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Rahul K. Dumbre et al.

/ Journal of Pharmacy Research 2012,5(12),5302-5304

Research Article
ISSN: 0974-6943

Available online through


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Effect of Chandraprabha Vati in Experimental Prostatic Hyperplasia and Inflammation in Rats


Rahul K. Dumbre*, Amol P. Kale1, Manisha B. Kamble2, V. R. Patil
TVESs Loksevak Madhukarrao Chaudhari College of Pharmacy, Faizpur, Maharashtra, India
1
PDEAs Seth Govind Raghunath Sable College of Pharmacy, Saswad, Pune, Maharashtra, India
2
Rajgad Dyanpeeths College of Pharmacy, Bhor, Pune, Maharashtra, India

Received on:12-07-2012; Revised on: 17-08-2012; Accepted on:26-09-2012


ABSTRACT
Chandraprabha vati, an Ayurvedic formulation, was studied for its effect in experimental prostatic hyperplasia induced by testosterone injection s.c for
21 days in rats and inflammation induced in rat hind paw by carrageenan injection s.c. The results showed that Chandraprabha vati at dosage of 100, 200
and 400 mg/kg orally for 21 days showed significant reduction of prostatic hyperplasia as indicated by decreased prostate weight and volume and
hispathological observations. It also significantly inhibited carrageenan induced hind paw oedema in dose dependant manner. These results highlight the
mechanism of its effect in prostate disorder like Benign Prostatic Hyperplasia (BPH) by inhibiting proliferative and inflammatory processes in prostate.
Key words: Chandraprabha vati, Ayurvedic formulation, Prostatic hyperplasia, Benign Prostatic Hyperplasia (BPH), anti-inflammatory.

INTRODUCTION
Benign prostatic hyperplasia (BPH) is age related disorder where there is
nonmalignant enlargement of the prostate due to excessive cellular growth
of both the glandular and the stromal elements of the gland. BPH is usually
associated with Lower Urinary Tract Symptoms (LUTS) which may present
with filling symptoms (frequency, urgency, and urge incontinence) or voiding
symptoms (hesitancy, poor urinary stream, straining, intermittent stream,
and a feeling of incomplete bladder emptying), or both including complaints
of nocturia (night-time voiding of urine). One-third of men over 50 years
old reported to develop some form of LUTS with 25% of these requiring
surgeries (transurethral resection) [1-5].
Prostate being an endocrinal dependent organ, hormonal imbalance; aging
and androgens are main cause for the development of BPH. Hence utilization
of androgen deprivation drugs affecting hypothalamicpituitarygonadal
axis like gonadotropin-releasing hormone (GnRH) analogues, anti-androgens,
and 5-reductase inhibitors decreases the size of the prostate and the
resistance to outflow through the prostatic urethra[6-8].
Prostatitis of different form is associated with BPH. It may be infectious or
non infectious prostatitis. Inflammatory cells and mediators like leucotrines,
prostaglandins, and thromboxanes etc are found in prostatic secretion.
Increase Urinary tract infections (UTIs) are frequently observed with BPH
and may be related to the amount of urinary retention due to BPH
conditions[9].
Some of the plants like the liposterolic extract of Saw Palmetto fruits
(Serenoa repens, or Sabal serulata) ; [10] extracts of Stinging Nettle root
(Urtica dioica L.); [10] the extract of Pygeum africanum bark; [11] have been
used, singly or in combination with other botanicals for the condition of
BPH. Ayurvedic formulation Chandraprabha vati is an important therapeutic
medicine recommended in BPH conditions.
Chandraprabha vati is a polyherbal formulation where each herb is mixed
and processed in specific manner. It is used for Samana Chikitsa (alleviative
treatment) or symptomatic treatment. It is a good Rasayana (rejuvenator)
useful in all three doshas. It opens channels and improves mobility of
Doshas. More specifically, it is used for genito-urinary ailments, muscular

*Corresponding author.
Mr. Rahul K. Dumbre
Plot No 430, Sector No 28
Nigdi Pradhikaran,
Pune-411044,M.H.India.

& joint pain, obesity, and cellulites[12-13]. Present study is done to understand
the effect of Chandraprabha vati in experimental prostatic hyperplasia and
inflammation in rats.
MATERIALS AND METHODS
Chemicals and Formulation
Chandraprabha vati formulation containing following contents was purchased
of Divya Pharmacy, Haridwar, India
Formula as per the B.R. (Bhaisajya Ratnavali)
Sr. No.

Name of Ingredient

% content

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.

