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The role of Cucurbita pepo in the management of patients affected by lower urinary tract symptoms due to benign prostatic hyperplasia: A narrative review

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Objective: Phytotherapeutic compounds are largely used in the treatment of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH) due to low side-effect profiles and costs, high level of acceptance by patients and a low rate of dropout. Here, we aimed to analyze all available evidence on the role of Cucurbita pepo in the treatment of LUTS-BPH. Material and methods: In May 2016 a systematic search was carried out thorough National Library of Medicine Pubmed, Scopus database and the ISI Web of Knowledge official website in order to identify all published studies on Cucurbita pepo and BPH. The following search strings were used: "Cucurbita pepo" OR "pumpkin seed" AND "prostate"; "Cucurbita pepo" AND "antiandrogen" OR "antiproliferative" OR "anti-inflammatory" OR "antioxidant activities"; "cucurbita pepo" OR "pumpkin seed" AND "LUTS" AND "symptoms improvement" OR "quality of life". We consider for the present analysis only studies related to LUTS-BPH. Results: Among all 670 screened, 16 were related to LUTSBPH and finally analyzed. Among all, ten of them were performed in "in vitro setting" showing anti-inflammatory and antiandrogen effect, and a reduction in prostate growth and detrusor activity, while six were clinical studies. In all studies an improvement in International Prostatic Symptoms Score (IPSS) and uroflowmetry parameters has been reported. In 4 studies, an improvement in quality of life has been reported. Conclusion: On the basis of our narrative review, the use of Cucurbita pepo in the management of patients affected by LUTS-BPH seems to be useful for improving symptoms and quality of life. However, future clinical trials are requested to confirm these promising results.
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Archivio Italiano di Urologia e Andrologia 2016; 88, 2
136
REVIEW
The role of Cucurbita pepo in the management of patients
affected by lower urinary tract symptoms due to benign
prostatic hyperplasia: A narrative review
Rocco Damiano 1, Tommaso Cai 2, Paolo Fornara 3, Corrado Antonio Franzese 4,
Rosario Leonardi5, Vincenzo Mirone 6
1 Department of Urology, University of Catanzaro, Catanzaro, Italy;
2 Department of Urology, Santa Chiara Regional Hospital, Trento, Italy;
3 Department of Urology, Martin-Luther-University, Halle Saale, Germany;
4 Urology, ASL NA3 SUD, Naples, Italy;
5 Urology, GECAS Institute, Catania, Italy;
6 Department of Urology, University of Naples, Federico II, Naples, Italy.
Objective: Phytotherapeutic compounds
are largely used in the treatment of lower
urinary tract symptoms (LUTS) related to benign prostatic
hyperplasia (BPH) due to low side-effect profiles and costs,
high level of acceptance by patients and a low rate of drop-
out. Here, we aimed to analyze all available evidence on the
role of Cucurbita pepo in the treatment of LUTS-BPH.
Material and methods: In May 2016 a systematic search
was carried out thorough National Library of Medicine
Pubmed, Scopus database and the ISI Web of Knowledge
official website in order to identify all published studies on
Cucurbita pepo and BPH. The following search strings were
used: “Cucurbita pepo” OR “pumpkin seed” AND
“prostate”; “Cucurbita pepo” AND “antiandrogen” OR
“antiproliferative” OR “anti-inflammatory” OR “antioxidant
activities”; “cucurbita pepo” OR “pumpkin seed” AND
“LUTS” AND “symptoms improvement” OR “quality of
life”. We consider for the present analysis only studies relat-
ed to LUTS-BPH.
Results: Among all 670 screened, 16 were related to LUTS-
BPH and finally analyzed. Among all, ten of them were per-
formed in “in vitro setting” showing anti-inflammatory and
antiandrogen effect, and a reduction in prostate growth and
detrusor activity, while six were clinical studies. In all stud-
ies an improvement in International Prostatic Symptoms
Score (IPSS) and uroflowmetry parameters has been report-
ed. In 4 studies, an improvement in quality of life has been
reported.
Conclusion: On the basis of our narrative review, the use of
Cucurbita pepo in the management of patients affected by
LUTS-BPH seems to be useful for improving symptoms and
quality of life. However, future clinical trials are requested
to confirm these promising results.
KEY WORDS:BPH; Cucurbita pepo; LUTS; Prostate disease;
Pumpkin seed.
Submitted 27 May 2016; Accepted 5 June 2016
Contributions: RD, TC, CAF, RL data collecting; RD,
TC analyzing and manuscript writing; VM, CAF, RL
and PF supervision.
Summary
Conflict of interests: the Authors declare no potential conflict of interests.
Funding: Chefaro pharma supported the publication of this narrative review.
