Curr Hypertens Rep (2017) 19: 77

DOI 10.1007/s11906-017-0775-5

ANTIHYPERTENSIVE AGENTS: MECHANISMS OF DRUG ACTION (ME ERNST, SECTION EDITOR)

Herbs Used for the Treatment of Hypertension and their

Mechanism of Action
Steven G. Chrysant 1 & George S. Chrysant 2

Published online: 18 September 2017

# Springer Science+Business Media, LLC 2017

Abstract There is great interest lately, in the use of herbs for Introduction
the treatment of hypertension and cardiovascular disease
(CVD). Herbs and plants contain many phytochemicals that The use of complementary and alternative medicine (CAM)
have been effective in the treatment of CVD and hypertension. for the treatment of various health conditions that include hy-
Accumulating scientific evidence provides a reason for the use pertension, cardiovascular diseases (CVDs), dyslipidemias,
of herbs by health practitioners for treating their patients. The and diabetes mellitus is gaining increasing popularity in the
rationale for this expanding use of herbs is the belief of pa- USA and worldwide, since a large proportion of patients relies,
tients in a “holistic medicine” and that herbs are natural, safe, at least in part, on herbs as a complement to conventional
and effective. However, there are reasons of concern with the therapy for the primary care of these conditions [1–3]. Over
use of herbs, because they are not regulated or supervised the last decade, the National Health Statistics Reports (NHSR)
carefully and their use could lead to serious complications or have shown a steady and substantial increase in the use of
interactions with their combination with traditional medicines. CAM and according to NHSR, 4 out of 10 (40%) of US adults
In addition, their use is associated with significant out of pock- interviewed used CAM [1]. This high CAM utilization is
et expenses, because their use is not compensated by health fueled by a number of factors like, ease of access, relative
insurance providers. In this review, we present the scientific affordability, an anecdotal perception of higher safety, and ef-
evidence for the use of herbs. ficacy without any scientific evidence to back up their claims
[4•]. Although many herbs have shown promising potential,
many of them remain untested and their use is either poorly
Keywords Herbs and hypertension . Herbal effectiveness . monitored or not monitored at all, and their interactions, when
Herb safety . Hypertension . Cardiovascular disease . Herb combined with existing orthodox, pharmaceuticals could lead
costs to serious adverse effects [4•]. Besides the unsure efficacy and
safety of herbs, they also result in significant out of pocket
expenses, due to the fact that herbs are not covered by health
This article is part of the Topical Collection on Antihypertensive Agents: insurance. According to a 2007 estimate by the NHSR, this
Mechanisms of Drug Action resulted in $33.9 billion expenses by US adults for purchasing
CAM products and visiting CAM practitioners [5•]. Since ef-
* Steven G. Chrysant
ficacy and safety continue to be a major issue with the use of
schrysant@yahoo.com
herbal remedies, it becomes imperative for the regulatory au-
thorities to put in place appropriate measures for the protection
1
University of Oklahoma College of Medicine, Oklahoma, OK, USA of public health by ensuring that all herbal medicines sold are
2
INTEGRIS Baptist Medical Center, 5700 Mistletoe Court, safe and effective. In order to get a better perspective of the
Oklahoma, OK 73142, USA current and overall safety and effectiveness of herbal remedies,
77 Page 2 of 10 Curr Hypertens Rep (2017) 19: 77

a focused Medline search of the English language literature Table 1 Annual costs of complementary and alternative medicine by
2007 NHSR
between 2011 and 2017 was performed, and 34 papers with
information on the antihypertensive effectiveness, mechanism Total annual costs of CAM $33.9 billion
of action, and costs of herbal products were selected and will
be discussed in this review. Self-care costs $22.0 billion (64.8%)
NVNMNP $14.8 billion (43.7%)
CAM practitioner’s fees $11.9 billion (35.2%)
Yoga, tai chi, and qigong classes $4.1 billion (12.0%)
Reasons for Patients of Using CAM Homeopathic medicine $2.9 billion (8.7%)
for the Treatment of Hypertension Relaxation techniques $0.2 billion (0.6%)

