ArticlePDF Available

Abstract and Figures

Background: Rhus coriaria L. from the family Anacardiaceae is a medicinal plant traditionally used for the treatment of cardiovascular disorders. The recent study was designed to evaluate the effects of this medicinal plant in hypertensive patients. Material and Methods: A randomized, double-blind, placebo-controlled clinical trial was conducted on 80 hypertensive patients who received captopril 25 mg/day. The patients were randomly divided into 2 groups: the first group received R. coriaria capsules (500 mg twice a day) and captopril (25 mg once a day), and the second one received placebo capsules (500 mg starch twice a day) and captopril (25 mg once a day), for 8 weeks. Blood pressure (BP) and body weight index (BMI) in all patients were determined every week. Phytochemical analysis was performed by extracting phenolic compounds of R. coriaria fruits and analyzing by HPLC–DAD/QTOF-MS. Results: The most abundant phenolic compounds of R. coriaria were identified as luteolin, apigenin, and quercitin. Results showed that hypertension was decreased significantly in R. coriaria group compared to baseline and placebo group after 8 weeks, but BMI was not demonstrated marked change in comparison with baseline and placebo group. Conclusion: This finding suggests that R. coriaria could be used as effective natural remedy for management of hypertension. Since flavonoids are the main chemical constituents of this plant, its antihypertensive activity could be attributed to them.
Content may be subject to copyright.
Sumac as a novel adjunctive treatment in
hypertension: a randomized, double-blind,
placebo-controlled clinical trial
Hamidreza Ardalani,
*
a
Maryam Hassanpour Moghadam,
b
Roja Rahimi,
c
Jalal Soltani,
d
Azadeh Mozayanimonfared ,
e
Mehdi Moradi
e
and Ali Azizi
f
Background: Sumac (Rhus coriaria L., Anacardiaceae) is a medicinal plant traditionally used for the
treatment of cardiovascular disorders. This study was designed to evaluate the eects of Sumac fruits in
hypertensive patients. Material and Methods: a randomized, double-blind, placebo-controlled clinical
trial was conducted on 80 hypertensive patients who were receiving captopril (25 mg day
1
). The
patients were randomly divided into 2 groups: the rst group received R. coriaria fruit capsules (500 mg
twice a day) and captopril (25 mg once a day), and the second one received placebo capsules (500 mg
starch twice a day) and captopril (25 mg once a day), for 8 weeks. Blood pressure (BP) and body weight
index (BMI) in all patients were determined every week. Phytochemical analysis of R. coriaria fruits was
performed by using HPLC-DAD/QTOF-MS for analysing its phenolic compounds. Results: data indicated
that hypertension was decreased signicantly in R. coriaria group compared to baseline and placebo
groups after 8 weeks, but BMI did not demonstrate a marked change in comparison with baseline and
placebo groups. Moreover, the most abundant phenolic compounds identied in R. coriaria fruits were
luteolin, apigenin, and quercetin avonoids. Discussion: this nding suggests that R. coriaria fruits could
be used as an eective natural remedy for management of hypertension. Since avonoids were the main
chemical constituents of this plant, its antihypertensive activity could be attributed to such compounds.
Introduction
Hypertension (HTN: blood pressure above 140/90 mmHg) is one
of the most important medical problems worldwide.
1
It is the
most common, readily identiable and reversible risk factor for
stroke, myocardial infarction, congestive heart failure (CHF),
renal failure, atrial brillation, aortic dissection, and coronary
and peripheral arterial diseases.
2,3
The global burden of HTN is
increasing due to escalating obesity, population aging and
urbanization in developed and developing countries.
4
Preven-
tion and treatment of obesity, avoidance of high sodium chlo-
ride intake, appropriate amounts of aerobic physical activity,
adequate dietary and calcium intakes, limiting alcohol
consumption and avoiding cigarette smoking are appropriate
strategies to reduce cardiovascular disease risk, morbidity and
mortality due to HTN.
5
The sympathetic nervous system over-
activity
6
and increase in norepinephrine cause hypertrophy of
cardiac and vascular cells and stimulate renin release.
7
So,
renal, hormonal and vascular mechanisms are involved and
conspire in a myriad of ways to produce HTN. Over time,
endothelial dysfunction, neuro-hormonal activation, vascular
inammation and elevated blood pressure (BP) cause re-
modelling of both small and large arteries which further
perpetuates HTN. As a result, apart from life style modication,
most patients need multiple antihypertensive drugs of dierent
classes to overcome multiple mechanisms suspected to have
a role in inducing their HTN. Initiation of drug therapy is rec-
ommended for individuals with systolic BP above 140 mmHg or
diastolic BP more than 90 mmHg when re-measured at least
three times over at least four weeks. However, if the level of BP is
very high (>180/110 mmHg) or symptomatic end organ damage
is manifested at rst presentation; medication should be star-
ted before the denite diagnosis is established. The degree of
benet derived from antihypertensive agents is related to the
magnitude of the BP reduction.
8
Lowering systolic BP by 10
12 mmHg and diastolic BP by 56 mmHg confers relative risk
reductions of 3540% for stroke and 1216% for coronary heart
disease (CHD) within ve years of initiating treatment.
9
The
optimal goal of antihypertensive therapy in patients with
60 years old or older, who do not have diabetes or chronic
a
Department of Horticultural Sciences, Science and Research Branch, Islamic Azad
University, Tehran, Iran. E-mail: hrardalani@srbiau.ac.ir
b
Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical
Sciences, Mashhad, Iran
c
Department of Tradition al Pharmacy, School of Traditional Medicine, Tehran
University of Medical Sciences, Tehran, Iran
d
Department of Phytopathology, Bu-Ali Sina University, Hamedan, Iran
e
Department of Cardiology, Hamedan University of Medical Science, Hamedan, Iran
f
Department of Horticultural Sciences, Faculty of Agriculture, Bu-Ali Sina University,
Hamedan, Iran
Cite this: RSC Adv.,2016,6, 11507
Received 30th Octob er 2015
Accepted 5th January 2016
DOI: 10.1039/c5ra22840a
www.rsc.org/advances
This journal is © The Royal Society of Chemistry 2016 RSC Adv.,2016,6, 1150711512 | 11507
RSC Advances
PAPER
kidney disease, is <150/90 mmHg; and in patients with 18 to
59 years old without major comorbidities, is <140/90 mmHg.
