Conference PaperPDF Available

Diuretic efficacy of Matricaria chamomilla in normotensive and salt-induced hypertensive rats

Authors:

Abstract and Figures

Background and objectives: Traditionally Chamomile (Matricaria chamomilla L.) has various medicinal uses. It has soothing, calming, sedative, and anti-inflammatory effects. The present study was designed to evaluate the effectiveness of decoction of Chamomile on urine flow rate, urinary and serum electrolyte concentration, urinary sodium and potassium excretion rates, urine and serum creatinine concentration, glomerular filtration rate, and the percentage of reabsorbed of filtered sodium, in normal and salt loaded hypertensive rats. Methods: The study was carried out on 30 rats, which were divided into two groups. The first group involved twelve normotensive rats and were subdivided into two subgroups each of 6 rats. The first subgroup served as a control group. The second subgroup received decoction Chamomile orally for 3 weeks. The second group included 18 induced hypertensive rats and were divided into 3 subgroups each of 6 rats. The first subgroup served as a positive control. The second and third subgroups received decoction of Chamomile and of Chlorthalidone respectively. Results: Chamomile decoction produced a significant increase in urine flow, Sodium excretion rate, Glomerular filtration rate and urinary creatinine level without significant effects on blood pressure, heart rate, and serum creatinine and blood urea in normal rats. Unlike Cholothalodone Chamomile decoction did not induce diuresis and has no significant effects on blood pressure in normal and hypertensive rate. However, the same dose of chamomile significantly increased serum potassium level in both normal and hypertensive rats. Conclusion: Chamomile has mild diuretic activity in normal rats and its effects resemble that of potassium sparing diuretics.
Content may be subject to copyright.
The Second International Conference College of Medicine, HMU, 22nd - 24th November, 2017, Divan Hotel - Erbil - Kurdistan, Iraq
360
Diuretic efficacy of Matricaria chamomilla in normotensive and salt-induced hypertensive rats
Kawa F. Dizaye * Asma A. Otraqchy **
*Correspondent author: Prof. Dr. Kawa Dizaye, College of Medicine, Hawler Medical University,
Erbil, Iraq,
** Raparin teaching hospital, directorate of Health, Erbil, Iraq,
Abstract
Background and objectives: Traditionally Chamomile (Matricaria chamomilla L.) has various
medicinal uses. It has soothing, calming, sedative, and anti-inflammatory effects. The present study
was designed to evaluate the effectiveness of decoction of Chamomile on urine flow rate, urinary and
serum electrolyte concentration, urinary sodium and potassium excretion rates, urine and serum
creatinine concentration, glomerular filtration rate, and the percentage of reabsorbed of filtered
sodium, in normal and salt loaded hypertensive rats.
Methods: The study was carried out on 30 rats, which were divided into two groups. The first group
involved twelve normotensive rats and were subdivided into two subgroups each of 6 rats. The first
subgroup served as a control group. The second subgroup received decoction Chamomile orally for 3
weeks. The second group included 18 induced hypertensive rats and were divided into 3 subgroups
each of 6 rats. The first subgroup served as a positive control. The second and third subgroups
received decoction of Chamomile and of Chlorthalidone respectively.
Results: Chamomile decoction produced a significant increase in urine flow, Sodium excretion rate,
Glomerular filtration rate and urinary creatinine level without significant effects on blood pressure,
heart rate, and serum creatinine and blood urea in normal rats. Unlike Cholothalodone Chamomile
decoction did not induce diuresis and has no significant effects on blood pressure in normal and
hypertensive rate. However, the same dose of chamomile significantly increased serum potassium
level in both normal and hypertensive rats.
Conclusion: Chamomile has mild diuretic activity in normal rats and its effects resemble that of
potassium sparing diuretics.
Key: Matricaria chamomilla, Cholothalodone, Diuretic, Hypertensive rats
The Second International Conference College of Medicine, HMU, 22nd - 24th November, 2017, Divan Hotel - Erbil - Kurdistan, Iraq
361
Introduction:
Diuretics have been used effectively to treat millions of hypertensive patients. They reduce both
systolic and diastolic blood pressures in the most of hypertensive patients, They are administered
alone or in combination with other antihypertensive agents form the basis of therapy for the
majority of hypertensive patients 1. Because of their efficacy, low cost, and low side effects profile,
diuretics are first choice to be prescribed for patients with hypertension, as well as their synergistic
effect when combined with other antihypertensive agents; and their usefulness in patients with heart
failure 2.
Traditionally, in most countries all over the world many plants have been used for their diuretic
effect, for example the ripe fruits of Carum carvi and the leaves of Tanacetum vulgare are two
widely available plant materials, that are used as diuretics in the Moroccan traditional medicine 3.
Urticaria diocia, is another example, which is used by Kurdistan folks 4.
Many other herbal plants exerting diuretic property, were traditionally used, e.g. Mangifera indica,
Mimosa pudica, Lipidium sativum, and Achyranthes aspera 5. Doradilla that has a long history in the
Mexican traditional system of medicine for gall and renal stones, through its diuretic action 6.
Chamomile or Matricaria chamomilla L. (M. chamomilla) is usually referred to as the "star among
medicinal species" a well-known medicinal plant species from the Asteraceae family. It has
multitherapeutic, cosmetic, and nutritional values have been established through years of traditional
and scientific uses and researches, it is one of the highly favored and much used medicinal plant in
folk and traditional medicine 7.
