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Possible Role of Natural Nephroprotective; Hemidesmus indicus in Congestive Heart Failure

Authors:
  • SVKM’s NMIMS School of Pharmacy and Technology Management (SPTM)
  • Sau. Mathurabai Bhausaheb Thorat Institute of D. Pharmacy

Abstract and Figures

Hemidesmus indicus R.Br. is a treasure of the forest and herbal wealth. It is being used as folk medicines and as an ingredient in Ayurveda and Unani preparations against diseases of blood, inflammation, diarrhea, urinary disorders and rheumatism etc. The objective of the present study was to evaluate the role of natural nephroprotectant Hemidesmus indicus for the treatment of congestive heart failure. Hemidesmus indicus extracts were evaluated by using salt water induced left ventricular hypertrophy in Spargue dawley rat model. The property was evaluated using serum creatinine, urea, SGOT, SGPT and urine albumin, creatinine, Na+, K+ and Ca++ as biochemical parameters and histopathological changes including myocyte diameter, neutrophil infiltration and cardiac hypertrophy. Results obtained from the present study indicates that aqueous and methanolic extracts have more significant inhibitory effect on salt water feeding induced severity of microalbuminuria, serum urea and creatinine, myocyte diameter and retention of Na+ and water and increases the serum calcium level. We conclude from the present study that, potent natural nephroprotectant Hemidesmus indicus is also a potent cardioprotective.
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Phcog Res Vol 1/Issue 6 | Available Online : www.phcogres.com 367
Pharmacognosy Research [Phcog Res]
Vol 1, Issue 6, Nov-Dec, 2009 Page 367-374
(An Ofcial Publication of Pharmacognosy Network Worldwide)
Received: 19 08, 2009
Modied: 10 09, 2009
Accepted: 18 09, 2009
PHCOG RES.: Research Article
Possible Role of Natural Nephroprotective; Hemidesmus indicus
in Congestive Heart Failure
Chidrawar V. R.*, Ushir Y. V.1, Sudarshan S.2, Patel K. N.3, Patel N. J.4 and Vadalia K. R.5
* Department of Pharmacology, Shree H. N. Shukla Institute of Pharmaceutical Education and Research,
Rajkot-360001 (GS), India
1Department of Pharmacognosy and Phytochemistry, Shree H. N. Shukla Institute of Pharmaceutical
Education and Research, Rajkot-360001 (GS), India
2Department of Pharmaceutics, Shree H. N. Shukla Institute of Pharmaceutical Education and Research,
Rajkot-360001 (GS), India
3Department of Pharmacognosy, Arihant School of Pharmacy and Bio-Research Institute. Gandhinagar. Gujarat, India
4Department of Pharmacology, Saraswati Institute of Pharmaceutical Sciences, At: Dhanap, N.H. 8,
Dist: Gandhinagar, (GS), India
5Department of Pharmaceutical Analysis, Shree H. N. Shukla Institute of Pharmaceutical Education
and Research, Rajkot-360001 (GS), India
* Correspondence: vijay_pharmacology@yahoo.com
ABSTRACT
Hemidesmus indicus R.Br. is a treasure of the forest and herbal wealth. It is being used as folk medicines and as an ingredient
in Ayurveda and Unani preparations against diseases of blood, inammation, diarrhea, urinary disorders and rheumatism etc.
The objective of the present study was to evaluate the role of natural nephroprotectant Hemidesmus indicus for the treatment of
congestive heart failure. Hemidesmus indicus extracts were evaluated by using salt water induced left ventricular hypertrophy
in Spargue dawley rat model. The property was evaluated using serum creatinine, urea, SGOT, SGPT and urine albumin,
creatinine, Na+, K+ and Ca++ as biochemical parameters and histopathological changes including myocyte diameter, neutrophil
inltration and cardiac hypertrophy. Results obtained from the present study indicates that aqueous and methanolic extracts
have more signicant inhibitory effect on salt water feeding induced severity of microalbuminuria, serum urea and creatinine,
myocyte diameter and retention of Na+ and water and increases the serum calcium level. We conclude from the present study
that, potent natural nephroprotectant Hemidesmus indicus is also a potent cardioprotective.
Keywords: Hemidesmus indicus, left ventricular hypertrophy, myocytes, microalbuminuria, Cardioprotective.
INTRODUCTION
Heart failure (HF) is one of the most common causes of
death and disability in industrialized nations and is among
the syndromes most frequently encountered in clinical
practice (1,2). A number of blood tests are routinely
performed in the diagnosis of heart failure; blood
gas analysis to assess respiratory gas exchange; serum
creatinine and urea to assess renal function, serum alanine
and aspartate-aminotransferase plus other liver function
test (3). The magnitude of albumin excretion is directly
corrected with risk for end stage renal disease and the
rate for progression to renal failure (4). The greater the
magnitude of albuminuria, the faster the decline in renal
function. In adults, persistent microalbuminuria suggests
not only the existence of renal disease, but also an increase
Possible Role of Natural Nephroprotective; Hemidesmus indicus in Congestive Heart Failure
368 Phcog Res Vol 1/Issue 6 | Available Online : www.phcogres.com
risk for heart failure; therefore microalbuminuria is a
strong and independent predictor of clinical HF (5).
