Hypertension Research (2013) 36, 570–579

& 2013 The Japanese Society of Hypertension All rights reserved 0916-9636/13 OPEN
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REVIEW

Chinese herbal formulas for treating hypertension

in traditional Chinese medicine: perspective
of modern science
Xingjiang Xiong1,3, Xiaochen Yang1, Yongmei Liu1, Yun Zhang1, Pengqian Wang2,3 and Jie Wang1

Hypertension, which directly threatens quality of life, is a major contributor to cardiovascular and cerebrovascular events. Over
the past two decades, domestic and foreign scholars have agreed upon various standards in the treatment of hypertension, and
considerable progress has been made in the field of antihypertensive drugs. Oral antihypertensive drugs represent a milestone
in hypertension therapy. However, the blood pressure standard for patients with hypertension is far from satisfactory. The study
of Chinese herbal formulas for treating hypertension has received much research attention. These studies seek to integrate
traditional and Western medicine in China. Currently, Chinese herbal formulas are known to have an outstanding advantage with
regard to bodily regulation. Research shows that Chinese medicine has many protective mechanisms. This paper addresses the
process of the antihypertensive mechanisms in Chinese herbal formulas for treating hypertension. These mechanisms are to be
discussed in future research.
Hypertension Research (2013) 36, 570–579; doi:10.1038/hr.2013.18; published online 4 April 2013

Keywords: Chinese herbal formulas; traditional Chinese medicine; treatment efficacy

INTRODUCTION preventive medicine (that is, ‘treat what is not yet ill’; the
Cardiovascular and cerebrovascular events are the major causes of ‘Huangdineijing’ and ‘Nanjing’ classics in traditional Chinese
mortality worldwide.1 Hypertension, a chronic disease in which the medicine (TCM) theory).4 This proverb promotes interventions to
blood pressure (BP) in the arteries is elevated, is a major contributor the internal organs that are not affected by the ongoing morbidity
to vascular morbidity and mortality. Patients with hypertension are process and can be compared with avoiding target-organ damage
more likely to have heart, brain, kidney and peripheral vascular (TOD) due to sustained high BP. (b) In a comprehensive
diseases than those with normal BP. Over the past two decades, intervention, the treatment focuses on risk factors and includes
domestic and foreign scholars have agreed upon various standards in optimal antihypertensive strategies, such as antihypertensive therapy
the treatment of hypertension. Robust evidence from randomized combined with lipid-lowering therapy or antihypertensive therapy
trials shows that the treatment of hypertension is remarkably effective, combined with homocysteine-lowering therapy. (c) The therapeutic
and a small reduction in BP might cause a large reduction in the risk target changes from the simple goal of lowering BP to improving the
of cerebrovascular event and myocardial infarction.2 Oral antihyper- complications associated with TOD to reduce the long-term risk of
tensive drugs represent a milestone in therapy for hypertension and CVD, thereby achieving an ideal BP. (d) Furthermore, the treatment
other cardiovascular diseases (CVDs); furthermore, they provide the emphasizes on effectively controlling BP, especially with regard to
primary and secondary prevention strategies to combat these reducing BP variability (BPV).5
diseases.3 In addition, maintaining an active lifestyle, improving Considerable progress has been made in the field of antihyperten-
diet, monitoring total caloric intake and practicing adequate sive drugs. For example, renin–angiotensin–aldosterone system
exercise have pivotal roles in hypertension treatment. Therapeutic (RAAS) has a crucial role in the regulation of BP and cardiovascular
strategies are based on the following principles. (a) Early intervention remodeling. The RAAS inhibitor is currently considered an important
includes the prevention and treatment of pre-hypertension. In cornerstone of reducing the risk of cardiovascular events.6 Aside from
addition, the goal of therapy has changed from ‘the lower, the the commonly used oral antihypertensive drugs, such as angiotensin-
better’ to ‘the earlier, the better’, which coincides with ancient converting enzyme inhibitor (ACEI), angiotensin II type 1 receptor

1Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China and 2Department of Endocrinology, Traditional Chinese

Medicine Hospital of Mentougou District, Beijing, China

3These authors contributed equally to this paper.