10
Control is enhanced when access to health care is readily
available, frequent contact with the same physician is main-
tained, and physician performance is monitored.
11
The side
eects of antihypertensive drugs such as dizziness, dehydra-
tion, constipation and drowsiness have a pivotal role in
discontinuation of therapy.
12
In recent years, herbal remedies
such as saron, celery, hawthorn and garlic are used for
management of hypertension.
13
Rhus coriaria L., commonly
called tanner's Sumac is a member of Anacardiaceae family.
Benecial eects of Sumac on cardiovascular diseases are re-
ported.
14,15
However, clinical antihypertensive activity of R. cor-
iaria has not been investigated yet. The aim of the present work
was to investigate the ecacy of Sumac fruits in management of
hypertension, as well as analysing its chemical components.
Our results clarify the ecacy of this medicinal plant on clinical
BP. So, the results of this study introduce this plant as a prom-
ising herbal antihypertensive agent.
Results
Out of 95 patients, 80 patients [39 (48.75%) females and 41
(51.25%) male] accomplished this trial. The R. coriaria group,
included 21 (53.75%) men and 18 (46.25%) women with an
average age of 59.76 6.17 years old, and the placebo group
included 21 (51.25%) men and 20 (48.75%) women with an
average age of 57.52 7.43 years old. The baseline systolic
blood pressure/diastolic blood pressure (SBP/DBP) values in
R. coriaria and placebo groups were 145.34/90.95 mmHg and
143.64/90.51 mmHg, respectively; and the baseline BMI values
in R. coriaria and placebo groups were 30.83 kg m
2
and 31.13
kg m
2
, respectively. There were no signicant dierences
between demographic characteristics of the outpatients in these
two groups (P > 0.05) (Table 1).
At the end of week 8, the SBP/DBP values in R. coriaria and
placebo groups were 115.21/78.33 mmHg and 131.39/81.66
mmHg, respectively; and BMI values were 30.29 kg m
2
in
R. coriaria and 30.54 kg m
2
in placebo group. Also, it was
obvious that, R. coriaria decreased systolic (Fig. 1) and diastolic
BP (Fig. 2). These results showed a signicant decrease in BP
level in R. coriaria group as compared to the placebo group aer
8 weeks (P < 0.05) and no signicant decrease on BMI in two
groups aer 8 weeks (Fig. 3) (P > 0.05).
There was a signicant reduction in SBP and DBP aer 8
weeks of R. coriaria administration when compared with base-
line. However, such an eect was not observed in the placebo
group (P > 0.05) (Table 2).
Clinical complications were determined as any unwanted
eects that occurred from the time of informed consent until
one month aer the last treatment dose. No serious adverse
eects were reported or observed during this trial, except for the
R. coriaria group in which a patient reported drowsiness. Among
the patients who could not accomplish this study there were no
reports of any side eects, and most of them le due to missing
the follow up. In placebo group two patients reported insomnia
Table 1 Baseline characteristics of the outpatients
a
Placebo R. coriaria P-value
Sex Female 21 21 0.46
Male 20 18
Age 57.52 7.43 59.76 6.17 0.33
Weigh 80.61 9.69 81.55 7.40 0.82
BMI 31.13 1.95 30.83 2.21 0.42
SBP 143.64 1.79 145.34 2.08 0.92
DBP 90.51 1.81 90.95 1.97 0.93
a
BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic
blood pressure. Dierences between groups were analysed by ANOVA
followed by Tukey's honestly signicant dierence test. Values are
expressed as mean SD.
Fig. 1 Decrease in (SBP) Systolic Blood Pressure in response to Sumac
in comparison with placebo. Statistical analyses showed a signicant
dierence between Sumac and placebo group and baseline (P < 0.05).
Fig. 2 Decrease in Diastolic Blood Pressure (DBP) in response to
Sumac in comparison with placebo. Statistical analyses showed
a signicant dierence between Sumac and placebo group and
baseline (P < 0.05).
11508
| RSC Adv.,2016,6, 1150711512 This journal is © The Royal Society of Chemistry 2016
RSC Advances Paper
and headache. All groups were well matched, and no statisti-
cally signicant dierences were observed among groups on the
frequency of side eects (Table 3).
In this study the ecacy and tolerability of R. coriaria fruit
extracts combined with captopril in improving BP and
decreasing BMI was investigated. The results showed that
R. coriaria signicantly decreased BP in hypertensive patients
compared to the baseline and group received only captopril
aer 8 weeks (Table 4). Therefore, R. coriaria may serve as an
eective complementary therapy along with conventional anti-
hypertensive agents for reducing hypertension.
According to HPLC-DAD/QTOF-MS analyses, 191
compounds in R. coriaria along with their retention times (t
R
),
mass of each phytochemical, as well as the MS/MS fragment
ions used in the characterization process were identied. The
HPLC analyses showed that apigenin, luteolin and quercetin
were the most abundant compounds in R. coriaria fruits (Fig. 4,
Table 5).
Discussion
In many hypertensive patients, keeping BP in an optimal range
is dicult and prescribing several drugs from dierent phar-
macological classes of antihypertensive agents with high dosage
is frequently needed. Increasing the number and dosage of
drugs in 24 hours enhances the possibility of developing
medical side eects but reduces patient's compliances. As
a result, discontinuation of treatment is not far-fetched.
Currently, introduction of some adjunctive therapies, such as
herbal drugs and exercise, seems reasonable. Furthermore,
optimizing the modiable cardiovascular risk factors (i.e. high
BMI and low physical activity) is important and should be taken
into account.
The results from phytochemical analysis demonstrated that
the most abundant constituents of R. coriaria were polyphenolic
compounds including hydrolysable tannins, avonoids and
Fig. 3 Body Mass Index (BMI) in response to Sumac in comparison
with placebo group. Statistical analyses showed no signicant dier-
ence between Sumac and placebo group, as well as baseline (P < 0.05).
Table 2 BMI, SBP and DBP reduction obtained with the R. coriaria
compared with placebo in patients during 8 weeks
a
Placebo R. coriaria P-value
BMI 0.59 2.45 0.54 3.12 0.71
SBP 12.25 6.12 30.13 4.45* 0.03
DBP 8.85 3.54 12.62 3.81* 0.04
a
BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic
blood pressure. Values are expressed as mean SD. *P < 0.05, when
compared between groups.