Mustak (Cyperus rotundus)


Devdaru (Cedrus deodara)
Chitraka (Plumbago zeylanica)
Vidanga (Embelia ribes)
Marich (Piper nigrum)
Pippali (Piper longum)
Swarna Makshik Bhasma
Daruharidra (Berberis aristata)
Vacha (Acorus calamus)
Pimpal Mool (Piper longum)
Dhanyaka (Coriandrum sativum)
Gajj pippali (Piper chaba)
Chavak (Piper retrofractum)
Sunthi (Zingiber officinale)
Saindhava (Rock salt)
Ela (Elettaria cardamomum)
Chirayat (Swertia chirata)
Haridra (Curcuma longa)
Ativisha (Aconitum heterophyllum)
Javakhar (Potasium carbonate)
Dantimool (Boliospermum montanum)
Tejpatra (Cinnamomum tamala)
Twak (Cinnamomum zeylanicum)
Vansalochan (Bambusa arundinacia)
Lauha Bhasma
Sugar
Purified Guggulu (Commiphora mukul)
Purified Shilajit (Asphaltum)
Triphala (Terminalia belarica,
Terminalia chebula,Emblica officinalis)
Kachur (Curcuma zedoaria)
Kamal jad (Nelumbo nucifera)

0.92
0.92
0.92
0.92
0.92
0.92
0.92
0.92
0.92
0.92
0.92
0.92
0.92
0.92
0.92
0.92
0.92
0.92
0.92
0.92
3.66
3.66
3.66
3.66
7.34
14.68
7.34
29.36
0.92

Journal of Pharmacy Research Vol.5 Issue 12.Decemeber 2012

0.92
3.66

5302-5304

Rahul K. Dumbre et al. / Journal of Pharmacy Research 2012,5(12),5302-5304


All ingredients are finely powdered and mixed together and tablets are
formed. Other chemicals were obtained as follows: Testosterone Propionate
(German Remedies, India-Testoviron); Finasteride (Dr. Reddy, India-Finax);
Carrageenan and Indomethacin from Sigma Aldrich.
Animals
Male rats of Sprague-Dawley strain weighing between 240-300 gm were
used for the experiments. All the animals were obtained from Animal House
of S.G.R.S College of Pharmacy, Saswad. The animals were fed ad libitum
with standard pellet(Chakan Oil Mills, Pune, India) diet and had free access
to water. All the protocols of animal experiments were approved by the
Institutional Animal Ethics Committee. Animals were maintained at a
temperature of 251C and relative humidity of 45 to 55% under 12-h
light:12-h dark cycle. They were housed individually in the polypropylene
cages after surgery.
Effect of Chandraprabha vati in experimentally induced BPH
The rats were castrated and their testes removed. 6 days after castration
animals were divided into following groups of negative control, test groups
and positive control. Normal non castrated rats are taken as normal control.
Negative control received testosterone propionate 0.5mg/0.1ml by s.c route.
Test groups, Chandraprabha vati, were divided in dose range of 100mg/kg,
200mg/kg and 400mg/kg and dosage was given orally. Positive control
Finasteride was given at dose of 5mg/kg orally. Half hour after oral dosing
the test groups and positive control group received testosterone propionate
0.5 mg/0.1ml by s.c route. Dosing was done for 3 weeks. 24 hours after last
dosing animals were sacrificed and prostate removed. Prostate weight and
volume was measured. The volume was measured (by the formula: 1/2(a x
b2), where a and b refer to longer and shorter dimension, respectively)
Prostate was fixed in 10% formalin. The formalin fixed tissues were
embedded in paraffin and thin sections taken were stained by H & E staining
process [14, 15].

Table 1: Effect of Chandraprabha vati on the volume and weight index


of prostate gland of castrated rat.
Group

Dose
(mg/kg)

B.W. (g)

Control
Negative
Finasteride
Chandraprabha
vati (CV)

Water
5
100
200
400

26614.3
27211.5
26310.7
26113.5
25914.8
26110.5

Volume of
prostate (cm3)

Wet weight index of prostate


(mg/100 g B.W.)

0.290.05**
0.710.03
0.320.07**
0.470.05**
0.440.08*
0.490.02*

12914.3**
3117.3
1589.7**
26510.6*
24011.3**
18711.9**

n=6, meanS.E.M. * p, <0.05, ** p, <0.01 vs.Negative Group. B.W. represents body weight.
Histopathology of prostates of negative control show significant gland
crowding, epithelial hyperplasia, fibrovascular proliferation in stroma and
decreased acini diameter as compared to normal control. Significant reduction
in gland proliferation, epithelial and cellular hyperplasia and stromal
proliferation at dose of 100, 200, 400 mg/kg for Chandraprabha vati compared
to negative control was observed. The effect was more pronounced at
400mg/kg dose that was comparable with positive control Finasteride (Table
2)
Table 2: Results of histopathology of prostate glands.
Group

Gland
crowding

Epithelial
Stromal
Stromal
hyperplasia hyperplasia inflammation

Normal Control
Testosterone control
Standard
(Finasteride 5mg/kg +testosterone)
Test Group)
(100 mg/kg CV+ testosterone
Test Group
(200 mg/kg CV + testosterone)
Test Group
(400mg/kg CV) + testosterone)

+++
++

++
+

+++
+

++

++

++

++

+
+++

:- Mild Hyperplasia
:- Severe Hyperplasia

++ :- Moderate Hyperplasia.
:- Absent Hyperplasia.

