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The histological and histometrical effects of Urtica dioica extract on rat's prostate hyperplasia

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Benign prostatic hyperplasia (BPH) is a common disease in human that gradual overgrowth of the prostate gland leads to impinge on the urethra with impairment in urinary function. Numerous plants improve uncontrolled growth of the prostate gland and improve urinary tract symptoms associated with BPH. In this study, 25 healthy adult male Wistar rats were divided randomly in five groups: G1 (Control group) received ordinary feed without any treatment, G2 received 10 mg kg(-1) testosterone subcutaneously, G3 received 50 mg kg(-1) nettle root extract orally, G4 received 50 mg kg(-1) nettle root extract orally and 10 mg kg(-1) testosterone, G5 received 10 mg kg(-1) almond oil (Almond oil was used as testosterone solvent) subcutaneously. After six weeks, volume and weight of each lobe were measured and samples were taken. The 5 to 6 µm thickness sections were made using paraffin embedding method and stained by hematoxylin and eosin and periodic acid-Schiff. The results showed that prostate volume and ratio of prostate to body weight were increased significantly in the testosterone. Histological and histometrical results showed that dorsal and lateral type 1 and 2 lobes were not changed significantly but the ventral and anterior lobes have changed significantly. Over all, the nettle root could prevent from some of prostatic hyperplasia effects, so that percentage of folded alveoli in ventral lobe reduced insignificantly.
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ORIGINAL
ARTICLE
Veterinary Research Forum. 2015; 6 (1) 23 - 29
Journal Homepage: vrf.iranjournals.ir
The histological and histometrical effects of Urtica dioica extract on
rat’s prostate hyperplasia
Hamid Reza Moradi1, Naeem Erfani Majd1*, Saleh Esmaeilzadeh2, Sayed Reza Fatemi Tabatabaei1
1 Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran; 2 Department of Pathobiology, Faculty of
Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
Article Info
Abstract
Article history:
Received: 29 December 2013
Accepted: 15 July 2014
Available online: 15 March 2015
Benign prostatic hyperplasia (BPH) is a common disease in human that gradual overgrowth
of the prostate gland leads to impinge on the urethra with impairment in urinary function.
Numerous plants improve uncontrolled growth of the prostate gland and improve urinary tract
symptoms associated with BPH. In this study, 25 healthy adult male Wistar rats were divided
randomly in five groups: G1 (Control group) received ordinary feed without any treatment, G2
received 10 mg kg-1 testosterone subcutaneously, G3 received 50 mg kg-1 nettle root extract
orally, G4 received 50 mg kg-1 nettle root extract orally and 10 mg kg-1 testosterone, G5
received 10 mg kg-1 almond oil (Almond oil was used as testosterone solvent) subcutaneously.
After six weeks, volume and weight of each lobe were measured and samples were taken. The 5
to 6 µm thickness sections were made using paraffin embedding method and stained by
hematoxylin and eosin and periodic acid-Schiff. The results showed that prostate volume and
ratio of prostate to body weight were increased significantly in the testosterone. Histological
and histometrical results showed that dorsal and lateral type 1 and 2 lobes were not changed
significantly but the ventral and anterior lobes have changed significantly. Over all, the nettle
root could prevent from some of prostatic hyperplasia effects, so that percentage of folded
alveoli in ventral lobe reduced insignificantly.
© 2015 Urmia University. All rights reserved.
Key words:
Histometry
Hyperplasia
Prostate
Rat
Urtica dioica
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
*Correspondence:
Naeem Erfani Majd. PhD
Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
E-mail: naeemalbo@yahoo.com
Veterinary
Research
Forum
24
HR. Moradi et al. Veterinary Research Forum. 2015; 6 (1) 23 - 29
Introduction
Prostate gland plays an important role in active
reproductive period of males. Extensive research has been
done on the relationship between structure and function
in various ways in number of animals and humans.1 The
prostate is an exocrine gland which its function and
development are androgen-dependent.2 Androgens play
an important role in developing prostate disorders
including prostate cancer and benign prostatic hyper-
plasia.3 Benign prostatic hyperplasia is the most common
male genital tract problems that prevalent with aging.4 So
far, many researches have been done in relation to the
prevention and treatment of this disease. Rat prostate
gland has different lobes which their structures are
different significantly.5 Therefore, there are different
reports about response of the gland to testosterone.