Table 3 Frequency of reported adverse eects among the three study
groups
a
R. coriaria group Placebo group P-value
Weakness 1 0 1.61
Drowsiness 0 0 1.00
Insomnia 0 1 1.83
Headache 0 1 1.00
a
The Fisher's exact test was applied for analysis of side eects in both
groups.
Table 4 Characteristics of randomized subjects before and after 8
weeks
a
Variable Placebo R. coriaria P-value
BMI (kg m
2
)
Week 0 31.13 1.95 30.83 1.84 0.31
Week 8 30.54 1.14 30.29 1.48
SBP (mmHg)
Week 0 143.64 1.79 145.34 2.08 0.03
Week 8 131.39 2.75 115.21 2.89*
DBP (mmHg)
Week 0 90.51 1.81 90.95 1.97 0.04
Week 8 81.66 1.81 78.33 1.97*
a
BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic
blood pressure. Values are expressed as mean SD. *P < 0.05, when
compared with baseline data.
Fig. 4 HPLC analyses and base peak chromatograms (BPC) of UV at
280 nm, for the hydro-methanol extract of R. coriaria fruits.
This journal is © The Royal Society of Chemistry 2016 RSC Adv.,2016,6,1150711512 | 11509
Paper RSC Advances
anthocyanins. This analysis is almost in accordance with our
previous analysis on a sample of R. coriaria collected from
dierent place. However a new compound, benzoic acid, 3,4,5-
trihydroxy-2-oxo-1,3-propanediyl ester, was identied in the
present study. Other investigations have indicated that Sumac
is highly rich in cyanidin and galloyl-galactose and anthocyanin
derivatives.
16,17
A number of studies have shown that avonoids
such as quercetin can play important roles in decreasing BP.
18,19
The potential of quercetin as an eective vasodilator has been
indicated.
20
In addition, reductions in systolic, diastolic and
mean arterial pressures were observed in stage 1 hypertensive
patients aer a high dose quercetin treatment in a randomized,
double-blind, placebo-controlled, crossover study.
21
Apigenin,
another avonoid in R. coriaria, showed antihypertensive
activity in spontaneously hypertensive rats via up-regulating the
expression of angiotensin-converting enzyme 2 in kidney.
22
Renin is a crucial enzyme in the reninangiotensin system, and
its inhibition is considered as a useful approach to the treat-
ment of hypertension. Gallic acid as another main phenolic
compound of R. coriaria has exhibited inhibitory eect on renin.
It seems that galloyl moiety and ortho-trihydroxy phenyl struc-
tures are favorable for the renin-inhibitory activity.
23
Oxidative stress, due to the accumulation of free radicals,
may play an important role in pathogenesis of cardiovascular
diseases like hypertension.
24
Oxidative stress stimulates the
proliferation and hypertrophy of vascular smooth muscle and
collagen deposition which lead to narrowing of the vascular
lumen caused by thickening of the vascular media.
25
Also,
increased oxidative stress can damage the endothelium and
increase vascular contractile activity.
26
All these eects can
explain how oxidative stress can be a cause of hypertension. So,
treatment with antioxidant components is suggested for
improving BP.
27
As mentioned the R. coriaria is highly rich in
antioxidative phenolic components, such as tannins and
avonoids.
28
Thus, adjunctive therapy with R. coriaria can
provide further protection as it contains powerful antioxidants
and plays an important role in preventing free radical-induced
damage in vessels endothelium.
29
The eect of avonoid intake on body weight and BMI is
already investigated.
30
Indeed, benecial antioxidant eects can
modulate BMI.
31
Also it is observed that a source of avonoid
(green tea) can reduce body weight and body fat in overweight
individuals.
32
Additionally, animal studies have shown an anti-
obesity eect for avonoids, through mechanisms such as fatty
acid catabolism or intervention on glucose uptake.
33
However in
our study R. coriaria as a reach source of avonoids could not
decrease BMI in patients aer 8 weeks of administration.
Adverse eects such as vertigo, ashing, insomnia and head-
ache have been reported previously in administration of anti-
hypertensive drugs.
34
Our ndings indicated that R. coriaria did
not have serious side eects in administered dose, although
more investigations are needed. Moreover, long term studies
with larger sample size is recommended for better under-
standing of the R. coriaria eects on BP and BMI is being
recommended.
Experimental
Plant material
Sumac (R. coriaria L.) fruits with voucher specimen no. 21121
were obtained from the Shahid Beheshti University of Medical
Sciences, Teharn, Iran (identied by Prof. Dr Valiollah Moza-
farian). The samples were transferred to the lab, dried at 70
C
for 24 hours and stored at 5
C until used.