INTRODUCTION
Benign prostatic hyperplasia (BPH) affects most men
after the age of 50 years and is considered the most com-
mon urologic disease among elderly men (1). BPH is a
chronic disease with early initiation and slow progres-
sion, due to an overgrowth of the epithelial and stromal
cells from the transition zone and the periurethral area
(2). It is essentially a histological diagnosis, which can be
clinically manifested as benign prostatic enlargement
(BPE) in almost half of the cases. BPH starts as a simple
micro nodular hyperplasia and evolves into a macro-
scopic nodular enlargement that gradually results in
benign prostatic obstruction (BPO). The increase in pro-
static size may eventually compress the urethral canal
leading to BPO characterized by progressive develop-
ment of lower urinary tract symptoms (LUTS) as urinary
hesitancy and frequency, dysuria, sexual dysfunction,
increased risk of urinary infection and at least urinary
retention. Aging, dietary factors, presence of androgens,
growth factors, oxidative stress and chronic prostatic
inflammation are necessary for the development and
progression of BPH, but the pathogenesis is still largely
unresolved and there is no consensus as to which is the
primary one (3). In the management of BPH, is necessary
to reduce cell growth by blockage of testosterone con-
version in DHT, and reduce the sustaining of the chron-
ic prostatic inflammation. Patient acceptability of treat-
ment is key to decreasing the human and economic bur-
den of this condition. Maintaining sexual function is a
crucial topic nowadays. Alpha blockers, 5-alphareduc-
tase inhibitors (i-5AR) and phosphodiesterase 5
inhibitors (i-PDE5), as monotherapy or in combination,
have been used in BPH treatment (4). Notwithstanding
these drugs have a positive effect on the patient with BPH,
side effects (including sexual ones) progressively favor
patient withdrawal from therapy and progressively
enhance interest in drugs of plant origin with less adverse
effects (5). Phytotherapy dates back thousands of years,
and currently represent almost 50% of all medicine pre-
DOI:10.4081/aiua.2016.2.136
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Cucurbita pepo in BPH
scribed for BPH in Italy. Nowaday, due to low side-effect
profiles and costs, high level of acceptance by patients and
low rate of drop-out, the use of phytotherapy is progres-
sively increasing. Here, we focused our attention on
Cucurbita pepo. Cucurbita is a well-known traditional
herbal medicinal product used from centuries worldwide
and its medicinal use was described in many manuscripts
and textbooks. The Cucurbita genus comprises many
species widespread in Europe, Asia and America.
Cucurbita pepo in the form of ethanolic pumpkin seed soft
extract has been used for more than thirty years in the
European Community, mainly as a remedy for various dif-
ficulties associated with an enlarged prostate gland and
micturition problems related to overactive bladder (6, 7).
The active compounds in Cucurbita pepo L. seeds are
Δ5-, Δ7- and Δ8-sterols: Δ7-sterols, which are largely
predominant in Cucurbita pepo, are considered to be the
key active constituents of pumpkin seed in the treat-
ment of benign prostatic hyperplasia. Much smaller
amounts of Δ5- and Δ8-sterols are also present in
Cucurbita pepo (7-11). High content of carotenoids,
polyunsaturated fatty acids and liposoluble vitamins
have also a role in its activity (12). Therefore, in the
present narrative review, we summarize all evidence
available on the role of Cucurbita pepo in the manage-
ment of patients affected by LUTS due to BPH.
MATERIALS AND METHODS
Search strategy and evidence acquisition
We searched electronic databases including PubMed, the
Scopus database and the ISI Web of Knowledge for pub-
lished studies that analyzed the role of Cucurbita pepo in
the management of patients affected by LUTS due to
BPH up to May 31, 2016. The following Medical Subject
Headings terms and free text were used: “Cucurbita pepo
OR “pumpkin seedAND “prostate”; “Cucurbita pepoAND
antiandrogen” OR “antiproliferativeOR “anti-inflammato-
ry” OR “antioxidant activities”; cucurbita pepo” OR pump-
kin seed” AND “LUTS” AND “symptoms improvement” OR
quality of life”. There was no restriction on population or
publication year. Additionally, we conducted a manual
search using the bibliographies of all the identified stud-
ies, reviews, and editorials to identify references that we
may have missed during our primary search. Finally, the
search included original articles, review articles and edi-
torials and these were reviewed in order to select relevant
articles. When necessary, we contacted the authors to
obtain any relevant information we found to be missing
from published papers.
The Figure 1 shows the study selection process diagram.
Selection criteria
Inclusion criteria: (1) all studies related to LUTS-BPH; (2)
all pre-clinical and clinical trials.
Exclusion criteria: (1) the language of the studies was not
English or German; (2) if multiple publications for the
same data from the same study group occurred, only the
most informative and recent article was recruited into final
analysis; (3) letters to Editor, review articles, commen-
taries, clinical guidelines, or case reports and case series.
RESULTS
Six-hundred and seventy studies were selected up to May
31, 2016. After the first-step analysis, 16 studies were
included in this narrative review. Ten studies were consid-
ered in the pre-clinical setting and 6 in the clinical setting.
Pre-clinical setting
Antioxidant activity. Four commercially available pump-
kin seeds (Cucurbita pepo, Cucurbita moschata, Cucurbita
maxima and Cucurbita mixta) extracts were screened for
their antioxidant activity and their inhibitory activity
against lipid peroxidation (13). The results showed that
radical scavenging activity depends on their total pheno-
lic content. In particular, pumpkin seed water extracts
inhibited lipid peroxidation at 1.5 mg/ml, while the ace-
tone extracts inhibit 50% of lipoxygenase activity at the
range from 0.16 to 0.80 mg/ml.
Antiandrogen activity. In an in vitro study in human
prostate fibroblasts, the isolated pumpkin Δ7-sterols
showed antiandrogenic activity dose-dependently block-
ing the binding of dihydrotestosterone (DHT). The cul-
tures were incubated with 120 ng labeled DHT for 24
hours and the binding rate was calculated as a difference
from the concentration remaining in the supernatant.
The binding rate in the control was 63%. In the cultures
pre-treated with 120 ng or 240 ng pumpkin sterols (each
in a double set-up) the binding rate was 51.7% and
43.3% or 37.5% and 38.3% respectively (14).
Furthermore, Schmidlin and Kreuter (15) described influ-
ence of the Cucurbitae pepo extract on activity of aro-
matase and 5-α-reductase Type II in the homogenates of
human and rat placenta. By using 10 mg/ml-concentration
extract, about 50% reduction of aromatase activity and
90% of 5-α-reductase Type II inhibition were achieved.
Subsequently, in the “in vivo” prostate hypertrophy model
the pumpkin extract (100mg/kg) reduced prostate weight
of 31% vs 76% of the subcutaneous Finasteride injection
(1 mg/kg).
Figure 1.
Selection process of studies.
