K.K Hullatti et al, J.
Global Trends Pharm Sci, 2020; 11 (2): 7925 - 7932
An Elsevier Indexed Journal ISSN-2230-7346
Journal of Global Trends in Pharmaceutical Sciences
SALURETIC EFFECT OF ALKALOIDAL FRACTION FROM CYCLEA PELTATA
ROOT IN RATS
J. Rodrigues1, K.K Hullatti2*, B.S. Unger3
1
Department of Pharmacology, KLE College of Pharmacy, Belagavi, KLE Academy of Higher
Education and Research, Belagavi-590010, Karnataka, India
2
Department of Pharmacognosy, KLE College of Pharmacy, Belagavi, KLE Academy of Higher
Education and Research, Belagavi-590010, Karnataka, India
3
Division of Pharmacology & Toxicology, ICMR-NITM, Belagavi, 590010, Karnataka, India
ARTICLE INFO ABSTRACT
Key Words
Benzylisoquinoline, The aim of the present study was to evaluate the diuretic and saluretic potential of
Diuretic, Lipschitz test, four fractions of Cyclea peltata root extract in rats. The diuretic effect was
Menispermaceae, evaluated using the Lipschitz model in rats. The four fractions petroleum ether
Potassium sparing.
fraction (1 mg/kg p.o), methanol fraction (6 mg/kg p.o), dichloromethane fraction
Access this article online (6 mg/kg p.o) and aqueous fraction (60 mg/kg p.o) were administered to the rats.
Website: The groups were compared with standard group that received Furosemide (20
https://www.jgtps.com/ mg/kg p.o). The urinary output of each group was recorded every hour for 5 hours
Quick Response Code: and urine and serum and samples were analysed for Na+, K+ and Cl- ions.
Alkaloidal rich dichloromethane fraction significantly increased the urine output
and excretion of Na+ and Cl- ions in the urine and reduced Na+ levels significantly
in serum. Insignificant reduction in K + ions was seen in serum. The results provide
an evidence for the potentially favourable effects of alkaloidal fraction of C.
peltata root extract as diuretic and saluretic with a possible potassium sparing
property.
INTRODUCTION (CHF) and are effective in relieving symptoms,
reducing the intracardiac pressure and
Abnormalities often develop in fluid improving the cardiac performance. [2] The
volume and electrolyte composition and can World Health Organization (WHO) has
cause conditions that are clinically important. reported that raised blood pressure is estimated
Diuretics belong to a class of drugs which to cause around 7.5 million deaths worldwide
increase the rate of urine flow and help to and accounts for 12.8% of total of all deaths.[3]
adjust the volume and composition of fluids in Diuretics are one of the drugs used as first line
the body by promoting loss of ions and water. [1] treatment in hypertension. These drugs are also
Cardiovascular diseases (CVD) represent an often indicated in the treatment of other
increasing cause of mortality globally and conditions such as liver cirrhosis, nephritic
developing countries like India are also syndrome, urinary stones and urinary tract
struggling to manage its impact. Diuretics find infections (UTI). Such wide application has
use in treatment of Congestive Heart Failure made them the most frequently prescribed
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K.K Hullatti et al, J. Global Trends Pharm Sci, 2020; 11 (2): 7925 - 7932
drugs in medicine. However, there are certain coarse powder, and subjected to cold
limitations in the use of existing diuretics such maceration using 70% v/v ethanol for 24 hours.
as electrolyte imbalance, metabolic alterations The marc was dried and then subjected to
and hypovolemia.[4] The rising incidence of soxhlet extraction using ethanol (95% v/v) as
such disorders associated to electrolyte solvent. The macerate and percolate were then
imbalance and oedema has necessitated the combined and concentrated using rotary
development of effective treatment strategies evaporator (Buchi). The residue obtained was
with minimal systemic adverse effects. The further subjected to fractionation.[9]
health benefits of herbs and botanicals have Preparation of fractions of plant extract:
increased the popularity of traditional and The fractionation of ethanolic extract
folklore medicines. There are a number of was carried out according to the generic
medicinal plants in the Indian system of scheme described by Cos et al. [9] with minor
medicine, which have been employed as drugs modifications (Figure 1). The four fractions
possessing diuretic activity and are considered obtained were methanol, petroleum ether,
as mild and nontoxic.[5] Cyclea peltata Hook. f. dichloromethane and water. The solvent free
& Thoms (Menispermaceae), commonly fractions were obtained using rotary evaporator
known as Patha, is a slender twinning shrub then packed in air tight containers and stored at
that often climbs tall trees. It is claimed to 4°C in refrigerator till further use for
possess anti-inflammatory and diuretic experimental purpose.