The reasons for using herbs for the treatment of hypertension Table constructed from data from reference 5
and other cardiovascular diseases either alone or in combina- CAM complementary alternative medicine, NVNMNP non-vitamin non-
tion with conventional drugs are due to several factors. These mineral natural products
include their belief in the “holistic concept” of medicine that
herbs are effective and safe in contrast to conventional medi-
Allium sativum (Garlic)
cines, and they are less expensive than conventional drugs
[6–9]. In addition, there is the desire by the patients to have
Garlic in different preparations (powder, extract) has been used
control of their own care due to the perception that CAM is less
extensively for thousands of years and by different countries
authoritative and complicated than conventional therapy and is
around the world for the treatment of hyperlipidemia, the pre-
also more compatible with their own religious beliefs and phi-
vention of CVD, as well as the treatment of hypertension, with
losophies [9]. It is of interest that the increased desire to use
good results. The BP-lowering effects of garlic have been re-
herbal treatment is not a reflection of the economic or educa-
ported by several studies and reviews and are listed in Table 2. In
tional status of an individual, since the use of CAM is higher
a randomized, double-blind, placebo-controlled study, Ried
among well-educated and wealthier older individuals. Indeed,
et al. [16] tested the effects of aged garlic in 88 patients with
70% of the population in developed countries have utilized
uncontrolled BP to receive either aged garlic extract (1200 mg/
herbal medicine for the treatment of hypertension and other
day) or placebo. After 12 weeks of follow-up, the BP was sig-
CVDs [10]. This is not surprising due to the belief that herbs
nificantly reduced with garlic by 11.5 ± 1.9/6.3 ± 1.1 mmHg
contain thousands of bioactive components that have known
(p < 0.001) compared to placebo. Central hemodynamic mea-
therapeutic applications [11]. There is also, a recent interest in
sures including central BP, central pulse pressure (PP), pulse
adapting the Chinese concept of “holistic regulation” in herbal
wave velocity (PWV), and arterial stiffness tended to improve
medicine, in which the organism is considered as a whole,
with garlic compared to placebo. In this study, garlic was effec-
instead of the western medicine’s concept, that focuses on a
tive in significantly lowering the brachial BP and improving
specific disease target and ignores the whole patient [12•]. The
central hemodynamics and it was highly tolerated and accept-
concept of holistic and herbal medicine is being widely em-
able by the patients. In a systematic review and meta-analysis,
braced by many developed countries with CAM now being the
Rohner et al. [17] analyzed the effects of garlic treatment on BP
mainstream in the UK, the rest of Europe as well as Australia
in nine double-blind trials involving 482 patients with hyperten-
and the USA [4•, 13•, 14]. Because these products are not
sion. After a follow-up ranging from 12 to 26 weeks and using
covered by health insurance, the out of pocket expenses of
different garlic preparations and different doses ranging from
purchasing CAM products and visiting CAM practitioners
600 to 900 mg/day, the BP was decreased by 12.6/6.2 mmHg
are in billions of dollars annually (Table 1).
on average, which was significantly lower compared to placebo.
In another review and meta-analysis, Wang et al. [18] analyzed
the results of garlic treatment in 18 randomized trials involving
Most Commonly Used Herbs for the Treatment 799 hypertensive and normotensive subjects. After a follow-up
of Hypertension and Cardiovascular Diseases ranging from 12 to 24 weeks and different doses of garlic treat-
ment ranging from 300 to 2400 mg/day, the BP was decreased
There is a growing interest in the USA for the use of herbal and by 4.4/2.7 mmHg in the hypertensive but not in the normoten-
plant products by health practitioners and pharmacologists for sive subjects and was superior to placebo treatment. However,
the treatment of CVD and hypertension. Several studies and these studies showed significant heterogeneity in the BP effects
meta-analyses have demonstrated their BP-lowering effects as of garlic treatment [17, 18]. Regarding the mechanism of the
well as their tolerance and acceptability by patients [5•, 6–15]. BP-lowering effects of garlic, these have been attributed to a
The results from these studies of the most commonly used number of active sulfur compounds that have been reported to
herbs are listed in Table 2 and will be discussed here. modulate endothelium-relaxing factors including stimulation of
Curr Hypertens Rep (2017) 19: 77 Page 3 of 10 77

Table 2 Clinical trials demonstrating the blood pressure-lowering effects of herbs

Herb name Trial design Patients no. Condition status Dose mg/day F-U weeks Effect mmHg Reference no.