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138
Anti inflammatory activity. Three different extracts of
pumpkin seeds showed immunological activity suppress-
ing dose dependently mitogen-induced neopterin produc-
tion and tryptophan degradation induced by cytokine
interferon-γ(IFN-γ) (16). In particular, pumpkin seeds of
Cucurbita pepo (citrullinina GREB. var. styriaca GREB) from
biological culture were finely grounded (10 g of the pow-
der was added to 100 ml of medium Roswell Park
Memorial Institute (RPMI 1640). Then the peripheral blood
mononuclear cells (PMBC) were isolated from the whole
blood from healthy human donors and stimulated with
phytohaemagglutinin and concanavalin-A. Tryptophan
and neopterin concentrations, two biochemical pathways
stimulated by cytokine interferon-γ, were measured in the
supernatants in order to assess the anti-inflammatory
activity of the pumpkin seeds extracts. Finally, a dose
dependant suppression of mitogen-induced neopterin
production and tryptophan degradation was recorded
compared to control PMBCs. Likewise, Fahim et al. (17)
used an experimental murine model of arthritis to test
anti-inflammatory activity of pumpkin seed oil adminis-
tered in intramuscular injection. For comparison, other
two groups of rats respectively received indomethacin –a
classic anti-inflammatory agent – and no further treat-
ment. Blood samples were collected to measure: blood
glutation (GSH), plasma total proteins, albumin serum
sulfhydryl group (SH-gps), ceruloplasmin (CP) and lyso-
somal marker – N-acetyl-β-D-glucosaminidase (NAG).
After completing the experiment, liver samples were used
for determination of glucose-6-phosphate dehydrogenase
(G6P DH) activity and protein content of liver
homogenates was established. Adjuvant inoculation
resulted in decrease of serum SH-gps, with an increase of
serum CP reduction of blood glutathione and total pro-
teins and albumins levels. Liver G6P DH activity was
markedly increased. The treatment with pumpkin seed oil
resulted in normalization of altered parameters, notably in
chronic phase, except serum NAG influence. Pumpkin oil
administration inhibited paw oedema during the chronic
phase in about 44% as compared to the control untreated
group. It reduced also liver G6P DH activity to almost
50% of the arthritic groups’ level. No increase in the anti-
inflammatory effects of indomethacin combined with
pumpkin seed oil was observed.
Bladder contractility. The effects of non-specified water sol-
uble extract of pumpkin seeds and soybean germ extract
on in-bladder pressure (cystometrogram) and urination
frequency of male rats were tested (18). Pumpkin seed
water-soluble extract (250 mg/kg) compared to control
solvent (1% dimethyl sulfoxide diluted in sterile physio-
logical saline) and soybean germ extract significantly
increased bladder volume, decreased urination frequency
and increased urination delay index. According to the
authors, the observed effects of the relaxation of the blad-
der and decrease of in-bladder pressure are related to the
increased productions of NO via the arginine/NO path-
way. Arginine is present in the pumpkin seed extract in
two fold the concentrations of other amino acids. It was
suggested that arginine/NO metabolism, independently of
adrenaline and acetylcholine, is involved in relaxation of
urination muscle at a stage of full bladder (19).
Prostate gland growth. Abdel-Rahman et al. (20) performed
a comparative study to examine the effect of pumpkin
seeds diet implementation on prostate growth. The
authors used an experimental model where benign pro-
static hyperplasia (BPH) in ventral prostate was induced
by orally administering citral (C10H16O) into stomach of
male rats. Citral was administered to all rats except nega-
tive control group. The rats were subsequently grouped
according to their diet – normal or different level of pump-
kin seeds – and sacrificed. Briefly, citral significantly
increased prostate weight (P < 0.05), while pumpkin seeds
given orally dose-dependently inhibited citral induced
hyperplasia of the prostate, especially at high concentra-
tion seed dose (10%, p < 0.02). In a testosterone-induced
BPH murine model Gossell-Williams et al. found that
administration of testosterone significantly increased
prostate size ratio (weight of prostate/b.w. of the rat) (p <
0.05) although this increase was significantly inhibited by
treatment with pumpkin seed oil at 4.0 mg/100 g b.w.
Gossell-Williams (21). Likewise, Tsai et al. (22) tested
pumpkin seed oil efficacy for 14 days, in experiments per-
formed in rats on the model of prostatic growth induced
by subcutaneous daily injection of testosterone (1.25
mg/kg/day) together with prazosin (30 μg/kg/day) (T-P).
Pumpkin seed oil (PSO) (2.5 ml/kg/day) extracted from
pumpkin seeds was administered concomitantly together
with T-P. As compared with T-P alone group, the T-P
group treated with PSO had significant lower weight ratio
for ventral prostate (p = 0.01) and lower protein levels
within ventral lobe and dorsolateral lobe (p = 0.03 and p
= 0.003, respectively).
Table 1 summarizes all evidence available in the pre-clin-
ical setting.
Clinical setting
Hamvas et al. (23) reported an overall improvement of
urinary symptoms after 10 months of medication with
Cucurbita pepo. The daily dosage was 3 x 2 capsules in
the first month and 3 x 1 capsule for the rest of the time.