Correspondence: Dr X Xiong or X Yang or Dr J Wang, Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beixiange 5#, Xicheng
District, Beijing 100053, China.
E-mail: 5administration@163.com or avill1988@126.com or wangjie0103@yahoo.cn
Received 4 July 2012; revised 26 November 2012; accepted 12 December 2012; published online 4 April 2013
 Antihypertensive mechanisms of TCM
X Xiong et al
571

(AT1R) blockers, beta blockers and aldosterone receptor antagonist, differentiation, were analyzed further with regard to the aspects
new RAAS inhibitors have been recently researched and developed. shown in Table 1.
For instance, Aliskiren, the first orally active direct rennin inhibitor,
is a novel antihypertensive drug that inhibits the first step of RAAS. THE ANTIHYPERTENSIVE MECHANISM OF CHINESE HERBAL
It blocks the conversion of angiotensinogen to angiotensin I (Ang I) FORMULAS FOR TREATING HYPERTENSION
to reduce the secretion of Ang II.7 Compared with ACEI and ARB, Reduce BPV
direct rennin inhibitors stop the ‘ACE escape phenomenon’ and do For many decades, the major goal of antihypertensive treatment was
not influence the plasma rennin activity during long-term use.8–10 to lower BP to a defined level. Recently, several investigators have
Furthermore, angiotensin II type 2 receptor, a new type of shown that BPV is another critical cardiovascular risk factor that
RAAS inhibitor, can prevent the production of anti-vascular should also be emphasized in the treatment of hypertension.36 BPV
smooth muscle cells (anti-VSMC), relax blood vessels and reverse refers to the physiological fluctuations of BP over time that result
cardiovascular remodeling. Aldosterone synthase (CYP11B2) from the complex interactions of the dynamic regulations of in vivo
inhibitors can inhibit the final step of biochemical reactions neuroendocrine systems. These interactions are multifaceted
catalyzed by the enzymes of in vivo aldosterone synthesis process, phenomena that include both short- and long-term components
thereby reducing aldosterone synthesis. Preventing the reactive that can be estimated using the s.d. of the BP values over a day or
elevation of aldosterone, compared with aldosterone receptor using the night-to-day BP ratio. Studies show that, aside from
antagonist, is a new way to antagonize aldosterone. In addition, increasing average BP, the load and circadian rhythm of BP are
a significant amount of valuable research has come from modern closely associated with cardiac and vascular remodeling as well as
medicine and pharmacology. Recently, other, newer agents, TOD.37 If patients clearly have TOD, then their BPV will increase
including a antihypertensive vaccine against Ang I, Ang II, AT1R, because of their constantly high systolic pressure at night.
endothelin receptor antagonist (Bosantan, Darusentan, Siaxsentan Furthermore, increased BPV is associated with a higher incidence of
and Tezosentan), chymase, Ang 1-7, neutral endopeptidase-ACE dual the cardiovascular morbidity complications related to hypertension.
inhibitors (omapatrilat, sampatfilt) and so on, are being developed. The mechanisms of BPV that lead to TOD might be relevant to
Despite their proven benefits, achieving an ideal BP level in patients vascular endothelial injury, RAAS activation, inflammatory response
with hypertension is not satisfactory because only 25% of patients stimulation and the acceleration of target organ apoptosis. Because of
achieve this goal, and recurrent cardiovascular events still occur in the relevant predictions of these associated mechanisms, the adverse
those who take antihypertensive drugs. At the same time, numerous prognostic significance of increased BPV has clinical experts
adverse reactions, including headache, dizziness, orthostatic increasingly concerned.
hypotension and decreased sexual function, limit the clinical Recent studies have shown that various syndromes are highly
practice of antihypertensive drugs. Thus, reducing the occurrence correlated with BPV. Liver fire (Gan huo shang yan)/liver-yang
and development of hypertension is necessary to prevent TOD hyperactivity (Gan yang shang kang) syndrome and phlegm-fluid
