 36.2 percent) as a “medium
50
= 30.4 percent), apricot seed
50
2
= 0.994)
between the overall concentration of tocochromanols in seed oils and the DPPH radical scavenging activity. This finding shows that various tocopherol and tocotrienol homologs quench DPPH free radicals
with comparable potency.
Anti-inflammatory activities
Many chronic illnesses, including rheumatoid arthritis, are caused by oxidative stress and inflammation
(RA). The impact of oxidative stress in the onset and development of joint disorders cannot be overstated
(Knight, 2000). ROS (reactive oxygen species) cause oxidative damage that accumulates throughout
the life cycle. It is worth noting that radical-related damage affects DNA, proteins, and lipids, all of
which have been implicated in the development of arthritis. Arslanbaş et al. (2020) investigated the anti-
inflammatory potential of pumpkin seed oil. The authors observed that injecting carrageenan into the
hind paws of rats enhanced vascular permeability and/or blood flow, causing edema to expand in size
in all treatment groups and initiating the vascular phase of the inflammatory process. Pro-inflammatory
cytokines such as TNF-, IL-6, and IL-1, as well as histamine and serotonin, are inflammation mediators
that are produced during the first hour of the vascular phase (first phase). These mediators are responsible
for rashes, edema, and secretions (Al-Zuhair et al., 1997; Ben Khedir et al., 2016). The inflammation
persisted, intensifying and reaching a climax in the second hour. The findings indicated that Turkey
PSO (40 and 100 mg/kg dosages) inhibited rat paw edema over time. According to this circumstance,
PSO has an antagonistic impact on all inflammatory mediators in the vascular and cellular phases. PSO
dosages of 40 and 100 mg/kg were observed to substantially lower the percentage of inflammation in
the fourth hour (p < 0.05). Al-Okbi et al. (2016) performed a research comparing the anti-inflammatory
properties of Egyptian and European kinds of PSO in a rat adjuvant arthritis model, and their findings
were congruent with those of Arslanbaş et al. (2020).
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Bioactive Compounds of Cucurbitaceae Seed Oils as Nutraceuticals and Health-Promoting Substances
THERAPEUTIC EFFECTS OF CUCURBITACEAE SEED OILS
Anti-hypertensive and Anti-cardiovascular Affects
Pumpkin seed oil (PSO) and watermelon seed oil (WSO) were shown to have antihypertensive, cardio-
protective, and antihypercholesterolemic effects by El-Mosallamy et al. (2012) and Eke et al. (2021).
In fact, PSO greatly decreased the rise in systolic blood pressure by L-NAME and normalized the
L-NAME-induced electrocardiogram changes. When compared to the L-NAME-treated group, PSO
considerably reduced the raised levels of plasma malondialdehyde, a hallmark of lipid peroxidation,
increased oxidative stress, and reverted the lowered levels of nitric oxide metabolites to near normal
levels. When compared to the olive oil-treated group, WSO doses of 2 mL/kg and 5 mL/kg substantially
reduced blood cholesterol, triglyceride, and LDL (low density lipoprotein), but increased HDL (highdensity lipoprotein) and VLDL (very low density lipoprotein). According to the scientists, the considerable decrease in cholesterol levels discovered suggests that consuming WSO regularly for 28 days
may suppress 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, a rate-limiting enzyme
in cholesterol production (Okediran et al., 2015). These results are consistent with those obtained from
experimental animals given a diet supplemented with Egusi melon seed oil for six weeks (Eidangbe et
al., 2010; Francis et al., 2019).
Anti-diabetic Effet
Eke et al. (2021) investigated the anti-diabetic properties of watermelon seed oil (WSO) in albino rats.
To that end, thirty Wistar albino rats were split into five groups of six individuals each (A-E; n = 6).
Group A acted as the control group, receiving just chow and water; groups B and C got 2 mL/kg and 5
ml/kg of WSO, respectively, while groups D and E received 2 mL/kg and 5 mL/kg of olive oil (Goya
extra virgin), respectively, once daily for 28 days. Because of its capacity to prevent hepatic fibrosis and
damage in rats, olive oil was selected as a standard oil. The oils used in this research (WSO and olive oil
as a control) were given by gastro-oral gavage. On days 8 and 15 of therapy, the oral glucose tolerance
test (OGTT) was performed. After fasting overnight, the animals were administered an oral glucose load
of 300 mg/kg body weight. A glucometer was used to measure the glucose levels in the rats’ tail vein
at 0, 15, 30, 45, and 60 minutes. In the first and second weeks of the trial, blood glucose levels in the
temoin, watermelon seed oil, and olive oil treatment groups dramatically increased after 30 minutes of
loading with 300 mg/kg glucose solution. Oral treatment of WSO and olive oil to rats enhanced glucose
tolerance at 60 minutes due to increased glucose absorption from the gastrointestinal tract as compared
to the healthy untreated group. Sebbagh et al. (2009) observed a comparable finding in a healthy and
diabetic model of rats on a diet supplemented with Citrullus colocynthis, sunflower, and olive oils. These
results suggested that watermelon seed oil and olive oil had the capacity to decrease postprandial glucose
increase in diabetic subjects, presumably owing to their high linoleic acid content.
