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Antihypertensive Indigenous Lebanese Plants: Ethnopharmacology and a Clinical Trial


Abstract and Figures

Hypertension is highly prevalent among the Lebanese adult population and is indeed the major cause of mortality in Lebanon. Traditional use of antihypertensive medicinal plants has long been practiced. The aim of this study is to document this traditional knowledge and clinically test the antihypertensive capacity of three of the most commonly used wild plant species Mentha longifolia, Viola odorata and Urtica dioica. Ethno-pharmacological data was collected by personal interviews with herbalists and traditional healers using a semi structured survey questionnaire and assessing relative frequency of citation (RFC). The clinical study was conducted by a randomized, blind, placebo-controlled trial in 29 subjects with mild hypertension distributed in four groups, three plant extract treatments and one placebo. Systolic (SBP) and diastolic blood pressures (DBP) as well as mean arterial blood pressures (MAP) were monitored at weeks 4, 8, 12 and 16 during the treatment with 300 mL/day of plant extract. Results showed that M. longifolia, U. dioica and V. odorata exhibited the highest values of RCF (0.95) followed by Allium ampeloprasum (0.94), Apium graveolens (0.92) and Crataegus azarolus (0.90). The clinical trial revealed dose-and duration-dependent significant reductions in SBP, DBP and MAP of subjects treated with M. longifolia, U. dioica or V. odorata. Our findings indicate that extracts of these plants present an effective, safe and promising potential as a phyto-therapuetical approach for the treatment of mild hypertension. More research on the phytochemistry, pharmacological effects and the underlying mechanisms is necessary.
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Antihypertensive Indigenous Lebanese Plants:
Ethnopharmacology and a Clinical Trial
Ali A. Samaha 1,2,3,4, Mirna Fawaz 2, Ali Salami 5, Safaa Baydoun 6, * and Ali H. Eid 7, 8, *
1Lebanese International University, Beirut, P.O. Box 146404, Lebanon
2Faculty of Health Sciences, Beirut Arab University, Beirut, P.O. Box 11-5020, Lebanon
3Lebanese University, Faculty of Public Health IV, Zahle, P.O. Box 6573/14, Lebanon
4Rayak University Hospital, Rayak, P.O. Box 1200, Lebanon
5Lebanese University, Rammal Hassan Rammal Research Laboratory, Physio-toxicity (PhyTox) Research
Group, Faculty of Sciences (V), Nabatieh, P.O. Box 6573/14, Lebanon
6Research Center for Environment and Development, Beirut Arab University,
Bekaa, P.O. Box 11-5020, Lebanon
7Department of Pharmacology and Toxicology, American University of Beirut,
Beirut, P.O. Box 11-0236, Lebanon
8Department of Biomedical Sciences, Qatar University, Doha, P.O. Box 2713, Qatar
*Correspondence: (S.B.); (A.H.E.)
Received: 7 April 2019; Accepted: 10 July 2019; Published: 20 July 2019
Hypertension is highly prevalent among the Lebanese adult population and is indeed the
major cause of mortality in Lebanon. Traditional use of antihypertensive medicinal plants has long
been practiced. The aim of this study is to document this traditional knowledge and clinically test the
antihypertensive capacity of three of the most commonly used wild plant species Mentha longifolia,
Viola odorata and Urtica dioica. Ethno-pharmacological data was collected by personal interviews
with herbalists and traditional healers using a semi structured survey questionnaire and assessing
relative frequency of citation (RFC). The clinical study was conducted by a randomized, blind,
placebo-controlled trial in 29 subjects with mild hypertension distributed in four groups, three plant
extract treatments and one placebo. Systolic (SBP) and diastolic blood pressures (DBP) as well as
mean arterial blood pressures (MAP) were monitored at weeks 4, 8, 12 and 16 during the treatment
with 300 mL/day of plant extract. Results showed that M. longifolia,U. dioica and V. odorata exhibited
the highest values of RCF (0.95) followed by Allium ampeloprasum (0.94), Apium graveolens (0.92)
and Crataegus azarolus (0.90). The clinical trial revealed dose- and duration-dependent significant
reductions in SBP, DBP and MAP of subjects treated with M. longifolia,U. dioica or V. odorata.
Our findings indicate that extracts of these plants present an eective, safe and promising potential
as a phyto-therapuetical approach for the treatment of mild hypertension. More research on the
phytochemistry, pharmacological eects and the underlying mechanisms is necessary.
Keywords: hypertension; herbal medicine; Urtica dioica;Viola odorata;Mentha longifolia
1. Introduction
Hypertension (HTN), commonly known as high blood pressure, remains a major contributor to
morbidity and mortality associated with cardiovascular diseases (CVD) and other conditions including
stroke, kidney failure, dementia, premature death and disability [
]. Recent data from 154 countries
confirms an increase in hypertensive cases from 17,307 per 100,000 in 1990 to 20,525 per 100,000
in 2015 [
]. Accumulating evidence also argues that high systolic blood pressure (SBP) (
140 mm Hg)
is responsible for 143 million disabilities as well as 14% of total deaths, mostly due to CVD [
]. This is
Biomolecules 2019,9, 292; doi:10.3390/biom9070292
Biomolecules 2019,9, 292 2 of 16
further confirmed by a meta-analysis of 1670 studies in 71 countries together involving 29.5 million
participants [
]. This study indeed reveals that the prevalence of HTN ranges from 4% to 78%, with
the highest worldwide blood pressure prevalence shifting from high income countries to low income
countries [5].
In Lebanon, several studies have emphasized the extent of the burden of HTN with a prevalence
of 36.9% [
], 29.3% [
] or 31.2% [
] among adults. In these studies, the control rate is reported at only
27%, 9.5% and 28.7%, respectively [
]. Alarmingly, 47% of proportional mortality in Lebanon is
directly related to CVD [
]. This is not surprising given the high prevalence of CVD risk factors among
the Lebanese population [10,11], among which hypertension is the most prominent [12].
There are many factors involved in regulating blood pressure (BP). These include cardiac output,
circulatory blood volume, vascular caliber, elasticity and reactivity, hormonal mediators as well as
neural stimulation. The factors that aect cardiac output include sodium intake, renal function, and
mineralocorticoids. Inotropic eects occur via extracellular fluid volume augmentation as well as
an increase in heart rate and contractility. As for the peripheral vascular resistance, the sympathetic
nervous system (SNS), humoral factors and local autoregulation are key players [
]. SNS elicits its
impact primarily by inducing vasoconstriction and promoting sodium retention. Humoral mediators
include vasoconstrictors such as endothelin, angiotensin II, catecholamines or vasodilators such as
nitric oxide (NO), prostaglandins and kinins [
]. Moreover, in arterial smooth muscle cells, secondary
messengers, such as cyclic AMP, are well-known to modulate cellular phenotypes such as adhesion
and actin cytoskeleton reorganization. Both phenotypic changes play a role in vasoconstriction and
thus in peripheral vascular disease including hypertension [
]. In addition, blood viscosity, blood
flow velocity and vascular wall conditions contribute to the regulation of BP [21].
Several drugs, belonging to dierent classes, are employed for the management or treatment of
HTN. The main drugs available are thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors,
angiotensin receptor II blockers and calcium channel blockers [
]. Additional medications that are
sometimes used are vasodilators, aldosterone antagonists,
-blockers, renin inhibitors and
central-acting agents [
]. Pharmacologic lowering of HTN in patients with disparate antihypertensive
mechanisms reduces the risk of, but does not entirely prevent, HTN-related CVD events, such as stroke,
heart failure, retinopathy and nephropathy [
]. Certainly, some of the remaining risk in treated cases
is attributable to BP levels that remain significantly above those in normotensive individuals.
Control of BP requires multiple antihypertensive agents in the majority of patients with
hypertension [
]. The availability of multiple antihypertensive agents aords the practitioner the
ability to use highly eective drug combinations that both reduce BP and protect target organs [
This is especially important in view of the high global prevalence of resistant hypertension [
Data from 3.2 million patients indicate that the prevalence of true-resistant hypertension was 22.9%,
56.0% and 12.3% in chronic kidney disease, renal transplant and elderly patients, respectively [
This study further confirmed the high need for new treatments for resistant hypertension [27].