and decrease the vascular morbidity and mortality related to retention (tan zhuo nei zu) syndrome are two major types of
hypertension.11,12 Developed novel classes of antihypertensive agents hypertension discussed in TCM. Compared with patients who suffer
must possess high efficacy. As always, fewer adverse effects are the from liver fire/liver-yang hyperactivity syndrome, patients with
research focus to prevent CVD. phlegm-fluid retention syndrome have more significant BP day-night
The study of Chinese herbal formulas for treating hypertension is circadian reductions and BP overload increases. Furthermore, it might
the most active area of research within TCM and integrative medicine injure target organs easily.38 Chinese herbal formulas for treating liver
in China. Over the past 30 years, significant progress has been made fire/liver-yang hyperactivity syndrome and phlegm-fluid retention
from theory and experiments in the clinical fields based on the syndromes, such as Qingxuanjiangya decoction,39,40 Niuhuangjiangya
inheritance and innovation of thoughts in TCM, to clarify the pill,41 Songlingxuemaikang capsule42–44 and Banxia baizhu tianma
treatment regulations and principles of hypertension. Currently, much decoction,45 can reduce BPV, control BP and improve clinical
attention has been paid to the holistic, multitarget and multidimen- symptoms both in vitro and in vivo.
sional pharmacological studies of TCM.13,14 Moreover, the efficacy of
TCM for treating hypertension is demonstrated by numerous Inhibiting the activity of sympathetic nerve
published cases and randomized trials.15–17 However, some trials Does sympathetic activation initiate and maintain BP elevation in
have found null results.18–21 Numerous randomized controlled trials patients with hypertension? Strong historical and contemporary
have been conducted in China to evaluate the efficacy of novel evidence supports this claim. The chronic activation of the sympa-
Chinese herbal formulas generated from well-known Chinese thetic nervous system is the dominant contributor to systemic
medicine formulas or from currently effective practices to treat hypertension that directly leads to elevation and fluctuation of BP
hypertension. Some trials have effectively treated hypertension.22,23 by increasing renin release and cardiac output as well as by promoting
An increasing number of systematic reviews and meta-analyses have vasoconstriction. Therefore, maintaining BP by suppressing sympa-
been conducted to assess the efficiency of TCM for treating thetic activity and balancing the sympathetic vagus nerve system is
hypertension, providing the best evidence supporting the use of necessary.46,47
TCM for patients who suffer from hypertension.24–34 The majority of Verticil, also known as the alkaloid of Rauwolfia verticallata, is an
these studies have positive findings that favor the practice of TCM. antihypertensive drug that is independently produced in China. It
These studies reveal the multi-protective mechanisms of Chinese consists of reserpine and ingredients such as a-receptor blockade. In
herbal formulas for treating hypertension. A recent study showed a addition, both berberine and isoliensinine have a strong effect with
strong association between TCM syndrome (also called ‘zheng’ or regard to blocking the a1 receptor that can reduce BP and the left
‘pattern’) and hypertension.35 Thus, Chinese herbal formulas, ventricular mass/body mass ratio in renovascular hypertensive rats
including classical prescriptions, experienced prescriptions, (as shown in Figures 1 and 2).48,49 Other TCM chemical components,
traditional Chinese patent medicine and others based on syndrome rhynchophylline and isorhynchophylline, can dilate peripheral vessels by

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Table 1 Chinese herbs and formulas with antihypertensive effect that are recommended in TCM

Disease Syndrome Chinese herbs and formulas Components TCM efficacy Antihypertensive effect Label

Hypertension Fire syndrome Tianma Gouteng Yin Rhizoma Gastrodiae (tall gastrodis tuber), Ramulus Uncariae Cum Suppressing liver yang hyperac- Reversing myocardial and interstitial Classical prescription of New