Matricaria Chamomilla has a wide range of therapeutic actions; soothing, calming, sedative,
relaxation, anti-inflammation, treating indigestion, hay fever, asthma, morning sickness, eczema,
and sore nipples 8. About 120 chemical constituents have been identified in chamomiles as
secondary metabolites, including 28 treptinoids, 36 flavonoids, and 52 additional compounds with
pharmacological activity 9.
Because little information is available about the activity of M. chamomilla to produce diuresis,
therefore this study is undertaken to evaluate the activity of M. chamomilla decoction as a diuretic
agent in normotensive and hypertensive animal model.
The Second International Conference College of Medicine, HMU, 22nd - 24th November, 2017, Divan Hotel - Erbil - Kurdistan, Iraq
362
Materials and Methods
Preparation of M. chamomilla decoction.
Dry M. chamomilla flowers were weighed and crushed to powder with a marble pestle and mortar,
then 15% w/v (150 g was added in 1000 ml of distilled water) heated in a steel kettle and allowed to
boil for 15 minutes. The flask was then placed on a shaker for four hours, at room temperature. After
shaking, the suspension was filtered through a series of filter papers to avoid the bacterial
contamination and stored at 4°C until use 10. After that, it's filled with distilled water up to 1000 ml
for making up the desired volume for dosage calculation, each rat was give 3 ml of the decoction
(1.3g/kg/day) by oral gavages every morning during the 21 days of the study.
Experimental Design.
Diuretic activity of prepared M. chamomilla decoction was studied on 30 adult male Wistar rats,
weighing 300350 gram which were divided into two groups. The first group involved twelve
normotensive rats, six rats sacrificed as a negative control and the other six rats received 3ml 15%
decoction of M. chamomilla every day during the 21 days of study period. The second group involved
18 hypertensive rats. Hypertension was induced by sodium load diet and water 11. The hypertensive
rats were subdivided into three subgroups, each of six rats. The first subgroup served as a positive
control. The second and third subgroups received 3 ml of 15% decoction Matricaria Chamomilla by
oral gavages, and 1 ml (5mg/kg) chlorthalidone respectively. All the rats were exposed to the same
environment.
Group I: Normal rats served as negative control.
Group II: Normal rats treated with decoction M. chamomilla (1.3 g/kg/day).
Group III: Hypertensive rats served as positive control.
Group IV: Hypertensive rats given 15% decoction M. chamomilla (1.3 g/kg/day).
Group VI: Hypertensive rats given chlorthalidone (5 mg/Kg).
Sample collections.
Urine samples.
Urine was collected 24 hour based, and measured after dosing by putting the rats in the metabolic
cages. Then urine volume of each rat was measured, and put in a urine container and the samples were
taken to the laboratory for creatinine and electrolytes in urine (sodium and potassium) analysis.
Blood samples.
At the end of drug and herbal treatment, all the rats were fasted overnight allowed free access to
water. At the morning of the next day, the rats were anesthetized by a combination of ketamine in a
dose of 75mg/kg with xylazine in a dose of 10 mg/kg intrapertoneally (IP) (Gallaly, 2012), then
The Second International Conference College of Medicine, HMU, 22nd - 24th November, 2017, Divan Hotel - Erbil - Kurdistan, Iraq
363
blood samples were taken from their hearts by direct cardiac puncture by the needle of a plastic
syringe.
Statistical Analysis
The results of serum and urine electrolytes concentrations, serum and urine creatinine concentration,
serum urea concentration, urine flow, sodium excretion rate, potassium excretion rate, glomerular
filtration rate, percentage of sodium reabsorbed of filtered load, blood pressure and heart rate of the
rats were analyzed statistically using SPSS software program package 21 and are expressed as mean ±
standard errors of means (M± SEM). Data analysis was made using one-way analysis of variables
(ANOVA). Comparison was made between groups using Duncan test and unpaired student t-test. A p
value of ≤ 0.05 was considered statistically significant.
Results
Effects of M. chamomilla decoction (15%) on blood pressure and heart rate in normal rats.
The blood pressure of normal rats treated with M. chamomilla was non-significantly higher than the
normal control rats (Table 1).
Table 1 Effects of M. chamomilla decoction (15%) on blood pressure and heart rate in normal
rats.
Parameters
Normal Rats (n=6)
Normal Rats /MC (n=6)
P value
Blood Pressure
(mmHg)
106 ±4
110 ±4
0.347
Heart Rate
(Beats/minute)
333 ±41
359 ±10
0.537
*MC: Matricaria chamomilla.
Effects of M. chamomilla decoction (15%) on urine flow, sodium excretion rate, potassium
excretion rate, GFR and % Na+ reabsorption of filtered load in normal rats.
The urine flow of the normal rats treated with 15% decoction of M. chamomilla was significantly
higher than the normal rats that did not receive the plant decoction, (Table 2). Sodium excretion rate,
was significantly increased in normal rats received M. chamomilla decoction. There was a slight and
non-significant elevation in Potassium excretion rate of normal rats received M. chamomilla
decoction, (Table 2). Glomerular filtration rate was significantly increased in M. chamomilla treated
rats by four folds in comparison to non-treated normal rats. The percentage of sodium ion
reabsorption was not significantly increased in the normal rats following daily administration M.
chamomilla decoction, (Table 2).
The Second International Conference College of Medicine, HMU, 22nd - 24th November, 2017, Divan Hotel - Erbil - Kurdistan, Iraq
364
Table 2. Effects of M. chamomilla decoction (15%) on urine flow, sodium excretion rate,
potassium excretion rate, GFR and % Na+ reabsorption of filtered load in normal rats.