Study design
A randomized, parallel-group, double-blind, and placebo-
controlled clinical trial was conducted on 80 hypertensive
patients in the Arad Hospital, Tehran, Iran, from September to
Table 5 Chemical compositions detected and characterised in R. coriaria fruits by HPLC-DAD/QTOF-MS
Peak Tentative assignment t
R
(min) [M + H] + (m/z)[M H] (m/z) Error (ppm) mSigma Molecular formula
1 Galloylhexose II 9.10 331.0669 0.6 14.9 C
13
H
16
O
10
2 Digalloyl-hexoside II 11.91 483.0773 1.3 1.8 C
20
H
20
O
14
3 Tri-galloyl-hexoside III 19.07 637.1100 635.0882 1.2 2.1 C
27
H
24
O
18
4 Benzoic acid, 3,4,5-trihydroxy-2-oxo-1,3-
propanediyl-ester
25.15 393.0449 3.7 46.8 C
17
H
14
O
11
5 Dihydroxybenzoic acetate-digallate I 28.14 544.9894 5.2 43.9 C
24
H
18
O
15
6 Dihydroxybenzoic acetate-digallate III 29.60 546.0121 3 37.5 C
24
H
18
O
15
7 Apigenin glucuronide 29.89 445.0245 446.0312 1.2 143.2 C
21
H
20
O
11
8 Galloyl-valoneic acid bilactone 31.10 623.1457 621.0412 2.2 26.7 C
22
H
22
O
21
9 Quercetin-rhamnose malic acid I 31.18 564.8637 563.1127 3.7 4.1 C
25
H
24
O
15
10 Quercetin I 32.14 302.0119 2.8 13.0 C
15
H
10
O
7
11 Quercetin-hexose malic acid IV 32.18 581.1312 1.0 46.1 C
25
H
24
O
16
12 Isorhamnetin hexose malic acid 33.57 594.9197 12.6 49.2 C
26
H
26
O
16
13 Kaempferol rhamnosemalic acid 33.81 548.1168 6.0 31.5 C
25
H
24
O
14
14 Quercitrin-O-gallate 34.75 599.1019 5.1 26.1 C
28
H
24
O
15
15 Isorhamnetin hexoside IV 34.80 477.1021 5.4 14.5 C
22
H
22
O
12
16 Di-benzopyranofuranacetic acid deriv. 35.30 515.0526 7.0 50.9 C
23
H
16
O
14
17 Luteolin 36.32 286.8776 285.0348 5.4 6.9 C
15
H
10
O
6
18 Quercetin II 36.58 303.0486 301.2481 0.5 2.4 C
15
H
10
O
7
11510 | RSC Adv.,2016,6,1150711512 This journal is © The Royal Society of Chemistry 2016
RSC Advances Paper
January 2014 with code of ethics no. 93776 (approval date: 2014
August). During 8 weeks aer, 80 patients (aged from 30 to
65 years old) with uncontrolled HTN stages [stage 1 (SBP: 140
159 and DBP: 9099 mmHg), stage 2 (SBP: 160179 and DBP:
100109 mmHg) or stage 3 (SBP: 180 and DBP: 110) that in their
medical history during the last 6 months, were receiving just
captopril as an antihypertensive therapy were enrolled in our
study. This study was done in accordance with the Declaration
of Helsinki. Patients who had SBP more than 180 mmHg at the
time of selection, documented secondary HTN, congestive heart
failure, moderate to severe valvular heart disease, recent history
of myocardial infarction (MI # 6 months), chronic renal failure,
as well as alcohol consumers and pregnant patients were
excluded. Informed consent was obtained from all participants
before the study began. All patients were assessed weekly for
8 weeks, and data were recorded at baseline and aer every
week. Parameters collected at baseline were BP, age, sex, weight,
height and marital status.
Interventions
All participants were divided randomly in two groups. Each
group contained 40 patients. In the Sumac group, patients
received captopril (25 mg day
1
once a day, before breakfast)
plus R. coriaria powder capsules [1000 mg day
1
: 500 mg BID
(twice a day), one capsule before lunch and one before dinner]
and patients in the placebo group received captopril (25
mg day
1
once a day, before breakfast) plus placebo capsules
(1000 mg day
1
starch: 500 mg BID, one capsule before lunch
and one before dinner) as an adjunctive therapy for 8 weeks.
R. coriaria and placebo capsules were prepared in the same way.
They were similar in shape, color, size and order. All capsules
were prepared by a pharmacist and packed in the same
container with a code number. Thus, participants and investi-
gators were all blind to the treatment group assignments.
Participants were not permitted to receive any other antihy-
pertensive drugs during the study time. All patients were
checked regularly and their compliance and medication
adherence were estimated through checking with the patient
and his/her care taker along with a pill count at each visit.
Measurement of BP
Standard BP was assessed by trained research nurses with
a random-zero sphygmomanometer in accordance with Amer-
ican Heart Association protocols.
35
Due to measurement bias at
each visit, controlling of BP was performed with the same nurse
and sphygmomanometer and from. Before assessing BP, the
patients were asked to seat comfortably with the le arm sup-
ported and positioned at the level of the heart and the back
resting against a chair. The measurement time was under the
morning fasting condition (12 2haer the last drug inges-
tion). The patients rested at least ve minutes and avoided
caeine or smoke within 30 minutes preceding the measure-
ment. The cu size (12 22 for small-size adults, 16 30 for
medium-size adults and 16 42 for large-size adults) was
encircled the le arm which lowered edge of its position in
2.5 cm above the antecubital space. Inated the bladder quickly
to a pressure 20 mmHg above SBP, was recognized by the
disappearance of radial pulse and then deated it 3 mmHg s
1
.
BP was recorded the Korotko phase 1 (appearance) and phase
5 (disappearance) as SBP and DBP, respectively. On each occa-
sion, at least three measurements were applied, separated by
10 minute intervals. If data showed variations of more than
5 mmHg, an additional measurement was applied until two of
them were close and the highest BP was recorded.
Ascertainment of BMI
BMI (body mass index) is a person's weight in kilograms divided
by the square of height in meters. BMI was calculated in the
baseline and in the last follow up session by the same trained
nurses.
Statistical analyses
All data were expressed as mean SD. The characteristics of
groups at baseline were compared by one-way analyses of vari-
ance (ANOVA). The changes in BP and BMI were analysed using
one-way repeated measures ANOVA and Tukey's post hoc and
their comparison with the baseline data. A P-value <0.05 was
considered to be statistically signicant. Statistical analyses
were performed using SPSS soware version 17.0 (SPSS Inc.,
Chicago, IL, USA).
Plant extraction and HPLC analyses
Extraction of phenolic compounds were done according to Abu-
Reidah et al.
36
Briey, one gram of R. coriaria dried fruit was
mixed with 16 mL of methanol/H
2
O (80 : 20, v/v) and sonicated
for 60 min. Then, the solvent was evaporated under vacuum at
40
C and the dry remnant was resolved in 0.5 mL of methanol/
H
2
O (80 : 20, v/v). The extract was centrifuged and the super-
natant was ltered through a in syringe lter (d ¼ 0.2 mm) and
stored at 15
C. Chromatographic analysis of extracts was
carried out by an Agilent 1200 series Rapid Resolution Machine
through an Agilent Zorbax C18 column (4.6150 mm, 5 mm).
Acetic acid 0.5% v/v and acetonitrile were used as mobile phases
A and B, respectively. The gradient program was set as follow:
0 min, 0% B; 20 min, 20% B; 30 min, 30% B; 40 min, 50% B;
50 min, 75% B; 60 min, 100% B; 62 min 0% B. Ultimately, the
initial conditions were held for 10 min for re-equilibration. The
injection volume and column temperature were 10 mL and
25
C, respectively. The HPLC system was coupled to a quadru-
pole time of ight (Bruker Daltonik GmbH, Bremen, Germany)
orthogonal accelerated Q-TOF mass spectrometer, tted out
with an electrospray ionization source (ESI). Analyses of
parameters were set by negative and positive ion modes, with
spectra obtained over a mass range from m/z 50 to 1100.