In this context, medicinal plants with cardio-vasculoprotective, hypotensive or antihypertensive
therapeutic values have been subject to enormous concerted research eorts during the last three
decades [
]. Clinical and preclinical studies demonstrate the beneficial eects of many plants and
further underscore their potential as a source for pharmaceutical drugs [
]. Interestingly,
plant-derived alkaloids like reserpine, rescinnamine and serpentine are still used to treat severe forms
of hypertension, with reserpine being roughly as eective as other first-line antihypertensive drugs [
In their attempts to control hypertension and its attendant complications amid the scarce
socioeconomic resources, rural communities in developing countries including Lebanon and the
Levant have resorted to herbal remedies. However, much scientific eorts are needed to validate the
eectiveness and elucidate the safety profile of such herbal remedies [
]. Numerous and chemically
diverse secondary metabolites that are actually optimized for exerting biological functions are still far
from being exhaustively investigated. While natural product-based drug discovery and development
represents a complex endeavor demanding a highly integrated interdisciplinary approach, published
Biomolecules 2019,9, 292 3 of 16
scientific evidence, technologic advances and research trends clearly indicate that natural products
will be among the most important sources of new drugs also in the future [
]. Moreover, there is a
clear demonstration that the rich flora biodiversity and associated ethno-pharmacological traditional
knowledge of the East Mediterranean region has indeed provided humanity with many important
drugs [
]. In Lebanon, despite of the citation of several native species of therapeutic value in the
treatment of mild hypertension, there have been very few studies that have specifically been conducted
in this regard.
This study endeavors to document the ethno-pharmacological traditional knowledge of wild
medicinal plants used in the treatment of hypertension and clinically test the blood-lowering eect of
some selected species. The mechanism of action of these medicinal plants will be discussed in light of
the available literature.
2. Materials and Methods
This study was conducted between October 2016 and September 2018 and has been registered in
the World Health Organization Clinical Trial Registry (ChiCTR1900021653) as a clinical trial. It consisted
of two stages. Stage I consisted of an ethno-pharmacological survey with herbalists and traditional
healers, followed by a clinical trial (stage II) to examine the eect of three of the most commonly
used species. This study involved 29 subjects with pre-hypertension and two additional risk factors
attending the outpatient department of Rayak University Hospital (RH), Bekaa, Lebanon but not willing
to undergo any treatment by pharmaceutical medications when they will need it. Ethical approval was
obtained both from Rayak Hospital and Beirut Arab University.
2.1. Ethnopharmacological Survery and Selection of Medicinal Plants
Collection of traditional ethno-pharmacological knowledge comprised personal interviews with
36 herbalists and traditional healers using semi-structured questionnaires. Specimens of selected plants
were collected and taxonomical identification was confirmed based on the determination keys that
were described in our recent publication [
] and references therein. Quantitative data analysis was
performed by computing the Relative Frequency of Citation (RFCs) as follows:
RFCs =FCs/N,
where FC
is frequency of citation i.e., the number of informants (herbalists and traditional healers)
reporting a particular species divided by the total number of informants participating in the survey (N).
In theory, this index varies from 0.0 to 1.0; the closer the values are to 1.0, the higher is the consensus
among the informants. Three herbs of the plant species that scored a RCF
of 1.00 were selected for the
clinical trial.
2.2. Plant Material and Extraction Procedure
Leaves of Mentha longifolia, flowers of Viola odorata and leaves of Urtica dioica were collected from the
wild where the species are abundantly found, namely from El Moukhtara, Jabal Moussa and Ta’anayel
regions. Samples of the plant material were deposited at the Research Center for Environment and
Development, Beirut Arab University. The weight of the starting material was 500 g. After air-drying,
the collected material was washed with distilled water, then soaked in aqueous-methanol (30:70) for
a total of three days with occasional shaking. The plant material was then filtered by a two-stage
approach using muslin cloths and Whatman grade-1 filter papers (Merck, Darmstadt, Germany).
This procedure was repeated twice, and the combined filtrate was condensed down to 20% of volume
using rotary evaporator (Buchi, Flawil, Switzerland) at 35–40
C under reduced pressure. A total of
5 mL of this volume was mixed with 295 mL of distilled water, which was consumed by the subjects.
Placebo liquid was prepared of distilled water tinted with a food colorant to have a similar appearance
to plant extracts.
Biomolecules 2019,9, 292 4 of 16
2.3. Clinical Trial
Three medicinal plants, M. longifolia,V. odorata and U. dioica, were selected based on the
ethnopharmacological survey and were examined for their anti-hypertensive properties on subjects
with mild hypertension. The trial consisted of a 16 week, single-blind, placebo-controlled approach and
was conducted under the approval of the Institutional Review Board (IRB) of Rayak Hospital (RH) that is
accredited by the Ministry of Public Health, Lebanon (Approval number ECO-R-9.0-2016). The patients
did not know to which group they were assigned or which herbal solution they were receiving until
after the follow-up period. Block randomization was utilized to minimize bias and variability between
dierent groups. For the purpose of obtaining this approval, a focus group consisting of a group of
cardiologists and nephrologists at RH was informed of the study background, rationale and approach.
Written consents assuring participating subjects that all information would be confidential and used
only for research purposes were obtained. Selection criteria included subjects of 40–65 years of age
with pre-hypertension and two additional risk factors such as positive family history for hypertension,
sedentarity and obesity. (SBP: 135 and 139 mmHg and/or DBP: 85 and 89 mmHg) who were not willing
to take any pharmaceutical medications but underwent lifestyle modifications (salt restriction) with no
detectable BP lowering response. Exclusion criteria included lactating or pregnant women, history of
allergy, kidney dysfunction, diabetes or any cardiovascular dysfunction. During the selection process,
subjects attended two screening visits with an interval of two weeks, each of which included medical
and life-style histories, physical examinations, laboratory tests and measurements of BP. In addition
to general laboratory testing, blood count, creatinine and electrolytes, all participants underwent
echocardiodoppler to assess left ventricular function, wall thickness and motion and valves’ functions;
also, a Doppler of the renal arteries as well as urinary metanephrines and serum thyroid-stimulating
hormone (TSH) were performed to rule out all causes of secondary hypertension. The mean ejection
fraction recorded among participants was 68%, and none of them was found to have motion wall
abnormalities, diastolic dysfunction nor significant valvulopathy. Renal arteries of all participants were
patent with good Doppler signal and urinary metanephrine levels were normal. Selected subjects were
randomly divided into four groups (three treatment and one placebo) each consisting of 7, 8 subjects
based on their taste preference. Selected subjects were instructed to take a dose of 300 mL/day every
morning before breakfast for 16 weeks. SBPs, DBPs and MAPs all participating subjects were monitored
at weeks 4, 8, 12 and 16 by the same physician. Systolic and diastolic BPs were measured from the left
arm using a mercury sphygmomanometer. Measurements were performed and repeated for three
times at intervals of 10-min in a sitting position. Safety was assessed by general physical examination
that was performed every two weeks, and subjects were regularly asked about experiencing any
incidence of treatment-related adverse events throughout the treatment and post-treatment follow-up
periods. Moreover, testing for liver and kidney functions was performed every 4th week (i.e., weeks 4,
8, 12 and 16) as well as four weeks after the end of the trail to assess for any post-treatment changes.
All subjects showed normal values throughout the trial and during the follow-up period.
2.4. Statistical Analysis
Statistical analysis was performed using the SPSS (IBM Corp. Released 2013, SPSS Statistics for
Windows Version 22.0, Armonk, NY, USA). Categorical and continuous variables were expressed
as frequencies and mean
standard deviation, respectively. Quantitative variables were tested for
normality distribution using the Kolmogorov–Smirnov test. Kruskal–Wallis test was used to study if
there was a significant dierence between the four groups (Placebo, Mentha longifolia (M.L.), Viola odorata
(V.O.) and Urtica dioica (U.D.)) over the 16-week duration. Friedman test was used to show if there was
a statistically significant dierence in performance over time for the systolic (SBP) and diastolic blood
pressures (DBP) as well as for the mean arterial blood pressures (MAP). Then a post hoc analysis with
Wilcoxon signed-rank tests was used to confirm when the dierences occurred compared to baseline.
The level of significance was set at p<0.05 for all statistical analyses. A priori statistical power analysis
Biomolecules 2019,9, 292 5 of 16
revealed that n=29 was the suitable sample size in order to assess standardized dierences in the
main parameters at 0.05 significance level of two-sided hypothesis, reaching a power >95%.
3. Results
3.1. Ethnopharmacological Data
Table 1illustrates a list of 26 native wild plant species cited by 36 herbalists and traditional healers
as “widely used for the treatment of HTN in Lebanon”. The value of RFCs of most (19 out of 26) plants
fell in the 0.72–0.95 range, with M. longifolia,U. dioica and V. odorata recording the highest values (0.95)
followed by A. ampeloprasum (0.94), A. graveolens (0.92) and C. azarolus (0.90). According to informants,
the perceived benefits and safety of cited species were the reasons for their popularity of use. All plant
parts appeared to obtain some therapeutic benefits with leaves and aerial parts recording the highest
citations (69.2%, 28.5% respectively). Notably, decoction was the principal means of preparation (65%)
and oral administration at a dosage of 1–3 cups/day for a duration of 3–6 months (90%) was the main
application method and the most ecacious dosage.