Hypertension Research
(decoction of Gastrodia and Uncis (gambir plant), Concha Haliotidis (sea-ear shell), Cortex tivity, clearing heat, activating remodeling Meanings of Treatment in mis-
Uncaria) Eucommiae (eucommia bark), Radix Achyranthis Bidentatae (two- blood and nourishing the kidney cellaneous diseases with Tradi-
toothed achyranthes root), Herba Taxilli (Chinese taxillus herb), tional Chinese Medicine
Fructus Gardeniae (Cape jasmine fruit), Radix Scutellariae (scu-
tellaria root), Herba Leonuri (Motherwort Herb), Sclerotium Poriae
Pararadicis (Indian bread with hostwood), and Caulis Polygoni
Multiflori (fleeceflower stem)
Huanglian Jie Du Tang Rhizoma Coptidis (golden thread), Radix Scutellariae (scutellaria Counteracting heart fire syn- Lowering the level of ET and TXA2, increasing Classical prescription of Arcane
(detoxicant decoction of root), Radix et Rhizoma Rhei (rhubarb root and rhizome), and drome, clearing heat and toxic the level of NO, 6-K-PG, and 6-K-PG/TXA2, Essentials from the Imperial
Coptis) Cortex Phellodendri Chinensis (amur cork-tree bark) materials and relieving headache and improving the balance of ET and NO Library dispensed by Wang Tao
and dizziness in Tang dynasty
Niuhuangjiangya pill Extract of scutellaria, Radix Codonopsis Tangshen (codonopsis Clearing liver heat, dissolving Reducing BPV, suppressing sympathetic activ- Traditional Chinese patent
root), Radix Astragali (milk-vetch root; astragalus root), Rhizoma phlegm, resting heart and ity, enhancing vagal activity, blocking AT1R, medicine
Chuanxiong (cnidium), Radix Paeoniae Alba (white peony root), calming the mind activating AT2R and inhibiting platelet adhe-
Borneolum Syntheticum (borneol), Semen Cassiae (cassia seed), sion and aggregation
Radix et Rhizoma Nardostachyos (nardostachys root), Radix
Curcumae (turmeric root tuber), Herba Menthae (field mint),
Calculus Bovis Artifactus (bistort rhizome), Cornu Saigae Tataricae
(antelope horn), Cornu Bubali (buffalo horn), and Margarita (pearl)
Songlingxuemaikang Radix Puerariae Lobatae (kudzuvine root), Margarita (pearl layer Calming the liver and subduing Reducing BPV, improving blood rheological Traditional Chinese patent
capsule powder), and Pinus armandi Franch (fresh pine needles) yang, tranquilizing the heart and condition and inhibiting inflammation and medicine
calming the mind atherosclerosis
Qingxuanjiangya decoction Folium llicis Latifoliae (ilex kudingcha), Rhizoma Gastrodiae (tall Clearing liver heat, calming the Reducing BPV, block ing RAAS, protecting Experienced prescription
gastrodis tuber), Radix Uncariae Macrophyllae (large leaf gambir liver and subduing yang and hypertensive renal damage and inhibiting dispensed by Academician
plant root), Radix Scutellariae (scutellaria root), Radix Cyathulae enriching and nourishing the inflammation Chen Keji
(cyathula root), Cortex Eucommiae (eucommia bark), Caulis liver and kidney
Polygoni Multiflori (fleeceflower stem; caulis polygoni multiflori),
Radix Rehmanniae (rehmannia root), Folium Mori (mulberry leaf),
and Flos Chrysanthemi Indici (chrysanthemum flower)
Jiangyatongmai decoction Radix et Rhizoma Salviae Miltiorrhizae (danshen root), Flos Calming the liver and subduing Reversing LVH Experienced prescription dis-
Carthami (Safflower), Radix Curcumae (turmeric root tuber), yang, invigorating blood and pensed by famous TCM physi-
Antihypertensive mechanisms of TCM
X Xiong et al