Mohammady et al. have reported that ventral lobe of rat
prostate has not responded to induction of hyperplasia
using of testosterone.6 But other researchers have
confirmed hyperplasia induced by testosterone in the
ventral lobe of rat’s prostate gland.7,8 Numerous medicinal
plants have proven to improve uncontrolled growth of the
prostate gland and improve urinary tract symptoms
associated with benign prostatic hyperplasia.7 Nettle is one
of the herbs which have wide therapeutic properties and it
is used for treatment of prostatic hyperplasia widely. It has
been reported that clinical symptoms of prostatic hyper-
plasia was improved with Nettle.9 Nettle root extract is
inhibitor of the aromatase enzyme in prostate tissue.
Aromatase converts testosterone into estrogen and
estrogen hormone is associated with prostate disease
most commonly.10 Lygans are one of the components of
nettle root extract which prevent binding of androgens to
sex hormone binding globulin in benign prostatic
hyperplasia,11 but these mechanisms of action are not
clear completely. The present study was purposed to
determine histomorphometrical changes of rat’s prostate
gland lobes following administration of testosterone and
nettle root extract.
Materials and Methods
In this study, 25 adult male Wistar rats with average
weight of 290 ± 20 g, and 3.5 to 4 months of age were
used. Animals were maintained in order to adapt to the
environmental conditions for one week. Testosterone
(Organon, Cidico, Egypt), nettle extract root (Barij Essence
Co., Kashan, Iran), almond oil (Kimiagar Toos Co.,
Mashhad, Iran) and testosterone measurement kit (DRG
Instruments, Marburg, Germany) were used. Rats were
divided randomly into five groups five animals each: G1
(control group) rats were fed on ordinary without any
treatment; G2 received 10 mg kg-1 testosterone sub-
cutaneously daily; G3 received 50 mg kg-1 nettle root extract
orally (by gavage) daily; G4 received 10 mg kg-1
testosterone along with 50 mg kg-1 nettle root extract
daily; G5 received 10 mg kg-1 almond oil subcutaneously
(Almond oil was used as testosterone solvent). The
experiment had continued for six weeks. After this
period, the rats were sacrificed using chloroform and
after weighting, blood samples were taken for measuring
of testosterone by enzyme-linked immunosorbent assay
(ELISA). Then, abdominal cavity was explored and
samples were taken from different lobes of rat's prostate
gland. Volume and weight of the prostate gland were
measured for each group. After removing the
attachments of the prostate to seminal vesicles, bladder
and urethra, the prostate volume was measured by water
displacement method in a graduated cylinders containing
distilled water. The 5 to 6 µm thickness sections were
made by paraffin embedding method and were stained
by hematoxylin and eosin (H & E) and periodic acid-
Schiff (PAS). Periodic acid-Schiff was used to indicate the
cell glycoprotein contents. The histomorphometrical
studies were done using digital Dino-Lite lens and Dino-
capture 1 software (AnMo Electronics Corp., New Taipei
City, Taiwan). Percentage of parenchyma to stroma was
measured by graduated ocular. Data are expressed as
mean ± standard deviation. One way analysis of variance
and post Hoc of Tukey was performed on the data.
Differences between groups were considered to be
significant in p < 0.05.
Results
Macroscopic findings. Table 1 shows the ratio of
prostate to body weight and prostate volume were
increased significantly in testosterone group compared to
the control, nettle and almond oil groups (p = 0.000).
Prostate volume in testosterone plus nettle group compared
to testosterone group were decreased significantly
(p = 0.028) but the ratio of prostate to body weight were
decreased insignificantly (Fig. 1). Prescribed nettle alone
lead to a significant reduction in prostate volume
compared to the control group (p = 0.028). Over all, the
volume of prostate and ratio of prostate to body weight in
testosterone and nettle groups were maximum and
minimum, respectively. Also, the statistical analysis data
showed that there was no significant difference in rat
weight of different groups. Thus, administration of this
hormone, almond oil and nettle root extract did not have
significant effect on body weight.
Microscopic findings: Ventral lobe. Testosterone
resulted in growth and proliferation of ventral prostate
epithelium severely and secretory cells were long
cylindrical cells and active in secretion (Fig. 2). The
secretory cells height (p = 0.000), number (in scale of 100
µm epithelium length) (p = 0.013) and folding in wall of
alveolus (p = 0.000) were significantly increased in the
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HR. Moradi et al. Veterinary Research Forum. 2015; 6 (1) 23 - 29
testosterone group (Figs. 3 and 4). Percentage of
parenchyma to stroma of ventral lobe was decreased
significantly in the testosterone group compared to the
control (p = 0.029) and almond oil groups (p = 0.048).
Nettle lead to folding reduction and decreased alveolar
wall thickness of the ventral lobe compared to control and
almond oil groups (Fig. 5). Diameter of secretory alveoli
was the lowest in nettle group than other groups.