Table 1.
Plant species and traditional practices traditionally used for the treatment hypertension (HTN)
in Lebanon.
Plant Species (Family) English Name Arabic Name Preparation and Administration RFCs
Allium ampeloprasum L.
(Amaryllidaceae) Leek Kerrat Decoction of bulbs and leaves, 1
cup/day. Medicinal food 0.94
Apium graveolens L. (Apiaceae) Wild Celery Krafs
Fresh juice of shoots and leaves, 1 cup
twice/week 0.92
Artemisia herba alba Asso (Asteraceae) White Worm-wood Shieh Infusion of aerial parts, 1 cup/day 0.64
Asparagus acutifolius L.
(Asparagaceae) Wild Asparagus Halyoun Decoction of stem tops, 1 cup/day 0.90
Calicotome villosa (Poir.) Link
(Fabaceae) Spiny broom Kandoul Decoction of seeds, 1 cup/day 0.35
Centaurium erythraea Rafn
(Gentianaceae) Spiked centaury Kantarioun Infusion of flowering aerial parts, 3
cups/day for 2 weeks 0.55
Crataegus azarolus L. (Rosaceae) Hawthorn Zaarour
Decoction of leaves, flowers or fruits 1
cup/day 0.90
Cupressus sempervirens L.
(Cupressaceae) Cypress Sarou Decoction of leaves, 1 cup/day 0.45
Equisetum telmateia Ehrh.
(Equisetaceae) Branched horsetail Zanab El-khayl Aerial parts Infusion/3cups/day for
8–12 weeks 0.75
Eryngium creticum Lam. (Apiaceae) Eryngo Kers Aanni Juice of young shoots and leaves, 1
cup/day 0.80
Foeniculum vulgare Mill Fennel Choumar Decoction of seeds, 2 cups/day 0.65
Fibigia clypeata (L.) Medik.
(Brassicaceae) Roman Shields Hachichet El
Oumeh Infusion of leaves, 1cup/day 0.90
Hordeum vulgare L. (Poaceae) Barley Sha’ir Decoction of seeds, 1 cup/day 0.94
Laurus nobilis L. (Lauraceae) Sweet bay Ghar Decoction of leaves, 1/2 cup/day 0.89
Matricaria aurea (Loefl.) Sch.Bip.
(Compositae) Chamomile Bebounej Infusion flowers, 3 cup/day as herbal
tea 0.85
Matricaria chamomilla L. (Asteraceae) Chamomile Bebounej Infusion of flowers, 3cup/day 0.85
Mentha longifolia L. (Lamiaceae) Horse Mint Na’na’a Infusion of leaves, 2cup/day 0.95
Melissa ocinalis L. (Lamiaceae) Lemon Balm Mallieseh Infusion of leaves, 2cup/day 0.45
Myrtus communis L. (Myrtaceae) Myrtle Hemblas Maceration of fresh fruits in oil,
essential oil 0.86
Paronychia argentea Lam.
(Caryophyllaceae) Silvery Paronychia
Hachichet El Ramel
Decoction of aerial parts, 1 cup/day 0.40
Peganum harmala L. (Nitrariaceae) Syrian rue, harmel Harmala Decoction of aerial parts, 1 cup/day 0.72
Plantago major L. (Plantaginaceae) Broadleaf plantain Lissan el Hamal Decoction, 1 cup/day 0.89
Portulaca oleracea L. (Portulacaceae) Purslane Bakleh Decoction of leaves, 3 cups/day 0.88
Raphanus raphanistrum L.
(Brassicaceae) Wild radish Fejel Barie Juice of aerial parts, roots Fresh 1/2
cup/day 0.94
Urtica dioica L. (Urticaceae) Stinging nettle Korrays
Decoction of young shoots and leaves,
3 cups/day 0.95
Viola odorata L. (Violaceae) Sweet violet Banafsaj Infusion of flowers., 3 cup/day 0.95
RFC: relative frequency of citation.
Biomolecules 2019,9, 292 6 of 16
3.2. Clinical Trial
Demographic characteristics of the sampled population, all Caucasians, are shown in Table 2.
Table 3demonstrates the mean baseline levels of BP (n=29). The subjects were men (19) and women
(10) with an average age of 53.5 years. The mean values of baseline SBP, DBP or MAP of both
plant-treated or the placebo groups fell in the range of 137.40
1.50 to 138.44
1.38 mmHg,
86.91 ±1.63
87.80 ±0.37 mmHg
and 103.74
1.19 to 104.68
0.61 mmHg, respectively, with no significant
dierence (p>0.01) between participating groups (Table 3). While no significant reduction (p>0.01) was
observed with BP of the placebo subjects over the 16-week trial, consistent reductions were clearly noted
with the plant treated groups (Table 3). Comparison of the repeated measures for SBP using Friedman’s
test showed a statistically significant dierence over time of testing for M.L. (
V.O. (
=24.571, p<0.001) and U.D. (
=31.119, p<0.001). From baseline to week 16 of intake, SBP
mean values fell from 137.64
0.38 to 128.64
0.38 mmHg (
1.88 mmHg) (Figure 1), DBP from
87.41 ±1.15 mmHg
to 81.53
1.49 mmHg (
1.72) (Figure 2) and MAP from
104.14 ±0.70 mmHg
to 97.24
0.95 mmHg (
1.15) (Figure 3) with M. longifolia. Indeed, for M.L., Wilcoxon signed-rank
tests showed that after week 4, there was a statistically significant decrease in the mean of SBP compared
to baseline (Z=
2.530, Z=
2.530, Z=
2.530 or Z=
2.646, with
,p=0.011 or
, for weeks 4, 8, 12 or 16, respectively). Likewise, the values of SBP, DBP and MAP with V. odorata
dropped from
137.40 ±1.51 mmHg
130.21 ±0.79 mmHg
7.19 ±1.92
), from
87.06 ±2.04 mmHg
82.29 ±0.52 mmHg
1.83), and from 103.84
1.65 mmHg to
98.26 ±0.44 mmHg
5.58 ±1.45
respectively (Figures 13). Wilcoxon signed-rank tests showed that after week 12, there was a statistically
significant decrease in the mean of the SBP compared to baseline (
, with
or p=0.016, for weeks 12 or 16, respectively). As for U. dioica, more profound changes were
observed with SBP dropping from
138.53 ±1.31 mmHg
126.64 ±2.70 mmHg
2.60), DBP
88.10 ±0.91 mmHg
80.64 ±1.62 mmHg
7.46 ±1.16
) and MAP from 104.91
0.85 mmHg to
1.13 mmHg (
8.94 ±1.14
) (Figures 13). Wilcoxon signed-rank tests showed that after week
4, there was a statistically significant decrease in the mean of SBP compared to baseline (Z=
2.524 or Z=
2.533, with
,p=0.012, p=0.011 and p=0.012, for weeks 4, 8,
12 or 16 respectively).
Table 2. Demographic characteristics of the sampled population.
Characteristics Treated Group (n=22) Placebo (n=7)
Age Groups (years)
40–47 7 2
48–57 9 3
58–65 6 2
Men 15 4
Women 7 3
Risk Factors
Smoking 22 7
Family history 22 7
Body Mass Index (Mean)
Overweight (20–25) 16 2
Obese (>30) 6 5
Biomolecules 2019,9, 292 7 of 16
Table 3.
SD of SBP, DBP and MAP measured over 16 week intake of 300 mL/day of M. longifolia (M.L.), V.odorata (V.O.) and U. dioica (U.D.) in mild
hypertensive subjects.
Group SBP Mean ±SD DBP Mean ±SD MAP Mean ±SD
M.L. (n=7) V.O. (n=7) U.D. (n=8) Placebo (n=7) M.L. (n=7) V.O. (n=7) U.D. (n=8) Placebo (n=7) M.L. (n=7) V.O. (n=7) U.D. (n=8) Placebo (n=7)
Baseline 137.64 ±0.38 137.40 ±1.51 138.53 ±1.31 137.41 ±0.89 87.41±1.15 87.06 ±2.04 88.10 ±0.91 86.91 ±1.64 104.14 ±0.70 103.84 ±1.65 104.91 ±0.85 103.73 ±1.19
Week 4
137.24 ±0.24
137.73 ±0.08 87.47 ±0.79 86.59 ±0.76 86.65 ±0.47 86.67 ±0.98
103.47 ±0.48
103.69 ±0.63
Week 8
135.70 ±0.38 133.78 a±1.59 137.44 ±1.22 85.84 a±0.89 86.10 ±1.00 84.53 a±1.03 86.50 ±2.00
102.64 ±0.68
103.49 ±1.41
Week 12
1.51 133.31
0.38 129.30
138.00 ±1.00 83.99 a±0.71 83.16 a±0.38 83.71a±1.92 87.01±1.25 98.01 a±0.58 99.86 a±0.31 98.90 a±1.35 104.01 ±0.85
Week 16
0.38 130.21
0.79 126.64
136.77 ±1.06 81.53 a±1.49 82.29 a±0.52 80.64 a±1.62 87.20 ±0.77 97.24 a±0.95 98.26 a±0.44 95.96 a±1.13 103.73 ±0.66
SD: standard deviation; SBP: systolic blood pressure; DBP: diastolic blood pressure; MAP: mean arterial blood pressure;
represents values that are significantly dierent at p<0.01 arterial
blood pressure.