Changes despite pre-treatment conditions in uroflow test
and patients symptoms perception were the used out-
comes. Control visits were scheduled after 4-7-10
months of medication. At the end of follow up, an
improvement in uroflowmetry parameters was recorded
(respectively: Qmax 15.4 vs 18 ml/sec, Qave 9.5 us 12.5
ml/sec, post voiding residual 90 vs 50 ml). Furthermore,
a reduction of nocturia, urinary frequency and relief of
urinary pain were reported. Finally, about 90% of
patients felt a “very goodor “good” improvement of their
urinary symptoms after therapy. In a multicentre setting,
Bach et al. (24) performed a randomized double-blind,
placebo-controlled study enrolling 476 men (mean age
63 yrs) suffering from mild or moderate BPH symptoms
and at early stages (I or II) of clinical BPH as defined by
Alken (25). The study was carried out in accordance with
recommendations of the International Consultation on
Benign Prostatic Hyperplasia (26). The duration of treat-
ment was 12 months and the main efficacy criterion was
the International Prostate Symptom Score (IPSS). After a
1 - month run-in-period under placebo, patients were
randomized to daily treatment for 12 months with either
2 x 500 mg of the soft extract (15-25:1, ethanol 92%,
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m/m) from pumpkin seeds (n = 233) or placebo (n =
243). Five post-randomization visits were scheduled
after 1, 3, 6, 9 and 12 months. An improvement of at
least 5 points in the IPSS at study end was defined as a
therapy response. Even though the 'placebo effect' was
considerable, this therapy response was reported by sig-
nificantly more patients in the Cucurbita group than in
the placebo group (65% vs. 54%, p = 0.021). Also, an
improvement of at least 3 points in the IPSS was report-
ed by more patients in the Cucurbita group (82.5%) than
in the placebo group (67.9%, ITT population). The mean
reduction in IPSS of 6.7 points (from 17.6 to 10.9) in the
pumpkin seed group was significantly greater than the
mean reduction of 5.5 points (from 17.7 to 12.2) after
placebo treatment (p = 0.014). No significant changes
were evident in either group in uroflowmetry parame-
ters, residual urine, quality of life, prostate volume or
serum prostate specific antigen levels. Likewise,
Friederich (27) performed an observational study includ-
ing 2245 patients with mild or moderate BPH symptoms
and administering 500 mg or 1.000 mg of pumpkin seed
soft extract daily for 12 weeks. During therapy IPSS
scores improved by 41% (7.7 points, from 18.6 to 10.9)
and quality of life index scores by 46% (from 3.4 to 1.8).
The average frequency of micturition decreased from 6.7
to 5.1 during the day and from 2.3 to 1 during the night.
Improvement of dysuric disorders, such as painful uri-
nation, micturition burning, feeling of pressure and ten-
sion was reported by 52 % of the patients. Diary record-
ed micturition frequency during the day and during the
night was reduced within just 4 weeks to mean values of
5.8 (day) and 2.1 (night), with further improvement
after 8 weeks to 5.2 and 1.5, reaching 4.8 during the day
and 1.1 during the night after 12 weeks of treatment. At
subgroup analyses, the most pronounced improvement
was observed for the micturition frequency during the
night, whereas patients with acute disorders benefited
most. In these patients nocturia was reduced by 60%
(from 2.35 to 0.94), and in patients with chronic com-
plaints by 48% (from 2.75 to 1.43). In a retrospective
survey involving urologists in private practice the treat-
ment progression of 185 patients (aged between 44 and
85 years) receiving pumpkin seed soft extract was
recorded and evaluated (28). Among those, 173 patients
received pumpkin seed soft extract as therapy to treat
LUTS due to BPH. Most patients (63%) took 1 capsule
per day, 27% took 2 capsules, and 9% of the patients
were treated with more than 2 capsules. The recorded
observation periods for individual patients ranged
between one week and several years. However, for the
majority (81%) data on the course of treatment were
recorded within the first 3 months. Urge symptoms and
micturition frequency were reduced in most patients.
The proportion of patients having reported more than
one micturition during the night at start of treatment was
reduced from 90% to 30%. Residual urine was found to
be reduced in 80% of the patients. Hong et al. (29) car-
ried out a randomized, double-blind, placebo-controlled
trial over 12 months, enrolling 47 patients with BPH
with mean age of 53.3 years and international prostate
symptom score over 8. The study design contemplated
four comparative study arms: sweet potato starch (group
Table 1.
Summary of experimental studies supporting a role of pumpkin seeds in the treatment of BPH-LUTS.
BPH-LUTS Author, year
etiology role Part of plant Model Main study finding
Xanthopoulou 2009
Winkler 2005
Fahim et al. 1995
Schilcher 1990
Schmidlin and Kreuter 2003
Hata 2005
Abdel-Rahman 2006
Gossell-Williams 2006
Tsai 2006
Seed extract
Seed extract
Seed oil
Pumpkin Δ7-sterols
Seed extract
Seed extract
Seed
Seed oil
Seed
Biochemical for Lipid peroxidation
Biochemical: blood stimulated
mononuclear cells from healthy men
Arthritis rats model
Biochemical: human prostate
fibroblasts culture
Biochemical: homogenates
of human and rat placenta
Urodynamic test in rats
BPH induced with citral in rats
BPH induced with testosterone in rats
Testosterone plus Prazosin
induced prostate growth in rats
Inhibited lipid peroxidation
Inflammatory induced pathways (IFN-γ
mediated) were reduced
Oxidative parameters commonly altered
during arthritis were modulate; furthermore a
reduction of rats’paw oedema was achieved
Dihydrotestosterone binding
Aromatase and 5-α-reductase Type II activity
reduction; reduction of prostate weight
Increase bladder volume
Decrease frequency
High concentration seed dose inhibites
prostate growth
Inhibition of testosterone induced prostatic
hyperplasia
Prostate weight was decreased
Prostate growth Androgen Inflammatory
Bladder
contractility
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A, placebo, 320 mg/day), pumpkin seed oil (group B,
320 mg/day), saw palmetto oil (group C, 320 mg/day) or
pumpkin seed oil plus saw palmetto oil (group D, each
320 mg/day). International prostate symptom score,
quality of life, serum prostate specific antigen, prostate
volume and maximal urinary flow rate were measured.
