Special Articles
Medicinal Herbal Agents that May Effect Blood Pressure
Amos Ziv, 1,6 M.Sc, Lee H. Goldstein, 2,7 MD, Yoram Sandhaus, 1 MD, Shay Pintov, 3,6 MD,
Matityau Berkovitch, 4,6 MD, Ahuva Golik, 5,6 MD
Shiram - Integrated Medical Services Research Unit, Assaf Harofeh Medical Center,
Internal Medicine C. Haemek Medical Center,
3
Shiram - Integrated Medical Services, Assaf Harofeh, Medical Center,
4
Clinical Pharmacology and Toxicology Unit, Assaf, Harofeh Medical Center, 5Department of
Internal Medicine A, Clinical, Pharmacology and Toxicology Unit, Assaf Harofeh
Medical Center6, Affiliated to Sackler School of Medicine,Tel Aviv University
7
Affiliated to Bruce Rapapport School of Medicine, Technion, Haifa
1
2
The concomitant use of medicinal herbal agents with conventional
medications for the treatment of a variety of medical disorders has
increased considerably in recent years. This trend is likely to continue
since public demand for these substances continues to grow and their
market availability is constantly increasing.
Herbs that may have an effect on blood pressure are commonly used
by the general population for the treatment of a variety of ailments
or specifically for reducing blood pressure. Patients and doctors
are often not aware of the effects these herbal agents may have
on blood pressure. In addition, some of these agents may interact
with drugs to cause adverse reactions. Although the prevalence of
severe herbal adverse drug reactions as reported by the FDA is very
low (1,2), information on the possible influence of these agents
on blood pressure may prove to be important and beneficial for
the general physician, pharmacist, nurse and the general patient
population.
Herbal agents have been used traditionally over the millennia by most
cultures around the world. The world health organization estimated
recently that 40-50% of the world population is currently using herbal
The Pharmacological Basis of Blood
Pressure Altering Herbs
The pharmacological effect of herbs on blood pressure varies
according to the active ingredients the herb contains. A number of
herbs used in Traditional Chinese Medicine for treating high blood
pressure have been studied extensively. These herbs may reduce
blood pressure through a variety of known physiological mechanisms.
The Proposed Mechanisms for Lowering Blood Pressure
Vasodilatation - several herbal substances have been shown to have
a vasodilatory effect. Garlic for example is thought to reduce blood
pressure by causing smooth muscle relaxation and vasodilation by
activating production of endothelium-derived relaxation factor (EDRF,
nitric oxide) (33).
Pueraria (Ge Gen – Radix Puerariae), a commonly used Chinese and
Japanese herb and specifically its major active ingredient, Puerarin,
appears to reduce both systolic and diastolic blood pressure and
diminish myocardial oxygen consumption (10). Puerarin might also
medicines. A survey on the use of complementary medicine in the US
have vasorelaxant properties, possibly by blocking beta-adrenergic
in 2002 (3). This data denotes a growing trend which is likely to
angiotensin II activity and platelet aggregation (12).
Since many herbal medicines have been noted to have an effect
have a diuretic effect. Alisma (Ze Xie – Rhizoma Alismatis), a Chinese
concomitant use of these agents with conventional medications. The
and hypertension, produces a strong diuretic effect by significantly
herbal medicines that may affect blood pressure.
volume by up to 63% (13). This herb may also induce a hypotensive
Effect on Blood Pressure
inhibition (14).
suggests that more than 38 million Americans used herbal medicine
receptors (11). Puerarin might also decrease plasma renin and
continue (4,5).