Allium sativum RTC 88 HTN 1200 12 − 11.5/− 6.3 BP 16

Allium sativum Rev 482 HTN 600–900 12 − 12.6/− 6.2 BP 17
Allium sativum Rev 799 HTN 300–2400 12–24 − 4.4/− 2.7 BP 18
Beetroot Juice RTC 35 HTN 250 ml 4 − 7.7/− 2.4 BP 21
Camelia sinensis RCT 95 HTN 3 CBT 42 − 2.7/− 2.3 ABP 23
Camelia sinensis Rev 821 HTN 4–6 CGT 42 − 3.2/− 3.4 BP 24
Coptis chinensis Rev 228 HTN 600 mg 4–8 − 4.9/− 2.0 BP 25
Crataegus species RTC 21 HTN 2000–5000 mg 4 days − 6.9/+ 0.6 ABP 29
Crocus sativus RTC 30 NTN 400 mg 1 − 11.0 SBP 33
Hibiscus sabdariffa RTC 193 HTN 250 mg 4 − 17.2/− 12.0 BP 35
Hibiscus sabdariffa RTC 65 HTN 3 × 240 ml ext 6 − 7.2/− 3.1 BP 36
Nigella sativa RTC 70 NTN 2.5 ml oil 8 − 10.6/− 9.6 BP 43
Panax (ginseng) RTC 64 HTN 3000 ext 12 − 17.4/− 7.2 BP 46
Panax (ginseng) RCO 23 NTN 400 1 − 4.4/− 3.6 BP 47
Panax (ginseng) RCT 90 HTN 300 8 − 3.1/− 2.3 BP 48
Salviae miltiorrhizae RTC 55 HTN 2000 ext 12 − 13.9/− 4.0 BP 52

F-U follow-up, RTC randomized controlled trial, RCO randomized cross-over trial, Rev review and meta-analysis, HTN hypertension, NTN
normotension, ABP ambulatory BP, SBP systolic BP, CBT cups black tea, CGT cups green tea, ext extract

production of nitric oxide (NO) and hydrogen sulfide (H2S) with beetroot juice (nitrate depleted juice 140 ml/day) and were
the most important being allicin and its inhibitory effect on the followed for 1 week. The high nitrate group had a reduction
angiotensin converting enzyme (ACE), all of which lead to BP in home BP of 4.9/3.5 mmHg compared to low-nitrate group
reduction [12•, 19]. Overall, garlic was well tolerated and had a BP reduction of 5.4/3.2 mmHg. Similar BP reductions were
high acceptance rate (93%) among the subjects treated. The only observed in the 24-h ABP. In this study, there was no difference
minor adverse effects included mild gastrointestinal problems. in BP reduction between the high- and low-nitrate groups in
The only contraindication to treatment with garlic is patients both home and 24-h ABP. The non-significant difference in BP
taking anticoagulants, because it could increase the bleeding reduction in this study between the high- and low-nitrate group
risks due to its platelet atiaggregatory effects [20]. could be attributed to fairly well-controlled BP from the con-
comitant treatment with 1–3 antihypertensive medications.
Beetroot The antihypertensive effects of beetroot juice have been attrib-
uted to the high supply of inorganic nitrates and the generation
Beetroot food supplements have been shown to exert favorable of endothelial NO from the chemical reduction of inorganic
effects on BP. In a randomized, placebo-controlled study, Kapil nitrite (NO2−).
et al. [21•] investigated the effects of beetroot juice dietary
supplement in 68 hypertensive patients, 34 treatment naïve, Camelia sinensis (Tea)
and 34 treated, ages 18–85 years. The patients were random-
ized to beetroot juice 250 ml/day (n = 32) or placebo (250 ml/ Collectively, the teas (black and green) prepared from Camellia
day nitrate-free beetroot juice) and were followed for 4 weeks. sinensis are the most frequently consumed beverages world-
Beetroot supplementation reduced the clinic BP by 7.7/ wide and are only second to water. Tea has pleiotropic effects
2.4 mmHg (p < 0.001), the mean 24-h ambulatory BP (ABP) that include its anti-inflammatory, antidiabetic, and antihyper-
by 7.7/4.2 mmHg (p < 0.0.001), and the home BP by 8.1/ tensive actions. Although the antihypertensive effects of tea are
3.8 mmHg (p < 0.001). The endothelial function was improved not well established, several studies have demonstrated signif-
by 20% (p < 0.001), and the arterial stiffness (PWV) was icant BP-lowering effects. In a randomized, placebo-controlled
reduced by 0.59 m/s (p < 0.01). The beetroot supplements were trial by Hodgson et al. [23], 95 hypertensive patients aged 35–
well tolerated, and there was no evidence of tachyphylaxis to 75 years were randomized to 3 cups/day of leaf black tea con-
treatment. In another randomized placebo-controlled, cross- taining 429 mg of polyphenols +96 mg caffeine or a placebo
over study by Bondonno et al. [22], 27 treated hypertensive matched of caffeine flavor drink. After a follow-up of 6 months,
patients mean age 63.2 years were randomized to treatment the 24-h ABP was reduced by 2.7/2.3 mmHg in tea consumers
with high-nitrate beetroot juice (140 ml/day) or low-nitrate compared to placebo consumers (p < 0.001). In a review on the
77 Page 4 of 10 Curr Hypertens Rep (2017) 19: 77