Rhizoma Cyperi (nutgrass galingale rhizome), Caulis Spatholobi dissolving stasis cian Guo Shikui
(suberect spatholobus stem), Fructus Trichosanthis (snakegourd
fruit), Bulbus Allii Macrostemi (long stamen onion bulb), Radix
Scutellariae (scutellaria root), Flos Chrysanthemi (chrysanthemun
flower), Semen Cassiae (cassia seed; foetid cassia seed), and
Concha Margaritiferae Usta (mother-of-pearl)
Jiangya capsule Radix Cyathulae (cyathula root), Radix Achyranthis Bidentatae Calming the liver, nourishing the Lowering the level of ET, increasing the level of Experienced prescription dis-
(two-toothed achyranthes root), Rhizoma Gastrodiae (tall gastrodis kidney and invigorating blood NO and improving the balance of ET and NO pensed by famous TCM physi-
tuber), Rhizoma Chuanxiong (Sichuan lovage root), Pheretima cian Zhou Wenquan
(earth worm), and Fructus Lycii (Chinese wolfberry fruit)
Xiaxi oral liquid Spica Prunellae (common self-heal fruit-spike), Radix Cyathulae Calming the liver fire Decreasing the content of myocardial AT1Rs by Experienced prescription
(cyathula root), and Fructus Leonuri (leonurus fruit) downregulating the expression of AT1 mRNA,
lowering the level of ET, increasing the level of
NO and improving the balance of ET and NO
Zhengejiangya decoction Concha Margaritiferae Usta (mother-of-pearl), Radix Puerariae Calming the liver and clearing Lowering the level of ET, increasing the level of Experienced prescription
Lobatae (pueraria root), Flos Chrysanthemi Indici (wild chry- the fire NO and improving the balance of ET and NO
santhemum flower), Semen Cassiae (cassia seed), and Cortex
Eucommiae (eucommia bark)
Tongmaining granule Rhizoma Gastrodiae (tall gastrodis tuber), Radix Achyranthis Calming the liver and subduing Reversing vascular remodeling Experienced prescription
Bidentatae (two-toothed achyranthes root), Radix Paeoniae Alba yang and dissolving blood stasis
(white peony root), Radix et Rhizoma Salviae Miltiorrhizae
(danshen root), Rhizoma Chuanxiong (Sichuan lovage root), Radix
Puerariae Lobatae (kudzuvine root) and so on
Qingxin capsule Cortex Eucommiae (eucommia bark), Ramulus Uncariae Cum Calming the liver fire and clear- Blocking RAAS, lowering levels of plasma ET Experienced prescription
Uncis (gambir plant), Radix Scrophulariae (figwort root), Cortex ing heart fire and ratio of ET/CGRP and elevating plasma
Moutan (tree peony bark), Plumula Nelumbinis (lotus plumule) levels of CGRP
and so on
Fluid retention Banxia Baizhu Tianma Tang Rhizoma Pinelliae Praeparatum (pinellia rhizome in ginger juice), Calming the liver, strengthening Blocking RAAS, reversing LVH, regulating Classical prescription of Medical
syndrome (decoction of Pinellia ter- Rhizoma Atractylodis Macrocephalae (white atractylodes rhi- the spleen and dissipating metabolism of glucose and lipid, lowering the Revelations dispensed by Cheng
nata, Atractylodes macroce- zome), Rhizoma Gastrodiae (tall gastrodis tuber), Pericarpium excessive fluid level of insulin and enhancing the insulin Zhongling in Qing dynasty
phala, and Gastrodia elata) Citri Reticulatae (aged tangerine peel), Poria (Indian bread), and sensitivity
Radix et Rhizoma Glycyrrhizae (liquorice root)
Zexietang jiawei decoction Rhizoma Alismatis (water plantain rhizome), Rhizoma Atractylodis Dissolving phlegm and draining Protecting hypertensive renal damage Modified classical prescription of
(modified decoction of Macrocephalae (white atractylodes rhizome), Herba Lycopi (hir- water-dampness Synopsis of Golden Chamber
Alisma) sute shiny bugleweed herb), and Rhizoma Acori Tatarinowii
(grassleaf sweetflag rhizome)
Wendantang jiawei decoc- Caulis Bambusae in Taenia (bamboo shavings), Fructus Aurantii Dissolving phlegm and boosting Lowering IMT, scores and areas of carotid Modified classical prescription of
tion (modified decoction for Immaturus (immature orange fruit), Rhizoma Pinelliae (pinellia qi plaque and improving endothelium-dependent Prescriptions Assigned to the
clearing away gallbladder rhizome), Pericarpium Citri Reticulatae (aged tangerine peel), dilation of brachial artery Three Categories of Pathogenic
heat) Poria (Indian bread), Radix et Rhizoma Glycyrrhizae (liquorice Factors of Diseases
 Table 1 (Continued )