Normal Rats (n=6)
Norm4al Rats /MC (n=6)
P value
0.0144 ±0.0015
0.0348 ±0.0037
0.001
2.98 ±0.54
11.5 ±1.43
0.001
0.7 ±0.21
1.11 ±0.12
0.057
0.20 ±0.04
2.76 ±0.44
0.04
88.5 ±2.15
96.7 ±0.5
0.087
* MC: Matricaria chamomilla, GFR: Glomerular filtration rate.
Effects of M. chamomilla decoction (15%) on urinary sodium, potassium and creatinine
concentration in normal rats.
Urinary Na+ concentration of rats treated with M. chamomilla decoction was increased significantly
in comparison to normal rats who did not receive, while urinary K+ concentration was slightly and
non-significantly decreased (Table 3). Urinary creatinin concentration was significantly increased in
M. chamomilla treated rats compared to the non-treated rats (Table 3).
Table 3. Effects of M. chamomilla decoction (15%) on urinary electrolytes and creatinine
concentrations in normal rats.
Normal Rats/MC (n=6)
P value
327.16 ±16.81
0.008
32.16 ±0.6
0.299
44.16 ±2.3
0.000
*MC: Matricaria chamomilla.
The Second International Conference College of Medicine, HMU, 22nd - 24th November, 2017, Divan Hotel - Erbil - Kurdistan, Iraq
365
Effects of M. chamomilla decoction (15%) on serum electrolytes and serum urea and
creatinine concentration in normal rats.
Serum sodium (Na+) concentration of normal rats treated with M. chamomilla was slightly and non-
significantly decreased, whereas serum potassium (K+) level was significantly increased, (Table 4).
Daily administration of M. Chamomilla had no significant effect on serum creatinine (S. Cr.) and
serum urea concentrations in normal rats (Table 4).
Table 4. Effects of M. chamomilla decoction (15%) on serum electrolytes and serum urea and
creatinine concentration in normal rats.
Parameters
Normal rats (n=6)
Normal rats/ MC (n=6)
P value
S. Na+ (mEq/L)
142.3 ±0.84
138.5 ±2.04
0.279
S. K+ (mEq/L)
4.28 ±0.09
6.4 ±0.397
0.022
S. Cr. (mg/dl)
0.6 ±0.44
0.58 ±0.65
0.28
S. Urea (mg/dl)
43.5 ±3.33
20.3 ±2.29
0.423
* MC: Matricaria chamomilla.
Effects of M. chamomilla decoction (15%) and CLTD (5 mg/kg) on blood pressure and heart rate
in hypertensive rats.
Matricaria Chamomilla decoction did not reduce blood pressure of hypertensive rats, but it
significantly reduced the heart rate. Whereas chlorthalidone could significantly decrease both blood
pressure and heart rate of hypertensive rats (Table 5).
Table 5. Effects of M. chamomilla decoction (15%) and CLTD (5mg/kg) on blood pressure and
heart rate in hypertensive rats.
Parameters
Hypertensive Rats
(n=6)
Hypertensive/MC
(n=6)
Hypertensive/CLTD
(n=6)
Blood Pressure
(mm.Hg)
121 ±1.86
a
123±3.79
a
107± 1.83
b
Heart Rate
(bpm)
407 ±11.66
a
355 ±10.87
b
337 ±11.54
b
MC: Matricaria Chamomilla. CLTD: Chlorthalidone.
The Second International Conference College of Medicine, HMU, 22nd - 24th November, 2017, Divan Hotel - Erbil - Kurdistan, Iraq
366
Effects of M. chamomilla decoction (15% W/V) and CLTD (5 mg/kg) on urine flow, sodium
excretion rate, potassium excretion rate, GFR and % Na+ reabsorption of filtered load in
hypertensive rats.
Urine flow of hypertensive rats receiving 15% decoction of M. chamomilla was slightly and non-
significantly increased. Whereas in hypertensive rats that received chlorthalidone, urine flow was
significantly increased (Table 6,).
Urinary sodium and potassium excretion rates of the hypertensive rats receiving M. chamomilla
decoction was non-significantly changed, while CLTD significantly increased both urinary sodium
and potassium excretion rates in hypertensive rats. (Table 6). Glomerular filtration rate in
hypertensive rats receiving M. chamomilla or chlorthalidone was non-significantly changed, as
shown in Table (3.6). Furthermore, both M. chamomilla and chlorthalidone had no detectable effects
on % Na+ reabsorption of filtered load in the hypertensive rats Table (6).
Table 6. Effects of M. chamomilla decoction (15%) and CLTD (5 mg/kg) on urine flow, sodium
excretion rate, potassium excretion rate, GFR and % Na+ reabsorption of filtered load in
hypertensive rats.
Parameters
Hypertensive rats
(n=6)
Hypertensive/ MC
(n=6)
Hypertensive/
CLTD (n=6)
Urine flow
(ml/min/kg)
0.0283± 0.0044
a
0.0316± 0.0043
a
0.055 ± 0.0073
b
Na+ excretion rate
(μEq/min/kg)
9.2±1.69
a
9.26 ±1.42
a
16.5 ±2.15
b
K+ excretion rate
(μEq/min/kg)
0.74 ±0.14
a
0.958± 0.13
a
1.66±0.18
b
GFR
(ml/min/kg)
0.99 ±0.18
a
2.24 ±0.5
a
2.2 ±0.7
a
% Na+ reabsorption
of filtered load
93.56 ±0.59
a
95.59±1.37
a
91.96 ± 1.6
a
MC: Matricaria chamomilla. CLTD: Chlorthalidone, GFR: glomerular filtration rate.