Diuretic Effect – Many commonly used herbs have been shown to
on blood pressure, it is important to recognize and identify the
medicinal herb commonly used to treat edema, urinary tract infections
purpose of this article is to introduce and describe commonly used
increasing sodium excretion. The rhizome (root) increased urine
response through other mechanisms such as Angiotensin-I
Approximately 100 herbs are reported in the literature to have an effect
Calcium Channel Blocking Effect – The Chinese herb Fang Ji (Radix
as having the potential to increase blood pressure, the majority of
Tetrandrine, a bisbenzylisoquinoline alkaloid, reduces blood pressure
(Panax Ginseng) is the only commonly used herb that may produce
type voltage-gated calcium channel (15). This herb is commonly used
dependant (9).
and coronary diseases.
on blood pressure (6-8). Although few of these herbs were described
stephania tetrandrae) which contains the highly active component
the agents show an ability to decrease blood pressure. Ginseng
by blocking inward calcium current in the benzothiazepine site of the L-
either a hypotensive or a hypertensive effect. These effects are dose
in Chinese medicine for the treatment of hypertension, angina pectoris
31
Israeli Bilingual Journal of Hypertension, No. 10, December 2007
Special Articles
Commonly Used Herbal Medicines
that Effect Blood Pressure
The following five herbal agents are commonly used by the general
population for a variety of different disorders.
Ginseng (Panax Ginseng) - A very popular plant root grown originally
in China and today also in Japan, Korea and North America. Ginseng
is commonly used as an adaptogenic agent for fatigue, insomnia,
anxiety, depression and immune enhancement. It is also used for
increasing resistance to environmental stress and as a general
enhancer of well-being. This herb is also used for improving physical
and athletic performance, improving cognitive function, concentration
and memory. Ginseng has a variety of active ingredients, consisting
mainly of ginsenoid saponins. Ginseng is marketed either as a single
herb compound or in combination with other herbs. The single herb
compound is available in tablet as well as in alcoholic extracts (known
as tinctures).
Experiments in dogs showed that intravenous administration of ginseng
extract caused an immediate drop in blood pressure. The effect was
long lasting suggesting that it might be facilitated by a Calcium channel
blocking like effect (16) and interference with calcium mobilization into
vascular smooth muscle cells (17). Rg1, one of the active ingredients
in Ginseng can stimulate the production and release of nitric oxide
(NO) from endothelial cells (18). Another ingredient, Ginsenoside Rb1
lowers blood pressure and acts as a CNS depressant (19). It also
interferes with platelet aggregation and coagulation. Interestingly,
Ginseng extracts exhibit a peripheral vasoconstricting effect in low
doses and peripheral vasodilatation in high doses. However, in cerebral
and coronary vessels it exhibits only a vasodilating effect resulting in
improvement in cerebral and coronary blood flow (42). These varying
effects can probably be attributed to the many different saponins that
present as the active ingredients in this herb.
The potential of Ginseng to increase BP should be emphasized as this
herb is not suitable for patients with hypertension and may interfere
with blood pressure lowering medications. There is some evidence
that Panax ginseng can inhibit the cytochrome P450 2D6 (CYP2D6)
enzyme by approximately 6% (20). However, contradictory research
suggests that Panax ginseng might not inhibit CYP2D6 (21). Until
more is known, Panax ginseng should be used cautiously in patients
taking drugs metabolized by these enzymes. Some of these drugs
include amitriptyline (Elavil), clozapine (Clozaril), codeine, desipramine
(Norpramin), donepezil (Aricept), fentanyl (Duragesic), flecainide
(Tambocor), fluoxetine (Prozac), meperidine (Demerol), methadone
(Dolophine), metoprolol (Lopressor, Toprol XL).
Ginko (Ginko Biloba) – The fruit and leaves of the Ginko tree
are commonly used orally for dementia, including Alzheimer's,
vascular, and mixed dementia. Ginkgo leaf is also used for conditions
associated with cerebral vascular insufficiency, especially in the
elderly, including memory loss, headache, tinnitus, vertigo, dizziness,
concentrating difficulty, mood disturbances and hearing disorders. It
is also used orally for ischemic stroke. Ginko is also used for cognitive
disorders secondary to depression and to improve cognitive behavior
and sleep patterns in patients with depression and chronic fatigue
syndrome (CFS); eye problems, including macular degeneration and
glaucoma; attention deficit-hyperactivity disorder (ADHD); thrombosis;
heart disease; arteriosclerosis and angina pectoris. The major active
ingredients in the herb are flavonoids and glycosides.