Biomolecules 2019,9, 292 8 of 16
Biomolecules 2019, 9, x FOR PEER REVIEW 8 of 16
Figure 1. Means ± SD of SBP, measured over 16-week intake of 300 mL/day of M. longifolia (M.L.),
V.odorata (V.O.) and U. dioica (U.D.) in mild hypertensive subjects. ** p < 0.01 (M.L. and U.D.
compared to Placebo at week 8 and M.L., V.O., and U.D. compared to Placebo at weeks 12 and 16).
Figure 2. Means ± SD of DBP, measured over 16-week intake of 300 mL/day of M. longifolia (M.L.),
V.odorata (V.O.) and U. dioica (U.D.) in mild hypertensive subjects.* p < 0.05 (U.D. compared to
Placebo), ** p < 0.01 (M.L., V.O., and U.D. compared to Placebo).
Baseline Week 4 Week 8 Week 12 Week 16
SBP (mm Hg)
Placebo M.L. V.O. U.D.
DBP (mmHg)
Placebo M.L. V.O. U.D.
Figure 1.
SD of SBP, measured over 16-week intake of 300 mL/day of M. longifolia (M.L.),
V.odorata (V.O.) and U. dioica (U.D.) in mild hypertensive subjects. ** p<0.01 (M.L. and U.D. compared
to Placebo at week 8 and M.L., V.O., and U.D. compared to Placebo at weeks 12 and 16).
Figure 2.
SD of DBP, measured over 16-week intake of 300 mL/day of M. longifolia (M.L.),
V.odorata (V.O.) and U. dioica (U.D.) in mild hypertensive subjects.* p<0.05 (U.D. compared to Placebo),
** p<0.01 (M.L., V.O., and U.D. compared to Placebo).
Biomolecules 2019,9, 292 9 of 16
Biomolecules 2019, 9, x FOR PEER REVIEW 9 of 16
Figure 3. Means ± SD of MAP, measured over 16-week intake of 300 mL/day of M. longifolia (M.L.),
V.odorata (V.O.) and U. dioica (U.D.) in mild hypertensive subjects. ** p < 0.01 (M.L. and U.D.
compared to Placebo at week 8 and M.L., V.O., and U.D. compared to Placebo at weeks 12 and 16).
For DBP, comparison of the repeated measures using Friedman’s test showed a statistically
significant difference over time of testing for M.L. (χ2 = 25.928, p < 0.001), V.O. (χ2 = 22.377, p < 0.001)
and U.D. (χ2 = 28.100, p < 0.001). For the M.L. group, Wilcoxon signed-rank tests showed that starting
week 8, there was a statistically significant decrease in the mean of DBP compared to baseline (Z =
2.366, Z = 2.366 or Z = 2.384, with p = 0.018, p = 0.018 or p = 0.017, for weeks 8, 12 or 16,
respectively). For V.O. group, it was observed that starting week 12, there was a statistically significant
decrease compared to baseline (Z = 2.209 or Z = 2.375 with p = 0.027 or p = 0.018, for weeks 12 or 16,
respectively). For the U.D. group, a significant difference was noted starting week 8 (Z = 2.521, Z =
2.524 or Z = 2.521, with p = 0.012, p = 0.012 or p = 0.012, for weeks 8, 12 or 16, respectively).
For MAP, comparison of the repeated measures using Friedman’s test showed a statistically
significant difference over time of testing for M.L. (χ2 = 26.171, p < 0.001), V.O. (χ2 = 25.943, p < 0.001)
and U.D. (χ2 = 31.300, p < 0.001). In particular, for the M.L. group, starting week 4, there was a
statistically significant decrease in MAP compared to baseline (Z = 2.043, Z = 2.366, Z = 2.366 or
Z = 2.388, with p = 0.041, p = 0.018, p = 0.018 or p = 0.017, for weeks 4, 8, 12 or 16, respectively). As for
the V.O. group, a significant decrease compared to baseline was noted starting week 12 (Z = 2.371
or Z = 2.366, with p = 0.018 or p = 0.018, for weeks 12 or 16, respectively). In the U.D. group, a
significant decrease compared to baseline was noted starting week 4 (Z = 2.521, Z = 2.524, Z = 2.521
or Z = 2.521, with p = 0.012, p = 0.012, p = 0.012 or p = 0.012, for weeks 4, 8, 12 or 16, respectively).
4. Discussion
The results of this ethnopharmacological survey indicate that 15 of the 26 reported species
exhibit high RCF values, reflecting the significant consensus among informants about the presumed
powerful therapeutic potential of these species [41]. Numerous previous ethnopharmacological
studies have shown that all plants of the list are still being used for the treatment of HTN by many
communities in different parts of the world [15,28–30,34,42–47]. In particular, the popular use of
some species such as A. ampeloprasum, A. graveolens, C. azarolus, M. longifolia, U. dioica and V. odorata
having very high RCF values (0.85–0.10) makes it tempting to speculate that their potential as a
valuable source for pharmaceutical novel drug discovery is promising [48–52]. Pharmacological
research and clinical trials have revealed the antihypertensive and vasodilatory activities of these
species, further supporting this traditional use [53,54]. Food species such as A. ampeloprasum, A.
graveolens and C. azarolus, among other species, appear to occupy considerable share of the list. This
Placebo M.L. V.O. U.D.
Figure 3.
SD of MAP, measured over 16-week intake of 300 mL/day of M. longifolia (M.L.),
V.odorata (V.O.) and U. dioica (U.D.) in mild hypertensive subjects. ** p<0.01 (M.L. and U.D. compared
to Placebo at week 8 and M.L., V.O., and U.D. compared to Placebo at weeks 12 and 16).
For DBP, comparison of the repeated measures using Friedman’s test showed a statistically
significant dierence over time of testing for M.L. (
=25.928, p<0.001), V.O. (
and U.D. (
=28.100, p<0.001). For the M.L. group, Wilcoxon signed-rank tests showed that
starting week 8, there was a statistically significant decrease in the mean of DBP compared to baseline
2.366 or Z=
2.384, with p=0.018, p=0.018 or p=0.017, for weeks 8, 12 or 16,
respectively). For V.O. group, it was observed that starting week 12, there was a statistically significant
decrease compared to baseline (Z=
2.209 or Z=
2.375 with p=0.027 or p=0.018, for weeks 12 or
16, respectively). For the U.D. group, a significant dierence was noted starting week 8 (Z=
Z=2.524 or Z=2.521, with p=0.012, p=0.012 or p=0.012, for weeks 8, 12 or 16, respectively).
For MAP, comparison of the repeated measures using Friedman’s test showed a statistically
significant dierence over time of testing for M.L. (
=26.171, p<0.001), V.O. (
=25.943, p<0.001)
and U.D. (
=31.300, p<0.001). In particular, for the M.L. group, starting week 4, there was a
statistically significant decrease in MAP compared to baseline (Z=
2.043, Z=
2.366, Z=
2.366 or
, with p=0.041, p=0.018, p=0.018 or p=0.017, for weeks 4, 8, 12 or 16, respectively). As for
the V.O. group, a significant decrease compared to baseline was noted starting week 12 (
2.366, with p=0.018 or p=0.018, for weeks 12 or 16, respectively). In the U.D. group, a significant
decrease compared to baseline was noted starting week 4 (Z=
2.521, Z=
2.524, Z=
2.521 or
Z=2.521, with p=0.012, p=0.012, p=0.012 or p=0.012, for weeks 4, 8, 12 or 16, respectively).