effects of black and green tea on BP reduction, Hartley et al. modest decreases of BP. In an older study by Walker et al.
[24] analyzed the results of 11 randomized control trials [28], hawthorn extras of 500 and 600 mg/day decreased sig-
(RCTs), seven with green tea and four with black tea, involving nificantly only the diastolic BP (DBP) by 13.1 mmHg.
821 participants. After a mean follow-up of 6 months, the black However, a recent study by Asher et al. [29] used hawthorn
tea reduced the BP by 1.85/1.27 mmHg, whereas the green tea extracts of 1000, 1500, and 2500 mg twice daily in a four-
reduced it by 3.18/3.42 mmHg. The treatment was well toler- period cross-over study in 21 mildly hypertensive subjects
ated, and there were no major adverse events related to treat- mean age 51 years to investigate its effects on BP-lowering
ment. Regarding the BP-lowering effects of tea, there are sev- and in flow-mediated vasodilation. In this study, there was no
eral potential mechanisms to account for this. Its major effect is change from baseline in ABP or in flow-mediated vasodila-
due to the flavonoids (catechins) content of tea. Flavonoids tion by hawthorn extracts. The actual changes in baseline ABP
stimulate NO production and reduce the plasma concentrations were − 8.2/+ 1.2, − 6.9/+ 0.2, and − 6.8/+ 0.7 with placebo and
of endothelin-1. These actions lead to reduction of vascular tone − 6.9/+ 0.2, − 6.8/+ 0.7, and − 5.8/+ 0.7 mmHg for the haw-
causing vasodilation and reduction in peripheral vascular resis- thorn extracts 1000, 1500, and 2500 mg twice daily, respec-
tance and BP. Another possible mechanism could be through tively (p = ns). Some of hawthorn’s individual constituents
weight reduction. It has been shown that flavonoids, which are (procyanidins and flavonoids) have been shown to increase
the same in green and black tea together with caffeine, could NO levels and to improve endothelial function, which could
reduce abdominal fat resulting in weight loss. indicate that hawthorn extracts have BP-lowering effects.
More studies are needed to demonstrate whether hawthorn
Coptis chinensis (Berberine) extras can be used for the treatment of hypertension. When
the participants of this study were asked whether they would
Coptis chinensis and its natural alkaloid berberine have been use hawthorn extracts for the treatment of their BP, 66.6% said
used for centuries by Chinese and Ayurvedic medicine. Its they would use it alone and 90.5% said they would use it in
activity in carbohydrate metabolism, endothelial function, combination with other antihypertensive drugs.
the cardiovascular system, and hypertension have generated
considerable interest in the Western countries in the last de- Crocus sativus (Saffron)
cade. Berberine is mainly used for the treatment of diabetes
mellitus, CVD, and hypertension [25, 26]. Regarding the an- Saffron is a stemless herb indigenous to Southwest Asia, Spain,
tihypertensive effects of berberine, a review and meta-analysis Greece, and Marocco and has been used over 4000 years for the
by Lan et al. [25] of 27 RCTs involving 2569 patients with treatment of various medical conditions including hypertension
different conditions including hypertension, berberine extract [30]. Saffron contains several ingredients that include crocin,
demonstrated significant BP-lowering effects. Of the 27 stud- picrocrocin, safranal, and crocetin, flavonoids, and anthocya-
ies, two involved in 228 hypertensive patients. These patients nins, which exhibit different mechanisms of action including
were randomized to active treatment with berberine 0.6 g/ antihypertensive and vasodilatory effects [30]. Several experi-
day + background antihypertensive therapy (n = 116) or to mental studies have shown significant antihypertensive and
control group with background antihypertensive therapy only vasodilatory effects of saffron ingredients [31, 32]. Also, a ran-
(n = 112). Berberine added to background therapy reduced the domized, placebo-controlled study in 30 volunteers demonstrat-
BP by 4.91/2.00 mmHg compared to control group. The hy- ed significant BP-lowering effects of Crocus sativus [33]. The
potensive effects of berberine were attributed to increased subjects were divided in three groups, ten each and were follow-
generation of NO through stimulation of NO synthase ed for 1 week. Group 1 received placebo, and groups 2 and 3
(eNOS) and the decreased catecholamine levels leading to received 200 and 400 mg tablets, respectively. The 400-mg dose
peripheral vasodilation and decrease in BP. In addition to of the herb resulted in significant reduction in systolic BP (SBP)
BP-lowering, berberine exerts significant antidiabetic effects in- and mean arterial pressure by 11 and 5 mmHg, respectively. The
cluding reduction of body weight [26]. Additional hypotensive herb was well tolerated, and no adverse effects were noted. The
mechanisms have been attributed to increased levels of prosta- mechanism of action of C. sativus for its antihypertensive and
glandin I2 (PGI2), opening the KATP and blocking the iCa2+ vasodilatory effects is possibly mediated through blockade of
voltage gated channels, thus blocking the Ca2+ cell influx [15•]. Ca2+ channels, opening of potassium channels, and antagonism
of the β-adrenoceptors.
Crataegus Species (Hawthorns)
Hibiscus sabdariffa (Roselle)
Hawthorns (hawberry, thorn apple) are shrubs that comprise
almost 300 species and have been used for centuries in tradi- Hibiscus, widely known as roselle, is a popular folk medicine
tional medicine for the treatment of CVDs [27]. Treatment of used for fever, hypertension, and other conditions. Roselle’s
hypertensive patients with hawthorn extracts resulted in BP-lowering effects have been studied in both animals [34]
Curr Hypertens Rep (2017) 19: 77 Page 5 of 10 77