So far, in groups B, C and D, the international prostate
symptom score were reduced after 3 months (respective-
ly from 20.7 ± 2.3, 18.3 ± 2.0, 19.0 ± 2.6 to 8.7 ± 1.5,
9.1 ± 1.4, 4.7 ± 17). Quality of life score was improved
after 6 months in group D (pumpkin seed oil plus saw
palmetto oil) from 3.8 ± 0.4 to 2.5 ± 0.4 and was main-
tained stable afterwards while those of groups B (pump-
kin seed oil) and C were improved after 3 months, com-
pared to the baseline value respectively from 4.2 ± 0.4 to
3.0 ± 0.4 and from 3.6 ± 0.3 to 3.0 ± 0.4). Finally, no
difference was found in prostate volume in all treatment
groups. Maximal urinary flow rate were gradually
improved in groups B (pumpkin seed oil) and C, with
statistical significance after 6 months in group B and
after 12 months in group C. More recently, Vahlensieck
et al. (30) investigated the efficacy of pumpkin seed in
men with LUTS suggestive of BPH performing a placebo
controlled three-armed randomized trial. Overall 1431
patients (aged 50-80 years) were randomly assigned to
either pumpkin seed (5 g b.i.d.), capsules with pumpkin
seed extract (500 mg b.i.d.) or placebo. The primary
outcome was a decrease in IPSS of > 5 points from base-
line after 12 months. Secondary outcome measure
included IPSS – related quality of life, IPSS single items
and diary recorded nocturia. After 12 months, the
response rate differed significantly between pumpkin
seed and placebo (58% vs 47%). Overall, 12 months of
treatment with pumpkin seed led to a clinically relevant
reduction in IPSS from (15.9 ± 1.8 and 15.8 ± 1.9, to
11.4 ± 5.5 and 10.2 ± 5.1) compared with placebo (from
16.1 ± 1.9 to 11.7 ± 5.4).
Adverse effects
To note, no adverse effects were registered from above
open clinical studies of pumpkin seeds. Only mild gas-
trointestinal complaints (diarrhoea, nausea, vomiting) in
Table 2.
Clinical studies on pumpkin seeds in men affected of BPH-LUTS.
Figure 2.
International Prostatic Symptoms Score analyzed
in clinical studies.
Author, year Study design Patients Comparator Treatment Outcomes measured
number length
Hamvas 1991 60 Pre-treatment 10 mo - Uroflow features improvement: Qmax 15.4 vs 18 ml/s;
Qave 9.5 vs 12.5 ml/s;
- Decrease in nocturia time, relief of dysuria and painful discharge
- About 90% referred a mild or very good improvement
in symptoms gravity
Bach 2000 Randomized 476 Placebo 12 mo - Significative Increase in response rate (ITT population):
controlled trial 67.5% vs 56.2%
- Decrease in IPSS 17.6 ± 3.7 vs 10.9 ± 4.5
- Mean IPSS after treatment/change to baseline (ITT): 10.9 ± 4.5
change: -6.7 (-38%) vs 12.2 ± 5.1 change: -5.5 (-31%)
Friederich 2000 Multicentric 2245 Pre-treatment 12 weeks - IPSS decreased from 18.6 to 10.9 (by 1.4%) and QoL score
improved from 3.4 to 1.8 (by 46.1%)
- 96% reported no undesired side effects
Burbach 2002 Retrospective 185 Pre-treatment 3 mo - Decrease in storage symptoms, nocturia (and PVR)
Hong 2009 Randomized placebo- 47 Placebo (four arms) 12 mo Overall:
controlled trial - Decrease IPSS: 20.7 ± 2.3 vs 8.7 ± 1.5
- Improvement of QoL score: 3.4 ± 0.4 vs 2.5 ± 04
Vahlensieck 2015 Randomized 1431 Placebo 12 mo - Decrease in IPSS (ITT): -5.4 ± 5.1, -4.2 ± 5.4 vs -4.0 ± 5.6
controlled trial (three arms: - IPSS response rate increased by 6%
pumpkin seed, - Improve in QoL 36% and 33,4% vs 29,2%
pumpkin seed
extract and placebo)
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no more than 4% of the patients was reported in in
Friederich study whereby it seems that upon administra-
tion within the therapeutic dose range, there is no risk of
serious side effects on all three RCTs. No sexual side
effects were reported during the use of Cucurbita pepo
compounds.
Table 2 shows all clinical studies performed in the man-
agement of LUTS-BPH. Moreover, Figure 2, Figure 3 and
Figure 4 show impact of the Cucurbita pepo on IPSS,
uroflowemetry parameters and patients QoL, respectively.
DISCUSSION
Main findings
Several studies performed in the pre-clinical and clinical
setting showed that the use of Cucurbita pepo in the man-
agement of patients affected by LUTS-BPH seems to be
useful for improving symptoms and quality of life.
Several aspects should be taken into account; in particu-
lar, some limitations of the evidence available need to be
considered.
Analysis of the evidences in the context
of the current knowledge
More recent knowledge about the physiological regula-
tion of bladder function makes it plausible that ubiqui-
tous substances may also contribute to the overall effect
of pumpkin seeds, in particular for maintaining normal
bladder function and preventing functional disorders.
Fatty oil of pumpkin seeds is characterized by a high
content of linoleic acid, accounting for 35-68% of the
total fatty acids (31, 32) Administration of this essential
precursor of prostaglandin metabolism (formation of
PGE2 and PG2α) might cause an increase in
prostaglandin synthesis. Prostaglandins are formed by
the detrusor muscle and increase its tone (33) resulting
in an improved bladder function.
The average tocopherol content of soft-shelled pumpkin
seeds is 0.5 mg/g, whereas in contrast to most other
plant oils γ-tocopherol is present in five- to ten-fold
higher concentrations than the α-isomer (34, 35).
According to more recent studies, γ-tocopherol is thought
to be significantly involved in the preventive role of vita-
min E and also to have a beneficial effect in chronic
inflammation (36-40). Medicinal pumpkin seeds are rich
in amino acids such as the NO precursors arginine, gluta-
mine and aspartic acid as well as γ-aminobutyric acids.
These are involved in the regulation of bladder function as
direct or indirect central neurotransmitters (41-43).