4. Discussion
The results of this ethnopharmacological survey indicate that 15 of the 26 reported species exhibit
high RCF values, reflecting the significant consensus among informants about the presumed powerful
therapeutic potential of these species [
]. Numerous previous ethnopharmacological studies have
shown that all plants of the list are still being used for the treatment of HTN by many communities in
dierent parts of the world [
]. In particular, the popular use of some species such
as A. ampeloprasum,A. graveolens,C. azarolus,M. longifolia,U. dioica and V. odorata having very high
RCF values (0.85–0.10) makes it tempting to speculate that their potential as a valuable source for
pharmaceutical novel drug discovery is promising [
]. Pharmacological research and clinical trials
have revealed the antihypertensive and vasodilatory activities of these species, further supporting
this traditional use [
]. Food species such as A. ampeloprasum,A. graveolens and C. azarolus, among
Biomolecules 2019,9, 292 10 of 16
other species, appear to occupy considerable share of the list. This is mostly a result of the positive
accumulated traditional experience derived from the consumption of such plants.
The highly popular use of C. azarolus found in this study is also supported by the findings of
other pharmacological studies and clinical trials [
]. Several mechanisms have been suggested
for the observed hypotensive eects. These include a role for endothelium-dependent NO-mediated
vasorelaxation and inhibition of Ca
influx to the smooth muscle [
]. Moreover, the role of
antioxidant, anti-inflammatory and anti-proliferative activities was reported [
]. In addition, inhibition
of angiotensin-converting enzyme by other Crataegus species has also been reported [
]. Such actions
are credited to the plant’s multiple components such as flavonoids (hyperoside, quercetin, rutin,
and vitexin), oligomeric proanthocyanidins [
] and quercetin [
]. Interestingly, some of these
phytochemicals, such as isoflavones, exhibit estrogen-like eects [
]. Knowing that estrogen
plays a very important role in hypertension [
], it would not be surprising that some of these
phytoestrogens modulate blood pressure. Indeed, there is an inverse association between dietary
intake of phytoestrogens and hypertension, both in the Mediterranean region [
] and elsewhere [
as well as in animal models [
]. Indeed, we have recently discussed how flavonoids play an important
role in the pathogenesis of hypertension [65].
The frequent use of Artemisia herba-alba Asso and Peganum harmala noted in this study is in full
accordance with the results of a study from Morocco [
]. The hypotensive and vasodilatory eects of
P. harmala (Syrian Rue or Esfand) have been associated with the activities of its isolated alkaloids [
Harmine, harmaline and harman were revealed to induce their actions by stimulating endothelial
cells to release NO, blocking voltage-dependent Ca
channels, or inhibiting phosphodiesterases,
thus resulting in an increase in cyclic AMP (cAMP) [
]. This cAMP not only stimulates relaxation of
vascular smooth muscles cells [
] but also modulates tracking of
2C-adrenoceptors to cell surface,
thus making it readily available for epinephrine, its natural agonist [18,19,69].
The use of the plants we listed above as a mode of alternative or complementary medicine is
believed to be largely attributed to the deep-rooted belief in the healing potential, accessibility and
lower risk of plants compared with synthetic drugs. Despite the promising therapeutic potential of
the cited species, informants were fully aware of the possible consequences of overuse and drug
interactions, particularly in the case P. harmala and A. herba alba. This belief is supported by convincing
arguments regarding the safety of both species as they have been reported to cause side eects in animal
and human case reports [
]. Importantly, some of the side eects may also be due to herb–drug
interactions, especially, that the concurrent use of both traditional and pharmaceutical medications
for treating hypertension or other chronic diseases is a worldwide tendency [
]. Indeed, a study
among hypertensive patients in Palestine revealed a majority of patients using herbal medicines did
not disclose this fact to their health providers [74].
Clear evidence of adverse reactions has indeed been reported [73,75]. Intriguingly, edible plants
such as A. ampeloprasum,A. graveolens and C. azarolus,M. longifolia,U. dioica and V. odorata among others
that are well established for their potential in alleviating hypertension may be considered as nontoxic
under moderate use. In this context, it is noteworthy that the importance placed by informants on M.
longifolia,U. dioica and V. odorata was remarkable. It was therefore believed that additional insights
into the use of these species may be gained by conducting a clinical trial that may contribute to the
development of eective, safe and perhaps novel moieties or formulations to curb the prevalence of
HTN among Lebanese people.
The results indicated in Table 3clearly indicate significant drops in SBP, DBP and MAP that are
duration-dependent. The reductions were particularly significant at weeks 12 and 16 with three plants
indicating the benefits of the tested plants in complementary therapy for mild hypertensive subjects
and supporting their traditional use. A reduction of 4–5 mmHg in SBP and 2–3 mmHg in DBP has
been estimated to reduce the risk of cardiovascular morbidity and mortality by 8–20% [
]. However,
the high SD values in some values reflect wide divergence from the means and high fluctuations, thus
highlighting the need for more trials. The examination of the eectiveness of extract in forestalling the
Biomolecules 2019,9, 292 11 of 16
progression of mild hypertension into a hypertensive state, as observed with certain antihypertensive
pharmaceutical medications, is also necessary [77].
Despite accumulated data, there are currently no clinical studies on the purported eectiveness of
the tested plants. Thus, our findings can only be discussed in view of ethnopharmacological studies
and wide spectrum of pharmacological activities involving tissue preparations and
in vivo
models. Specifically, the aqueous methanolic extract of M. longifolia was revealed to have significant
antihypertensive and negative chronotropic in normotensive and induced hypertensive rats [
This hypotensive eect was further confirmed by a more recent study of the crude extract of leaves
and its chloroform and aqueous fractions producing a dose-dependent fall in MAP in normotensive
anesthetized rats [
]. The functional nature of the blood-pressure-lowering eect was further studied
using isolated aortic ring rat preparations of rabbits, rats and guinea pigs [
]. The crude extract was
found to possess a combination of vasodilator and cardiac depressant constituents responsible for the
blood pressure lowering eect. The vasodilatory eect was mediated through a combination of Ca
channel blockade (concentrated in a non-polar fraction) and endothelium-dependent pathway linked
to vascular muscarinic receptors (concentrated in a polar fraction) [
]. The role of antioxidant eect of
phenolics and total flavonoids contents was also reported [79,80].
In this study, only a slight decrease in SBP at a dose of 45 mL/day of squeezed leaf juice for two
weeks was recorded. It may be argued that higher doses or longer durations may be required to induce
more eective BP-lowering eect evidently indicated in Table 2and Figure 1. This is in agreement
with the results of the examination of the ethanolic extract of U. dioica leaves, which was found to
significantly decrease elevated BP in renal artery-occluded hypertensive rats in a dose-dependent
manner [
]. More recently, the crude methanolic extract of the dried rhizomes and its fractions
were shown to significantly reduce blood pressure in high NaCl induced hypertensive rats under
anesthesia [
]. The
in vitro
examination on rat and rabbit aorta rings attributed this eect to NO
mediated vasorelaxation and Ca
blocking eects involving both endothelial cells and smooth muscle
fibers. Urtica dioica supplementation was also found to increase plasma antioxidant capacity and
reduce systemic oxidative stress [
]. The finding of the significant drop in both SBP, DBP and MAP
herein indicated together with the results of previous pharmacological studies are consistent with the
reported high content of U. dioica of bioactive phenolic compounds and other compounds known to
have significant antioxidant activity and vasorelaxant properties with various proposed underlying
mechanisms of action [83,84].
The hypotensive eect of V. odorata in this study concurs with the results of the dose-dependent
lowering eect of MAP found in anaesthetized rats [
]. In isolated guinea-pig atria, the extract showed
negative inotropic and chronotropic eects, similar to that caused by verapamil, a standard Ca
antagonist known to cause cardiac depression through the inhibition of Ca
inward current during
the action potential plateau [
]. This indicated that the observed cardiac inhibitory eect of the plant
extract might be causing a decrease in cardiac output and ultimately a decrease in the blood pressure.
When tested in pre-contracted rat aortic preparations, the plant’s extract inhibited both high K
phenylephrine (PE) induced vasoconstriction by blockage of Ca
influx through voltage-dependent
channels and receptor-operated channels caused by high K
and PE, respectively [
]. In addition,
when the control responses of PE were taken in Ca
free medium, the crude extract inhibited the
PE-induced peaks, indicating that the inhibition of Ca
release from internal stores through inositol-1,4,
5-trisphosphate-sensitive sarcoplasmic reticulum mechanism [86,87].
The antioxidant potency of V. odorata was confirmed in other studies [
]. Furthermore, blocking
voltage-dependent Ca
channels or suppressing Ca
release from the sarcoplasmic reticulum in
PE-induced or spontaneously contracting isolated rabbit tissue preparations was also confirmed in
a recent study [
]. Importantly, a phytochemical screening of V. odorata extracts and essential oils
revealed the presence of a wide range of bioactive compounds [
], making it an attractive plant for
further cardiovascular investigations.