and man [35, 36]. In a randomized, double-blind trial by glycosides are the main active components of ginseng that
Herrera-Arellano et al. [35], 193 patients ages 25–61 years mediate its antihypertensive and cardiovascular effects [45].
with stage I or II hypertension were randomized to treatment Regarding its antihypertensive effects, several clinical trials
with Hibiscus sandariffa 250 mg/day (n = 100) or lisinopril have shown a significant BP-lowering effect compared to pla-
10 mg/day (n = 93) and followed for 4 weeks. H. sabdariffa cebo. In a randomized, double-blind, placebo-controlled
decreased the BP by 17.2/12 mmHg, and 65.12% achieved BP study, Mucalo et al. [46] investigated the effects of
control. There were no significant clinical or metabolic ad- American ginseng (AG) on arterial stiffness and BP reduction
verse effects noted, and the drug was tolerated by 100% of in 64 diabetic hypertensive patients mean age 63 ± 9.3 years.
patients. In another randomized, double-blind, placebo- The patients were randomized to AG extract 3 g/day or pla-
controlled trial by McKay et al. [36], 65 treatment naive cebo and were followed for 12 weeks. AG reduced the BP by
prehypertensive and mildly hypertensive subjects ages 30– 17.4/7.2 mmHg (p = 0.0001), the augmentation index (AIx)
70 years were randomized to 3 servings/day of 240 ml by 4.5% (p < 0.041), and the PP by 6.4 mmHg (p < 0.018). In
H. sabdariffa or placebo and were followed for 6 weeks. another similar randomized, double-blind, cross-over study,
H. sabdariffa lowered the SBP by 7.2 mmHg vs placebo— Jovanovski et al. [47] studied the effects of Korean red gin-
1.3 mmHg (p = 0.030), but not the DBP compared to placebo. seng (Rg3-KRG) on arterial stiffness and BP in 23 normoten-
Participants with higher baseline BPs showed greater reduc- sive subjects mean age 25 ± 2 years. The subjects were ran-
tions in BP. No adverse clinical or metabolic effects were domized to either 400 mg Rg3-KRG extract or 400 mg wheat
noted. This showed that hibiscus tea incorporated into the diet bran on two separate visits with a 7-day washout period. AIx
could lower the BP of hypertensive subjects. The antihyper- and central BP were measured by applanation tonometry.
tensive effects of H. sabdariffa have been attributed to in- Compared to control, Rg3-KRG produced significant reduc-
creased production of NO, inhibition of Ca2+ channels, and tions in AIx by 4.3 ± 8.9% (p < 0.03), central SBP by
the opening of KATP channels [37–39]. 5.0 ± 7.9 mmHg (p = 0.01), central DBP by
3.9 ± 6.6 mmHg (p = 0.01), and brachial BP by 4.4 ± 10.0/
Nigella sativa (Black Cumin, Seed of Blessing) 3.6 ± 6.4 mmHg (p < 0.05), 3 h after intervention compared to
control. Yet, in another study, the effects on BP of Panax
Nigella sativa has been used for centuries by different coun- ginseng extract (Ginseol K-g1) were studied by Rhee et al.