Conclusions
In this study, administration of R. coriaria fruit capsules [1000
(2 500) mg day
1
] augmented the eects of antihypertensive
drugs in hypertensive's patients. Without causing any consid-
erable side eect, R. coriaria was shown to be an eective
therapeutic adjuvant. Moreover, the eects of Sumac could be
This journal is © The Royal Society of Chemistry 2016 RSC Adv.,2016,6, 1150711512 | 11511
Paper RSC Advances
attributed to avonoids as the dominant constituents in this
plant. However, further research is required to clarify the
mechanisms behind these observations.
Acknowledgements
The authors gratefully acknowledge the Vice Chancellor of
Research, Tehran University of Medical Sciences for nancial
supports (grant number no. 93776).
References
1 A. Iyer, V. Chan and L. Brown, Curr. Cardiol. Rev., 2010, 6,
291.
2 J. R. Sowers, M. Epstein and E. D. Frohlich, Hypertension,
2001, 37, 10531059.
3 P. K. Gupta, H. Gupta and A. Khoynezhad, Pharmaceuticals,
2009, 2,6676.
4 M. M. Ibrahim and A. Damasceno, Lancet, 2012, 380, 611
619.
5 S. Zhang, Z. Ding, H. Liu, Z. Chen, J. Wu, Y. Zhang and Y. Yu,
Obstet. Gynecol. Surv., 2013, 68, 825834.
6 R. G. Victor and M. M. Shaq, Curr. Hypertens. Rep., 2008, 10,
241247.
7 P. G. Guyenet, Nat. Rev. Neurosci., 2006, 7, 335346.
8 E. L. Schirin, Am. J. Hypertens., 2004, 17, 11921200.
9 A. E. Lammers, Heart, 2014, 100, 13051307.
10 M. Page, Am. J. Manag. Care, 2014, 20,56.
11 D. A. Huetteman and H. Bogie, in Cardiovascular Genomics,
Springer, 2009, pp. 5773.
12 G. Cio, G. F. Mureddu and C. Stefenelli, Exp. Clin. Cardiol.,
2006, 11, 305.
13 M. Imenshahidi, H. Hosseinzadeh and Y. Javadpour,
Phytother. Res., 2010, 24, 990994.
14 G. Beretta, G. Rossoni, N. A. Santagati and R. M. Facino,
Planta Med., 2009, 75
, 14821488.
15 H. Zargham and R. Zargham, Mcgill J. Med., 2008, 11, 119.
16 I. M. Abu-Reidah, R. M. Jamous and M. S. Ali-Shtayeh, Jordan
J. Biol. Sci., 2014, 7, 233244.
17 F. V. Romeo, G. Ballistreri, S. Fabroni, S. Pangallo,
M. G. L. D. Nicosia, L. Schena and P. Rapisarda, Molecules,
2015, 20, 1194111958.
18 J. Moline, I. Bukharovich, M. Wol and R. Phillips, Med.
Hypotheses, 2000, 55, 306309.
19 P. Knekt, J. Kumpulainen, R. J
¨
arvinen, H. Rissanen,
M. Heli
¨
ovaara, A. Reunanen, T. Hakulinen and A. Aromaa,
Am. J. Clin. Nutr., 2002, 76, 560568.
20 F. Perez-Vizcaino, J. Duarte, R. Jimenez, C. Santos-Buelga
and A. Osuna, Pharmacol. Rep., 2009, 61,6775.
21 R. L. Edwards, T. Lyon, S. E. Litwin, A. Rabovsky,
J. D. Symons and T. Jalili, J. Nutr. , 2007, 137, 24052411.
22 H. Sui, Q. Yu, Y. Zhi, G. Geng, H. Liu and H. Xu, Weisheng
Yanjiu, 2010, 39, 693696, 700.
23 F. Li, Y. Takahashi and K. Yamaki, Biomed. Res., 2013, 34,
167171.
24 A. M. Briones and R. M. Touyz, Curr. Hypertens. Rep., 2010,
12, 135142.
25 N. R. Madamanchi, A. Vendrov and M. S. Runge, Arterioscler.,
Thromb., Vasc. Biol., 2005, 25,2938.
26 U. F
¨
orstermann, Puegers Arch., 2010,
459, 923939.
27 L. G. Ranilla, Y.-I. Kwon, E. Apostolidis and K. Shetty,
Bioresour. Technol., 2010, 101, 46764689.
28 M. Kosar, B. Bozan, F. Temelli and K. Baser, Food Chem.,
2007, 103, 952959.
29 A. Tyagi and N. Delanty, Epilepsia, 2003, 44, 228235.
30 S. Egert, A. Bosy-Westphal, J. Seiberl, C. K
¨
urbitz, U. Settler,
S. Plachta-Danielzik, A. E. Wagner, J. Frank,
J. Schrezenmeir and G. Rimbach, Br. J. Nutr., 2009, 102 ,
10651074.
31 C. Razquin, J. Martinez, M. Martinez-Gonzalez, M. Mitjavila,
R. Estruch and A. Marti, Eur. J. Clin. Nutr., 2009, 63, 1387
1393.
32 M. P. Nantz, C. A. Rowe, J. F. Bukowski and S. S. Percival,
Nutrition, 2009, 25, 147154.
33 M. A. McAdams, R. M. Dam and F. B. Hu, Obesity, 2007, 15,
188.
34 E. Escobar, J. Hum. Hypertens., 2002, 16, S61S63.
35 A. V. Chobanian, G. L. Bakris, H. R. Black, W. C. Cushman,
L. A. Green, J. L. Izzo, D. W. Jones, B. J. Materson, S. Oparil
and J. T. Wright, Hypertension, 2003, 42, 12061252.
36 I. M. Abu-Reidah, M. S. Ali-Shtayeh, R. M. Jamous, D. Arr
´
aez-
Rom
´
an and A. Segura-Carretero, Food Chem., 2015, 166, 179
191.