Biomolecules 2019,9, 292 12 of 16
5. Conclusions
This study presents the first scientific evidence regarding the antihypertensive eects of M.
longifolia,V. odorata and U. dioica, three commonly used plants of the Lebanese flora. The perceived
benefits and safety of the discussed species were the reasons for their popularity of use. The clinical
trial we conducted further supports the antihypertensive potential of these plants, especially that
the extracts were well-tolerated without any clinically significant eects. For this reason, extracts of
these plants present an eective, safe and promising potential as a phyto-therapeutical approach
in the treatment and management of mild hypertension. Nonetheless, one major limitation of this
study is the absence of a dose–response that could be used to better assess the pharmacological
responses. Another limitation is the lack of accurate characterization, such as by mass spectrometry or
high-performance liquid chromatography (HPLC), of the extracts. Therefore, more research on the
pharmacological eects and the underlying mechanisms is still warranted.
Author Contributions:
Conceptualization, A.A.S, S.B. and A.H.E.; methodology, A.A.S, S.B. and A.H.E;
formal analysis, A.A.S, M.F, A.S., S.B and A.H.E.; investigation, A.A.S, M.F., and S.B; resources, A.A.S, S.B.; data
curation, A.A.S, M.F. and S.B; writing—original draft preparation, A.A.S, S.B. and A.H.E.; writing—review and
editing, A.H.E.; Statistical Analysis—A.S.; funding acquisition, A.A.S and S.B.
Funding: This research received no external funding.
Conflicts of Interest: The authors declare no conflicts of interest.
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... Alkaloids of the first class (peganine and its derivatives) are found only in the aerial part, and β-carboline (the main ones are harmine and harmaline) are found only in the roots ( Figure 1). According to the literature, Peganum harmala has antibacterial [95], anti-inflammatory [96], anti-fungal [97], and antitumor effects [92], and is used to treat hypertension [98], cough [99], diabetes [100], jaundice [94], malaria [101], tremor paralysis, Parkinson's disease, and Alzheimer's disease [92,102]. Despite the wide spectrum of action, the medicine uses peganin hydrochloride (ampoules and tablets) for the treatment of myopathy and myasthenia gravis and harmine hydrochloride for the treatment of encephalitis, tremor paralysis, and Parkinson's disease [103]. ...
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Due to population growth, instability of climatic conditions, and reduction of the areas of natural ecosystems, it becomes necessary to involve modern biotechnological approaches to obtain highly productive plant material. This statement applies both to the creation of plant varieties and the production of new pharmaceutical raw materials. Genetic transformation of valuable medicinal plants using Agrobacterium rhizogenes ensures the production of stable and rapidly growing hairy roots cultures that have a number of advantages compared with cell culture and, above all, can synthesize root-specific substances at the level of the roots of the intact plant. In this regard, special attention should be paid to the collection of hairy roots of the Institute of Plant Physiology RAS, Russian Academy of Sciences, the founder of which was Dr. Kuzovkina I.N. Currently, the collection contains 38 hairy roots lines of valuable medicinal and forage plants. The review discusses the prospects of creating a hairy roots collection as a basis for fundamental research and commercial purposes.
... M. longifolia (L.) L. is known for its potential in treating hypertension. In humans, a randomized, blind, placebo-controlled trial including 29 subjects with mild hypertension showed that the hydro-alcoholic extract of M. longifolia leaves led to a dose-and durationdependent reductions in systolic and diastolic blood pressures as well as in mean arterial blood pressures, thus confirming an effective, safe and promising potential for this plant as a phyto-therapeutical for hypertension therapy [113] (Table 3). ...
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Numerous plants, plant extracts, and plant-derived compounds are being explored for their beneficial effects against overweight and liver diseases. Obesity is associated with the increased prevalence of non-alcoholic fatty liver disease (NAFLD), becoming the most common liver disease in Western countries. Obesity and NAFLD are closely associated with many other metabolic alternations such as insulin resistance, diabetes mellitus, and cardiovascular diseases. Many herbs of the Lamiaceae family are widely employed as food and spices in the Mediterranean area, but also in folk medicine, and their use for the management of metabolic disorders is well documented. Hereby, we summarized the scientific results of the medicinal and nutraceutical potential of plants from the Lamiaceae family for prevention and mitigation of overweight and fatty liver. The evidence indicates that Lamiaceae plants may be a cost-effective source of nutraceuticals and/or phy-tochemicals to be used in the management of metabolic-related conditions such as obesity and NAFLD. PubMed, Google Scholar, Scopus, and SciFinder were accessed to collect data on traditional medicinal plants, compounds derived from plants, their reported anti-obesity mechanisms, and therapeutic targets.
... U. dioica was also evaluated for its cardiovascular effect on humans. Samaha et al. [48] conducted a randomized, blinded, placebo-controlled study of individuals with mild hypertension for sixteen weeks, which demonstrated that the extract obtained from U. dioica leaves reduces blood pressure, in addition to being safe and promising for the treatment of hypertension mild. Haouari and Rosado, [49] published a mini review showing the hypotensive and diuretic effects of various parts of the plant. ...
Several exotic plants (non‐native) are used in Brazilian traditional medicine and are known worldwide for their possible diuretic actions. Among the wide variety of plants, standing out Achillea millefolium L., Camellia sinensis L. Kuntze, Crocus sativus L., Hibiscus sabdariffa Linn., Petroselinum crispum (Mill.) A.W. Hill, Taraxacum officinale (L.) Weber, and Urtica dioica L., whose effects have already been the subject of some scientific study. In addition, we also discussed other exotic species in Brazil used popularly, but that still lack scientific studies, like the species Arctium lappa L., Carica papaya L., Catharanthus roseus (L.) G. Don, Centella asiatica (L.) Urb, Citrus aurantium L., and Persea americana Mill. However, generally, clinical studies on these plants are scarce. In this context, different plant species can be designated for further comprehensive studies, therefore, promoting support for developing an effective medicine to induce diuresis.
... In addition, it has been revealed to be extremely useful for the treatment of microbial and parasitic infections, cancer, jaundice, stomach diseases, snakebites, diabetes, liver and kidney problems, wounds, diuretic, libido, pulmonary diseases, hypotensive, blood purification, urticaria, allergic rhinitis, prostate disorders, hemorrhoids, and galactagogue and as a depurative. Apart from this, these species have also been reported to be used for exorcism, postcalving care, sprains, bones fracture, hematuria, neck sore, and yolk sore [2,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. ...
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Urtica dioica belongs to the Urticaceae family and is found in many countries around the world. This plant contains a broad range of phytochemicals, such as phenolic compounds, sterols, fatty acids, alkaloids, terpenoids, flavonoids, and lignans, that have been widely reported for their excellent pharmacological activities, including antiviral, antimicrobial, antihelmintic, anticancer, nephroprotective, hepatoprotective, cardioprotective, antiarthritis, antidiabetic, antiendometriosis, antioxidant, anti-inflammatory, and antiaging effects. In this regard, this review highlights fresh insight into the medicinal use, chemical composition, pharmacological properties, and safety profile of U. dioica to guide future works to thoroughly estimate their clinical value.
... One more distinct species of the genus artemisia that is A. herba-alba recognized for its therapeutic medicinal characteristics, it was consumable in an easy way and available in both traditional as well as in contemporary medicine. A. herba-alba was utilized as a folk remedy for the prevention of arterial hypertension (Mohamed et al. 2010;Samaha et al. 2019). ...
Artemisia and its allied species have been employed for conventional medicine in the Northern tem-perate regions of North America, Europe, and Asia for the treatments of digestive problems, morning sickness, irregu-lar menstrual cycle, typhoid, epilepsy, renal problems, bron-chitis malaria, etc. The multidisciplinary use of artemisia species has various other health benefits that are related to its traditional and modern pharmaceutical perspectives. The main objective of this review is to evaluate the traditional, modern, biological as well as pharmacological use of the essential oil and herbal extracts of Artemisia nilagirica, Artemisia parviflora, and other allied species of Artemi-sia. It also discusses the botanical circulation and its phy-tochemical constituents viz disaccharides, polysaccharides, glycosides, saponins, terpenoids, flavonoids, and carot-enoids. The plants have different biological importance like antiparasitic, antimalarial, antihyperlipidemic, antiasthmatic,antiepileptic, antitubercular, antihypertensive, antidiabetic, anxiolytic, antiemetic, antidepressant, anticancer, hepatopro-tective, gastroprotective, insecticidal, antiviral activities, and also against COVID-19. Toxicological studies showed that the plants at a low dose and short duration are non or low-toxic. In contrast, a high dose at 3 g/kg and for a longer dura-tion can cause toxicity like rapid respiration, neurotoxicity, reproductive toxicity, etc. However, further in-depth studies are needed to determine the medicinal uses, clinical efficacy and safety are crucial next steps.