It has been clinically proved that profound reduction
of cardiac output and arterial hypotension in severe HF
may lead to acute renal failure (6). Early complications of
cardiac insufciency include renal vasoconstriction and the
development of sodium and water retention, which are
hallmark of the very early stages of congestive heart failure
(CHF). The interplay between the direct consequences
of renal disease and other risk factors for HF are likely
to contribute to this phenomenon (7). Moreover, HF
and kidney failure shall be managed by similar means of
non-pharmacological and pharmacological therapeutic
interventions. There are some natural drugs they have been
shown both cardioprotective and nephroprotective action
including; Curcuma longa (8, 9), Ginkgo-biloba (10), Ocimum
sanctum (11, 12), Genus Angelica (13) and Rheum emodi (14,
15). With this background the present study has been
designed to evaluate the potent and scientically proven
natural nephroprotective drug of Indian system of medi-
cine, Hemidesmus indicus R.Br (16) (family: Asclepiadaceae)
for its scientic applicability in the treatment of CHF.
MATERIALS AND METHODS
Materials
UV- Spectrophotometer (SHIMADJU-1601), Flame
photometer (Elico CL-361), Research centrifuge
(REMI-24), Soxhlet extractor, Research microscope
(Medzer).
Commercial enzyme kits including Creatinine, Urea,
and SGOT & SGPT purchased from Span Diagnostic
Ltd. Surat, India. All chemicals used in this study were of
AR grade.
Methods
In the present study, the roots of Hemidesmus indicus were
collected from the forest area of Gandhinagar, Gujarat.
The roots were authenticated by Taxonomist available
in B.V.V.S. Ayurvedic College, Bagalkot, Karnataka.
Soon after authentication, all roots were dried at room
temperature, until they were free from the moisture.
Finally roots were subjected to get coarse powder and
then passed through sieve no.40 to get uniform powder.
The sieved powder was stored in airtight, high-density
polyethylene containers before extraction.
Plant material
The roots of Hemidesmus indicus were collected from the
forest area of Junagadh district, authenticated and roots
were subjected to get coarse powder and then passed
through sieve no: 40 to get uniform powder. The sieved
powder was stored in airtight, high density polyethylene
container before extraction.
Plant preparation
The powder was subjected to hot continuous extraction
(Soxhlet) 12 hours cycle with 90% methanol (50–55°C);
nally the drug was macerated with water. After the
extraction the solvent was distilled off & excess solvent
completely removed by using rotary ash evaporator to
get semisolid mass, % yield was calculated and extracts
were preserved in refrigerator below 10°C for further
study. The suspension of methanol extract was prepared
by using 0.5% Tween- 80 in normal saline and solution of
aqueous extract was prepared by using normal saline as
solvent for the experiment (17).
Animal selection
Spargue dawley rats of 2 weeks age of either sex were
used in this study. The animals were maintained under
suitable nutritional and environmental conditions
throughout experiment. All the pharmacological
experimental protocols were approved by the
Institutional animals ethics committee (Reg no:
821/01/a/ CPCSEA, dated 6th August, 2007) H.S.K.
College of Pharmacy, Bagalkot. Before and during the
experiment, rats were fed with standard diet (Gold
Moher, Lipton India Ltd)
Acute toxicity study
Healthy Swiss albino mice of either sex weighing 15–20 g,
starveted overnight were divided into 3 groups (n=6) and
fed with increasing doses (1, 2, and 5 mg/kg) of extract
and the toxicity was evaluated as per the guidelines for
non-clinical toxicity investigation of Herbal Medicine
(Annexure-I) given by ministry of Health and family
Welfare Govt. of India (18).
Experimental design
All the animals were randomly divided into the nine groups
of six animals each, in which one group was common for
both the extract and served as normal rats which received
only vehicle (0.5% Tween- 80, 2 ml/kg p.o). From
remaining eight groups four groups for each extract in
which one group served as control which received salt
water and vehicle while remaining three groups received
drug extract in a dose of 100, 200 and 400 mg/kg p.o.
along with salt water.
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Chidrawar V. R. et al., Phcog Res. 2009; 1:6: 331–355
Organ to body weight ratio
Body weight of each animal was measured before the
salt water and drug treatment were started. Percentage
change in body weight was calculated by weighing animal
just before scarifying them. After sacrifying each animal,
the vital organs; heart, liver, lungs, kidneys were isolated
and weighed them in a wet condition to measure organ to
body weight ratio (19).
Biochemical parameters
Urine was collected for 24 hrs. using metabolic cages after
8th week of study. Serum was obtained from blood collected
by retroorbital method under light ether anesthesia. Urine
albumin (20), creatinine (alkaline picrate method), urea
(DAM method), SGOT, and SGPT (2, 4-DNPH method)
were estimated by using commercial enzyme kits (Span
Diagnosis Ltd.). sodium, potassium and calcium ion
concentration was estimated by ame photometer.
Histology
Samples of heart tissue were excised and rinsed in 0.9%
saline blotted dry of saline and excess blood. They were xed
in 12% formalin for 24 hr. the tissues, after xation, were
washed in water to remove excess xative. Washed tissues
were then dehydrated through a graded series of ethyl
alcohol, cleared with xylene and embedded in parafn wax.
Sections were cut at 3μm with microtome blade, and mounted
on clean glass slide. The sections were routinely stained with
haemotoxyllin and eosin. The stained slides were observed
(400X) in research microscope and photographed.
Myocytes diameter
To assess myocardial hypertrophy quantitatively, the short
axis diameters of myocytes were measured at the level of
the nucleus. In each animal, 100 myocytes were sampled
in each slice at papillary muscle level so that the sampling
points were evenly distributed from the subendocardium
to the subepicardium.