Secretory cells were low to high cuboidal in the nettle
group and nucleus was heterochromatin and located in the
basal cytoplasm. The percentage of folded alveoli and their
diameters were decreased in the ventral lobe of nettle plus
testosterone group compared to testosterone group, but it
was not the same as control group (Fig. 6). The secretory
cells height and number were increased significantly in
testosterone plus nettle group compared to control and
almond oil groups (p = 0.000), (Table 2).
Fig. 1. Macroscopical view of rats prostate in control and
testosterone groups. The prostate enlargement by testosterone is
observable. SV: Seminal Vesicle, A: anterior lobe, V: Ventral lobe
UB: Urinary bladder, U :Urethra.
Fig. 2. Histological structure of ventral lobe in the testosterone
group, (H & E). The increase of alveoli folding and height of the
secretory epithelium are considerable.
Fig. 3. Histological structure of ventral lobe in the control group,
(H & E). The high densities of secretory alveoli are considerable.
Connective tissue between the secretory alveoli (arrows).
Table 1. Macroscopic parameters of prostate in different groups (Mean ± SD).
Groups
Body weight (g)
Absolute weight (g)
Prostate weight/Body weight × 10-3
Prostate volume (mL)
Control
316.17 ± 20.86
2.63 ± 0.20bc
7.70 ± 0.44b
3.20 ± 0.45ab
Testosterone
296.14 ± 12.87
3.76 ± 0.46a
12.02 ± 1.03a
4.60 ± 0.65a
Nettle
310.89 ± 25.15
2.59 ± 0.27bc
7.80 ± 0.30b
2.30 ± 0.27c
Testosterone + Nettle
289.20 ± 6.18
3.24 ± 0.08ab
11.46 ± 0.96a
3.70 ± 0.27ab
Almond oil
313.51 ± 23.98
2.44 ± 0.54c
7.15 ± 1.00b
2.40 ± 0.42c
abc Different letters in each column indicate significant differences (p < 0.05).
Table 2. The characteristic changes of the rat prostate ventral lobe in the experimental groups (Mean ± SD).
Groups
Epithelial
thickness
(µm)
Number of cells
in scale
100 µm
Percentage of
folded secretory
alveolar units
Percentage of
parenchyma to
stroma
Diameter of
alveolar units
(µm)
Control
14.20 ± 0.81b
12.85 ± 0.84b
38.02 ± 3.94b
88.00 ± 3.60b
224.64 ± 8.77ab
Testosterone
23.04 ± 2.73a
17.00 ± 3.06a
71.99 ± 14.59a
77.00 ± 5.70a
240.78 ± 32.62a
Nettle
12.82 ± 2.68b
12.25 ± 0.88b
27.95 ± 8.24c
87.20 ± 7.00b
188.01 ± 20.04b
Testosterone + Nettle
23.37 ± 2.97a
18.05 ± 1.68a
55.70 ± 12.60ab
80.80 ± 6.10ab
220.3 ± 24.82ab
Almond oil
12.14 ± 0.50b
13/00 ± 1.26b
31.14 ± 8.33c
89.20 ± 3.35b
253.42 ± 30.54a
abc Different letters in each column indicate significant differences (p < 0.05).
BPH
Control
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HR. Moradi et al. Veterinary Research Forum. 2015; 6 (1) 23 - 29
Fig. 4. Histological structure of ventral lobe in the testosterone
group, (H & E). Increase in alveoli folding is considerable. Stromal
connective tissue (S) was increased between the secretory alveoli.
Fig. 5. Histological structure of ventral lobe in the nettle group,
(H & E). The expanding of secretory alveoli and their thin-walled
are considerable (arrow).
Fig. 6. Histological structure of ventral lobe in the testosterone +
nettle group, (H & E). Decrease in folded secretory alveoli (A) in
the periphery of a lobe (P) is considerable.
Microscopic findings: Anterior lobe. Normally,
epithelium in the anterior lobe had a lot of folds (Fig. 7).
However, under the influence of testosterone, height and
number of epithelium folds were grown, thus, they filled
alveolar cavity. Muscle cells were increased in several
layers around alveoli compared to control group (Fig. 8).
Proliferations of secretory cells were seen in testosterone
group. Also, the number of secretory cells in 100 µm
length of epithelium were increased significantly in the
testosterone group (p = 0.045). Secretory cells in
different prostate lobes was PAS positive reaction in
normal rat prostate, but staining intensity was more in
the anterior lobes. Hyperplasia was observed in the
secretory alveoli of anterior lob. Folds were expanded in
the lumen of secretory alveoli and the numbers of folded
alveoli were increased.
Fig. 7. Histological structure of anterior lobe in the control group,
(H & E). The alveoli epithelium of anterior lobe have numerous
folds normally. Muscle layer surrounding the secretory alveoli (M).