Disease Syndrome Chinese herbs and formulas Components TCM efficacy Antihypertensive effect Label

root), Radix Codonopsis (codonopsis root), Radix Curcumae

(turmeric root tuber) and so on
Deficiency Yinianjiangya decoction Ramulus Uncariae Cum Uncis (gambir plant), Concha Haliotidis Enriching and nourishing kidney Lowering the level of ET, increasing the level of Experienced prescription
syndrome (sea-ear shell), Plastrum Testudinis (Tortoise plastron), Rhizoma yin, calming the liver and sub- NO and improving the balance of ET and NO
Pinelliae (pinellia rhizome), Pericarpium Citri Reticulatae (aged duing yang
tangerine peel), Fructus Aurantii (orange fruit), Radix Achyranthis
Bidentatae (two-toothed achyranthes root), Herba Leonuri
(Motherwort Herb), Herba Taxilli (Chinese taxillus herb), Radix
Polygoni Multiflori Praeparata cum Succo Glycines Sotae
(prepared fleeceflower root) and so on
Jiangzhitiaoya granule Radix Polygoni Multiflori (fleeceflower root), Fructus Lycii Supplementing kidney, invigor- Lowering levels of plasma ET and ratio of Experienced prescription
(Chinese wolfberry fruit), Semen Cassiae (cassia seed), ating blood and calming the liver ET/CGRP and elevating plasma levels of
Fructus Crataegi (Chinese hawthorn fruit), Flos Chrysanthemi CGRP
(chrysanthemun flower), Rhizoma seu Herba Gynostemmatis
Pentaphylli (gold theragran), Folium Nelumbinis (lotus leaf),
Theae (Tea) and so on
Jiangyamaijing liquid Herba Taxilli (Chinese taxillus herb), Semen Cassiae (cassia seed), Supplementing liver and kidney, Protecting hypertensive renal damage Experienced prescription
Fructus Crataegi (Chinese hawthorn fruit), Fructus Lycii (Chinese fortifying the spleen, harmoniz-
wolfberry fruit), Fructus Schisandrae Chinensis (Chinese magno- ing the stomach dissolving
livine fruit), Concha Ostreae (oyster shell) and Flos Chrysanthemi phlegm and blood stasis
(chrysanthemun flower)
Bushenyixin tablet Herba Epimedii (aerial part of epimedium herb), Semen Planta- Supplementing kidney, boosting Regulating metabolism of glucose and lipid, Experienced prescription
ginis (plantago seed) and so on the heart, clearing liver heat and lowering the level of insulin and serum uric
draining water acid and enhancing the insulin sensitivity
Others Tongxinluo capsule Scorpio (scorpion), Scolopendra (centipede), Hirudo (leech), Invigorating blood and unblock- Lowering the level of ET, increasing the level of Traditional Chinese patent
Eupolyphaga seu Steleophaga (ground beetle), Periostracum ing the collaterals NO, improving the balance of ET and NO, medicine
Cicadae (cicada moulting), Radix et Rhizoma Ginseng (ginseng), inhibiting the platelet activation and vascular
Borneolum Syntheticum (borneol), Radix Paeoniae Rubra (red inflammation
peony root) and so on
Shexiangbaoxin pill Moschus (musk), Ginseng Extract, Calculus Bovis Artifactus Warming and dredge with aro- Reversing myocardial and interstitial Traditional Chinese patent
(bistort rhizome), Cortex Cinnamomi (cassia bark), Styrax (storax), matics, boosting qi and nourish- remodeling medicine
Venenum Bufonis (toad venom), and Borneolum Syntheticum ing the heart
(borneol)
Xue ling Angelica Invigorating blood Blocking calcium channel Experienced prescription
Gadol — Supplementing qi and activating Elevating the mRNA expression of CPT-1 in Chinese herb
blood circulation heart by improving the hemodynamic index and
enhancing the level of adiponectin and the
expression of its related signal transduction
molecules
X Xiong et al