Observational studies (27), retrospective surveys (28)
and randomized controlled trials (24, 29, 30) provide
further evidence on beneficial effects of Cucurbita pepo
for patients with LUTS related to benign prostatic hyper-
plasia, as reduction of urge and micturition frequency
was observed. The published literature shows that the
benefits of pumpkin seeds treatment depend on the tonic
influence on the bladder, sphincter relaxation and allevi-
ation of micturition symptoms. It was therefore suggest-
ed that pumpkin seeds could be used in patients without
significant obstruction of the prostate and low risk for
disease progression (44). Provided that the patient
undergoes regular urological control visits, medical treat-
ment with seeds of Cucurbita pepo can be recommended
for patients with micturition symptoms related to BPH in
early disease stages, including those with symptoms of
overactive bladder.
Limits
The few available studies were often outdated and enrolled
a small number of patients, and only three RCTs were of
good quality. Other limits are difficulties in data extraction
on changes in patients classification (Alken versus IPSS).
Nevertheless all studies analyzed showed improvement in
micturition parameters related to LUTS/BPH.
CONCLUSION
In the context of the present narrative review, Cucurbita
pepo seems to show significant efficacy in improving uri-
nary symptoms with mild adverse effects however few
clinical studies support the use of that drug. Moreover,
Figure 3.
Quality of Life assessment.
Figure 4.
Qmax assessment in clinical studies.
Damiano tabelle nostre!_Stesura Seveso 01/07/16 11:10 Pagina 141
Archivio Italiano di Urologia e Andrologia 2016; 88, 2
R. Damiano, T. Cai, P. Fornara, C.A. Franzese, R. Leonardi, V. Mirone
142
all clinical studies are based on the evidence raising from
experimental studies in pre-clinical setting that showed
an interesting action of pumpkin seed elements on some
BPH etiological mechanism. Large randomized study are
needed to confirm these interesting result and recom-
mend the use of pumpkin seed in the management of
patients affected by LUTS due to BPH.
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Correspondence
Rocco Damiano, MD
damiano@unicz.it
Department of Urology, Magna Graecia University of Catanzaro
Viale Europa - Germaneto 88100 Catanzaro, Italy
Tommaso Cai, MD
Department of Urology, Santa Chiara Regional Hospital
Trento, Italy
Paolo Fornara, MD
Department of Urology, Martin-Luther-University
Halle Saale, Germany
Corrado Antonio Franzese, MD
Urology, ASL NA3 SUD, Naples, Italy
Rosario Leonardi, MD
Urology, GECAS Institute, Catania, Italy
Vincenzo Mirone, MD
Department of Urology, University of Naples, Federico II
Naples, Italy
Damiano tabelle nostre!_Stesura Seveso 01/07/16 11:10 Pagina 143
... C. pepo, commonly known as field pumpkin, is part of the Cucurbitaceae family and is native to North America (Damiano et al., 2016). Here, extractions from the seeds are commonly used for LUTS and BPH management (Damiano et al., 2016). ...
... C. pepo, commonly known as field pumpkin, is part of the Cucurbitaceae family and is native to North America (Damiano et al., 2016). Here, extractions from the seeds are commonly used for LUTS and BPH management (Damiano et al., 2016). Nutritional and medicinal benefits are due to the content of proteins (25 -50%) and oils (40 -60%) (Abdel-Rahman, 2006). ...
... C. pepo oil is rich in oleic, linolenic, palmitic and stearic fatty acids, alongside squalene, tocopherols, phytosterols and carotenoids (lutein and zeaxanthin) (Ramak and Mahboubi, 2019;Ratnam et al., 2017). Important phytosteroids includes β-sitosterol, spinasterol, campesterol, stigmasterol, with Δ5-, Δ7-, and Δ8-sterols being prominent (Damiano et al., 2016;Ramak and Mahboubi, 2019). Although considered a common herb used and investigated in BPH (Azimi et al., 2012;Cicero et al., 2019;Dedhia and McVary, 2008;Hong et al., 2009), C. pepo was investigated in only four articles included in this systematic review (Carbin et al., 1990;Coulson et al., 2013;Giannakopoulos et al., 2002;Vahlensieck et al., 2015). ...
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Background : The use of herbal medicine and alternative medicine is reported to be in up to 50% of prescriptions for benign prostate hyperplasia (BPH) in Europe, along with an increased global interest for holistic medicinal approaches. This study aimed to systematically review the published evidence investigating the use of herbal medicines as a treatment for BPH in clinical trials based on PRISMA guidelines. Methods : A literature search was conducted using PubMed, Cochrane, Medline, and Scopus databases, including English language clinical trials (Jadad score of ≥ 4) that investigated herbal medicine as a sole intervention, reporting at least one of the following outcomes: International Prostate Symptom Score (IPSS); American Urological Association Symptom Index (AUASI); Maximum Urinary Flow Rate (Qmax); Post-void residual volume (PRV); Prostate volume (PV); Serum Prostatic Specific Antigen (PSA); Quality of Life (QoL) Scores. Results : Following article screening, 28 articles were included. The most frequently studied herbs in isolation or in combination were Serenoa repens (54%), Urtica dioica (14%), Cucurbita pepo (14%), lycopene (14%), Pygeum africanum (14%) and Linum usitatissimum (7%). These herbal-based formulations mostly improved the symptoms associated with BPH (IPSS/AUASI, Qmax, PSA, QoL scores, PRV and PV). This review further discusses these herbs and the outcomes, with a focus on the potential mechanisms of action. Conclusions : There are limited high quality clinical trials investigating herbal medicine on BPH, where S. repens is significantly more represented than other popular herbs for BPH, such as C. pepo, U. dioica, P. africanum, and lycopene. Although the included studies broadly found positive positive results for standardised outcomes for LUTS and urinary flow, there was great variability in the study designs requires caution in interpretation. As these herbs are supported by in vivo and in vitro studies on potential mechanisms of actions, comparison of efficacy of mono-herbal and poly-herbal approaches, standardized extract based on identification of active constituents, as well as dosage and long-term safety.