Ethnopharmacological relevance Okra (Abelmoschus esculentus (L.) Moench) is traditionally used by different populations of Africa, América, Asia, and Europa to control diabetes. Although its action has been evaluated in several preclinical rodent trials, they have not been systematically analyzed. Objective To evaluate the effectiveness of using okra in the treatment of diabetes in experimental rodent models. Material and methods Controlled and randomized rodent animal trials with induced diabetes published between January 2000 and January 2021 were searched in the PubMed, Scopus, Scielo, and Web of Science databases. The search strategy included studies comprising the descriptors: animal species, diabetes induction method, intervention time, part of okra fruit used (whole, seeds, or peels), and dose as well as observed effects on biochemical and metabolic parameters. The systematic review was carried out according to the PRISMA statement, Cochrane bias risk tool (SYRCLE's RoB tool), and registered for systematic review protocols (PROSPERO). Results A total of 326 articles were identified and after the exclusion of studies with gestational animal models, non-rodent animals, and non-diabetic animals, 11 studies involving 388 rodents were selected for the synthesis of results. The diabetes induction methods included streptozotocin, streptozotocin-nicotinamide, alloxan monohydrate, insulin resistance by high-fat diets or formulation described in AIN - 76, and feeding with high-fat food. Both Wistar albino rats, Sprague-Dawley males, and rats of both sexes of the Long-Evans lineage as well as male albino mice and C57BL females were included in the experiments. Studies showed that extracts of the fruit, the fresh fruit, or its various fractions had positive effects on the following markers: glycated hemoglobin, cholesterol, HOMA-IR, oral glucose tolerance test, and blood glucose, in acute (2 and 24 h), and chronic (up to 4 months) treatment. Conclusion An important hypoglycemic effect of okra in its various fractions on induced diabetes was observed by different authors. Moreover, okra promoted improvement in metabolic markers such as insulin sensitivity, lipid profile, and bodyweight loss.
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Metabolic syndrome is a serious health condition, yet a common worldwide disorder. It includes several risk factors such as hypertension, dyslipidemia, and high glucose levels which lead the patients to higher risks of cardiovascular diseases, diabetes, and stroke. Phytotherapy plays an important role in treating components of metabolic syndrome. Nettle (Urtica dioica) is considered a valuable plant due to bioactive compounds such as formic acid and rich sources of flavonoids. To acknowledge the role of nettle in metabolic syndrome, several mechanisms have been suggested such as alterations in potassium and calcium channels which improve hypertension. Antihyperlipidemic properties of nettle are mediated by inhibition of HMGCoA reductase and amelioration of lipid peroxidation via antioxidant effects. Also, one of the flavonoids in nettle, quercetin, is responsible for decreasing total cholesterol. Moreover, nettle is responsible for anti-diabetic effects through processes such as increasing insulin secretion and proliferation of pancreatic β-cells. This review aims to gather different studies to confirm the potential efficacy of nettle in metabolic syndrome.
Stinging nettle (Urtica dioica/urens) herbaceous perennial flowering plant in the Urticaceae family. Urere, the root of its Latin name means “to burn,” referring to the burning pain upon contact with the hairs on its leaves. This stinging property is lost when the plant is dried or extracted. Stinging nettle leaf may be beneficial for allergic rhinitis, hypertension, dyslipidemia, diabetes, and osteoarthritis, whereas stinging nettle root may be beneficial for menopause, benign prostatic hyperplasia, acute and chronic prostatitis, and estrogen-sensitive cancer prophylaxis. This chapter examines some of the scientific research conducted on stinging nettle, both alone and in combination formulas, for treating numerous health conditions. It summarizes results from several human studies of stinging nettle’s use in treating allergic, cardiovascular, cardiometabolic, genitourinary, musculoskeletal, and oncologic disorders. Finally, the chapter presents a list of stinging nettle’s (roots and leaves) Active Constituents, different Commonly Used Preparations and Dosage, and a Section on “Safety and Precaution” that examines side effects, toxicity, and disease and drug interactions.
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Introduction: Herbal medicines (HMs) have shown therapeutic and toxicological potentials. Thus, the WHO expanded the pharmacovigilance (PVG) scope to include HMs. This study appraised the state of PVG system in Nigeria for the safety monitoring of HMs using WHO core PVG indicators. Methods: Between January and June 2019, 39 PVG experts were requested to independently appraise the PVG system in Nigeria for safety monitoring of HMs using WHO PVG core structural (CSIs), process (CPIs) and outcome (COIs) indicators. The 27 indicators (CSIs = 10, CPIs = 9 and COIs = 8) were scored 3, 2, 1 and 0 for adequate, fairly adequate, inadequate and uncertain states, respectively. CSIs index (CSII) was determined by dividing the summation of CSIs mean score by total obtainable score (30) and expressed in percentage. This was applied to CPIs and COIs to obtain CPIs index (CPII) and COIs index (COII), respectively. Results: The mean ± standard deviation (SD) of participants’ age was 43.6 ± 10.3 years with mean ± SD work experience of 15.3 ± 9.3 years. Majority had doctoral degree (35.9%; 14/39; P >0.05) and were medical doctors (28.2%; 11/39; P > 0.05). Twelve of the 27 indicators scored at least 2.0 and CSIs, CPIs, and COIs accounted for 75.0% (9/12), 0.0% (0/12) and 25.0% (3/12), respectively ( P < 0.05). The total mean score was 27.3 ± 0.2 for CSIs as against 8.0 ± 0.3 for CPIs and 11.2 ± 0.4 for COIs ( P < 0.05). The CSII, CPII and COII were 91.0%; 29.6% and 46.7%, respectively ( P < 0.05). Conclusion: Most of the structural elements are in place for safety monitoring of HMs in Nigeria. However, the process and outcome of PVG indicate an inadequate state. Thus, deliberate efforts are required to ensure the realization of PVG objectives.
Sida rhombifolia (Malvaceae) is popularly used as a treatment for several pathological conditions; however, there is a lack of studies that identify its compounds and that evaluate comprehensively the safety of its consumption. Therefore, the aim of this study was to determinate the phytochemical constitution of the crude extract of Sida rhombifolia (CESR), and its safety in models of acute and repeated doses (28 days) toxicity. The tested dose for the model of acute toxicity was 2000 mg/kg doses for the repeated dose model were 150, 300 e 600 mg/kg. Hematological, biochemical, histopathological and oxidative markers were investigated. HPLC-DAD-MS analysis evidenced the presence of caffeic acid, coumarin, and rutin. In the acute toxicity model the only altered parameters were tissue ROS, and AST and BUN in serum. As for the repeated dose experiment both hematological and biochemical markers remained within the values of reference for the species. Obtained results demonstrate that the CESR did not present significant toxic effects when administrated orally to male and female rats in acute and repeated doses.
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Aim: This study was designed to evaluate the effects of dietary and lifestyle habits on several blood lipid parameters in the Lebanese population. Methods: This was a cross-sectional study for 2,000 individuals, of whom 1,003 completed the survey about their dietary and lifestyle habits. Anthropometric measurements and blood tests were performed and recorded. Results: Up to 53.2% of the population was hypercholesterolemic. Gender and age contributed to the prevalence of high levels of low density lipoprotein cholesterol (LDL-C) or triglycerides. Prevalence of hypercholesterolemia, hypertriglyceridemia and high LDL-C levels was higher in smokers, physically inactive or those who consume fatty meat or eggs. Prevalence of hypercholesterolemia was not affected by consumption of whole milk, skimmed milk or fruits and vegetables. However, the prevalence of hypertriglyceridemia and high LDL-levels was higher in individuals who consumed whole milk, and lower in those who consumed skimmed or fruits and vegetables. Conclusion: Hyperlipidemia affects more than half of the Lebanese population. The finding that the majority of the individuals were unaware of their lipid profile mandates warrant efforts for both patient and public education.
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Phytoestrogens are naturally occurring nonsteroidal phenolic plant compounds that, due to their molecular structure and size, resemble vertebrate steroids estrogens. This review is focused on plant flavonoids isoflavones, which are ranked among the most estrogenic compounds. The main dietary sources of isoflavones for humans are soybean and soybean products, which contain mainly daidzein and genistein. When they are consumed, they exert estrogenic and/or antiestrogenic effects. Isoflavones are considered chemoprotective and can be used as an alternative therapy for a wide range of hormonal disorders, including several cancer types, namely breast cancer and prostate cancer, cardiovascular diseases, osteoporosis, or menopausal symptoms. On the other hand, isoflavones may also be considered endocrine disruptors with possible negative influences on the state of health in a certain part of the population or on the environment. This review deals with isoflavone classification, structure, and occurrence, with their metabolism, biological, and health effects in humans and animals, and with their utilization and potential risks.