11512 | RSC Adv.,2016,6,1150711512 This journal is © The Royal Society of Chemistry 2016
RSC Advances Paper
... [32,44,45,67] while another clinical study concluded that RC was not able to change the BMI. [33] On the subject of hyperglycaemia, there are several animal studies that show the hypoglycaemic effect of RC, however, the study of Khayatnouri et al. surprisingly showed a significant increase in blood sugar after administration of RC in rats. [47] Giancarlo et al. demonstrated that the hypoglycaemic effect of RC is exerted through inhibition of α-amylase which is the main enzyme responsible for the breakdown of starch to more simple sugars (glucose, maltose and maltotriose). ...
... In the case of hypertension, RC (1 g/day) in combination with captopril was shown to be more effective than the placebo, [33] but there are not enough clinical studies to make an accurate decision. ...
Article
Objectives Rhus coriaria L. (RC) is a deciduous shrub with several pharmacological activities. Evidence of the effects of RC on weight, hyperlipidaemia, hypertension and diabetes mellitus have been presented in this study. Books, thesis and internet-based resources such as PubMed, Web of Science, Scopus, EMBASE, Cochrane, Ovid and Google Scholar were searched for the English, Arabic and Persian literature from 1966 to 2020 (December). The keywords were Rhus coriaria L., Sumac, metabolic syndrome and all its medical conditions (hyperlipidaemia, hypertension, obesity and diabetes mellitus). The inclusion criteria were full-text animal and human studies conducted on RC to evaluate its efficacy on any components of metabolic syndrome (MetS). Jadad scale was used to assess the quality of evidence. Key findings Reviewing 23 relevant studies demonstrated that RC is able to decrease the level of blood glucose, glycated haemoglobin, serum insulin and insulin resistance. Studies on hyperlipidaemia and obesity have very contradicting results, and there is no definite conclusion on the effect of RC on lipid profile. However, the hypotensive and effect of RC was confirmed in the existing studies. Summary According to the literature, RC can be considered as a promising curative candidate for MetS. However, further studies with larger sample size and higher methodological quality are needed.
... In addition, animal studies have shown an antiobesity effect for flavonoids through mechanisms such as fatty acid catabolism or intervention in glucose uptake (17). However, in contrast to our study, Ardalani et al. found that sumac as a rich source of flavonoids could not decrease BMI in patients over 8 weeks of administration (32). ...
... In addition, animal studies have shown an antiobesity effect for flavonoids through mechanisms such as fatty acid catabolism or intervention in glucose uptake (17). However, in contrast to our study, Ardalani et al. found that sumac as a rich source of flavonoids could not decrease BMI in patients over 8 weeks of administration (32). ...
... , is a plant belonging to the family Apocynaceae is widely cultivated in varied latitudes of the world and is the common line tree, known as a black creeper in English [13] . The literature study shows that Ichnocarpus frutescens L. roots have been used as diaphoretic, diuretic, demulcent, stimulant, dyspepsia, gall stones,tonic and diabetes. ...
Article
Full-text available
Objective: The present study aims to prepare novel polyherbal formulations in a unique and accessible tea bag form and also analyses the antidiabetic potentials in vitro. Material and method: The formulation was made from Ichnocarpus frutescens(IC), Ficus dalhousiae (FD), Creteva magna (CM), Alpinia galanga (AG) and Swertia chirata (SC) herbs and used in this study. Indian medicinal plants i.e., polyherbal were subjected to progressive phytochemical analysis and tests were carried out for the determination of α-amylase inhibition activity. The Phytochemical analysis revealed the presence of Alkaloids, Tannins, Anthraquinone, Flavonoids, Saponin and reducing sugar, as the active compounds. The tea infusions of the aforementioned plants were prepared in different formulations like F1, F2, F3, and F4. The formulations were tested for antidiabetic activity in vitro through the inhibition of alpha-glycosidase. Results: The F3 (91.6%) and F4 (92.7%) showed the higher inhibition data against porcine pancreatic α-amylase among the Four formulations. The minimum % alpha-amylase inhibition was recorded in F2 (90.4%) among the medicinal active plants studied. Conclusion: Hyperglycaemia level is reduced via a controllable condition of starch breakdown through pancreatic α-amylase inhibitors. Best results were obtained by the infusion containing The F2 formulation which showed significant antidiabetic activity. © 2022 iGlobal Research and Publishing Foundation. All rights reserved.
... , is a plant belonging to the family Apocynaceae is widely cultivated in varied latitudes of the world and is the common line tree, known as a black creeper in English [13] . The literature study shows that Ichnocarpus frutescens L. roots have been used as diaphoretic, diuretic, demulcent, stimulant, dyspepsia, gall stones,tonic and diabetes. ...
... Alternatively, natural medical products are frequently used as adjunctive therapy to improve long-term outcomes in patients with arterial hypertension and to reduce the number of antihypertensive drugs that are taken. Thus, it may potentially exclude the side effects concerned with combination therapy use [5]. ...
Article
Full-text available
Spirulina is a microalga that presents various important pro-health properties, for instance lowering blood pressure in the research. The study aims to appraise the efficacy of Spirulina administration on systolic (SBP) and diastolic blood pressure (DBP). Randomized controlled trials (RCTs) were retrieved by a systematic search of PubMed, Web of Science, and the Cochrane Library databases from inception to June 2021 according to a standardized protocol. The effect size of each study was counted from mean and standard deviation before and after the intervention and shown as Un-standardized mean difference and 95% confidence interval. Sensitivity analyses were performed. Meta-analysis on 5 RCTs with 230 subjects was eligible. The amount of Spirulina ranged from 1 to 8 g per day, and intervention durations ranged from 2 to 12 weeks. Data analysis indicated that Spirulina supplementation led to a significant lowering of SBP (Mean Difference (MD): −4.59 mmHg, 95% Confidence Interval (CI): −8.20 to −0.99, I square statistic (I2) = 65%) and significant lowering of DBP (MD: −7.02 mmHg, CI: −8.86 to −5.18, I2 = 11%), particularly in a subgroup of hypertensive patients. Spirulina administration might have a supportive effect on the prevention and treatment of hypertension. More exact randomized controlled trials are needed to clarify the effect of Spirulina supplementation on blood pressure.