Ginko is marketed either as a single herb compound or in combination
with other herbs. The single herb compound is available in tablets.
The vascular effect of Ginko extract is very well established.
Considerable clinical as well as experimental evidence suggest that
extracts from Ginko leaves induce vasodilation and improve vascular
blood flow, particularly in the regions of the deep seated medium
and small arteries (22). Overall, ginkgo leaf acts to increase cerebral
and peripheral blood flow microcirculation, and reduce vascular
permeability (23,24). Ginko also has a moderate blood pressure
lowering effect. Evidence suggests that ginkgo leaf extract seems to
increase pancreatic beta-cell function in response to glucose loading
and modestly reduce blood pressure (25).
There is conflicting evidence about whether ginkgo induces or
inhibits CYP3A4 (26, 27) Ginkgo does not appear to affect hepatic
CYP3A4 (28). However, it is not known if ginkgo affects intestinal
CYP3A4. Preliminary clinical research suggests that taking
ginkgo does not significantly affect levels of donepezil, a CYP3A4
substrate (29).
Although the evidence regarding the effect of Ginkgo on cytochrome
P450 is not conclusive, it is best that this herb be used cautiously
in patients taking drugs metabolized by CYP3A4. This may prove
particularly important with patients taking calcium channel blockers
such as Nifedipine, Diltiazem and Nicardipine.
Garlic (Allium Sativum) - The bulb of garlic is commonly used for a
variety of ailments. Garlic is used for hypertension, hyperlipidemia,
coronary heart disease, age-related vascular changes and
atherosclerosis, earaches, chronic fatigue syndrome (CFS), and
2007 ‫ דצמבר‬,10 ‫ גיליון‬,‫כתב עת דו לשוני ליתר לחץ דם‬
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Special Articles
Medicinal Herbal Agents that May Effect Blood Pressure
menstrual disorders. Garlic is also used for cancer prevention and to
treat infections. Garlic is regarded as a potent platelet aggregation
inhibitor. Many of the pharmacological effects of garlic are attributed
to the allicin, ajoene, and other organosulfur constituents such as
S-allyl-L-cysteine. Fresh garlic contains approximately 1% alliin. One
milligram of alliin is converted to 0.458 mg allicin which is regarded as
the major active compound in garlic. Further conversion yields ajoene.
The amount of allicin in garlic preparations is dependent upon the
method of preparation.
Taking low doses of garlic powder orally, 300 mg per day seems to
slow the age-related aortic elasticity decrease. Higher doses of 900
mg per day seem to slow development of atherosclerosis in both aortic
and femoral arteries when used over a four-year period (30,31).
Evidence suggests that taking garlic orally can modestly reduce blood
pressure by 2% to 7% after 4 weeks of treatment (32). Garlic is thought
to reduce blood pressure by causing smooth muscle relaxation and
vasodilation by activating production of endothelium-derived relaxation
factor [EDRF, nitric oxide (33)].
Clinical research suggests garlic oil can inhibit the activity of CYP2E1
by 39% (34). Garlic oil should be used cautiously in patients taking
drugs metabolized by these enzymes. Some drugs metabolized by
CYP2E1 include acetaminophen, chlorzoxazone (Parafon Forte),
ethanol and theophylline.
There is inconsistent information about the effects of garlic on
cytochrome P450 3A4 (CYP3A4) isoenzymes. Until more information
is available regarding this potential interaction, use caution when
considering concomitant use of garlic and other drugs metabolized
by this system. Drugs that might be affected include some calcium
channel blockers (diltiazem, nicardipine, verapamil).