Fig. 8. Histological structure of anterior lobe in the testosterone
group, (H & E). The number and length of the folds in alveoli are
increased, therefore the alveolar lumen (A) is filled and they
connected together. Thick muscle layers surrounding the
secretory alveoli are considerable.
27
HR. Moradi et al. Veterinary Research Forum. 2015; 6 (1) 23 - 29
The number and height of secretory cells of anterior
lobe were decreased in nettle plus testosterone group.
Epithelial thickness in the nettle group was decreased
insignificantly compared to the control group. Percentage
of parenchyma to stroma in the anterior lobe in
testosterone group was increased significantly
(p = 0.036), (Table 3).
Histometrical results showed that percentage of
parenchyma of dorsal lobe was increased in nettle group
compared to control group significantly (p = 0.046).
Percentage of parenchyma of lateral type 1 lobe was
decreased in nettle group compared to nettle plus
testosterone group significantly (p = 0.016). Diameter of
alveoli of dorsal lobe had significant increase in testosterone
group than almond oil group (p = 0.038). Diameter of
alveoli of lateral type 1 lobe had significant decrease in
nettle group compared to control group (p = 0.035).
Diameter of alveoli of lateral type 2 lobe had significant
decrease in testosterone group than almond oil group
(p = 0.020), (Tables 4, 5 and 6).
Serum testosterone. The serum testosterone levels
was increased significantly in both testosterone and
testosterone plus nettle groups compared to control,
almond oil and nettle groups (p = 0.000). The serum
testosterone levels did not have a significant difference
between testosterone and testosterone plus nettle groups.
The serum testosterone level was increased insignificantly
in the nettle group compared to the control group (Fig. 9).
Table 3. The characteristic changes in the rat prostate anterior lobe in the experimental groups (Mean ± SD).
Groups
Epithelial
thickness
(µm)
Number of cells
in scale
100 µm
Percentage of
folded secretory
alveolar units
Percentage of
parenchyma to
stroma
Diameter of
alveolar units
(µm)
Epithelial thickness
(µm)
Number of cells
in scale 100 µm
Percentage of
folded secretory
alveolar units
Percentage of
parenchyma to
stroma
Diameter of
alveolar units (µm)
Control
16.85 ± 2.30
11.40 ± 0.98b
100
75.40 ± 5.40b
443.96 ± 140.72ab
14.20 ± 0.81b
12.85 ± 0.84b
38.02 ± 3.94b
88.00 ± 3.60b
224.64 ± 8.77ab
Testosterone
17.66 ± 2.62
13.60 ± 1.44a
100
84.20 ± 2.60a
618.33 ± 191.23a
23.04 ± 2.73a
17.00 ± 3.06a
71.99 ± 14.59a
77.00 ± 5.70a
240.78 ± 32.62a
Nettle
14.27 ± 1.13
12.45 ± 1.02ab
100
82.00 ± 5.70ab
366.98 ± 82.50b
12.82 ± 2.68b
12.25 ± 0.88b
27.95 ± 8.24c
87.20 ± 7.00b
188.01 ± 20.04b
Testosterone + Nettle
15.72 ± 1.28
12.95 ± 0.94ab
100
82.40 ± 2.70ab
414.71 ± 8.05ab
23.37 ± 2.97a
18.05 ± 1.68a
55.70 ± 12.60ab
80.80 ± 6.10ab
220.3 ± 24.82ab
Almond oil
14.62 ± 1.28
11.35 ± 1.24b
100
75.40 ± 4.60b
366.26 ± 47.36b
12.14 ± 0.50b
13/00 ± 1.26b
31.14 ± 8.33c
89.20 ± 3.35b
253.42 ± 30.54a
ab Different letters in each column indicate significant differences (p < 0.05).
Table 4. The characteristic changes in the rat prostate lateral type 1 lobe in the experimental groups (Mean ± SD).