Article
Introduction Sumac has been shown to have a positive impact on lipid profile and hepatic function in some studies. The present study aimed to investigate the effect of sumac consumption on metabolic disorder related to non-alcoholic fatty liver disease (NAFLD) in Iran. It can suggest a therapeutic strategy to reduce the complications of this disease. Methods According to study inclusion and exclusion criteria 80 patients with NAFLD were selected. They were stratified according to sex, and age, and randomly allocated into two groups each comprised of 40 patients. One group received sumac powder (2 g) and another received placebo (dextrin) for 12 weeks. Blood pressure, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), lipid profile, leptin and steatosis status were assessed at baseline and end of the study. Results The administration of sumac powder decreased the systolic blood pressure (SBP) (p=0.02), but diastolic blood pressure (DBP) did not change (p=0.14). Also, AST, ALT, ALP, total cholesterol, LDL-C and triglyceride (TG) were decreased but HDL-C was increased in the sumac group compared to the placebo group (p<0.001). We did not find any change in GGT (p= 0.7) and Leptin between two groups (p=0.48). The status of steatosis was improved in the sumac group compared to placebo (p<0.001). Conclusion Our clinical trial study suggests that sumac powder may be a suitable choice for reducing blood pressure, serum liver enzymes and steatosis in individuals with NAFLD. Also, it can improve lipid profile. Additional studies with a longitudinal design are required to confirm our findings.
Article
Full-text available
Traditional medicine is a comprehensive term for ancient, culture-bound health care practices that existed before the use of science in health matters and has been used for centuries. Medicinal plants are used to treat patients with cardiovascular diseases, which may occur due to ailments of the heart and blood vessels and comprise heart attacks, cerebrovascular diseases, hypertension, and heart failure. Hypertension causes difficulty in the functioning of the heart and is involved in atherosclerosis, raising the risk of heart attack and stroke. Many drugs are available for managing these diseases, though common antihypertensive drugs are generally accompanied by many side effects. Medicinal herbs have several active substances with pharmacological and prophylactic properties that can be used in the treatment of hypertension. This review presents an overview of some medicinal plants that have been shown to have hypotensive or antihypertensive properties.
Article
Full-text available
Pomegranate (Punica granatum L.) peel and sumac (Rhus coriaria L.) fruit and leaf extracts were chemically characterized and their ability to inhibit table grape (cv. Italia) rots caused by Botrytis cinerea was evaluated on artificially inoculated berries. Different extraction methods were applied and extracts were characterized through Ultra Fast High Performance Liquid Chromatography coupled to Photodiode array detector and Electrospray ionization Mass spectrometer (UPLC-PDA-ESI/MS n) for their phenol and anthocyanin contents. The concentrated pomegranate peel extract (PGE-C) was the richest in phenols (66.97 g gallic acid equivalents/kg) while the concentrated sumac extract from fruits (SUF-C) showed the highest anthocyanin amount (171.96 mg cyanidin 3-glucoside equivalents/kg). Both phenolic and anthocyanin profile of pomegranate and sumac extracts were quite different: pomegranate extract was rich in cyanidin 3-glucoside, pelargonidin 3-glucoside and ellagic acid derivatives, while sumac extract was characterized by 7-methyl-cyanidin 3-galactoside and gallic acid derivatives. The concentrated extracts from both pomegranate peel and sumac leaves significantly reduced the development of Botrytis rots. In particular, the extract from 11942 pomegranate peel completely inhibited the pathogen at different intervals of time (0, 12, and 24 h) between treatment and pathogen inoculation on fruits maintained at 22–24 °C and high relative humidity (RH). This extract may represent a valuable alternative to control postharvest fungal rots in view of its high efficacy because of the low cost of pomegranate peel, which is a waste product of processing factories.
Article
Full-text available
Rhus coriaria L. (Sumac), belonging to the Anacardiaceae family, is an important and most used species of the genus Rhus in the Mediterranean region since antiquity. Sumac has long been used as a flavoring spice, drink, appetizer, and as acidulant in food recipes; in addition to its use in traditional medicine. The role of plant in leather and textile industry is also significant. R. coriaria is very rich in phenolics mainly, tannins and flavonoids, in addition to its abundance in organic acids. The leaves and fruits of R. coriaria are recognized to have defensive and beneficial effects on a wide set of diseases including, but not limited to, diabetes mellitus, cancer, stroke, oral-diseases, inflammation, diarrhea, and dysentery. On the other hand, Sumac extracts were found to possess a potential antiviral, antimicrobial, antifungal, antioxidant and hypolipidemic activities. This review updates the current phytochemical, biological and therapeutic knowledge so far exist on R. coriaria. It also aims at highlighting the importance of Sumac extracts as a promising and potential source of functional ingredients and nutriceuticals with desirable bioactivities, prompting the further use of Sumac in food preservation, pharmacology and functional food industries.
Article
Full-text available
Rhus coriaria L. (Sumac) is an important and a widely used crop in the Mediterranean basin as a food spice, and also in folk medicine due to its health promoting properties. Phytochemicals present in plant foods are -in part- responsible for these consequent health benefits. Nevertheless, detailed information on these bioactive compounds is still scarce. Therefore, the present work was aimed at investigating the phytochemical components of sumac fruit epicarp using HPLC–DAD/QTOF-MS in two different ionization modes. The proposed method showed powerful for the tentative identification of 211 phenolic and other phyto-constituents; most of which, have not been described so far in R. coriaria fruits. More than 180 phytochemicals (tannins, (iso)flavonoids, terpenoids, etc.) are reported herein in sumac fruits for the first time. The obtained results highlight the importance of R. coriaria as a promising source of functional ingredients, and boost its further use in food and nutraceutical industries.
Article
Full-text available
Antioxidant activity and phenolic compounds of sumac extracts were investigated. Sumac was extracted in methanol and subjected to solvent–solvent partitioning to yield two fractions as ethyl acetate and aqueous. Methanol extract was further fractioned over Sephadex LH-20 column. Antioxidant activity of extracts and fractions were screened using ferric thiocyanate and DPPH radical scavenging methods. Phenolic composition of active fraction(s) was determined by HPLC–MS systems. Those fractions which exhibited strong antioxidant activity were rich in anthocyanins and hydrolysable tannins. While gallic acid was the main phenolic acid in the extracts, anthocyanin fraction contained cyanidin, peonidin, pelargonidin, petunidin, and delphinidin glucosides and coumarates. Pentagalloyl glucose was abundant in the hydrolysable tannin fraction. Effective scavenging concentration (EC50) on DPPH radical was 0.70 μg/mL both in ethyl acetate and tannin fractions, and 5.33 μg/mL in anthocyanin rich fraction. Same extracts and fractions showed moderate lipid peroxidation inhibition effect compared with the synthetic antioxidants. The findings demonstrate that sumac can be used as a natural antioxidant.