Dang Gui / Dong Quai (Angelicae Gigantis Radix, Chinese
Angelica) -Dang Gui is the dried root of Angelica sinesis. This herb
is used extensively in Chinese medicine for a variety of gynecological
disorders such as premenstrual syndrome, dysmenorrhea, irregular
menstruation cycle, menstrual related bleeding disorders, menopausal
symptoms and infertility. Dang Gui is also used to manage
hypertension, rheumatism, ulcers, anemia, and constipation; and in
the prevention and treatment of allergic attacks. The root of Dang Gui
contains about 0.2-0.4% of essential oil. The major active ingredients
include ferulic acid, ligusticide, angelicide, brefeldin A, butylphthalide,
nicotinic acid, and succinic acid. The herb also contains several
coumarin constituents. Dang Gui is usually marketed as a single herb
compound administered as powder extract in capsules. This herb is
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Israeli Bilingual Journal of Hypertension, No. 10, December 2007
used extensively by the general population due to its potent effects on
Gynecological related disorders.
Dang Gui has a number of known cardiovascular and hematological
effects: the essential oil caused an increase in coronary blood flow
and decreased myocardial oxygen consumption; it also has mild
antiarrhythmic effect (35).
Some of the coumarin constituents of this herb can act as vasodilators
and antispasmodics. Osthol appears to inhibit platelet aggregation
and smooth muscle contraction and cause hypotension (36). An
Intravenous administration of 1-4 gr/kg of the aqueous extract of
the root significantly decreased arterial pressure and reduced the
resistance of coronary, cerebral and femoral arteries in dogs thus
significantly increasing blood flow (37). Preliminary research suggests
Dang Gui might protect against ischemia-reperfusion injury (38).
Dang Gui has been reported to inhibit platelet aggregation and its
concomitant use with coumadin increases the drug's anticoagulant
effects, increases INR and may increase the risk of bleeding (39).
Ma Huang (Herba Ephedra) - The dried herbaceous stem of Ephedra
sinica, Ephedra intermedia or Ephedra equisetina. Orally, ephedra
is used for weight loss and enhancement of athletic performance.
It is also used for allergies and allergic rhinitis; nasal congestion;
and respiratory tract conditions such as bronchospasm, asthma,
and bronchitis. Small doses of this herb are commonly used In
Traditional Chinese medicine for the treatment of asthma. All three
Ephedra herbs contain the phenylproamine alkaloids l-ephedrine,
d-pseudoephdrine. E. sinica contains 55-78% ephedrine and 12-23%
pseudoephedrine (40).
Use of Ma Huang as a dietary supplement is prohibited in most
countries including Israel. However, this herb is available for purchase
in a variety of exercise performance enhancing formulas as well as
weight loss formulas imported for private non commercial use.
Ephedrine, having a similar structure to epinephrine, is a well known
sympathomimetic agent, acting on both α-and β-adrenergic receptors.
By its β-adrenergic action, it relaxes bronchial muscles and produces
the antiasthmatic action. It produces myocardial stimulation by its
β1-agonist effect. Ephedrine also constricts blood vessels by its
α-agonistic effect, causing an increase in blood pressure and heart
rate and increasing myocardial contractility and cardiac output (40).
Use of this herb has been associated with severe adverse reactions
such as myocardial infarcts and cerebral accidents (41). The ability
of Ma Hunag to increase BP should be emphasized as this herb may
possibly interfere with blood pressure lowering medications.