Statistical analysis
Data was expressed as the means ± standard error of
means (S.E.M.) and statistical analysis was carried out
using student’s t-test. P values of less than 0.01 were
considered to be statistically signicant.
RESULTS
Serum and urine biochemical parameters
Feeding of salt water for six weeks signicantly increased
urine albumin/creatinine ratio, serum creatinine & urea.
Salt water feeding also decreased serum ca++ level than
compared to normal rats without affecting signicantly
the serum level of Na+ and K+ (Table 1). Increased
urine albumin/creatinine ratio by salt water feeding was
successfully reduced by 100, 200 and 400 mg/kg aqueous
extract. Methanolic extract also signicantly increased the
urine Na+ & K+ level than compare to salt water induced
urine electrolyte retention. Serum creatinine and urea was
also decreased by the treatment of methanolic extract.
Signicant increase in level of serum Ca++ was also
observed with methanolic extract treatment (Table 1).
Organ weight to body weight ratio
In salt water given rats wet weight of heart to body weight
ratio was decreased signicantly when compared to normal
water fed rats. Higher dose of aqueous extract signicantly
reduced wet weight of heart than compared salt water
fed rats. All three doses of aqueous extract signicantly
reduced wet weight of liver than compare to vehicle
treated group. Methanolic extract has no signicant effect
on heart when compared to salt water fed rats. Regular
treatment of animals with aqueous extract also inhibited
salt water induced decreased body weight (%) signicantly
at medium and maximum dose. But, methanolic extract
potentiated percent decrease in body weight initiated by
salt water administration (Table ).
Myocyte diameter
Cardiac hypertrophy was evidenced in salt water fed rats
with increased diameter of myocytes measured at center
of nucleus presence in 100 nos. of myocytes. All three
doses of aqueous extract inhibited salt water induced
hypertrophy signicantly. However, effect was much higher
in small dose than compare to moderate and higher doses.
Methanolic extract also signicantly decreased myocardial
cellular diameter than compare to salt water fed group.
But, much higher effect was observed with higher dose of
methanolic extract. (Table 3)
Histopathology
In salt water fed rat (Figure 1 & Figure 2) signicantly
increase in diameter of myocytes and also the gap between
myocytes, appeared when compared to normal water
fed rat (Figure 1). In aqueous treated group signicantly
decrease in gap between myocardial bers and appears to
be normal with 400 mg/kg dose (Figure 5), but it fails to
reduce gap between myocardial bers at 100 & 200 mg/
kg dose (Figure 3 & 4 respectively). In addition there was
also arrangement of myocytes nucleus in parallel manner
with 400 mg/kg dose. In methanolic extract at 100 mg/
kg dose (Figure 7) perivascular neutrophil inltration
Possible Role of Natural Nephroprotective; Hemidesmus indicus in Congestive Heart Failure
370 Phcog Res Vol 1/Issue 6 | Available Online : www.phcogres.com
Table 1: Effect of Hemidesmus indicus Aqueous Extract on Serum and Urine Biochemical Parameters
Treatment
Urine
albumin
(gm %)
Urine
Creatinine
(gm %)
Albumin/
creatinine
Urine
Na+(mEq/L)
Urine
K+(mEq/L)
Serum
creatinine
(mg/dl)
Serum Urea
(mg/dl)
Serum SGOT
(U/ml)
Serum SGPT
(U/ml)
SerumNa+
(mEq/L)
SerumNa+
(mEq/L)
SerumCa++
(mEq/L)
Water (2ml/kg;po) 0.54 0.045 92 99.0 110.9 0.88±0.107 40.30±1.44 50.06±5.69 80.61±7.32 129.06±12.43 139.98±22.25 11.78±1.04
Salt & Water (po) 6.01 0.030 200.33 35.6 60 2.76±0.18*** 76.13±9.71* 51.24±2.22 90.36±3.34 135.4±7.44 151.28±19.05 5.30±0.48**
AEHI (100 mg/kg) 3.12 0.072 43.33 869.61 125.9 1.25±0.16** 45.2±2.77* 86.03±5.81** 143.25±6.12*** 76.73±7.27** 104.18±13.19 10.46±0.37***
AEHI (200 mg/kg) 29 0.072 40.27 932.59 103.8 0.90±0.098*** 45.55±3.16 98.66±6.26*** 146.36±7.05*** 69.75±11.95* 81.7±7.93* 10.55±0.35***
AEHI (400 mg/kg) 3.27 0.061 53.60 872.77 136.5 0.97±0.07*** 44.13±1.47* 85.28±2.61*** 125.58±3.19*** 86.18±5.25** 134.43±3.93 7.5±3.09*
Salt & Water (po) 6.23 0.019 327.89 27.2 42.5 2.65±0.19*** 64.05±5.39* 56.11±3.49 89.76±1.29 144.95±11.51 131.01±14.20 5.73±0.32**
MEHI (100 mg/kg) 2.9 0.058 50 520.21 98.39 1.31±0.13** 45.08±2.62* 57.47±6.43** 81.71±2.20*** 140.76±4.51** 133.28±13.91 11.45±0.93***
MEHI (200 mg/kg) 3.01 0.055 60 1220 200.0 1.40±0.09*** 43.36±2.58 50±4.11*** 80.22±3.41*** 136±6.39* 122.51±10.31* 10.8±0.64***
MEHI (400 mg/kg) 3.65 0.056 65.17 2887 353.9 0.99±0.07*** 41.21±1.09* 46.11±2.61*** 80.63±2.51*** 94.43±5.97** 100.91±2.38 11.5±0.53*
Aqueous extract of dose 100, 200 7 400 mg/kg; po was administered daily by oral route for 4 weeks. Urine was collected for 24 hrs. using metabolic cages after 4th week of study. Na+, k+, ca++ were estimated by ame
photometer, albumin was estimated by using Biuret test. Serum was obtained from blood collected by retro orbital method was analyzed by ame photometer to estimate Na+, k+, ca++ concentration. Creatinine, urea, SGOT
and SGPT were estimated by using commercial enzyme kits. Results are expressed as mean ± SEM and analyzed by student't’ test. Results of salt water group are compared with normal group and extract treated groups
are compared with salt water group.