Article
Full-text available
Oxidative stress and inflammation are two sides of the same coin that are intricately combined to elicit a chronic pathophysiological stress state, especially as seen in cardiovascular remodelling. In this review, we argue that administration of deoxycorticosterone acetate (DOCA) and sodium chloride to uninephrectomised rats, defined as DOCA-salt hypertensive rats, provides a reliable animal model of oxidative and inflammatory stress in the cardiovascular system. The supporting evidence includes pathophysiological and biochemical changes together with pharmacological responses to synthetic and natural compounds that lower the concentrations of reactive free radical species and that curtail inflammatory responses in the cardiovascular system.
Article
It has been long appreciated that pulmonary arterial hypertension (PAH) in children is a heterogeneous disease with considerable morbidity and high mortality. While the introduction of specific disease targeting therapies, including prostanoids, endothelin receptor antagonists and phosphodiesterase-5-inhibitors, has improved symptoms and prognosis of patients with PAH, this remains a progressive and often fatal disease.1 Given the substantial costs of oral PAH therapies and—more importantly—the invasiveness and high maintenance of intravenous or subcutaneous prostanoid therapy, careful selection of patients likely to benefit from treatment is highly desirable. Despite considerable research efforts, however, a universally accepted risk stratification algorithm for children with PAH is still unavailable. Experienced clinicians have always appreciated that no risk marker should be seen in isolation and that the degree of pulmonary hypertension (ie, the absolute value of mean or systolic pulmonary arterial (PA) pressure) per se is insufficient to predict the outcome of patients. This is because even highly elevated PA pressures can be well tolerated as long as the RV is able to cope with increased ventricular afterload. The response of the RV to chronically increased afterload is highly individual and cannot currently be anticipated. Moreover, falling PA pressures on serial clinical assessment should be interpreted as signs of RV failure rather than pulmonary vascular disease regression (an unlikely scenario), unless clearly explained by newly established or escalated medical therapy. This empirical clinical observation was formally confirmed by the seminal work on primary PAH (nowadays referred to as idiopathic PAH) published in 1991. Combining data from multiple clinical centres in the USA participating in a registry for the characterisation of PAH in the 1980s, D'Alonzo et al derived a formula to estimate …
Article
Background: Hypertensive disorders of pregnant women are one of the important causes of maternal and perinatal morbidity and mortality. Evidence showed mental stress might be a risk factor of gestational hypertensive disorders. Objective: The objective of this study was to evaluate the relationships between mental stress and gestational hypertension/preeclampsia in pregnant women. Methods: Relevant studies were identified by PubMed, Cochrane, Chinese medical datasets (Wanfang, CNKI, and VIP Database). Only case-control or cohort studies evaluating an association of preeclampsia or gestational hypertension with mental stress were included in the present meta-analysis. Essential information was extracted from the qualified studies. Odds ratio (OR) was used as a pooled effect size. Potential heterogeneity and publication bias were detected as well. Results: Thirteen studies were included in the final analyses, which totally recruited 668,005 pregnant women. The results indicated that mental stress was associated with an increased risk of gestational hypertension (OR, 1.26; 95% confidence interval [CI], 1.00-1.59; P = 0.047) and preeclampsia (OR, 1.49; 95%CI, 1.27-1.74; P < 0.001). Meanwhile, work stress (OR, 1.50; 95% CI, 1.15-1.97; P = 0.003) and anxiety or depression (OR, 1.88; 95%CI, 1.08-3.25; P = 0.02)were positively associated with risk of preeclampsia. Conclusions: Mental stress during life or pregnancy may be a risk factor for gestational hypertension and preeclampsia among pregnant women.
Article
Renin is a crucial enzyme in the renin-angiotensin system, and the inhibition of its activity is considered as a useful approach to the treatment of hypertension. The inhibitory effect of catechinrelated compounds on renin was investigated in this work. It was found that epigallocatechin gallate (EGCg) possessed the strongest activity with an IC50 value of 44.53 μM and acted in an un ompetitive manner. Gallated catechins exerted higher inhibition than the ungallated forms, and gallic acid exhibited an inhibitory potency close to that of epicatechin gallate (ECg). Results indicated that the galloyl moiety and ortho-trihydroxy phenyl structures might be favorable for the renin-inhibitory activity of these compounds.
Article
Data from different national and regional surveys show that hypertension is common in developing countries, particularly in urban areas, and that rates of awareness, treatment, and control are low. Several hypertension risk factors seem to be more common in developing countries than in developed regions. Findings from serial surveys show an increasing prevalence of hypertension in developing countries, possibly caused by urbanisation, ageing of population, changes to dietary habits, and social stress. High illiteracy rates, poor access to health facilities, bad dietary habits, poverty, and high costs of drugs contribute to poor blood pressure control. The health system in many developing countries is inadequate because of low funds, poor infrastructure, and inexperience. Priority is given to acute disorders, child and maternal health care, and control of communicable diseases. Governments, together with medical societies and non-governmental organisations, should support and promote preventive programmes aiming to increase public awareness, educate physicians, and reduce salt intake. Regulations for the food industry and the production and availability of generic drugs should be reinforced.
Article
To determine the expressions of angiotensin-converting enzyme 2 (ACE2) in spontaneously hypertensive rats and the effect of apigenin. Sixty male SHR rats aged 12 weeks were randomly divided into 6 groups based on body weight and blood pressure. The rats in a normal control group and 4 experimental groups were given 0, 0.007, 0.026, 0.104 and 0.417 g/kg of apigenin respectively, and the rats in positive control group were given 12 mL/kg captopril. Systolic blood pressure (SBP) and heart rate were measured once a week; body weight was measured twice a week. At the end of the experiment, the expression of ACE2 mRNA was determined by real time PCR and the distribution and expression of ACE2 in kidney was determined by immunohistochemistry. SBP was measured by tail-cuff method. The transcription level of ACE2 mRNA in captopril positive control group and 0.417 g/kg bw apigenin group was significantly higher than the control group (P < 0.05). The immunohistochemistry results were consistent with the gene expression results. The effect of apigenin on lowering blood pressure was related to up-regulating the expression of ACE2 in kidney. However, further study is still needed for the possible mechanisms.