The Second International Conference College of Medicine, HMU, 22nd - 24th November, 2017, Divan Hotel - Erbil - Kurdistan, Iraq
367
Effects of M. chamomilla decoction (15%) and CLTD (5mg/kg) on urinary sodium, potassium
and creatinine concentration in hypertensive rats.
Urinary Na+ concentration of hypertensive rats treated with M. chamomilla or chlorthalidone were
non-significantly changed. Table (7). Whereas, urinary K+ concentrations of the hypertensive rats
received chamomile or chlorthalidone were slightly and significantly increased Table. (7).
Urinary creatinin concentration in hypertensive rats that received M. chamomilla decoction or
chlorthalidone were significantly higher than that of non-treated group. Table (7).
Table 7. The effects of M. chamomilla decoction (15%) and CLTD (5 mg/kg) on urinary
electrolytes and creatinin concentration in hypertensive rats.
Parameters
Hypertensive Rats
(n=6)
Hypertensive/MC
(n=6)
Hypertensive/CLTD
(n=6)
Urinary Na+
(mEq/L)
319.83±14
a
290 ±9.29
a
300 ±5.73
a
Urinary K+
(mEq/L)
26 ±1.8
a
30.3 ±0.88
b
30.6 ±1.02
b
Urinary Cr.
(mg/dl)
22 ±1.77
a
60 ±9.7
b
39 ±10.27
ab
Effects of M. chamomilla decoction (15%) and CLTD (5 mg/kg) on serum electrolytes and
serum urea and creatinine concentration in hypertensive rats.
Serum Na+ concentrations of hypertensive rats treated with M. chamomilla and chlorthalidone were
significantly lower than non-treated hypertensive rats. Table (8).
Serum K+ concentration of the hypertensive rats received M. chamomilla was significantly increased,
but in chlorthalidone treated rats, serum potassium concentration non significantly has been changed
(Table 8).
Serum Creatinine concentration in hypertensive rats that received M. chamomilla decoction was non-
significantly higher than the non-treated group. While in hypertensive rats receiving chlorthalidone,
serum creatinine was significantly higher than the non-treated group (Table 8).
Serum urea concentration in hypertensive rats treated with M. chamomilla was non- significantly
increased, whereas in chlorthalidone treated group the serum urea concentration was increased
significantly (Table 8).
The Second International Conference College of Medicine, HMU, 22nd - 24th November, 2017, Divan Hotel - Erbil - Kurdistan, Iraq
368
Table 8. Effects of M. chamomilla decoction (15%) and CLTD (5mg/kg) on serum electrolytes
and serum urea and creatinine concentration in hypertensive rats.
Parameters
Hypertensive Rats
(n=6)
Hypertensive/MC
(n=6)
Hypertensive/CLTD
(n=6)
S. Na+ (mEq/L)
146.5 ±0.88
a
135 ±2.65
b
135.8± 0.54
b
S. K+ (mEq/L)
3.85 ±0.07
a
5.38 ±0.43
b
3.98 ± 0.08
a
S. Cr. (mg/dl)
0.63±0.016
a
0.96±0.2
ab
1.11± 0.17
b
S. Urea (mg/dl)
20 ±0.83
a
35± 6.8
a
40.83 ±6
b
*MC: Matricaria chamomilla. CLTD: Chlorthalidone.
Figure 3.12 Effect of M. chamomilla decoction (15%) and CLTD (5mg/kg) on serum sodium
concentration in hypertensive rats.
Discussion.
In this experimental animal model, normal and hypertensive rats were used in order to investigate the
effects of M. chamomilla and CTLD on the measured parameters for instance total urine volume,
urine and serum electrolytes concentration, and urinary potassium and sodium excretion rate.
In this study urine flow of normal rats significantly increased after receiving 15% M. chamomilla.
This increase in urine flow by this plant decoction could be linked to a number of possible
mechanisms, it might be because of inhibition of sodium reabsorption, hence urinary sodium
concentration and urinary excretion rate of sodium is increased significantly, however it is not
related to the inhibition of antidiuretic hormone 12, as urine Na+ concentration and excretion rate
were increased significantly. Therefore, it can be suggested that the diuretic effect of M. chamomilla
is saluretic type, which indicates that the plant decoction has inhibited sodium reabsorption from the
renal tubules
In this study, glomerular filtration rate of normal rats receiving M. chamomilla was significantly
increased. This effect could be related to blocking of adenosine (A1) receptor, like theophylline,
therefore it increases urine output through increasing GFR and blocking NaCl reabsorption in the
proximal tubule and collecting duct 13 14.
Moreover, this rise in GFR induced by M. chamomilla decoction could be related to active
substances which may dilate afferent renal arterioles as do many calcium channel antagonists for
example nifedipine, nicardipine, and verapamil 15, or constricting renal efferent arterioles, In the
The Second International Conference College of Medicine, HMU, 22nd - 24th November, 2017, Divan Hotel - Erbil - Kurdistan, Iraq
369
efferent arteriole, Ang II appears to stimulate Ca2+ entry via store-operated Ca2+ influx (Loutzenhiser
and Loutzenhiser, 2000), resulting in an increase in GFR (Hall, 2011).