Groups
Epithelial
thickness
(µm)
Number of cells
in scale
100 µm
Percentage of
folded secretory
alveolar units
Percentage of
parenchyma to
stroma
Diameter of
alveolar units
(µm)
Epithelial thickness
(µm)
Number of cells
in scale 100 µm
Percentage of
folded secretory
alveolar units
Percentage of
parenchyma to
stroma
Diameter of
alveolar units (µm)
Control
14.48 ± 2.94
11.25 ± 0.40a
43.48 ± 5.36
74.20 ± 2.05ab
214.07 ± 23.07a
14.20 ± 0.81b
12.85 ± 0.84b
38.02 ± 3.94b
88.00 ± 3.60b
224.64 ± 8.77ab
Testosterone
16.78 ± 1.77
10.55 ± 0.54ab
43.55 ± 4.16
77.00 ± 1.87ab
209.74 ± 31.24ab
23.04 ± 2.73a
17.00 ± 3.06a
71.99 ± 14.59a
77.00 ± 5.70a
240.78 ± 32.62a
Nettle
15.62 ± 1.50
10.15 ± 1.05ab
53.68 ± 3.17
70.60 ± 1.95b
168.90 ± 19.76b
12.82 ± 2.68b
12.25 ± 0.88b
27.95 ± 8.24c
87.20 ± 7.00b
188.01 ± 20.04b
Testosterone + Nettle
16.57 ± 1.15
9.85 ± 0.63b
51.11 ± 5.93
78.20 ± 5.97a
203.74 ± 16.67ab
23.37 ± 2.97a
18.05 ± 1.68a
55.70 ± 12.60ab
80.80 ± 6.10ab
220.3 ± 24.82ab
Almond oil
13.46 ± 0.64
10.00 ± 0.75ab
44.85 ± 9.2
75.40 ± 3.29ab
199.51 ± 19.13ab
12.14 ± 0.50b
13/00 ± 1.26b
31.14 ± 8.33c
89.20 ± 3.35b
253.42 ± 30.54a
ab Different letters in each column indicate significant differences (p < 0.05).
Table 5. The characteristic changes in the rat prostate lateral type 2 lobe in the experimental groups (Mean ± SD).
Groups
Epithelial
thickness
(µm)
Number of cells
in scale
100 µm
Percentage of
folded secretory
alveolar units
Percentage of
parenchyma to
stroma
Diameter of
alveolar units
(µm)
Epithelial thickness
(µm)
Number of cells
in scale 100 µm
Percentage of
folded secretory
alveolar units
Percentage of
parenchyma to
stroma
Diameter of
alveolar units (µm)
Control
13.98 ± 1.86
11.40 ± 0.52
49.54 ± 4.01
74.40 ± 2.19
189.94 ± 22.34ab
14.20 ± 0.81b
12.85 ± 0.84b
38.02 ± 3.94b
88.00 ± 3.60b
224.64 ± 8.77ab
Testosterone
17.19 ± 1.48
11.15 ± 0.78
43.13 ± 3.07
74.80 ± 5.63
220.53 ± 26.39a
23.04 ± 2.73a
17.00 ± 3.06a
71.99 ± 14.59a
77.00 ± 5.70a
240.78 ± 32.62a
Nettle
15.03 ± 2.78
10.70 ± 0.97
48.41 ± 2.65
80.60 ± 2.97
177.95 ± 13.82b
12.82 ± 2.68b
12.25 ± 0.88b
27.95 ± 8.24c
87.20 ± 7.00b
188.01 ± 20.04b
Testosterone + Nettle
16.28 ± 1.24
10.15 ± 0.45
48.77 ± 4.09
80.40 ± 4.67
197.85 ± 24.51ab
23.37 ± 2.97a
18.05 ± 1.68a
55.70 ± 12.60ab
80.80 ± 6.10ab
220.3 ± 24.82ab
Almond oil
13.93 ± 0.96
10.20 ± 0.82
41.84 ± 4.84
75.00 ± 4.47
175.78 ± 11.72a
12.14 ± 0.50b
13/00 ± 1.26b
31.14 ± 8.33c
89.20 ± 3.35b
253.42 ± 30.54a
ab Different letters indicate significant differences (p < 0.05).
Table 6. The characteristic changes in the rat prostate dorsal lobe in the experimental groups (Mean ± SD).
Groups
Epithelial
thickness
(µm)
Number of cells
in scale
100 µm
Percentage of
folded secretory
alveolar units
Percentage of
parenchyma to
stroma
Diameter of
alveolar units
(µm)
Epithelial thickness
(µm)
Number of cells
in scale 100 µm
Percentage of
folded secretory
alveolar units
Percentage of
parenchyma to
stroma
Diameter of
alveolar units (µm)
Control
13.80 ± 2.82ab
10.30 ± 0.82
48.86 ± 9.49
69.40 ± 4.62b
195.11 ± 53.52ab
14.20 ± 0.81b
12.85 ± 0.84b
38.02 ± 3.94b
88.00 ± 3.60b
224.64 ± 8.77ab
Testosterone
16.20 ± 1.24a
12.30 ± 2.26
60.92 ± 6.71
72.00 ± 2.55ab
249.55 ± 33.71a
23.04 ± 2.73a
17.00 ± 3.06a
71.99 ± 14.59a
77.00 ± 5.70a
240.78 ± 32.62a
Nettle
14.01 ± 1.23ab
10.50 ± 0.91
58.38 ± 7.85
77.20 ± 3.96a
168.94 ± 32.29b
12.82 ± 2.68b
12.25 ± 0.88b
27.95 ± 8.24c
87.20 ± 7.00b
188.01 ± 20.04b
Testosterone + Nettle
16.98 ± 1.54a
10.85 ± 0.58
60.06 ± 5.78
69.80 ± 2.64ab
235.78 ± 32.06ab
23.37 ± 2.97a
18.05 ± 1.68a
55.70 ± 12.60ab
80.80 ± 6.10ab
220.3 ± 24.82ab
Almond oil
12.95 ± 0.94b
58.72 ± 11.10
58.72 ± 11.10
72.20 ± 5.67ab
174.58 ± 33.16b
12.14 ± 0.50b
13/00 ± 1.26b
31.14 ± 8.33c
89.20 ± 3.35b
253.42 ± 30.54a
ab Different letters in each column indicate significant differences (p < 0.05).