property.[6] The roots of C. peltata are useful in Preliminary Phytochemical screening: The
conditions such as painful swellings, cardiac extract and fractions were subjected to
disorders and in the management of urinary phytochemical screening for the presence of
stones.[7] Our previous study has shown that the various phytochemical constituents.[10]
alcoholic extracts of C. peltata roots have Animal selection: Healthy male Wistar Albino
effective diuretic activity in rats. [8] In view of rats weighing 150-250 g were procured from
this information, the present study was Shri. Venkateshwara Enterprises, Bangalore.
undertaken to evaluate 4 fractions of ethanolic They were housed in clean and transparent
extract of C. peltata root viz. Petroleum ether polypropylene cage in a group of six per cage
fraction, methanol fraction, dichloromethane and were maintained under 12/12 hr natural
fraction and aqueous fraction for their diuretic light-dark cycle at 25±2°C ambient
activity in rats. temperature, 45-55 % relative humidity. They
were allowed to acclimatize one week before
MATERIALS AND METHODS the experiment. The rats were allowed free
Chemicals and Kits: The chemicals and access to standard pellet and water ad libitum.
solvents used were of Analytical Grade. The The study was reviewed and approved by the
kits for the estimation of Na, K and Cl ions Institutional Animal Ethics Committee,
used were from CHEMPAK, Reckon KLEU’s College of Pharmacy, Belagavi
Diagnostics P. Ltd. Furosemide (Lasix®, Sanofi (1027/a/07/CPCSEA; 06/09/2014). All the
Aventis Pharmaceuticals, India) was purchased experimental procedures were carried out in
from the hospital pharmacy. accordance with Committee for the purpose of
Collection and authentication of plant Control and Supervision of Experiments on
material: Animals (CPCSEA).
The roots of C. peltata were collected Selection of dose: According to Acute Oral
in the month of August and September, from Toxicity studies previously reported, LD50 of
the wild along the Chorla Ghats, Karnataka. Cyclea peltata alcoholic extract was found to
The plant was authenticated by Taxonomist, be greater than 2000 mg/kg. Significant
Dr. Harsha Hegde (Scientist ‘D’) at Regional diuretic activity of the extract was seen at a
Medical Research Centre, Belagavi. The dose of 200mg/kg. In the present study, doses
herbarium was deposited in RMRC with were calculated based on the extractive value
Accession number RMRC-1274. of each fraction which corresponds to 200
Preparation of plant extract: The roots were mg/Kg of extract. The doses equivalent to
washed under running water and dried under 200mg/kg BW of main extract were thus
shade. The dried roots were pulverized to
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selected for each fraction: Methanol fraction as Tri-Terpenoids, alkaloids, flavonoids, tannins,
1mg/kg bw, petroleum ether fraction as 6mg/kg saponins, waxes and lipids. Phytochemical
bw, dichloromethane fraction as 6mg/kg bw evaluation of methanol Fraction showed
and water fraction as 60mg/kg bw.[8] presence of sterols and triterpenoids, petroleum
Evaluation of diuretic activity: The Lipschitz ether fraction showed presence of wax and
model was employed for the evaluation of lipids, dichlormethane fraction showed
diuretic and saluretic activity in rats.[11] The presence of alkaloids and aqueous fraction
overnight fasted animals were placed showed presence of tannins, flavonoids and
individually in metabolic cages with free access saponins.