In the present study, M. chamomilla decoction (15%) non significantly increased the percentage of
sodium reabsorption of filtered load of normal rats, because of increased sodium filtration as a result
of increased GFR.
Serum sodium concentration was not significantly changed as plasma concentration of Na+ should
remain constant due to effect of various hormones and enzymes, and because of osmotic properties
of plasma, as plasma osmolality is determined by plasma sodium 16.
In normal rats that administered M. chamomilla decoction urinary excretion rate of potassium was
non-significantly increased, due to the rise in urine flow, but their urinary potassium concentration
was non-significantly decreased. This indicates that M. chamomilla constituents increase sodium
excretion more than potassium. On the other hand, M. chamomilla decoction significantly increased
serum potassium concentration of normal rats, that it could cause hyperkalemia.
This diuretic activity of M. chamomilla is not attributed to blocking of aldosterone secretion because
this plant and unlike spironolactone 17, its diuretic activity was appeared after two hours. While the
aldosterone antagonist's diuretic effect usually appears after longer time, because they compete
aldosterone for mineralocorticoid receptor, which is an intracellular receptor of the nuclear receptor
family located in the kidneys, it modulates DNA transcription, causing synthesis of protein mediators
as the mechanism of gene transcription, thereby inhibiting distal Na+ retention and K+ secretion 18.
This increase in serum potassium indicates that the diuretic effect of M. chamomilla does not
resemble the action of the loop diuretic, such as furosemide, which acts in the thick ascending limb
of loop of Henle where it acts by inhibiting the Na+/K+/2Cl- co-transport carrier in the luminal
membrane, in which it increases the urine output followed by increased urinary excretion of
electrolytes, mainly Na+, K+, and Cl- (HL et al., 2015). Therefore, it can be suggested that the
diuretic activity of extract could be resemble the directly acting potassium-sparing diuretics such as
amiloride and triametrene (Tamargo et al., 2014), as they act on the late distal tubules and collecting
ducts, inhibiting Na+ reabsorption by blocking luminal sodium channels and decreasing K+ excretion
19. This could be related to high flavonoids content, that's similar to potassium sparing diuretics 20.
In the current study, blood urea and serum creatinine of normal rats administered chamomile
decoction were non-significantly decreased. Whereas urine creatinine concentration was significantly
increased. These indicate that M. chamomilla extract is safe in renal diseases and has beneficial
effects on kidney function (Schneider et al., 2016).
Studies that have done in last decades on plants to investigate their diuretic activity have
demonstrated that diuretic effect of the plants could be attributed to several compounds such as
The Second International Conference College of Medicine, HMU, 22nd - 24th November, 2017, Divan Hotel - Erbil - Kurdistan, Iraq
370
flavonoids, saponins or organic acids, 21. There is a relationship between the presence of these polar
secondary metabolites and their diuretic activity, which can produce diuresis they could have contact
with renal tissues 22.
There are several mechanisms that contribute to the hypertensive effect of dietary salt, including
water and salt retention, vascular abnormalities, and/or neurogenically mediated increases in
peripheral resistance 23. There are sequential steps by which salt intake influences arterial blood
pressure. They include an effect on plasma sodium concentration and extracellular fluid volume
(ECF). The greater rise in plasma sodium of sodium loaded rats, is due to a defect in the kidney's
ability to excrete salt and to regulate extracellular fluid volume 24.
In the current study, urine flow of hypertensive rats receiving 15% M. chamomilla decoction was
non-significantly increased. Which indicates that chamomile may have mild diuretic activity? In
hypertensive rats that received chlorthalidone, urine flow was significantly increased as a result of
increased water and sodium excretion rate, because it is a benzothiazide, which is a diuretic that
exerts its action by blocking the Na+ Cl- cotransporter in the luminal membrane of the distal
convoluted tubule leading to a modest natriuresis and diuresis respectively25. However, urinary
sodium concentration of hypertensive rats received M. chamomilla or chlorthalidone was non-
significantly decreased.
In this study, GFR of hypertensive rats that received M. chamomilla decoction or CLTD, was non-
significantly increased. Neither chamomile nor chlorthalidone had detectable effect on the
percentage of reabsorbed sodium of filtered load.
In this study hypertensive rats received CLTD or M. chamomilla decoction significantly decreased
serum sodium concentration. Because hyponatremia is seen within the first weeks of the start of
chlorthalidone treatment (Liamis et al., 2016), this effect is related to inhibition of sodium
reabsorption in the renal tubules.
In addition to hyponatremia, hypokalemia was seen in CLTD treated hypertensive rats, and this
thiazide-induced hypokalemia is related to the delivery of large amount of Na+ in the late distal
tubule and collecting duct and this promotes a transcellular exchange (transcellular shift) between K+
and Na+ as chlorothiazides inhibit sodium reabsorption only in distal tubules26.
In the current study, urinary creatinine concentration of hypertensive rats received M. chamomilla
decoction was significantly increased. However, their serum creatinine and serum urea have not been
changed significantly. This indicates that M. chamomilla is safe during renal disorders 27. Serum
creatinine and blood urea of hypertensive rats treated with chlorthalidone were slightly significantly
increased but it was within normal range.
The Second International Conference College of Medicine, HMU, 22nd - 24th November, 2017, Divan Hotel - Erbil - Kurdistan, Iraq
371
In this study unlike chlorthalidone, administration of M. chamomilla had no significant effect on
blood pressure of neither normal nor hypertensive rats. As it possesses a mild diuretic activity, and
could not counteract the hypertensive effects of sodium load. However, it significantly decreased HR
of hypertensive rats. This decrease in heart rate has no effects on blood pressure, as heart rate and
unlike to an increase in cardiac contractility, it has minimum effects on maintaining blood pressure13.