28
HR. Moradi et al. Veterinary Research Forum. 2015; 6 (1) 23 - 29
Fig. 9. Serum testosterone of the experimental groups (Mean ± SD).
* Different symbols indicate significant differences among the
experimental groups (p > 0.05).
Discussion
In the present study, the BPH which induced by
testosterone was characterized by parenchyma and
stroma changes and enlargement of rat’s prostate.
According to Porpiglia et al. and Pais studies which they
reported that prostate epithelial cells number and stroma
were increased in BPH.12,13 Eaton has reported that the
androgens are interacting with connective tissue cells of
the prostate gland.14 Recent studies showed that the rat
ventral prostate lobe is androgen-dependent but the
dorsal and lateral lobes are not dependent on it.15-18 The
fundamental biological differences exist between the
different lobes of the rat prostate.19 On the other hand,
Ahonen et al. reported that hyperplasia in the dorsal and
lateral lobes of rat prostate gland caused by hyper-
prolactinemia.20 Banerjee et al. has reported that the
dorsal and lateral lobes are more sensitive to androgens
in aged (24-month-old) Brown Norway rats than young
(6-month-old) rats.21 Therefore, the weight and protein
content are more in the dorsal and lateral lobes of 24-
month-old rats compared to the 6-month-old rats. Many
of studies have concentrated on the ventral, dorsal and
lateral lobes of prostate rat but the anterior lobe was less
considered and it was considered as separated structure
from the rat prostate.19,22,23 According to results of the
present study, ventral and anterior lobes were more
sensitive and showed more histomorphological changes
than dorsal and lateral lobes. Cunha et al. have reported
that the anterior lobe of rat prostate is similar to the
central zone of human prostate.2
We also observed that the oral administration of nettle
root extract (50 mg kg-1) leads to decrease the number of
folds in secretory alveolar epithelium and height of folds in
the anterior and ventral lobes tissue. Also, secretory cells
were altered from cuboidal to squamous which indicate the
decrease of secretory activity. These findings indicate that
nettle root extract may be effective for BPH. The
histological changes following administration of nettle
are similar to other medicinal plants such as Serenoa
repens and Echinacea. Nettle root extract polysaccharides
and lectins particularly are important in the prostate
gland disorders.24 Nettle root contains biologically active
compounds and its effect has been attributed to more
than one class of chemicals. Therefore, it is reported that,
the lignan, sterols, flavonoids, poly-saccharides, lectins,
and fatty acids are responsible for the pharmacological
effects of nettle.11,25
Serum testosterone levels were more significant in the
nettle root extract and testosterone plus nettle groups
than other groups. The change of testosterone serum
levels confirmed the nettle root extract effects. These
results confirmed Chrubasik et al.26 They showed that the
nettle root extract blocked reductase enzyme activity
and prevented the conversion of testosterone to dihydro-
testosterone (DHT). Therefore, the serum testosterone
level was increased by nettle, thus blood DHT levels were
decreased and cell proliferation in the prostate tissue was
reduced subsequently.26 Results of present study showed
that nettle had similar effect of finasteride which is used
for treatment of prostatic hyperplasia widely.27
According to the results of the present study, the
anterior and ventral lobes were more sensitive to
hormonal response than the dorsal and lateral (1 and 2)
lobes and they were distinguishable and separable from
other lobs. Therefore, the anterior and ventral lobes are
more suitable for prostate investigations. Finally, it was
concluded that prostatic hyperplasia could be reduced by
oral administration of nettle root extract and it has
protective effects on prostatic hyperplasia.
Acknowledgments
The authors wish to express their gratitude to the
research council of Shahid Chamran University of Ahvaz
for their financial support.
References
1. Mukerjee B, Rajan T. Morphometric study of rat
prostate in normal and under stressed conditions. J
Anat 2004; 53 (2): 29-34.