to water for 5 hours during the test period. The Evaluation of diuretic activity: The standard
animals were divided into the 6 groups Furosemide (Group II) showed significant
consisting of 6 animals each. (p<0.001), increase in the cumulative urine
Group I; (control); received normal saline 20 volume compared to the control group after 5
ml/kg hours. Among the four fractions, the
Group II; (Furosemide); received Furosemide dichloromethane fraction (Group V) showed
20 mg/kg highly significant (p<0.001) increase in the
Group III; received Methanol Fraction 1 cumulative urine volume compared to control
mg/kg (Group I) after 5 hours of administration. The
Group IV; received Petroleum Ether Fraction 6 diuretic action and diuretic activity of standard
mg/kg Furosemide group was higher compared to the
Group V; received Dichloromethane Fraction 6 control group. The dichloromethane fraction
mg/kg (Group V) also showed increased diuretic
Group VI; received Aqueous Fraction 60 action compared to that of control group. The
mg/kg. comparative diuretic activity was also
Collection and analysis of urine and serum: significantly higher than the control (Group I).
The urine volume was measured every hour for The results have been displayed in Table 1. The
5 hours and the total volume after 5 hours of standard Furosemide (Group II) showed
study was measured. The urine and serum significant increase in urine volume after 1
samples were used to analyse Na +, K+ and Cl- hour of administration of drug. The urine
ions concentrations using diagnostic kits. The volume significantly increased up to 3 hours of
diuretic action and diuretic activity were the study period compared to control (Group I).
calculated by the following equations: The dichloromethane fraction (Group V) also
showed significant increase in urine volume
𝐷𝑖𝑢𝑟𝑒𝑡𝑖𝑐 𝑎𝑐𝑡𝑖𝑜𝑛 = after 1 hour of administration and significantly
increased up to 3 hours of study period. The
𝑢𝑟𝑖𝑛𝑒 𝑜𝑢𝑡𝑝𝑢𝑡 𝑜𝑓 𝑡𝑒𝑠𝑡 𝑔𝑟𝑜𝑢𝑝 change in the urine volume was observed after
𝑢𝑟𝑖𝑛𝑒 𝑜𝑢𝑡𝑝𝑢𝑡 𝑜𝑓 𝑐𝑜𝑛𝑡𝑟𝑜𝑙 𝑔𝑟𝑜𝑢𝑝 every hour and the difference in urine volume
between test and control groups were
𝐷𝑖𝑢𝑟𝑒𝑡𝑖𝑐 𝑎𝑐𝑡𝑖𝑣𝑖𝑡𝑦 =
calculated after each hour. Furosemide (Group
𝑑𝑖𝑢𝑟𝑒𝑡𝑖𝑐 𝑎𝑐𝑡𝑖𝑜𝑛 𝑜𝑓 𝑡𝑒𝑠𝑡 𝑔𝑟𝑜𝑢𝑝 II) and the dichloromethane fraction (Group V)
𝑑𝑖𝑟𝑒𝑡𝑖𝑐 𝑎𝑐𝑡𝑖𝑜𝑛 𝑜𝑓 𝑓𝑢𝑟𝑜𝑠𝑒𝑚𝑖𝑑𝑒 𝑔𝑟𝑜𝑢𝑝 showed steady increase in diuresis (Figure 2).