This negative chronotropic effect of chamomile could be attributed to the direct effect of some its
active constituents on SA node, like ivabradine which has been shown to have similar effects on HR
in other species including rabbits, rats, dogs, and human
Conclusion: Chamomile has mild diuretic activity in normal rats and its effects resemble that of
potassium sparing diuretics.
References
1. Shah S, Anjum S, Littler W. Use of diuretics in cardiovascular disease:(2) hypertension.
Postgraduate medical journal 2004; 80(943): 271-6.
2. Sica DA. Thiazide‐Type Diuretics: Ongoing Considerations on Mechanism of Action. The
Journal of Clinical Hypertension 2004; 6(11): 661-4.
3. Lahlou S, Tahraoui A, Israili Z, Lyoussi B. Diuretic activity of the aqueous extracts of Carum
carvi and Tanacetum vulgare in normal rats. Journal of Ethnopharmacology 2007; 110(3): 458-
63.
4. Dizaye K, Alberzingi B, Sulaiman S. Renal and vascular studies of aqueous extract of Urtica
dioica in rats and rabbits. Iraq J Vet Sci 2013; 27: 25-31.
5. Dutta KN, Chetia P, Lahkar S, Das S. Herbal plants used as diuretics: a comprehensive review. J
Pharm Chem Biol Sci 2014; 2(1): 27-32.
6. Aguilar MI, Benítez WV, Colín A, Bye R, Ríos-Gómez R, Calzada F. Evaluation of the diuretic
activity in two Mexican medicinal species: Selaginella nothohybrida and Selaginella
lepidophylla and its effects with ciclooxigenases inhibitors. Journal of ethnopharmacology
2015; 163: 167-72.
7. Singh O, Khanam Z, Misra N, Srivastava MK. Chamomile (Matricaria chamomilla L.): an
overview. Pharmacognosy reviews 2011; 5(9): 82.
8. Haghi G, Hatami A, Safaei A, Mehran M. Analysis of phenolic compounds in Matricaria
chamomilla and its extracts by UPLC-UV. Research in pharmaceutical sciences 2014; 9(1): 31.
9. Pirzad A, Alyari H, Shakiba M, Zehtab-Salmasi S, Mohammadi A. Essential oil content and
composition of German chamomile (Matricaria chamomilla L.) at different irrigation regimes.
Journal of Agronomy 2006; 5(3): 451-5.
10. Bhaskaran N, Srivastava JK, Shukla S, Gupta S. Chamomile Confers Protection against
Hydrogen Peroxide‐Induced Toxicity through Activation of Nrf2‐Mediated Defense Response.
Phytotherapy Research 2013; 27(1): 118-25.
11. Dai S-Y, Peng W, Zhang Y-P, Li J-D, Shen Y, Sun X-F. Brain endogenous angiotensin II
receptor type 2 (AT2-R) protects against DOCA/salt-induced hypertension in female rats.
Journal of neuroinflammation 2015; 12(1): 47.
The Second International Conference College of Medicine, HMU, 22nd - 24th November, 2017, Divan Hotel - Erbil - Kurdistan, Iraq
372
12. Sahay M, Sahay R. Hyponatremia: a practical approach. Indian journal of endocrinology and
metabolism 2014; 18(6): 760.
13. Hughes AD. How do thiazide and thiazide-like diuretics lower blood pressure? Journal of the
Renin-Angiotensin-Aldosterone System 2004; 5(4): 155-60.
14. Merrikhi A, Ghaemi S, Gheissari A, Shokrani M, Madihi Y, Mousavinasab F. Effects of
aminophyllinein preventing renal failure in premature neonates with asphyxia in Isfahan-Iran. J
Pak Med Assoc 2012; 62: S48-S51.
15. Hayashi K, Ozawa Y, Fujiwara K, Wakino S, Kumagai H, Saruta T. Role of actions of calcium
antagonists on efferent arterioleswith special references to glomerular hypertension. American
journal of nephrology 2003; 23(4): 229-44.
16. Frenkel WJ. Susceptibility to hyponatremia in the elderly: causes and consequences: Universiteit
van Amsterdam [Host]; 2014.
17. Shlomai G, Sella T, Sharabi Y, Leibowitz A, Grossman E. Serum potassium levels predict blood
pressure response to aldosterone antagonists in resistant hypertension. Hypertension Research
2014; 37(12): 1037-41.
18. Funder JW. Mineralocorticoid receptor antagonists: emerging roles in cardiovascular medicine.
Integrated blood pressure control 2013; 6: 129.
19. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high
blood pressure in adults: report from the panel members appointed to the Eighth Joint National
Committee (JNC 8). Jama 2014; 311(5): 507-20.
20. Jadhav N, Patil C, Chaudhari K, Wagh J, Surana S, Jadhav R. Diuretic and natriuretic activity of
two mistletoe species in rats. Pharmacognosy research 2010; 2(1): 50.
21. Viapiana A, Struck-Lewicka W, Konieczynski P, Wesolowski M, Kaliszan R. An approach
based on HPLC-fingerprint and chemometrics to quality consistency evaluation of Matricaria
chamomilla L. commercial samples. Frontiers in plant science 2016; 7.