2. Cunha GR, Donjacour AA, Cooke PS. Endocrinology and
developmental biology of the prostate. Endocr Rev
1987; 8 (3): 338-362.
3. Kyprianou N, Huacheng T, Jacobs SC. Apoptotic versus
proliferative activities in human benign prostatic
hyperplasia. Hum Pathol 1996; 27: 668-675.
4. Emberton M, Andriole GL, De la Rosette J. Benign
prostatic hyperplasia: A progressive disease of aging
men. Urology 2003; (2): 267-273.
5. Hayashi N, Sugimura Y, Kawamura J, et al.
Morphological and functional heterogeneity in the rat
prostatic gland. Biol Reprod 1991; 45 (2): 308-321.
29
HR. Moradi et al. Veterinary Research Forum. 2015; 6 (1) 23 - 29
6. Mohammady T, Erfanimajd N, Morovvati H, et al.
Evaluation of concurrent administration of
testosterone and nettle extract on prostate gland of
Rat. Glob Vet 2011; 7 (2): 153-157.
7. Veeresh Babu SV, Veeresh B, Patil AA, et al. Lauric acid
and myristic acid prevent testosterone induced
prostatic hyperplasia in rats. Eur J Pharmacol 2010; 25,
626(2-3):262-265.
8. Li SH, Ryu JH, Park SE, et al. Vitamin C supplementation
prevents testosterone-induced hyperplasia of rat
prostate by down-regulating HIF-1α. J Nutr Biochem
2010; 21 (9): 801-808.
9. Safarinejad MR. Urtica dioica for treatment of benign
prostatic hyperplasia: A prospective, randomized,
double-blind, placebo-controlled, crossover study. J
Herbal Pharmacother 2005; 5 (4): 1-11.
10. Kraus R, Spiteller G, Bartsch W. (10-E, 12Z)-9-hydroxy
10,12-octadecadienic acid, an aromatase-inhibiting
substance from the root extract of Urtica dioica. Liebigs
Ann Chem 1991; 335-339.
11. Schöttner M, Gansser D, Spiteller G. Lignans from the
roots of Urtica dioica and their metabolites bind to
human sex hormone binding globulin (SHBG). Planta
Med 1997; 63 (6): 529-532.
12. Porpiglia F, Terrone C, Renard J, et al. Transcapsular
adenomectomy (Millin): A comparative study, extra
peritoneal laparoscopy versus open surgery. Eur Urol
2006; 49 (1): 120-126.
13. Pais P. Potency of a novel saw palmetto extract, SPET-
085, for inhibition of 5alpha-reductase II. Adv Therapy
2010; 27 (8): 555-563.
14. Eaton CL. Etiology and pathogenesis of benign prostatic
hyperplasia. Curr Opin Urol 2003; 13 (1): 7-10.
15. Ohlson N, Wikström P, Stattin P etal. Cell proliferation
and apoptosis in prostate tumors and adjacent non-
malignant prostate tissue in patients at different time-
points after castration treatment. Prostate 2005; 62
(4): 307-315.
16. Lee C, Sensibar JA. Proteins of the rat prostate. II.
Synthesis of new proteins in the ventral lobe during
castration-induced regression. J Urol 1987; 138 (4):
903-908.
17. Abate-Shen C, Shen MM. Molecular genetics of prostate
cancer. Genes Dev 2000; 14 (19): 2410-2434.
18. Sensibar JA, Alger B, Tseng A, et al. Proteins of the rat
prostate. III. Effect of testosterone on protein synthesis
by the ventral prostate of castrated rats. J Urol 1990;
143 (1): 161-166.
19. Jesik CJ, Holand JM, Lee C. An anatomic and histologic
study of the rat prostate. Prostate 1982;3 (1): 81-97.
20. Ahonen TJ, Harkonen PL, Rui H, et al. PRL signal
transduction in the epithelium compartment of rat
prostate maintained as long-term organ cultures in
vitro. Endocrinol 2002; 143: 228-238.
21. Banerjee PP, Banerjee S, Dorsey R, et al. Age- and lobe-
specific responses of the brown Norway rat prostate to
androgen. Biol Reprod 1994; 51: 675-684.
22. Wylot M, Laszczynska M, Sluczanowska-Glabowska S,
et al. Aging process of epithelial cells of the rat prostate
lateral lobe in experimental hyperprolactinemia
induced by haloperidol [Polish]. Ann Acad Med
Bialostocensis 2004; 49: 111-113.
23. Hernandes ME, Abraham SC, Fausto R, et al. Prostate
response to prolactin in sexually active male rats.
Reprod Biol Endocrinol 2006; 4: 28.