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Purpose of the Review Pharmacology remains the mainstay of treatment for hypertension across the globe. In what may seem like a well-trodden field, there are actually an exciting array of new pathways for the treatment of hypertension on the horizon. This review seeks to discuss the most recent research in ongoing areas of drug development in the field of hypertension. Recent Findings Novel areas of research in the field of hypertension pharmacology include central nervous system regulators, peripheral noradrenergic inhibitors, gastrointestinal sodium modulators, and a counter-regulatory arm of the renin-angiotensin-aldosterone system. Summary This review discusses these pathways in a look into the current status of emerging pharmacological therapies for hypertension.
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Natural extracts are complex mixtures that may be rich in useful bioactive compounds and therefore are attractive sources for new leads in drug discovery. This review describes drug discovery from natural products and in explaining this process puts the focus on ion-channel drug discovery. In particular, the identification of bioactives from natural products targeting nicotinic acetylcholine receptors (nAChRs) and serotonin type 3 receptors (5-HT3Rs) is discussed. The review is divided into three parts: "Targets," "Sources," and "Approaches." The "Targets" part will discuss the importance of ion-channel drug targets in general, and the α7-nAChR and 5-HT3Rs in particular. The "Sources" part will discuss the relevance for drug discovery of finding bioactive compounds from various natural sources such as venoms and plant extracts. The "Approaches" part will give an overview of classical and new analytical approaches that are used for the identification of new bioactive compounds with the focus on targeting ion channels. In addition, a selected overview is given of traditional venom-based drug discovery approaches and of diverse hyphenated analytical systems used for screening complex bioactive mixtures including venoms.
The biological activity and structural diversity of natural products are unsurpassed by any available synthetic screening libraries. As such, these privileged scaffolds serve as important, biologically prevalidated platforms for the design of compound libraries in the search for new drug candidates. Recent progress has focussed on improving the potency, selectivity and pharmacokinetics of bioactive natural products through structural modification, leading to the emergence of a number of drug-like lead compounds. Here, we review recent advances in the exploitation of terpenoid, polyketide, phenylpropanoid and alkaloid natural product scaffolds for inspiration in the design and development of important new drug candidates.
Flavonoids are a diverse group of bioactive polyphenolic compounds abundant in dietary plants and herbs. Regular consumption of flavonoids exerts cardio-vasculoprotective effects and may reduce the onset or progression of many cardiovascular diseases, particularly hypertension. Observational studies suggest inverse associations among either of these three combinations: a) anthocyanin intake and risk of myocardial infarction (MI), b) flavanone intake and risk of ischemic stroke and c) flavonol intake and risk of type 2 diabetes mellitus. Human randomized controlled trials (RCTs) show that catechins and quercetin impart significant blood pressure lowering effects. Mechanistically, flavonoids mediate their antihypertensive effects through increasing nitric oxide (NO) bioavailability, reducing endothelial cell oxidative stress or modulating vascular ion channel activity. In this review, we focus on the six main subgroups of flavonoids, namely flavones, flavonols, flavanols, flavanones, anthocyanins, and isoflavones. We further discuss their antihypertensive effects, and their possible mechanisms of regulating blood pressure. We conclude by addressing the safety of these compounds as well as their potential use in hypertension management and treatment.
Hibiscus sabdariffa (Malvaceae) is a plant that is widely recognised for its antihypertensive properties; however the constituent(s) responsible for this biological activity are presently unknown. The aim of this study was to identify the potential compounds that are responsible for the vasorelaxant activity of H. sabdariffa. Thereafter, the mechanisms involved in producing the vasorelaxation were investigated. The plant was extracted consecutively with hexane, ethyl acetate and methanol. The methanolic extract was subjected to bioassay-guided fractionation in order to isolate pure compounds that possessed vasorelaxant activity. The vascular effects of the pure compounds were studied on the rat aorta in vitro using myography techniques. Hibiscus acid produced a concentration-dependent relaxation of the rat aorta pre-contracted with either phenylephrine (3 μM) or KCl (60 mM), irrespective of the presence of the endothelium. When the tissue was pre-contracted with phenylephrine, the concentration required to produce 50% relaxation (IC50), was 0.09 ± 0.01 mg/ml. Hibiscus acid had no effect on the phasic contraction induced by phenylephrine in Ca²⁺-free physiological solution; but it did affect the component of the contraction that is due to Ca²⁺ influx. In parallel studies, garcinia acid, a diastereoisomer of hibiscus acid, was found to have an almost identical vasorelaxant effect. The vasorelaxant action of both compounds is most likely due to the inhibition of Ca²⁺ influx via voltage-dependent Ca²⁺ channels.
&NA; In 2010, 1.4 billion people globally had hypertension, with 14% controlled to systolic blood pressure (SBP, mmHg) below 140, which contributes to 18 million cardiovascular deaths annually. Recent hypertension guidelines endorsed SBP targets below 130 or lower for all or some hypertensive patients to reduce cardiovascular events (CVEs) more than the prior SBP target less than 140. In 2016, the Australian Guideline strongly recommended target SBP below 120 for adults at very high risk for CVE or aged above 75 years. In 2017 and 2018, the Canadian Guideline recommended automated office SBP (AOSBP) below 120 in adults at high risk and aged above 75 years (grade B). In 2017, the US Guideline recommended SBP below 130 for all adults (moderate-to-high risk class I; lower-risk grade IIb). In 2018, the European Guideline recommended SBP below 140 for all adults, and, if tolerated, a SBP range of 120–129 for adults aged below 65 years and 130–139 for adults aged at least 65 years (class I). The guidelines were variably influenced by Systolic blood PRessure INTervention trial and meta-analyses indicating fewer CVE when mean in-trial SBP was below 130 versus above 130. Clinicians considering lower SBP targets should be aware that: AOSBP preceded by 5-min rest is approximately 10–15 mmHg lower than usual office SBP; hypertensive patients with office SBP consistently versus intermittently below 140 have fewer CVE; benefits of mean office SBP or AOSBP below 120 remain unproven and could increase adverse events. Clinicians worldwide will do well to control SBP to below 140 in most hypertensive patients on most visits, which should lead to mean in-clinic SBP of 120–129.
South Africa contains 9% of the worldʼs higher plants, and despite its rich biodiversity, it has one of the highest prevalence of hypertension in Africa. This review provides information on medicinal plants embraced in South Africa for hypertension management, with the aim of reporting pharmacological information on the indigenous use of these plants as antihypertensives. This review not only focuses on the activity of antihypertensive medicinal plants but also reports some of its phytochemical constituents and other ethnopharmacological and therapeutic properties. Information obtained from scientific and or unpublished databases such as Science Direct, PubMed, SciFinder, JSTOR, Google Scholar, Web of Science, and various books revealed 117 documented antihypertensive plant species from 50 families. Interestingly, Asteraceae topped the list with 16 species, followed by Fabaceae with 8 species; however, only 25% of all plant species have demonstrated antihypertensive effects originating from both in vitro and in vivo studies, lending credence to their folkloric use. Only 11 plant species reportedly possess antihypertensive properties in animal models, with very few species subjected to analytical processes to reveal the identity of their bioactive antihypertensive compounds. In this review, we hope to encourage researchers and global research institutions (universities, agricultural research councils, and medical research councils), particularly those showing an interest in natural products, for the need for concerted efforts to undertake more studies aimed at revealing the untapped potential of these plants. These studies are very important for the development of new pharmaceuticals of natural origin useful for the management of hypertension.
Elevated blood pressure (BP) is a major determinant of morbidity and mortality burden related to cardio‐metabolic risk. Current guidelines indicate that controlling and lowering BP promotes cardiovascular (CV) risk reduction. Among antihypertensive agents, angiotensin receptor blockers (ARBs) are characterized by an efficacy profile equivalent to other antihypertensive agents, and are provided with excellent tolerability profile and low discontinuation rates during chronic treatments. Moreover, CV outcomes are reduced by ARBs. Olmesartan is a long‐lasting ARB which proved to achieve a comparable or more effective action in lowering BP when compared with other ARBs. Olmesartan, in fact, displayed a larger and more sustained antihypertensive effect over the 24‐hours, with a buffering effect on short‐term BP variability. These are important features which differentiate olmesartan from the other principles of the same class and that may help to control the increased CV risk in presence of high BP variability. Olmesartan shows similar benefits as other ARBs in terms of all‐cause and CV mortality, and a favourable tolerability profile. Combination of olmesartan with long‐lasting calcium channel blockers and thiazide diuretics represents a rational and effective therapy. Thus, ARBs, including olmesartan, represent one of the most effective and safe treatment for patients with arterial hypertension. This article is protected by copyright. All rights reserved.