22. Meléndez-Camargo ME, Contreras-León I, Silva-Torres R. Diuretic effect of alkaloids fraction
extracted from Selaginella lepidophylla (Hook. et Grev.) Spring. Boletín Latinoamericano y del
Caribe de Plantas Medicinales y Aromáticas 2014; 13(1).
23. Weinberger MH. Pathogenesis of salt sensitivity of blood pressure. Current hypertension reports
2006; 8(2): 166.
24. Meneton P, Jeunemaitre X, de Wardener HE, Macgregor GA. Links between dietary salt intake,
renal salt handling, blood pressure, and cardiovascular diseases. Physiological reviews 2005;
85(2): 679-715.
25. Woodman R, Brown C, Lockette W. Chlorthalidone decreases platelet aggregation and vascular
permeability and promotes angiogenesis. Hypertension 2010; 56(3): 463-70.
26. Liamis G, Mitrogianni Z, Liberopoulos EN, Tsimihodimos V, Elisaf M. Electrolyte disturbances
in patients with hyponatremia. Internal medicine 2007; 46(11): 685-90.
27. Dhalla IA, Gomes T, Yao Z, et al. Chlorthalidone Versus Hydrochlorothiazide for the Treatment
of Hypertension in Older AdultsA Population-Based Cohort Study. Annals of internal medicine
2013; 158(6): 447-55.
ResearchGate has not been able to resolve any citations for this publication.
Article
Full-text available
Chamomile has been used as an herbal medication since ancient times and is still popular because it contains various bioactive phytochemicals that could provide therapeutic effects. In this study, a simple and reliable HPLC method was developed to evaluate the quality consistency of nineteen chamomile samples through establishing a chromatographic fingerprint, quantification of phenolic compounds and determination of antioxidant activity. For fingerprint analysis, 12 peaks were selected as the common peaks to evaluate the similarities of commercial samples of chamomile obtained from different manufacturers. A similarity analysis was performed to assess the similarity/dissimilarity of chamomile samples where values varied from 0.868 to 0.990 what indicating that samples from different manufacturers were consistent. Additionally, simultaneous quantification of five phenolic acids (gallic, caffeic, syringic, p-coumaric, ferulic) and four flavonoids (rutin, myricetin, quercetin and keampferol) was performed to interpret the quality consistency. In quantitative analysis, the nine individual phenolic compounds showed good regression (r > 0.9975). Inter- and intra-day precisions for all analyzed compounds expressed as relative standard deviation (CV) ranged from 0.05% to 3.12%. Since flavonoids and other polyphenols are commonly recognized as natural antioxidants, the antioxidant activity of chamomile samples was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and ferric reducing/antioxidant power (FRAP) assay. Correlation analysis was used to assess the relationship between antioxidant activity and phenolic composition, and multivariate analysis (PCA and HCA) were applied to distinguish chamomile samples. Results shown in the study indicate high similarity of chamomile samples among them, widely spread in the market and commonly used by people as infusions or teas, as well as that there were no statistically significant differences among them, which in turn is a proof of high quality of commercially available samples of chamomile. The study indicated that the combination of chromatographic fingerprint and quantitative analysis can be readily utilized as a quality consistency method for chamomile and related medicinal preparations. Moreover, the applied strategy seems to be the most promising for the assessment of the investigated plant material.
Article
Full-text available
Recent studies demonstrate that there are sex differences in the expression of angiotensin receptor type 2 (AT2-R) in the kidney and that AT2-R plays an enhanced role in regulating blood pressure (BP) in females. Also, brain AT2-R activation has been reported to negatively modulate BP and sympathetic outflow. The present study investigated whether the central blockade of endogenous AT2-R augments deoxycorticosterone acetate (DOCA)/salt-induced hypertension in both male and female rats. All rats were subcutaneously infused with DOCA combined with 1% NaCl solution as the sole drinking fluid. BP and heart rate (HR) were recorded by telemetric transmitters. To determine the effect of central AT2-R on DOCA/salt-induced hypertension, male and female rats were intracerebroventricularly (icv) infused with AT2-R antagonist, PD123,319, during DOCA/salt treatment. Subsequently, the paraventricular nucleus (PVN) of the hypothalamus, a key cardiovascular regulatory region of the brain, was analyzed by quantitative real-time PCR and Western blot. DOCA/salt treatment elicited a greater increase in BP in male rats than that in females. Icv infusions of the AT2-R antagonist significantly augmented DOCA/salt pressor effects in females. However, this same treatment had no enhanced effect on DOCA/salt-induced increase in the BP in males. Real-time PCR and Western blot analysis of the female brain revealed that DOCA/salt treatment enhanced the mRNA and protein expression for both antihypertensive components including AT2-R, angiotensin-converting enzyme (ACE)-2, and interleukin (IL)-10 and hypertensive components including angiotensin receptor type 1 (AT1-R), ACE-1, tumor necrosis factor (TNF)-α, and IL-1β, but decreased mRNA expression of renin in the PVN. The central blockade of AT2-R reversed the changes in mRNA and protein expressions of ACE-2, IL-10, and renin, further increased the expressions of TNF-α and IL-1β, and kept higher the expressions of AT1-R, ACE-1, and AT2-R. These results indicate that endogenous AT2-R activation in the brain plays an important protective role in the development of DOCA/salt-induced hypertension in females, but not in males. The protective effect of AT2-R in females involves regulating the expression of brain renin-angiotensin system components and proinflammatory cytokines.