24. Collier HO, Chesher GB. Identification of 5-
hydroxytryptamine in the sting of the nettle (Urtica
dioica). Brit J Pharmacol 1956; 11 (2): 186-189.
25. Akbay P, Ahmet Basaran A, Undeger U, et al. In vivo
immunomodulatory activity of flavonoid glycosides
from Urtica dioica L. Phytother Res 2003; 17 (1): 34-37.
26. Chrubasik JE, Roufogalis BD, Wagner H, et al. A
comprehensive review on the stinging nettle effect and
efficacy profiles. Part II: Urtica radix. Phytomedicine
2007; 14 (7-8): 568-579.
27. Cayatte C, Pons C, Guigonis JM, et al. Protein profiling of
rat ventral prostate following chronic finasteride
administration: identification and localization of a
novel putative androgen-regulated protein. Mol Cell
Proteomics 2006; 5 (11): 2031-2043.
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Several medicinal plants are traditionally used in different regions of Africa for the treatment of male infertility, sexual asthenia, erectile dysfunction, and impotency or used as an aphrodisiac. Scientific studies, mostly conducted in vitro or in animals, have proven the acclaimed traditional use of these plants to enhance sexual activities or sperm concentration, motility, and viability. Some of the mechanisms of actions associated with these plants include increased level of testosterone and the relaxation of the smooth cavernosal muscles. However, some plants were also shown to have detrimental effects on the male reproductive system. This may be due to the varying modes of plant extraction, duration of treatment, experimental design, dosage used, quality of the plant, or toxic effects. There is a need to standardize the protocols as well as to better understand the mechanism of actions of the respective plants. Further studies should be conducted using human subjects.
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The article discusses the effectiveness of herbal medicine in inflammatory diseases of the prostate. This literature review presents clinical studies of the successful use of herbal ingredients in the treatment of chronic prostatitis and relief of lower urinary tract symptoms (LUTS). Biological active substances of Urtica dioica, Cucurbita moschata, Saw palmetto (Serenoa repens), and zinc are effective in the treatment of chronic prostatitis due to anti-inflammatory, antiproliferative, antiandrogenic and antioxidant action. Phytopreparations containing these substances can be recommended as the first line of correction of LUTS in chronic forgive categories III and IV; as a general tonic for men leading a sedentary lifestyle over the age of 35 years.
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Benign prostatic hyperplasia (BPH) is a disease that impairs the well-being of many aged men. To alleviate BPH symptoms or to find a cure for this disease, key molecules should be identified that control prostate cell proliferation. Recently, HIF-1alpha has attracted attention in this context, because it is highly expressed in hyperplasic prostates and prevents prostate cell death. Thus, given that vitamin C inhibits HIF-1alpha expression in several malignant tumors, we examined its therapeutic potential in BPH. HIF-1alpha was noticeably induced by testosterone in prostate cells, and this HIF-1alpha induction was abolished by vitamin C. Vascular endothelial growth factor (VEGF) promoter activity reporter assays and semi-quantitative RT-PCR revealed that vitamin C inhibited HIF-1-dependent VEGF expression. Furthermore, HIF-1alpha suppression by vitamin C was rescued by knocking down HIF-prolyl hydroxylase-2, suggesting that vitamin C destabilizes HIF-1alpha via prolyl hydroxylation. Moreover, vitamin C treatment abolished cell proliferation induced by testosterone treatment to the control level. These results suggest that vitamin C inhibits testosterone-induced HIF-1alpha expression and by so doing effectively prevents prostate hyperplasia. In male rats, testosterone treatment for 4 weeks induced prostate hyperplasia. Furthermore, HIF-1alpha and VEGF levels were significantly elevated in hyperplasic prostates. In vitamin C-treated rats, however, most prostate hyperplasia parameters and prostrate HIF-1alpha/VEGF levels were markedly reduced. Accordingly, our findings indicate that vitamin C could be further developed clinically for use as an anti-BPH agent.
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I. Introduction MALE accessory sex glands such as the prostate, seminal vesicle, and bulbourethral gland have served in various capacities as models for investigating the action of androgens in regulating epithelial growth, RNA and protein synthesis, and secretory activity. The most extensively studied gland of this group is the prostate. This gland is found exclusively in mammals and produces many components of semen such as fructose, zinc ions, and various proteins important for the formation of the copulatory plug in rodents. The impetus for investigating regulation of prostatic growth and function stems in part from the many pathological complications which affect this gland. The prostate is the site of various types of inflammatory and infectious conditions (1) as well as benign and malignant proliferative changes in aging males. Despite extensive research, little of the pathogenesis or natural history of these diseases has been elucidated (2). Benign prostatic hypertrophy (BPH), a disease in which t...