tries (Europe, Middle East, Africa, and South and Southwest [48], in 90 subjects mean age 55.2 ± 11.8 years with BPs
Asia) for different ailments including diabetes, gastrointesti- ranging from 120 to 159/80–99 mmHg. The subjects were
nal diseases, and hypertension [40]. N. sativa and its most divided into three groups. Group-1 (placebo), group-2
active product thymoquinone have been reported by several (100 mg K-g1), and group 3 (300 mg K-g1) and were follow-
studies to lower BP in humans as well as in different animal ed for 8 weeks. At week 4, the levels of seated SBP (sSBP)
models of hypertension [41–43]. In a randomized, placebo- and seated DBP (sDBP) were decreased from baseline by 3.1/
controlled clinical trial, Fallah Huseini et al. [43] tested the 2.3 mmHg only with the high dose (300 mg) of K-g1
BP-lowering effects of N. sativa seed oil in 70 healthy vol- (p < 0.05). However, at week 8, the differences between the
unteers ages 34–63 years. The subjects were randomized to groups were no longer different. There were no significant
receive 2.5 ml seed oil or placebo twice daily for 8 weeks. clinical or metabolic adverse events noted. Regarding the
N. sativa seed oil decreased the SBP by 10.6 mmHg BP-lowering effects of P. ginseng, these have been attributed
(p < 0.002) and the DBP by 9.6 mmHg (p < 0.04). The to its vascular effects mediated by dramatic increase in eNOS
results of this recent study agree with the results of an older expression and increased production of NO in addition to
study in mild hypertensive patients. In this study, N. sativa blockade of Ca2+-gated channels [46, 48].
seed extract 100 and 200 ml twice daily for 8 weeks reduced
the BP by 2.2/2.0 mmHg [44]. In addition to BP-lowering, Salviae miltiorrhizae (Chinese Sage)
N. sativa reduced total and LDL cholesterol. The antihyper-
tensive effects of Nigella sativa have been attributed to its Salviae miltiorrhizae, known as Danshen or red Chinese sage,
vasorelaxant effects by blocking voltage-gated Ca2+ chan- is one of the oldest and most frequently consumed Chinese
nels and reducing oxidative stress [41, 42]. herbs and is commonly used for the treatment of CVDs [49].
Its antihypertensive effects have been mostly studied in ani-
Panax (Ginseng) mals where it has been shown to exert a significant BP-
lowering effect [50, 51]. So far, there is only one study pub-
Panax species have been used in folk medicine for centuries in lished in human subjects regarding the antihypertensive ef-
Asian countries and lately in the USA, European, and other fects of S. miltiorrhizae by Yang et al. [52]. In this study, 55
countries for various ailments that include CVD and hyper- Taiwanese patients with uncontrolled mild to moderate hyper-
tension [45]. Heterogenous triterpenoid saponins and steroid tension with current conventional treatment ages 18–80 years
77 Page 6 of 10 Curr Hypertens Rep (2017) 19: 77