Article
Full-text available
Hyponatremia is an important and common clinical problem. The etiology is multifactorial. Hyponatremia may be euvolemic, hypovolemic or hypervolemic. Proper interpretation of the various laboratory tests helps to differentiate the various types of hyponatremia. Treatment varies with the nature of onset -acute or chronic, severity and symptoms. Normal saline forms the mainstay of treatment for hypovolemic hyponatremia while 3% NaCl and fluid restriction are important for euvolemic hyponatremia. Hypervolemic hyponatremia responds well to fluid restriction and diuretics. There have been several recent advances in the last year with revision in the guidelines for treatment and availability of vaptans. Judicious use of vaptans may help in treatment of hyponatremia.
Article
Full-text available
Spironolactone was first developed over 50 years ago as a potent mineralocorticoid receptor (MR) antagonist with undesirable side effects; it was followed a decade ago by eplerenone, which is less potent but much more MR-specific. From a marginal role as a potassium-sparing diuretic, spironolactone was shown to be an extraordinarily effective adjunctive agent in the treatment of progressive heart failure, as was eplerenone in subsequent heart failure trials. Neither acts as an aldosterone antagonist in the heart as the cardiac MR are occupied by cortisol, which becomes an aldosterone mimic in conditions of tissue damage. The accepted term "MR antagonist", (as opposed to "aldosterone antagonist" or, worse, "aldosterone blocker"), should be retained, despite the demonstration that they act not to deny agonist access but as inverse agonists. The prevalence of primary aldosteronism is now recognized as accounting for about 10% of hypertension, with recent evidence suggesting that this figure may be considerably higher: in over two thirds of cases of primary aldosteronism therapy including MR antagonists is standard of care. MR antagonists are safe and vasoprotective in uncomplicated essential hypertension, even in diabetics, and at low doses they also specifically lower blood pressure in patients with so-called resistant hypertension. Nowhere are more than 1% of patients with primary aldosteronism ever diagnosed and specifically treated. Given the higher risk profile in patients with primary aldosteronism than that of age, sex, and blood pressure matched essential hypertension, on public health grounds alone the guidelines for first-line treatment of all hypertension should mandate inclusion of a low-dose MR antagonist.
Article
The aerial parts of Selaginella lepidophylla (Hook. et Grev.) Spring, are used in Mexican folk medicine to treat renal diseases. The aim of this study was to measure the diuretic response of an aqueous extract (200 mg/kg) and alkaloids fraction at different doses (10, 40 y 100 mg/kg) of this plant and compare it with that induced by furosemide (4 mg/kg). Extract, alkaloids fraction, furosemide and vehicle were administered orally to adult rats and the effects in sodium, potassium and water balance were measured. The extract, the alkaloids fraction and the furosemide produced important and significant increments in urinary excretion of sodium, potassium and water with respect to control group. This increment was dose dependent of the alkaloids fraction, the highest dose produced a major effect. Potassium excretion increased but it was less than the one induced by furosemide. These results suggest that the aqueous extract and rich fraction in alkaloids from S. lepidophylla induce diuretic response.
Article
Chamomile (Matricaria chamomilla L.) is a widely used medicinal plant possessing several pharmacological effects due to presence of active compounds. This study describes a method of using ultra performance liquid chromatography (UPLC) coupled with photodiode array (PDA) detector for the separation of phenolic compounds in M. chamomilla and its crude extracts. Separation was conducted on C18 column (150 mm × 2 mm, 1.8 μm) using a gradient elution with a mobile phase consisting of acetonitrile and 4% aqueous acetic acid at 25°C. The method proposed was validated for determination of free and total apigenin and apigenin 7-glucoside contents as bioactive compounds in the extracts by testing sensitivity, linearity, precision and recovery. In general, UPLC produced significant improvements in method sensitivity, speed and resolution. Extraction was performed with methanol, 70% aqueous ethanol and water solvents. Total phenolic and total flavonoid contents ranged from 1.77 to 50.75 gram (g) of gallic acid equivalent (GAE)/100 g and 0.82 to 36.75 g quercetin equivalent (QE)/100 g in dry material, respectively. There was a considerable difference from 40 to 740 mg/100 g for apigenin and 210 to 1110 mg/100 g for apigenin 7-glucoside in dry material.
Article
The objective of this study was to identify factors associated with the blood pressure (BP) response to spironolactone-aldosterone receptor antagonist as an add-on therapy in patients with resistant hypertension (HTN). We retrospectively reviewed the data of subjects with resistant HTN who were treated with add-on spironolactone in a large HTN clinic. A paired Student's t-test was used to assess the differences between the BP values before and during spironolactone administration, and multivariate analysis was used to assess the predictors of a satisfactory BP response (a decrease in systolic BP >10%). We analyzed the data of 48 hypertensive participants. The add-on spironolactone therapy had a significant BP-lowering effect in both systolic and diastolic BP values (P<0.01 for both). Baseline serum potassium levels of <4.5 mEq l(-1) were associated with a satisfactory BP response (P<0.01). Furthermore, every decrement of 1 mEq l(-1) of serum potassium was independently associated with a fivefold higher rate of achieving a satisfactory BP response to spironolactone therapy (P=0.024). Additional factors independently associated with an improved systolic BP response were old age (P=0.033), body mass index (P=0.033) and high baseline systolic BP (P=0.004). Our results support the use of add-on spironolactone therapy in patients with resistant HTN who are elderly and obese and have high systolic BP and serum potassium levels <4.5 mEq l(-1).Hypertension Research advance online publication, 27 March 2014; doi:10.1038/hr.2014.77.