Special Articles
Herb Name
Ginseng
(Panax Ginseng)
Ginko
(Ginko Biloba)
Ma Huang
(Herba Ephedra)
Dang Gui
(Angelicae Sinesis)
Garlic
(Allium Sativum)
Common Uses
Fatigue, Insomnia,
Depression, Immune
Enhancement,
Hypotension
Active Ingredients
Ginsenoids Saponins
(Rb1, Rg1)
Dementia,
Ginkolides,
Cerebrovascular
Insufficiency, Memory
Floavone Glycosides
Loss, Poor Concentration
Weight Loss
Enhance Athletic
Performance
Asthma, Nasal
Congestion,
Allergic Rhinitis
Hypertension,
PMS, Irregular
Menstruation Cycle,
Menstrual Bleeding
Disorders, Menopausal
Symptoms, Infertility
Phenylproamine
Alkaloids, L-Ephedrine,
D-Pseudoephedrine
Ferulic Acid, Ligusticide,
Angelicide, Brefeldin A,
Butylphthalide, Nicotinic
Acid, Succinic Acid,
Coumarin Constituents
Hypertension,
Hyperlipidemia,
Coronary Heart Disease,
Atherosclerosis,
Alliin, Allicin, Ajoene,
Earaches, Infections,
S-Allyl-L-Cysteine
Chronic Fatigue
Syndrome (CFS),
Menstrual Disorders,
Cancer Prevention
Summary
Medicinal herbal agents provide a promising potential for the treatment
of a variety of medical disorders. Considerable resources are currently
being devoted by large pharmaceutical companies as well as by
government agencies to evaluate feasibility to develop drugs from
these agents. Market availability of medicinal herbs as well as public
demand for these agents are constantly increasing and this trend is
likely to continue. Herbs are used by the public for the treatment of
a variety of medical disorders including high blood pressure. Many
of these herbs may directly affect blood pressure or indirectly alter
the function of blood pressure lowering medications. Improper use
Proposed Mechanisms
Of Action
Calcium Channel
Blocking,
Effect on
Blood Pressure
↑ High Doses
Nitric Oxide Production
and Release
Increase Cerebral And
Peripheral Blood Flow,
Reduce Vascular
Permeability
Increase
↓ Low Doses
Decrease
↓ Moderately
Decreases
Possible/known Herb
- Drug Interactions
Cytochrome P450:
CYP2D6
Amitriptyline, Clozapin,
Codeine, Desipramine,
Donepezil, Fentanyl
Flecainide Fluoxetine
Meperidine, Methadone,
Metoprolol
Inconclusive:
Cytochrome P450
CYP3A4
Nifedipine, Diltiazem,
Nicardipine
-and -Adrenergic
↑ Increases
Methylxanthines,
QT Interval Prolonging
Drugs,
CNS Suppressants
Increases Coronary
Blood Flow, Decreased
Myocardial Oxygen
Consumption,
Antiarrhythmic,
Vasodilator
Protection Against
Ischemia-Reperfusion
Injury, Inhibition of
Platelet Aggregation
↓ Decreases
Anticoagulant Drugs,
Antiplatelet Drugs,
Warfarin (Coumadine)
Sympathomimetic:
Agonist
Improve Aortic Elasticity,
Slow Development of
Atherosclerosis,
↓ Moderately
Moderately Reduce Blood
Decreases
Pressure,
Strongly Inhibit Platelet
Aggregation
Cytochrome P450:
CYP3A4
CYP2E1
Acetaminophen,
Chlorzoxazone Ethanol,
Theophylline.
Diltiazem, Nicardipine,
Verapamil
of herbal agents in conjunction with conventional medications may
counteract or intensify the drug's effect and may produce harmful
adverse reactions.
It is therefore imperative that doctors and health care practitioners
acquire information from their patients regarding the use of herbal
supplements. Patient intake should routinely include questions
regarding the use of herbal supplements. Doctors should openly and
positively encourage their patients to reveal information about use of
dietary supplements and should check for possible interactions. In
addition, doctors and health care practitioners should be familiar with
the commonly used herbal agents and should utilize internet and other
resources that provide information regarding these substances.
2007 ‫ דצמבר‬,10 ‫ גיליון‬,‫כתב עת דו לשוני ליתר לחץ דם‬
28
Special Articles
Medicinal Herbal Agents that May Effect Blood Pressure
In light of the high prevalence use of blood pressure lowering
medications and since a substantial number of popular medicinal
herbs affect blood pressure, awareness of health care practitioners
and patients to this issue should further be heightened.
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