... Today, medicinal plants and their bioactive components are widely accepted as an emerging source of alternative therapy for the management and treatment of various human diseases [2,3]. It is estimated that over 80% of the world population in one way or the other uses medicinal plants and their phytotherapeutic compounds as alternative primary healthcare due to their bioavailability, accessibility, efficacy, affordability, and low associated side effects [4,5]. They are not only used for healthcare remedies but can also serve as novel sources of unlimited raw materials for the discovery of new drugs. ...
... The extract of different parts of C. pepo (leaves, seeds, flowers, and fruits) has shown to exhibit various pharmacological activities such as antioxidants, anti-inflammatory [16], anti-proliferative [17], anti-depressant, anti-ulcer, inhibition of lipid peroxidation [18], anti-diabetic [19], anti-bacterial, anti-viral, anti-hypercholesterolemic, and sedative-hypnotic effects [20]. In traditional medicine, the leaves are used as an analgesic or blood booster [21], to remove biliousness, and for treatments of rheumatism, benign prostatic hyperplasia, burns, and wound injuries [4,14]. Despite the acclaimed ethnopharmacological use of C. pepo in the treatment of many diseases, there are few or no scientific data from experimental studies as regards its toxicity profile, wound healing, and anti-inflammatory effects. ...
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In traditional medicine, Cucurbita pepo L. is used for the treatment of rheumatism, diabetes, inflammations, and wound injuries. This study was conducted to evaluate the phytochemical constituents, safety profile, wound healing, and anti-inflammatory activities of Cucurbita pepo leaf extract in rats. The phytochemical analysis of C. pepo extract was carried out using gas chromatography-mass spectrometry (GC-MS). In acute toxicity tests, the rats orally received a single dose of 5 g/kg extract of C. pepo. In a subacute toxicity study, the rats received 200, 400, and 800 mg/kg of the C. pepo extract via daily gavage for 14 days. Bioactive compounds 1-octen-3-ol, nonanal, trans-β-ionone, phytol, trans-farnesol, and squalene were identified. There were no toxic effects detected in any of the evaluated parameters, namely liver, kidney, haematological, lipid, and antioxidant enzymes. In wound healing, C. pepo extract showed greater % wound contraction and tensile strength, as well as reduced wound healing time (12 days) and epithelialization when compared to the control (normal saline) and povidone-iodine treated groups. Rats treated with C. pepo extract elicit anti-inflammatory activity. The findings of this study revealed that the C. pepo extract has wound healing and anti-inflammatory properties with a wide margin of safety.
... The plant is known to be a good source of nutrients such as vitamin A and C [1]. Several studies have provided insight into its use for health purposes such as urinary function and urodynamic effects [10][11][12][13], hyperplasia of the prostate gland [11][12][13][14][15], anti-inflammation and antioxidation [16][17][18][19], hypolipidemic and hepatoprotective activities [20][21][22], and antiparasitic effects [23]. ...
... The plant is known to be a good source of nutrients such as vitamin A and C [1]. Several studies have provided insight into its use for health purposes such as urinary function and urodynamic effects [10][11][12][13], hyperplasia of the prostate gland [11][12][13][14][15], anti-inflammation and antioxidation [16][17][18][19], hypolipidemic and hepatoprotective activities [20][21][22], and antiparasitic effects [23]. ...
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Aim: The study analysed the bioactive compounds (BACs) present in aqueous ethanol, dichloromethane, and n-hexane extracts of pumpkin (Cucurbita pepo) using Gas chromatography–mass spectrometry (GC-MS) technique. Methodology: The dried grounded seed C. pepo were successively extracted using the three solvents and GC-MS analysis was performed to identify the differential quantitative BACs in the extracts of C. pepo seeds. Results: The GC-MS results revealed the presence of 5, 22, and 17 for aqueous ethanol, dichloromethane, and n-hexane extracts respectively. Of the over 434 bioactive compounds present in C. pepo, palmitic, stearic, linoleic compounds and their derivatives were the bioactive compounds found in all three extracts. Scientific evidences suggest that palmitic, stearic, linoleic, barbituric acids, and their derivatives have significant biological effects. Compounds without documented scientific evidence such as Silane, dimethyl(2-methoxyethoxy) octadecylocy-, (22R)-6.alpha., 11.beta., 21 Trihydroxy-16.alpha., 17.alpha.-propylmethylenedioxypregna-1,4-diene-3,20-dione, and Galactopyranose, 1,2,3,4,6-pentakis-O-(trimethylsilyl)-, .beta.-d- were found in n-hexane extract, while 2-hydroxy-1-(hydroxymethyl)ethyl ester E, Z-1,3,12-Nonadecatriene was found in dichloromethane extract. Conclusion: Results of this study may provide a foundation for the application of C. pepo in nonclinical setting and the designing of new drug for several clinical purposes.
... The properties showed the excellence of pumpkin seeds in treating BPH conditions. 55 Pumpkin seeds have also been shown to inhibit testosterone conversion to DHT, preventing testosterone-induced BPH in a rat model and treating BPH. 56 ...
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Benign prostatic hyperplasia (BPH) is a severe illness affecting middle-aged and geriatric male patients. This disease normally occurs at the age of 40 or above and is also associated with sexual dysfunction. Alpha-blockers and 5α-reductase inhibitors are the preferred drugs practiced to treat BPH. However, invasive surgical therapy remains the gold standard for managing the condition in the case of refractory and intricate BPH conditions. Due to the fear of sexual dysfunction and the detrimental influence on their quality of life, most patients seek to avoid synthetic drugs and surgery. For this reason, several patients turn to phytotherapy and other alternative therapies. The authors looked at the existing perceptions of epidemiology, etiology, and pathophysiology associated with BPH in this review article. In addition, this article contained basic information on the pathological roles of inflammation in BPH and various diagnoses and treatment options. It was well reported that the administration of medicinal herbs played a vital role in managing BPH. In recent years, many researchers worldwide have reported the efficiency and safety of phytochemicals in managing numerous pathological disorders in-vivo and in-vitro conditions and the prevention of illness.