AEHI: Aqueous extract of Hemidesmus Indus
MEHI: Methanolic extract of Hemidesmus indicus
*P<0.05,
**P<0.01,
***P<0.001
Table 2: Effect of Hemidesmus indicus Aqueous & Methanolic Extract on Organ weight to body weight ratio
% Change in
body weight
Organ weigh to body weight ratio (mg/gm)
Treatment Heart/ BW Liver/BW Lung/BW Kidney/BW
Water(2ml/kg;po) 17.35 ± 1.68 4.18±0.25 43.22±2.03 7.18±0.52 4.55±0.32
Salt & Water (po) -33.29±2.31** 3.82±0.18 48.63±1.77 6.22±0.42 4.24±0.21
AEHI (100mg/kg; po) -26.06±3.51 3.33±0.16 33.92±1.12*** 6.47±0.65 3.72±0.25
AEHI (200 mg/kg; po) -17.97±3.05* 3.58±0.30 36.71±1.87** 8.12±0.65 4.20±0.24
AEHI (400 mg/kg; po) -13.67±3.93 3.16±0.06* 33.78±0.58*** 8.06±1.13 3.94±0.12
Salt & DMSO 10% (po) -3.84±2.36 3.24±0.05* 45.05±1.13 6.58±0.54 4.23±0.07
MEHI (100 mg/kg; po) -31.35±1.65 3.55±0.18 50.23±2.41 5.96±0.30 4.69±0.18
MEHI (200 mg/kg; po) -29.57±1.85* 3.45±0.28 50.57±2.59 5.87±0.09 4.87±0.33
MEHI (400 mg/kg; po) -23.32±2.84 3.70±0.37 54.01±3.27* 5.79±0.29 5.41±0.47
Aqueous extract of dose 100, 200 7 400 mg/kg; po and Methanolic extract of dose 100 and 400 mg/kg; po was administered daily by oral route for 4 weeks. Results are expressed as mean ± SEM and analyzed by
student't’ test. Results of salt water group are compared with normal group and extract treated groups are compared with salt water group. Negative sign indicates decrease in body weight when compared to body wt. of animals
prior to studies.
AEHI: Aqueous extract of Hemidesmus Indus
MEHI: Methanolic extract of Hemidesmus Indus
*P<0.05,
**P<0.01,
***P<0.001
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Chidrawar V. R. et al., Phcog Res. 2009; 1:6: 331–355
Table 3: Effect of Hemidesmus indicus Aqueous &
methanolic Extract on Myocyte diameter
Treatment Diameter (micron)
Water (2ml/kg; po) 21.45±0.59
Salt & Water (po) 32.83±0.68***
AEHI(100mg/kg; po) 24.53±0.60***
AEHI (200 mg/kg; po) 26.60±0.66**
AEHI (400 mg/kg; po) 25.90±0.61***
DMSO 10% (2 ml/kg; po) 21.45±0.59
Salt & DMSO 10% (po) 30.76±0.90***
MEHI (100 mg/kg; po) 27.36±0.50*
MEHI(200 mg/kg; po) 26.89±0.58*
MEHI (400 mg/kg; po) 23.18±0.63***
Aqueous extract of dose 100, 200 7 400 mg/kg; po and Methanolic extract
of dose 100,200 and 400 mg/kg; po was administered daily by oral route for 4
weeks. Results are expressed as mean ± SEM and analyzed by student ‘t’ test
& results of salt-water group are compared with normal group and extract treated
groups are compared with salt water group.
AEHI: Aqueous extract of Hemidesmus Indicus
MEHI: Methanolic extract of Hemidesmus Indicus
*P<0.05,
**P<0.01,
***P<0.001
Figure 1: Effect of vehicle (Normal group)
Figure 2: Effect of salt and vehicle (water)
Figure 3: Effect of 100 mg/kg aqueous extract
Figure 4: Effect of 200 mg/kg aqueous extract
Figure 5: Effect of 400 mg/kg aqueous extract
was evident along with presence of neutrophils in
between myocytes. Moderate dose of methanolic extract
was associated with myocytes apoptosis/necrosis with
the presence of fat deposition, neutrophil inltration
and enlarged diameter of myocytes (Figure 8). 400
Possible Role of Natural Nephroprotective; Hemidesmus indicus in Congestive Heart Failure
372 Phcog Res Vol 1/Issue 6 | Available Online : www.phcogres.com
Figure 6: Effect of salt and vehicle (DMSO)
Figure 7: Effect of 100 mg/kg methanolic extract
Figure 8: Effect of 200 mg/kg methanolic extract
Figure 9: Effect of 400 mg/kg methanolic extract
mg/kg dose of the extract reduce gap in myocyte with
potentially inltration of neutrophils and apoptosis/
necrosis of myocytes.