Anti-prostate Effect
The benefits of pumpkin seed oil derived from Cucurbita pepo (CP) oil were studied in a clinical study
involving approximately 2000 males suffering from benign prostatic hypertrophy (BPH) (Friederich et
al., 2000). The authors demonstrated that an oral administration of 500-1000 mg/day of CP oil for 12
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Bioactive Compounds of Cucurbitaceae Seed Oils as Nutraceuticals and Health-Promoting Substances
weeks reduced the International Prostate Symptom Scores by 41.4 percent and that more than 96 percent
of the patients experienced no adverse effects, indicating that CP oil significantly improved urinary
dysfunction in patients (Friederich et al., 2000). Gossell-Williams et al. (2006) discovered that CP oil
prevented testosterone-induced prostate hypertrophy in rats. In this study, rats given 0.3 mg/100 g body
weight of testosterone experienced an increase in prostate size ratio, which was prevented by giving
them 2.0 or 4.0 mg/100 g body weight of CP oil. Similarly, Nishimura et al. (2014) investigated the
impact of another pumpkin seed oil, Cucurbita maxima (CM oil). Authors found that CM oil was safe,
well tolerated, and helpful in avoiding urinary problems such as overactive bladder (OAB) and benign
prostatic enlargement in these investigations (BPH). These effects were linked to the CM oil’s sitosterol
concentration, showing its potential for the prevention or treatment of urinary diseases such as OAB. In
the same study, Hong et al. (2009) investigated the effects of pumpkin seed oil and saw palmetto oil on
symptomatic benign prostatic hyperplasia in Korean males. These trials found that patients who received
pumpkin seed oil, saw palmetto oil, or a combination of pumpkin seed oil and saw palmetto oil for more
than a year improved in benign prostate hypertrophy (BPH) symptoms when compared to those who
received a placebo. While the therapeutic effectiveness of this two-oil combination did not increase, no
negative effects were identified. According to the findings of these researches, pumpkin seed oil and
saw palmetto oil are clinically safe and may be useful as supplemental and alternative therapies for the
treatment of BPH.
Hepatoprotective Effect
Citrullus lanatus seed oil; CLSO (125 mg) and CLSO (250 mg) were given orally to CCl4-induced
rats for 10 days and compared to normal silymarin (100 mg/kg) orally. ALT (alanine aminotransferase),
AST (aspartate aminotransferase), and ALP (alkaline phosphatase) values, which were elevated owing to CCl4-induced liver damage, drop considerably among the treated groups and are equivalent to
the standard medicine silymarin (Madhavi et al., 2012). Oluba et al. (2008) investigated Egusi melon
seed oil (EMO). The extracted oil was employed in diet formulation and given to rats for 6 weeks (as
a supplement to a cholesterol-based diet) to examine its influence on blood activities of LDH (Lactate
dehydrogenase), ALT, AST, and γ-GT (gamma-glutamyltranspeptidase). The serum activities of the
enzymes were significantly reduced (p < 0.05) in rats given Egusi melon oil.
Beneficial Effects on Skin Care
Previous research has demonstrated that treating skin lesions with Cucurbitaceae seed oil with a high level
of polyunsaturated fatty acids (PUFAs) (more than 50% of total fatty acids) enhances wound healing and
inflammation elimination (Bardaa et al., 2016; Safar, 2019). Bardaa et al. (2015) performed a research
to evaluate the therapeutic properties of pumpkin and linseed oils. The experiment was carried out on
rats with second-degree burns. The findings revealed that rats given linseed, pumpkin, and “CytolCentella®” had a larger percentage of wound contraction (98.68, 96.71, and 92.54 percent, respectively)
than the control group (58.38 percent). Biopsies histomorphometric study demonstrated that pumpkin
oil and CytolCentella® may considerably boost collagen formation by 64.9 percent and 61.2 percent,
respectively. Nakai (Kalahari melon) seed oil was also researched for its ability to preserve good skin.
In reality, melon seed oil includes a variety of fatty acids that may be useful when applied to the skin
topically. Komane et al. (2017) investigated the safety (irritancy potential test) and effectiveness (tran-
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Bioactive Compounds of Cucurbitaceae Seed Oils as Nutraceuticals and Health-Promoting Substances
sepidermal water loss, hydration, and occlusivity tests) of topically administered Kalahari melon seed
oil on healthy Caucasian adult female volunteers (n = 20). When used topically, Kalahari melon seed
oil did not irritate the skin (observed at 24, 48, 72 and 96 h). The irritancy level findings demonstrated
that using Kalahari melon seed oil decreased transepidermal water loss and boosted moisture retention.
Effect on Sex Hormones
The impact of various traditionally derived edible seed oils (sesame, peanut, and melon oils) on albino
wistar rats’ sex hormones - prolactin, progesterone, testosterone, estradiol, luteinizing hormone (LH), and
follicle stimulating hormone (FSH) - was investigated. The findings showed that supplementing with 5%
and 10% Citrullus lanatus seed oil induced a substantial rise (p < 0.05) in prolactin (with a corresponding
drop in progesterone), LH, estradiol, and testosterone compared to the controls (Agiang et al., 2015).