Statistical analysis: All data are expressed as Evaluation of Saluretic activity: The
Mean ± SEM. The data were analysed using concentrations of Na+, K+ and Cl- ions were
one way ANOVA followed by Post-hoc test significantly greater in the urine of Furosemide
using Graphpad prism software (Version 5.01) group (Group II) compared to control (Group
The values were considered significant when I). The dichloromethane fraction (Group V)
p<0.001. showed significantly greater Na+, K+ and Cl-
RESULTS AND DISCUSSION ion concentrations in the urine compared to
Phytochemical evaluation of extract and control group. The Na+/K+ ratio in case of
fractions: Phytochemical evaluation of extract Furosemide (Group II) and dichloromethane
and fractions showed presence of Sterols and fraction (Group V) groups was significantly
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higher (p<0.05) and (p<0.05) respectively dichloromethane fraction showed significant
compared to control (Group I). The ratio of increase in Na+ and Cl- ions in urine, indicating
dichloromethane fraction (Group V) was increased excretion of these ions in the urine
significantly higher than the Furosemide group and thus increased saluretic effect, similar to
(Group II). The other fractions did not show that seen in the Furosemide group. However,
any significant increase in the Na+/K+ ratio. the excretion of K+ ions in urine was found to
Summary of results has been displayed in be less than that of Furosemide. The Na+/K+
Table 2. A significant decrease in the Na+, K + ratio was significantly greater than Furosemide
and Cl- ion concentrations was seen in the which may indicate a potassium sparing
serum of the Furosemide group (Group II) effect.[13] Moreover, the electrolyte
compared to control (Group I). The concentrations in the serum were significantly
dichloromethane fraction (Group V) showed reduced by Furosemide, but the
significant decrease in the Na+ and Cl- ion dichloromethane fraction significantly reduced
concentration in serum compared to control only Na+ and Cl- ion concentrations in the
(Group I). The results have been displayed in serum with insignificant reduction in the K+ ion
Table 3. Several medicinal plants are concentration in serum. This may further
traditionally being used in case of swellings suggest a potassium sparing action. The
and as diuretics. In the Indian traditional Furosemide group, showed significant increase
system of medicine, the root of C. peltata has in the urine volume and showed rapid and
been claimed to have diuretic property and are considerable diuresis in the first hour of
found to be rich in saponins, alkaloids and administration. The duration of action was for a
flavonoids.[6] Previously, the ethanolic extract period of 3 hours. Among the four fractions,
of C. peltata root extract has shown significant the dichloromethane fraction showed
diuretic activity in rats.[7] In the present study, significant increase in urine volume and
the four fractions of ethanolic extract of diuretic activity. The effect was rapid and urine
C.peltata root were evaluated for diuretic output was stimulated up to 3 hours of the
activity and the pharmacological response was study period, similar to that observed in case of
compared with that produced by furosemide, a Furosemide group. Based on the pattern of
widely used diuretic in clinical practice. The excretion of electrolytes in the urine and the
renal system that is responsible for the time course of diuresis, the saluretic action of
production, storage and elimination of urine out the dichloromethane fraction was found to be
of the body, plays an important role in similar to Furosemide, which acts on the
regulating extracellular fluid volume by Na+/K+/2Cl- transporter system in the loop of
adjusting the electrolyte and water excretion. Henle.[14] However, a potassium sparing action
Disturbance in this filtration system may result was also observed, suggesting more than one
in edema and electrolyte imbalance giving rise mechanism of action probably due to the
to various conditions.[12] The renal water presence of different potent phytoconstituents
reabsorption is driven by the active transport of in the fraction. Upon phytochemical screening
Na+. Thus, Na+ and water movements are of the fractions, dichloromethane fraction
strongly linked. Any treatment affecting the (Group V) was found to contain alkaloids.