DISCUSSION
Drugs acting on kidney and its performance have very
signicant role in control of cardiovascular complications
and failure. This is the reason in extensive use of diuretics
and ACE inhibitors for HF conditions, where they are
able to control symptoms, exercise tolerance, survival in
patients without improving functional capacity. With this
background present study was carried out to know whether
natural nephroprotective can be used in CHF induced by
salt water feeding and evaluated its effect by considering
organ/Body weight ratio, serum and urine biochemical
parameters, myocytes diameter and histopathological
conditions.
The Dahl-salt sensitive rats model has some advantages
when compared to available models in consistency in the
transition from LV hypertrophy to CHF, and compensated
circulatory state to decompensated state can be achieved
without and invasive and/or specialized surgical procedure
therefore, this has been considered in our present study
with little modication (20).
Supplementation of high salt diet to immature rats
leads to development of systemic hypertension, renin
angiotensin system activation and vascular sensitization.
These pathologic changes leading to development of LV
hypertrophy, decrease contractility of LV myocardium
and pulmonary congestion causing shorter life expectancy
and death. At the age of 10 weeks animals were started
dying just after the salt water feeding for 8 weeks which
conrms the earlier model. The postmortem pathological
examination conrms these changes and demonstrated
pathophysiology of HF also indicating the usefulness
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Chidrawar V. R. et al., Phcog Res. 2009; 1:6: 331–355
of experimental model for study the mechanism and
treatment of HF.
A dynamic reduction of venous capacity results
in enhanced venous return, thereby increasing left
ventricular end diastolic volume and pressure (21) leads
to increased length of left ventricular muscle bers and
myocytes diameter (22), this compensatory mechanism
will be lead to HF. At the cellular level changes associated
with the transition to contractile dysfunction include
deregulation of Ca++ homeostasis (23), myocytes enter
a maladaptive proliferative phase in which fetal isoforms
are expressed evidenced with increased myocytes
diameter (24). Physiologically the retention of Na+, K+
and water are common to seen excessive in serum level
while vasoconstriction is a pathologic phenomenon (25).
The profound reduction of cardiac output and arterial
hypotension in severe HF may lead to renal failure there
conditions will be associated with rise in the blood content
of urea, creatinine and phosphate. Microalbuminuria is
recognized as an early sign of kidney disease as well as an
independent risk factor for CV diseases. The magnitude
of microalbuminuria is directly correlated with rate of
progression in renal failure, hypertension and CV risk
factors leading to HF.
Salt water feeding group shown an increase in serum
Na+ and K+ level similar to earlier study may be leading to
hypertension by increased norepinephrine (NE) vascular
sensitivity25. Serum Ca++ homeostasis was also decreased
in this group substantiating the earlier study on change in
Ca++ homeostasis in HF condition.
Salt water fed rats also shown signicant increase in
serum creatinine and urea level signaling the kidney failure.
Excess loss of albumin through urine was also observed
in this group indicating renal damage. Microalbuminuria
(the ratio between albumin and creatinine in urine), which
is prominent in renal failure condition; this was also
supported by their ratio as there is a signicant increase in
microalbuminuria in this group when compared to control.
The enlargement of myocytes was also observed in this
group as a compensatory process in HF condition.
The nephroprotective property of Hemidesmus indicus
was evidenced with aqueous and methanolic extract
preparation. Aqueous extract signicantly inhibited
the effect of salt water feeding modulated biochemical
factors and reduced serum urea/creatinine level and also
increased the level of urine creatinine. This extract also
maintains homeostasis in serum Ca++ level (altered by
salt water) may increase its cellular availability leading to
increased cardiac output proposed in earlier studies. All
three doses of Aqueous extract signicantly (P< 0.001)
decreased salt water induced change in liver/body weight
ratio, simultaneously increased the level of SGPT and
SGOT. Cardiac remodeling property of Hemidesmus indicus
was also evidenced by its signicant reduction in myocytes
diameter in salt water induced hypertrophy. Signicant
inhibitory action of aqueous extract on salt water induced
increased serum Na+ may desensitize the NE action on
vascular system and this factor may prevent the disease
progression.
This methanolic extract increase urine Na+ and K+ level
and salt water induced serum Na+ and K+ signicantly
showing its diuretic property which was supported by
earlier studies, also inhibited salt water decreased serum
Ca++ level and brought it to normal; but this extract
decreased the body weight of animals higher than that of
salt water treated groups showing its inability in improving
the health status. More ever all animals in the dose of
200 mg/kg methanolic extract were died in 10th week of
study; histopathological examination indicates myocytes
apoptosis and necrosis. Compared to methanolic extract
aqueous extract of Hemidesmus indicus have shown
promising effects for the treatment of CHF.
CONCLUSION
From the results obtained in our laboratory we propose
the cardioprotective activity aqueous extract of
Hemidesmus indicus possibly mediated through its diuretic,
inhibition of pulmonary congestion, ability in remodeling
of cardiac hypertrophy, reduced vascular sensitivity
to NE, improved renal performance. Improvement in
cardiac performance may also be related to increase in
serum calcium level leading to increase in uptake of Ca++
by myocytes thereby increase the cardiac output. We
conclude from this study that the plant Hemidesmus indicus
known as a natural nephroprotective could be useful for
CHF condition because of its multidimensory, molecular,
cellular and pharmacological activities produced by its
active constituents.
ACKNOWLEDGEMENT
The author (s) deeply acknowledges to the Principal Prof.
I.S. Muchandi and Head of Dept. Dr. H.R. Chitme of
H.S.K. College of Pharmacy, Bagalkot, Karnataka for
extending laboratory facilities for carrying out this study
successfully.