were randomized to either to Danshen extract capsules Coreandrum sativum (Cilantro, Coriander)
1000 mg twice daily (n = 30) or placebo capsules (n = 25)
and were followed for 12 weeks. The seating BPs prior to Coriandrum sativum is being used in several countries as a
randomization were 153.1 ± 9.4/85.6 ± 10.8 in the Danshen culinary ingredient as well as traditional medicine for the treat-
group and 157.3 ± 17.5/87.8 ± 8.7 mmHg in the placebo ment of CVDs and gastrointestinal ailments [15•]. So far, there
group. After 12 weeks of treatment, the SBP was reduced by have not been any clinical trials for the treatment of hyperten-
13.9 mmHg with Danshen vs 4.2 mmHg with placebo sion. In animal studies, C. sativum has produced a dose-
(p = 0.005) and the DBP was reduced by 4.0 mmHg with dependent reduction in SBP and DBP in normotensive
Danshen vs 3.2 mmHg for placebo, respectively (p = ns). Sprague-Dawley rats [56]. Its antihypertensive effects have
The drug was well tolerated, and there were no adverse inter- been attributed to its vasodilatory and antioxidant properties.
actions with the other antihypertensive drugs. The antihyper-
tensive mechanism of Danshen is mediated though vasodila- Cymbopogon citrate (Lemongrass)
tation by the increased generation of NO and its antioxidant,
anti-proliferative, and anti-inflammatory effects [50–52]. Lemongrass has been used widely by traditional medicine in
several countries including Brazil, China, and Southern Asia
for the treatment of hypertension due to its active vasodilating
ingredient citral [56]. Lemon grass has been shown to reduce BP
Herbs with Possible Antihypertensive Effects
in an experimental hypertensive rat model [57], but not in hu-
in Human Subjects
man subjects. The BP-lowering effects of lemongrass have been
attributed to its vasorelaxant and antioxidant properties [57].
There are several herbs with possible antihypertensive prop-
Besides these herbs, there are also several other herbal
erties from animal studies, but without confirmation of these
medicines used primarily by the traditional Chinese medicine
actions by clinical trials with human subjects.
for the treatment of hypertension and cardiovascular diseases
in man recently published in English in a review by Hao P.
Andrographis paniculata (King of Bitter) et al. [58]. However, the original publications are all in
Chinese.
Andrographis paniculata is a plant commonly known as the
“King of bitter” and has been used by Asian traditional med-
icine for the treatment of the common cold, CVD, and hyper- Mechanisms of Action of Antihypertensive Herbs
tension [15•]. Several labdane-type diterpenoid compounds
have been identified in A. paniculata extracts with potential In order to understand the antihypertensive action of herbs, it
antihypertensive effects, due to increase in NO release and the is necessary to examine their effect on the various factors or
inhibitory effects on ACE and reactive oxygen species (ROS) processes that are involved in the development and mainte-
in SHR [53]. nance of hypertension. These factors include the role of vas-
cular smooth muscle cells, the role of endothelial cells, the role
of ROS, and the role of hormones endothelin-1 and angioten-
Apium graveolens (Celery)
sin II (Ang II). The mechanisms of action of the main herbs
used for the treatment of hypertension are summarized in
Apium graveolens has been shown to significantly decrease
Table 3 and will be discussed here.
the BP in deoxycorticosterone acetate-induced hypertension
in rats as well as in SHR [54]. The antihypertensive effect is
attributed to inhibition of intracellular Ca2+ influx through
The Role of Vascular Smooth Cells
voltage-gated calcium channels.
The vascular smooth muscle cell participation in the develop-
Bidens pilosa (Blackjack) ment of hypertension is through their increased growth and
encroachment on vascular lumen leading to increase in periph-
Bidens pilosa belongs to the family of Asteraceae and has eral vascular resistance [59]. This process is generated through
been shown to exhibit antihypertensive effects in different the interaction of various modulating factors that either stim-
hypertensive rat models [55]. B. pilosa is an easy to grow ulate or inhibit vascular smooth muscle cell (VSMC) growth.
herb that is widely distributed throughout the world as The most important factors that are involved in the vascular
rich source of food and medicine for animals and humans. remodeling are platelet-derived growth factor (PDGF), the
However, its effects and side effects have not been studied fibroblast growth factor (FGF), the endothelin-1, the Ang II,
in human subjects [55]. and the Ca2+-calmodulin interaction, which controls the
Curr Hypertens Rep (2017) 19: 77 Page 7 of 10 77