... Oil, soft extract and Δ7-sterols from Uromedic ® pumpkin, a registered cultivar of the medicinal pumpkin, has shown anti-androgenic effects in experimental studies [15]. In addition to specific Δ7-sterols, other components in pumpkin seeds may contribute to the pharmacological effects, such as oleic acid with binding affinity toward muscarinic receptors [16] and y-tocopherol with antiinflammatory properties [17]. ...
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Purpose To assess the symptoms, quality of life and sexual well-being in patients with lower urinary tract symptoms due to benign prostatic hyperplasia LUTS/BPH treated with pumpkin seed soft extract (PSE) in routine practice. Methods This noninterventional study included 130 men treated for up to 24 months. The International Prostate Symptom Score (IPSS) and related quality of life, Aging Males’ Symptoms Scale (AMS), and International Index of Erectile Function (IIEF-5) were recorded. Descriptive statistical methods were applied. The mean with 95% confidence interval (CI) was calculated for the primary end point (change in IPSS after 12-month treatment). Results Analysis at 12 months included 83 patients [mean (SD) age 65.2 (8.7) years and IPSS (15.6 (3.4), IPSS-QoL 3.4 (0.9)]. AMS and IIEF-5 indicated mild or mild to moderate disorder regarding sexual well-being and erectile dysfunction, respectively. After 12 months, the mean IPSS change from baseline was − 4.7 (95% CI − 5.4 to − 3.9), with 83% (95% CI 65.3 to 84.1) and 53% (95% CI 42.3 to 63.7) of the patients achieving reductions by at least 3 and 5 points, respectively. The proportion of patients with IPSS-QoL below 3 points (mostly satisfied) was 11% (9/83) at baseline and rose to 62% (51/83) and 73% (40/55) at 12 and 24 months, respectively. AMS and IIEF-5 scores did not indicate a negative impact on sexual function during treatment. Conclusion In men with a moderate LUTS suggestive of BPH, a low progression risk and an active sex life, treatment with pumpkin seed soft extract provided symptomatic relief, improved IPSS-QoL, and maintained sexual well-being. Trial registration DRKS00010729, June 22, 2016.
... After 3 months of treatment, the patients reported symptomatic relief and improved quality of life. Simultaneously, only mild gastrointestinal complaints were reported in no more than 4% of the patients [18]. ...
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Background In clinical practice, plant extracts are an option to treat mild-to-moderate lower urinary tract symptoms suggestive of benign prostate hyperplasia (LUTS/BPH). However, only a few herbal extracts have been investigated in long-term placebo-controlled studies. The safety and efficacy of a well-tolerated proprietary pumpkin seed soft extract (PSE) were investigated in two randomized placebo-controlled 12-month studies (Bach and GRANU study). Both trials studied LUTS/BPH patients with an International Prostate Symptom Score (IPSS) ≥13 points at baseline. The Bach study demonstrated positive effects of PSE compared to placebo, but no difference between treatments was observed in the GRANU study. We aimed to assess the efficacy of PSE in a meta-analysis using the patient-level data of these two studies. Methods Pooled analysis was performed in the intention-to-treat set using last-observation-carried-forward (ITT-LOCF). An IPSS improvement of ≥5 points after 12 months of therapy was the predefined response criterion. Logistic regression and ANCOVA models included the covariables treatment group, study, center size, and baseline IPSS. Each analysis was repeated for the per-protocol (PP) set. Results The ITT/PP analysis sets consisted of 687/485 and 702/488 patients in the PSE and placebo groups, respectively. At the 12-month follow-up, the response rates in the PSE group were 3% (ITT) and 5% (PP) higher than those in the placebo group. The odds ratio of response obtained by logistic regression analysis for comparing PSE versus placebo was 1.2 (95% CI 0.9, 1.5), favoring PSE (ITT- LOCF). For the IPSS change from baseline to 12 months, the ANCOVA estimated difference between the treatment groups was 0.7 points (95% CI 0.1, 1.2) in favor of PSE. The variables study, baseline IPSS, and center size had a relevant influence on treatment response. Conclusion Although the Bach and the GRANU study showed contradictory results, the analysis in a pooled form still pointed towards an advantage of PSE; namely, more patients in the PSE group showed an IPSS improvement of at least 5 points after 12 months. Therefore, the results of this meta-analysis suggest that patients with moderate LUTS/BPH may benefit from PSE treatment in terms of symptomatic relief.
... Urinary flow, micturition time, residual urine, frequency of micturition and a subjective assessment of the effect of treatment were all significantly improved. In another experiment, effect of oil preparation on the urodynamics was studied and the extract from seeds could remarkably reduce the bladder pressure, increase the bladder compliance and reduce the urethral pressure (Damiano et al., 2016;Nishimura et al., 2014;Xu et al., 1994). ...
Chapter
Full-text available
Cucurbit plants were used actively as traditional herbal remedies for various diseases. The medicinal importance of plants lies in some chemical substances or secondary metabolites that produce a specific physiological action on the human body. Secondary metabolites are non nutritive chemical constituents of plants which are restricted in distribution in the particular plant species. The scarcity of scientific reports of vegetable gourds compared to the traditional usage and folkloric beliefs has further limited us in proper inclusion of cucurbits in our diet and versatile utility. The versatile utility of gourd vegetables as folk medicine and functional food ingredient provoked a compilation of a comprehensive review of these vegetables about their traditional usage and nutritional and medicinal properties together with their phytochemicals. Understanding the nutritional potential of gourd vegetables from scientific reports may influence both the work areas and consumers in the appropriate direction. In this sense, the present chapter aims to provide compilation of references and a detailed overview to the folk medicinal uses of Cucurbita plants. Brief discussion of phytochemicals and its activities are given in the text and for further details, cited references in the text and tables can be consulted.
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