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... reported that an aqueous root extract of H. indicus exhibited nephroprotective activity in male albino Wistar rats, with a dosage of 100 mg/kg resulting in reduced tubular degeneration and dilatation after 19 hours of observation. Sudarshan and Patel (2009) [49] investigated the cardioprotective activity of aqueous and methanolic root extracts, using SD rats with dosages of 100, 200, and 400 mg/kg. They found that after 6 weeks, creatinine was reduced. ...
... reported that an aqueous root extract of H. indicus exhibited nephroprotective activity in male albino Wistar rats, with a dosage of 100 mg/kg resulting in reduced tubular degeneration and dilatation after 19 hours of observation. Sudarshan and Patel (2009) [49] investigated the cardioprotective activity of aqueous and methanolic root extracts, using SD rats with dosages of 100, 200, and 400 mg/kg. They found that after 6 weeks, creatinine was reduced. ...
... Aqueous and methanolic root extracts (100, 200 and 400 mg/kg) displayed cardioprotective efficacy in salt water-induced ventricular hypertrophy in rats. This was mediated via inhibition of microalbuminuria, serum urea, calcium and creatinine levels, myocyte diameter, and retention of sodium ion (Na + ) and water and through an increase in serum calcium level (Chidrawar et al., 2009). In addition, the ethanolic root extract (0.09 g/l, 15 min) showed cardio-active effect mediated through protection of ischemic myocardium against contractile dysfunction, arrhythmias, and reduced irreversible tissue damage following ischemia in rat hearts (Khandelwal et al., 2010). ...
Article
Ethnopharmacological relevance: Hemidesmus indicus (L.) R. Br. ex Schult. (Apocynaceae) is widely used in traditional medicine in the different parts of the Indian subcontinent due to the various biological activities attributed to its different parts, especially the roots. It has traditionally been used for treating snakebites, scorpion stings, diabetes, urinary diseases, dyspnea, menorrhagia, oligospermia, anorexia, fever, abdominal colic and pain, dysentery, diarrhea, cough, rheumatism, pain including headache, inflammation, pyrosis, skin diseases, leprosy, sexually transmitted diseases and cancer. In Ayurveda, the plant is used in the treatment of bone-loss, low body weight, and fever, stress, topical wound and psoriasis. Besides, Ayurvedic literature also depicts its use as anti-atherogenic, anti-spasmodic, memory enhancing, immunopotentiating and anti-inflammatory agents. Aim of the study: In this review, we aim to present a comprehensive update on the ethnopharmacology, phytochemistry, specific pharmacology, and toxicology of H. indicus and its bioactive metabolites. Possible directions for future research are also outlined in brief. Materials and methods: Popular and widely used international databases such as PubMed, Scopus, Science Direct, Google Scholar and JSTOR were searched and traditional literature were consulted using the various search strings to retrieve a number of citations related to the ethnopharmacology, biological activity, toxicology, quality control and phytochemistry of H. indicus. All studies on the ethnobotany, phtochemistry, pharmacology, and toxicology of the plant up to May, 2019 were included in this review. Results: H. indicus has played an important role in traditional Indian medicine (including Ayurveda) and also in European medicine. The main pharmacological properties of H. indicus include hepatoprotective, anti-cancer, anti-diabetic, antioxidant, neuroprotective, anti-ophidian, cardioprotective, nephroprotective, anti-ulcerogenic, anti-inflammatory, and antimicrobial properties. Phytochemical evaluations of the roots have revealed the presence of aromatic aldehydes and their derivatives, phenolics, triterpenoids and many other compounds, some of which were attributed to its bioactivity. This review also compiles a list of Ayurvedic formulations and commercial preparations where H. indicus has been used as an active ingredient. We have included the critical assessment of all the papers cited in this manuscript based on experimental observation and other important points which reflects the loop-holes of research strategy and ambiguity of the papers reviewed in this manuscript. Conclusions: The study presents an exhaustive and updated review on the traditional, pharmacological and phytochemical aspects of H. indicus with notes on its quality control and toxicological information. Although the crude extracts of H. indicus exhibit an array of pharmacological activities, it is high time to identify more active phyto-constituents by bioactivity-guided isolation besides elucidating their structure-activity relationship. More designed investigations are needed to comprehend the multi-target network pharmacology, to clarify the molecular mode of action and to ascertain the efficacious doses of H. indicus. Moreover, H. indicus is not fully assessed on the basis of its safety and efficacy on human. We hope this review will compile and improve the existing knowledge on the potential utilization of H. indicus in complementary and alternative medicine.
... Kidney failure shall be managed by similar means of non-pharmacological and pharmacological therapeutic interventions. [11] Vitex negundo L. (Tamil-vella nochi, Hindi-Nirgundi) belongs to the family Lamiaceae. It is an aromatic large shrub. ...
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The aim of the present study was to investigate the renoprotective and antioxidant activities of methanolic extract of leaves of Vitex negundo against cisplatin induced nephrotoxicity in male albino rats. Male albino rats were randomly divided into four groups of six rats each, group I was served as the normal control group, group II was served as the cisplatin treated group, group III was served as the silymarin treated group and group IV was served as Vitex negundo treated group.After 15 days treatment, The kidney of each rat was excised, cleaned, weighed, rinsed in ice-cold saline, homogenized and centrifuged. Collected renal tissue supernatant were used for the analysis of level of malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD) and glutathione peroxidase (GPx) in all groups. Histological examination was also carried out in all groups.Vitex negundo treated rats revealed significant reduction in MDA level and increased in GPx, CAT and SOD activities in kidney tissue homogenates. Additionally, histopathological examinations revealed markedly ameliorated cisplatin induced toxicity on kidney structure.Our results proved that vitex negundo has antioxidant and protective effects against cisplatin induced oxidative stress. Thus, it could be used as a dietary supplementation to reduce toxic side effects of anticancer drugs.