Effects of Pumpkin Seed Oil in Cancer Models
Plant chemicals that have structural and functional similarities to mammalian estrogens and can bind to
mammalian estrogen receptors are known as phytoestrogens (Benassayag et al., 2002). Because of their
mild inhibitory action on aromatase, phytoestrogens may influence the risk of breast cancer (Lacey et
al., 2005). Importantly, low to high intake of pumpkin seeds, as well as soybeans and sunflower seeds,
was linked to a considerably decreased risk of breast cancer (Zaineddin et al., 2012). A population-based
case-control study of postmenopausal German women looked at the relationship between phytoestrogen-
rich foods and dietary lignans and breast cancer risk. Data on dietary profiles were acquired from 2,884
cases and 5,509 controls using a validated food frequency questionnaire that included extra items on
phytoestrogen-rich foods. The findings offered support for a decreased incidence of postmenopausal breast
cancer related with higher intake of sunflower, pumpkin, and soybean seeds (Zaineddin et al., 2012).
Richter et al. (2013) investigated the effects of phytoestrogen extracts extracted from pumpkin seeds
on estradiol synthesis and ER/PR expression in breast cancer and trophoblast tumor cells, as enhanced
estradiol production was recorded in MCF7, BeWo, and Jeg3 cells in a dose dependent manner. MCF-7
cells treated with varied doses of estradiol (10, 50, and 100 g/mL) exhibited the same pattern of ER and
PR expression. However, ERα expression was greatly reduced, ERβ expression remained unchanged,
and PR expression was increased (Richter et al., 2013). The levels of ERα, ERβ, and PR expression in
Jeg-3 and BeWo cells did not alter substantially when treated with pumpkin seed extract vs. untreated
cells (Richter et al., 2013). Nonetheless, further in-depth preclinical research is needed to investigate
the possible function of pumpkin seed lignans in breast cancer prevention and/or therapy. Plant new
ribosome-inactivating proteins (RIPs) have been shown to have antiviral, antifungal, and insecticidal
effects. As a result, they may play essential roles in the plant defense system and have a high potential
for medical or agronomic uses, such as anticancer medicines or antiviral transgenic tobacco (Krishnan
et al., 2002). Moschatin, a new RIP, has been isolated and described from ripe pumpkin seeds (Cucur-
bita moschata) (Xia et al., 2003). Using the anti-human melanoma McAb Ng76, a new immunotoxin
Moschatin-Ng76 was successfully synthesized, which effectively reduced the development of targeted
melanoma cells M21 with an IC
free Moschatin (Xia et al., 2003). These findings suggest that Moschatin might be employed as a novel
and effective chemopreventive drug against melanoma (Xia et al., 2003).
of 0.04 nM, which is 1500 times lower dosage than that found with
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Bioactive Compounds of Cucurbitaceae Seed Oils as Nutraceuticals and Health-Promoting Substances
Pumpkin Seed Oil Extracted from Cucurbita maxima Improves
Urinary Disorder in Human Overactive Bladder (HOB)
Nishimura et al. (2014) investigated the impact of Cucurbita maxima pumpkin seed oil on urinary
dysfunction in overactive bladder patients (OAB). This research included 45 participants (male: female
ratio = 25:20; ages 41-80 years). For 12 weeks, an extract of pumpkin seed oil from Cucurbita maxima
(10 g oil/day) was taken orally. Urinary function was assessed after 6 and 12 weeks using the Overactive
Bladder Symptom Score (OABSS). The individuals’ OABSS was dramatically lowered by pumpkin seed
oil derived from Cucurbita maxima. Such findings imply that pumpkin seed oil extracts from Cucurbita
maxima and Cucurbita pepo are beneficial for urinary diseases such as OAB in people. Although the
molecular mechanism of the seed oil for the alleviation of urinary tract problems is not fully known,
Friederich et al. (2000) hypothesize that sitosterols found in the seed oil are responsible for alleviating
these disorders.
CONCLUSION
Cucurbitaceae seed oils have been shown to have a variety of nutritious and bioactive components.
They possess a high concentration of biologically active substances such as oleic and linoleic acids,
phenolic compounds, flavonoids, tocopherols, and sterols, which have a favorable impact on humans.
The percentages varied based on the place where the seeds were grown and the sorts of seeds analyzed.
The existence of bioactive chemicals is completely supported by their health advantages, which include
anti-inflammatory, hypoglycemic, hepatoprotective, and anticancer properties, as well as an intriguing
antioxidant potential. As a result, in the near future, several industries, including food and pharmaceuticals, will use the Cucurbitaceae seeds as a raw material, resulting in mass production of oils and
dietary supplements. This book chapter is intended to serve as a starting point for further research into
Cucurbitaceae seed oils based therapeutic product formulations.
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Bioactive Compounds of Cucurbitaceae Seed Oils as Nutraceuticals and Health-Promoting Substances
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