Anti-inflammatory activity of formulations


The rats were divided into normal vehicle control, test groups, and positive
control. Acute inflammation was produced by subplantar administration of
0.1 ml of 1% carrageenan in normal saline in the right paw of rats.
Chandraprabha was given in dose of 100, 200 and 400 mg/kg orally, Positive
control received Indomethacin 10mg/kg orally. The paw volume is measured
at 0, 1, 2, 3 hours after carrageenan administration by plethysmometer
(Ugo Basile). Dosing was done 1 hour before carrageenan administration.
The amount of inflammation was compared with the 0 hour reading of the
same rat and percentage anti-inflammatory activity calculated by comparing
difference in percentage inflammation with control group [15].

Chandraprabha vati showed significant anti-inflammatory activity in


carrageenan induced rat paw inflammation inhibition in dose response. The
effect at dose of 400mg/kg was comparable with standard Indomethacin
(Table 3).

Statistical Analysis
The data was expressed as mean SEM. The results were analyzed
statistically using ANOVA and students t test. The minimum level
significance was considered as P<0.05

n=6, values are expressed as Mean of % inflammation S.E.M ; * p, <0.05,


** p, <0.001 when compared with control group.

Table 3: Anti-inflammatory activity of Chandraprabha vati.


Group

Control
Chandraprabha
vati (CV)
Indomethacin

RESULTS
21 days s.c injection of testosterone at dose of 0.5mg/0.1 ml significantly
increased prostate weight and volume of castrated animals compared to
normal animals. Chandraprabha vati, at all doses 100, 200, 400mg/kg, showed
effect on volume and weight of prostate after 21 days treatment. Both
Chandraprabha vati at dose of 400mg/kg and positive control Finasteride at
5mg/kg significant and comparable reduction in prostate volume and weight
compared to testosterone treated (negative control) animals (Table 1).

Dose
mg/kg
orally

100
200
400
10

Mean of % inflammation and increase in paw volume


1hr
27.62.3
26.13.1
15.83.2*
11.42.4**
3.71.3**

2hr
45.24.0
36.73.1
29.33.9*
21.03.1**
22.23.2**

3hr
59.02.6
42.12.4**
33.04.1**
25.13.9**
20.61.7**

DISCUSSION
Benign Prostatic Hyperplasia is a complex disease where various mechanisms
are leading to enlargement of tissue and retention of urine. Age related
hormonal imbalance of testosterone/estrogen and activity of testosterone
and dihydrotestosterone after binding to cellular androgen receptors set
complex secondary reactions that signal the cell to produce growth factors
resulting in hyper plastic growth of prostate. High amounts of 5 alpha
reductase enzyme activity that convert testosterone to dihydrotestosterone
(active form of androgen in prostate) in prostate as well as abundance of
estrogen receptor are responsible for BPH prostates[16-23].
Prostatic inflammation represents an important factor in influencing

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Rahul K. Dumbre et al. / Journal of Pharmacy Research 2012,5(12),5302-5304


prostatic growth and progression of symptoms. Inflammatory mediators
secreted by prostatic stromal cells is mediating low level, cumulative increase
in proliferation of both epithelial and stromal cells that characterizes age
related development of BPH. Activation CD4+ lymphocytes, Prostate
Specific Antigen (PSA) and initiation of proinflammatory processes by
presence of growth factors and cytokines, autoimmune mechanisms in
prostate, oxidative stress by Nitric Oxide (NO) and other oxygen species,
presence of COX (Cycloxygenase) activity leads to activation of
hyperproliferative pathways in prosatate . COX-2 inhibition is reported to
increase apoptotic activity in prostatic cell in human BPH tissue. [24-29]

11.
12.
13.
14.

Thus, BPH may be viewed as a form of asymptomatic inflammatory


prostatitis, whose pathogenesis may be triggered by a multitude of factors
and pathways. Among pro-inflammatory cytokines and chemokines
produced by the prostatic microenvironment, stromal-derived IL-8 may be
considered a key link between chronic inflammation and stromal cell
proliferation. In particular, the effect of these pathways may represent a
common denominator for all 3 components of BPH: static, dynamic, and
inflammatory.
Inhibition of testosterone induced proliferation in castrated rat by Ayurvedic
formulation Chandraprabha vati is indicative of blockage of processes of
androgen mediated growth of prostate. Secondly anti-inflammatory activity
shown in carrageenan induced oedema model is indicative of inhibition of
COX and prostaglandin mechanisms in prostate. This finding has initiated
studies in exploration of many other Ayurvedic formulations and further
mechanisms in benign prostatic hyperplasia.

15.

16.

17.

18.

ACKNOWLEDGEMENT
Authors are thankful to Dr. Sujit Joshi, MD (Path) for carrying out histopathological study of samples.

19.

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Source of support: Nil, Conflict of interest: None Declared

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