... It may be suggested that both KV and CL offer protection against L-NAME induced renal dysfunction in these animals. These observations are consistent with the studies of Chidrawar et al [45] and Bhalodi et al [46] in which extracts of Hemidesmus indicus and Benincasa cerifera attenuate the serum urea levels of rats with cardiovascular disorder, respectively. ...
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Kolaviron (KV) (biflavonoid from Garcinia kola) and extract of Curcuma longa (CL) are frequently used in folk medicine for treatment of hypertension. One of their mechanisms of action is to enhance antioxidant properties in animals. N(G)- nitro- l- arginine methyl- ester (L- NAME) is L- arginine analogue, which by binding to Nitric Oxide Synthase (NOS) may induce hypertension partly due to increase in tissues oxidative stress. To investigate the effect of L- NAME on some biochemical indices and the possible protective effect of KV or CL. Four groups consisting of 6 rats each were used. One group served as control, second group received L- NAME (40 mg/kg/day). Third and fourth groups were treated with KV and CL, respectively and also received L- NAME. KV and CL were given at a dose of 200 mg/kg/day. L- NAME caused a significant (P <0.05) increase in the levels of serum urea, creatine kinase and alanine aminotransferase relative to controls. L- NAME treated rats had markedly decreased hepatic catalase (CAT), superoxide dismutase (SOD), glutathione- S- transferase (GST) and reduced glutathione (GSH) levels. Precisely, L- NAME decreased CAT, SOD, GST and GSH by 48, 52, 76 and 40%, respectively. L- NAME intoxication significantly decreased (P <0.05) renal GSH and SOD levels. Also, L- NAME caused a significant (P <0.05) induction of lipid peroxidation (LPO) in the animals. Administration of KV or CL with L- NAME caused significant (P <0.05) inhibition of LPO and augments tissue antioxidant indices. These results confirm the adverse effect of L- NAME on biochemical indices and, the ability of kolaviron or Curcuma longa to ameliorate the alterations.
... Kidney failure shall be managed by similar means of non-pharmacological and pharmacological therapeutic interventions. [13] Euphorbia hirta is frequently seen growing in open waste spaces, grasslands, roadsides and pathways. It is slenderstemmed, annual, hairy plant with many branches from the base to top, spreading up to 40 cm in height, and is reddish or purplish in color. ...
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Euphorbia hirta (L.) (Euphorbiaceae) is a very popular herb amongst practitioners of traditional medicine and used in the treatment of female disorders, respiratory ailments, tumors, jaundice, digestive problems, wounds, etc. We aimed to evaluate the protective effect of E. hirta against nitrobenzene-induced nephrotoxicity in albino rats. The nephroprotective activity of the ethanol extract of E. hirta (400 mg/kg body weight) was studied in nitrobenzene-induced albino rats (1000 mg/kg body weight). The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and the levels of reduced glutathione (GSH), total thiols and vitamin C in the kidney tissues were determined. Histopathologic investigation was performed in the kidney tissue samples. Nitrobenzene administration significantly (P < 0.01) enhanced the lipid peroxidation and significantly (P < 0.05) depleted the levels of SOD, CAT, GPx, GST, GSH, total thiols and vitamin C. Treatment with the ethanol extract of E. hirta significantly normalized the antioxidant levels. The nephroprotective activity was also supported by histopathologic studies of kidney tissue. The results indicate that the ethanol extract of E. hirta ameliorates renal dysfunction and could be used as an effective protector against nitrobenzene-induced nephrotoxicity, primarily through its antioxidant capacity.
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Plant-derived bioactive products and their structural diversity have made a significant contribution to various pharmacological activities including cancer and other infectious diseases. Application of natural products and their derivatives in multi-faceted anti-cancer effects and advanced disease management is extensively under consideration at the level of primary, secondary and tertiary care prevention. Hemidesmus indicus (L.) R. Br. ex Schult belongs to the family Apocynaceae and extensively used in poly-herbal preparations and several biological activities. The connection between chronic inflammation and cancer has drawn considerable interest and acceptance. The activation of genes that regulate cell signaling pathways associated with inflammation can take control over various aspects of the disease process. Among the various signaling pathways (STAT-3, HIF-1, NF- κB, IL-1, Cox-2, TNF-α, and oncogenic Kinase (P13k, IKK, IRAK1/4, JAK, MARK/ERK, and Syk/Src) are essential for establishing a connection between inflammation and cancer. Due to this theoretical basis, the inflammatory response to cancer has emerged as the center of attention for novel preventive and therapeutic approaches. To reduce inflammation, immunomodulatory medications are often used in cancer therapy. Although considering the adverse reactions associated with synthetic immunomodulatory substances and cytotoxic cancer drugs, it is essential to explore the development of innovative anti-inflammatory agents to enhance cancer treatment. Several reports suggest that bioactive phytochemicals obtained from H. indicus demonstrate anti-inflammatory properties in the context of cancer. There is a need for further investigation into the cellular processes under- lying anti-inflammatory effects of H. indicus, in order to develop a comprehensive understanding of its potential in cancer treatment. However, many phytochemicals need to be further explored for their application in biomedical treatments. Moreover, studies regarding molecular mechanisms and mode of action, effective and safe doses of H. indicus, and its phytochemicals for the treatment of inflammation associated with cancer and other pharmacological activities needs to be explored. Overall, the present review describes and concludes the role of H. indicus to investigate the mechanism and to improve the cancer prevention. In addition, safety, toxicity and clinical evaluation is also discussed.