Table 3 Summary of mechanisms of action of the main antihypertensive herbs

Herb Mechanisms of action

Allium sativum Vasodilation from increased of NO and H2S levels. Blockade of ACE
Beetroot Vasodilation from increased levels of NO from inorganic NO2−
Camelia sinensis Vasodilation from increased levels of NO from flavonoids contained in Camelia. Reduction of endothelin-1
Coptis chinensis Increased levels of NO, PGI2, blocking Ca2+ voltage channels, opening KATP channels, and decreasing catecholamine levels
Crataegus species Vasodilation from increased production of NO from procyanidins and flavonoids contained in Crataegus species
Crocus sativus Vasodilation from crocin, picrocrocin, safranal, crocetin, flavonoids, and anthrocyanins contained in Crocus sativus
Hibbiscus sabdariffa Vasodilation from increased production of NO, blockade of Ca2+ voltage channels, and opening of KATP channels
Nigella sativa Vasodilation through blockade of Ca2+ voltage channels and reduction of oxidative stress
Panax ginseng Vasodilation from increased production of NO and blockade of Ca2+ voltage channels
Salviae miltiorrhizae Vasodilation from increased production of NO and from antiproliferative, antioxidant, and anti-inflammatory effects

NO nitric oxide, H2S hydrogen sulfide, ACE angiotensin converting enzyme, NO2− inorganic nitrite, PGI2 prostaglandin I2

vascular tone through the cross-bridge cycling of the contrac- The Role of the Renin-Angiotensin-Aldosterone
tile proteins actin and myosin [59–62]. Several herbs System
discussed in this review interfere with the action of these fac-
tors and decrease the BP. The renin-angiotensin-aldosterone system (RAAS) plays a
very important role in the regulation of BP, mostly through
the generation of Ang II by the conversion of Ang I to
Ang II by the ACE. Ang II generation causes vascular
Endothelial Cells
remodeling and peripheral vasoconstriction leading to in-
crease in systemic vascular resistance through stimulation
The endothelial cells play a significant role in many aspects of
of the AT1 receptor. In addition, Ang II stimulates the
cardiovascular homeostasis, since endothelial cell function is
release of aldosterone from the adrenal glands leading to
regulated by a variety of receptors. These receptors induce the
plasma volume expansion through salt and water retention
release of vasoactive substances that regulate the vascular tone
adding to its hypertensive effects. Several herbs discussed
and smooth muscle cell function like the vasodilators, NO,
in this review have been shown to interfere with the action
prostaglandin I2 (PGI2), and endothelial-derived hyperpolar-
of ACE and the generation of Ang II [59].
izing factor, as well as the vsosoconstrictors, endothelin-1,
thromboxane, and PDGF [63]. When there is an imbalance
between these vasoactive agents, an increased production of
Discussion and Conclusion
ROS may result, leading to endothelial dysfunction and even-
tually, the development of hypertension [64]. However, endo-
The data presented in this review indicate that herbs are fairly
thelial dysfunction can be reversed by several herbal remedies
safe and effective in inducing moderate reductions in BP ei-
discussed in this review, accounting for their antihypertensive
ther alone or in combination with current antihypertensive
properties.
drugs and are becoming part of evidence-based medicine for
the treatment of hypertension. Their pharmacological actions
appear to favorably mediate several parameters implicated in
Reactive Oxygen Species the pathogenesis of hypertension through their action on vas-
cular smooth muscle cells, endothelial cells, ROS, and inhibi-
Clinical evidence indicates that increased generation of ROS tion of RAAS. The use of herbal medicines continues to in-
by different pathologic states has been shown to play a signif- crease in popularity, and the past decade has witnessed a tre-
icant role in the pathogenesis of atherosclerosis, hypertension, mendous surge in the acceptance and public interest in natural
and other vascular complications through oxygen reactive rad- therapies in both the developing and the developed countries.
icals like, hydrogen peroxide (H2O2), and superoxide (O2−) The World Health Organization (WHO) estimates that as
and hydroxyl (OH−) anions [64]. ROS regulate many cellular many as 5.6 billion people (80%) of the world population
processes in the vasculature such as cell growth, contraction/ are using herbal medicines for primary health care [4•].
dilation, and other processes important in maintaining vascu- However, as the global use of herbal medicinal products con-
lar tone and integrity [65, 66]. Several herbs listed in this tinues to grow and many new products are introduced into the
review have been shown to modify ROS and decrease the BP. market, public health issues surrounding their safety are
77 Page 8 of 10 Curr Hypertens Rep (2017) 19: 77

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note that there can be interactions of herbs with existing anti- perspectives on how to discover drugs from herbal medicines:
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Conflict of Interest The authors declare no conflicts of interest relevant medicinal products in the European Union: focus on the traditional
to this manuscript. herbal medicines category. Drug Inf J. 2011;45:15–23.
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