renal Na+ transport will also affect the water C.peltata has been reported to contain various
reabsorption. Diuretics act by increasing the bisbenzylisoquinoline alkaloids such as
urine volume (water excretion) and a net loss of cycleapeltine, cycleadrine, cycleacurine,
[15]
solutes (i.e. electrolytes) in the urine. Thus they cycleanorine. Several studies have suggested
not only promote the loss of water but also that Dopamine acting via D-2 receptors may
cause a net loss of electrolytes, mainly Na + act as an inhibitory modulator of aldosterone
ions thereby exerting a saluretic effect.[1,4] In secretion and doperminergic receptor agonists
treatment of conditions such as hypertension, may contribute to natriuretic effects.[16]
maintaining electrolyte balance plays an Bisbenzylisoquinoline alkaloids of reticuline-
important role. In the present study, the type have been reported to display selectivity
concentration of electrolytes in urine were towards D2 receptors.[17]
analysed and among the fractions, the
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Table 1: effect of various fractions of C. peltata root extract on cumulative urine volume and
diuretic activity
Urine volume (ml) Cumulative
urine
Diuretic
Groups volume
1hr 2hrs 3hrs 4hrs 5hrs action
after 5hrs
(ml)
Control 0.28± 0.07 0.98±0.13 1.33±0.17 1.40±0.14 0.68±0.19 4.68± 0.14 1.00
3.87±0.18* 6.10±0.37 3.22±0.53* 16.08±
Furosemide 1.8±0.16 ** 1.43±0.34 3.43
* ** * 0.63**
Petroleum
0.82±0.0.2
ether 0.57±0.06* 0.93±0.07 2.27±0.21* 1.73±0.23 6.08± 0.30* 1.30
0
fraction
Methanol
0.37±0.042 0.73±0.08 1.30±0.14 1.48±0.16 1.53±0.36 5.32± 0.29 1.14
fraction
Dichloro
1.55±0.16 2.73±0.14* 3.97±0.33* 9.68±
methane 1.03±0.48 0.38±0.09 2.07
** * * 0.46**
fraction
Aqueous
0.33±0.07 1.07±0.16 1.55±0.20 1.83±0.48 0.90±0.36 5.68± 0.31 1.21
fraction
Table 2: Effect of various fractions of C. peltata root extract on concentration of electrolytes in
urine
Groups Na+ (mmol/lt) K+ (mmol/lt) Cl- (mmol/lt) Na+/K+
Control (20ml/kg p.o) 89.19±3.80 55.53±1.13 67.71±4.51 1.543±0.05
Furosemide (20mg/kg 137.70±3.68*
85.57±2.40** 94.23±2.37** 1.712±0.02
i.p) *
Petroleum ether fraction
104.3±1.22* 64.90±1.86* 69.19±2.83 1.607±0.04
(1mg/kg p.o)
Methanol fraction
89.98±7.03 59.74±1.80 65.26±2.23 1.513±0.14
(6mg/kg p.o)
Dichloromethane fraction
129.6±2.63** 67.28±2.04** 83.53±2.20** 1.932±0.08
(6mg/kg p.o)
Aqueous fraction
80.43±0.66 52.24±2.29 68.73±2.97 1.55±0.07
(60mg/kg p.o)
Table 3: Effect of various fractions of C. peltata root extract on concentration of electrolytes in
serum
Groups Na+ (mmol/lt) K+ (mmol/lt) Cl- (mmol/lt)
Control (20ml/kg p.o) 139.1±0.80 5.875±0.035 133.0±0.91
Furosemide (20mg/kg
116.5±0.60** 4.785±0.15** 117.6±1.06**
i.p)
Petroleum ether fraction
135.9±0.72* 5.69±0.07 128.6±±0.83*
(1 mg/kg p.o)
Methanol fraction
136.7±1.17 5.675±0.11 132.4±1.02**
(6mg/kg p.o)
Dichloromethane
121.6±0.43** 5.798±0.11 126.8±2.10
fraction (6mg/kg p.o)
Aqueous fraction
137.8±0.76 5.675±0.084 130.2±1.19
(60mg/kg p.o)
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Figure 1: Scheme of extraction and fractionation
Figure 2: Time course of diuresis of various fractions of C.peltata root extract
Table and figure titles and legends:
Table 1: effect of various fractions of C. peltata root extract on cumulative urine volume and diuretic
activity
For statistical verification the comparison was made between control vs fractions, Values are expressed as
mean± SEM, n=6, *p <0.05, **p <0.001.
Table 2: Effect of various fractions of C. peltata root extract on concentration of electrolytes in urine
Na+ is sodium ion, K+ is potassium ion, Cl- is chloride ion. Na+/K+ is the sodium-potassium ion ratio. For
statistical verification the comparison was made between control vs fractions, Values are expressed as
mean± SEM, n=6, P values: *p <0.05, **p <0.001.
Table 3: Effect of various fractions of c. peltata root extract on concentration of electrolytes in serum
Na+ is sodium ion, K+ is potassium ion, Cl- is chloride ion. Na+/K+ is the sodium-potassium ion ratio. For
statistical verification the comparison was made between control vs fractions, Values are expressed as
mean± SEM, n=6, *p <0.05, **p <0.001.
Figure 1: Scheme of extraction and fractionation
Figure 2: Time course of diuresis of various fractions of C. peltata root extract
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