Chapter
Hemidesmus indicus (L.) R. Br. is commonly known as Indian Sarsaparilla or Anantmula. Traditionally, it has been utilised as a vital herb for the treatment of several disorders. Indian Sarsaparilla is rich in a wide range of phytoconstituents such as pregnane glycosides, steroids, terpenoids, aromatic aldehydes, lignans, saponins, flavonoids and aliphatic acids which may further contribute to its pharmacological properties. This chapter gathers and compiles the traditional ethnobotanical and ayurvedic aspects of H. indicus and recently updated knowledge regarding the pharmacology, phytochemistry, adulteration, and current trends of this medicinally important herb in the field of modern phytomedicine. It also presents the ayurvedic pharmacology of this herb and summarizes the biomedical researches in as much as it helps glean a better understanding of H. indicus safety and effectiveness in humans, and describes the various natural products and polyherbal medicines containing H. indicus.
Chapter
Full-text available
Hemidesmus indicus (L.) R. Br. is commonly known as Indian Sarsaparilla or Anantmula. Traditionally, it has been utilised as a vital herb for the treatment of several disorders. Indian Sarsaparilla is rich in a wide range of phytoconstituents such as pregnane glycosides, steroids, terpenoids, aromatic aldehydes, lignans, saponins, flavonoids and aliphatic acids which may further contribute to its pharmacological properties. This chapter gathers and compiles the traditional ethnobotanical and ayurvedic aspects of H. indicus and recently updated knowledge regarding the pharmacology, phytochemistry, adulteration, and current trends of this medicinally important herb in the field of modern phytomedicine. It also presents the ayurvedic pharmacology of this herb and summarizes the biomedical researches in as much as it helps glean a better understanding of H. indicus safety and effectiveness in humans, and describes the various natural products and polyherbal medicines containing H. indicus.
Article
The root of Hemidesmus indicus R. Br., commonly known as Indian Sarsaparilla, is used traditionally to treat a wide variety of illnesses including rheumatism, leprosy, impotence, urinary tract and skin infections. The anticancer, antioxidant, anti-inflammatory, antipyretic, analgesic, antimicrobial, antidiabetic, hepatoprotective, cardioprotective, renoprotective, neuroprotective and immunomodulatory properties of H. indicus have been investigated in numerous in vivo and in vitro studies. Among these, the antioxidant and antimicrobial activity was well documented. This review details the phytochemistry and therapeutic applications of H. indicus root. Copyright © 2012 John Wiley & Sons, Ltd.
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The potent mineralocorticoid aldosterone has a multifaceted role in the pathogenesis of congestive heart failure. In addition to its contribution to salt and water retention, it also promotes organ fibrosis. Although angiotensin-converting–enzyme inhibitors have important therapeutic benefit in heart failure, they do not eliminate the effects of aldosterone. Thus, recent studies have underscored the value of aldosterone-receptor antagonists, such as spironolactone, in the treatment of chronic heart failure. This review article gives an in-depth update on the mechanisms of action of aldosterone and their implications for therapy.
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Hypertension, left ventricular hypertrophy (LVH), hypercreatininemia, and microalbuminuria (MA) are independent risk factors for cardiovascular disease (CVD). Hypertension increases the risk of CVD by two- to three-fold and LVH (especially concentric) is a risk factor for coronary heart disease, heart failure, stroke, and peripheral arterial disease. In people with hypertension, a serum creatinine level of 1.7 mg/dL or more may be an even stronger CVD risk factor than diabetes, smoking, LVH, or systolic blood pressure. Similarly, MA is a strong and independent predictor of CVD morbidity and mortality in people with and without diabetes and/or hypertension. Impaired renal sodium handling and sodium retention are physiological hallmarks of the very early stages of heart failure. Heart failure is a physiologically delicate condition that can decompensate with excess dietary salt intake or over diuresis, or compensate with cautious therapy designed to block the sodium retention and simultaneously interrupt excessively activated neurohumoral mechanisms.
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Myocardial infarction (MI) was produced in rats with 85, 200 and 300 mg/kg of isoproterenol (ISO) administered subcutaneously (sc) twice at an interval of 24 h. Shift in antioxidant parameters, lactate dehydrogenase (LDH) together with morphological and histopathological changes were investigated. Two hundred mg/kg ISO dose was selected for the present study as this dose offered significant alteration in biochemical parameters along with moderate necrosis in heart. Effect of pre- and co-treatment of hydroalcoholic extract of Ocimum sanctum (Os) at different doses (25, 50, 75, 100, 200 and 400 mg/kg) was investigated against ISO (200 mg/kg) induced myocardial infarction in rats. Modulation of various biochemical parameters and membrane integrity was studied. Os at the dose of 25, 50, 75 and 100 mg/kg reduced significantly glutathione (GSH), superoxide dismutase (SOD) and LDH levels. It also inhibited the lipid peroxidation as observed by the reduced thiobarbituric acid reactive substances (TBARS) levels. In the present study Os at the dose of 50 mg/kg was found to demonstrate maximum cardioprotective effect. Above results were further confirmed by histopathological findings. Thus from the present study it is concluded that Os may be of therapeutic and prophylactic value in the treatment of MI.