Ganoderma spore — Supplementing qi, relieving Elevating the mRNA expression of CPT-1 in Chinese herb
uneasiness and relieving cough heart by improving the hemodynamic index and
and asthma enhancing the level of adiponectin and the
expression of its related signal transduction
molecules
Astragalus injection Astragalus saponin Supplementing qi Reverse myocardial and interstitial remodeling Traditional Chinese medicine
injection
Erigeron injection 4,5,6-Trihydroxy flavonoids-7 glucuronide Activating blood and removing Reversing myocardial, interstitial and vascular Traditional Chinese medicine
stasis and dredging the collat- remodeling injection
Antihypertensive mechanisms of TCM

erals to stop pain

Puerarin injection 8-b-D-Glucopyranosyl-40 ,7-dihydroxy isoflavone — Decreasing the mRNA expression of AT1 and Traditional Chinese medicine
ACE2 mRNA in heart and clearing free radicals injection
Verticil — — Inhibiting the activity of sympathetic nerve Active ingredients
Berberine — — Blocking a1 receptor Active ingredients
Isoliensinine — — Blocking a1 receptor Active ingredients
Rhynchophylline — — Inhibiting vasomotor center and blocking sym- Active ingredients
pathetic nerves or ganglions
Isorhynchophylline — — Inhibiting vasomotor center and blocking sym- Active ingredients
pathetic nerves or ganglions
Tetrandrine — — Blocking calcium channel, reducing the total Active ingredients
intracellular calcium, relaxing arteriolar smooth
muscle and decreasing peripheral resistance

Abbreviations: ACE2, angiotensin converting enzyme; AT(1/2)R, angiotensin II type (1/2) receptor; BPV, blood pressure variability; CGRP, calcitonin gene-related peptide; CPT-1, carnitine palmitoyl transferase; ET, endothelin; LVH, left ventricular hypertrophy;
NO, nitric oxide; RAAS, renin–angiotensin–aldosterone system; TXA2, thromboxane A2.
573

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O O HO
O OH
HO O
O O OH

N+ H2O
HO OH
O
CI– Figure 5 Chemical structure of Puerarin.
O

Figure 1 Chemical structure of berberine.

vasoconstriction as well as the proliferation and migration of smooth
muscle cells, formation of foam cells, aggregation and adhesion of
O platelets, bradykinin degradation, nitric oxide (NO) reduction and
endothelin (ET) increases by acting on AT1R.52 Qingxuanjiangya
N
OH decoction and Qingxin capsule might safely and effectively lower BP in
O patients with mild or moderate degrees of hypertension, improve
their clinical symptoms and more effectively improve their quality of
life. This mechanism might be related to their ability to inhibit the
OH
activity of the circulatory renin–angiotensin system.39,53
O
N AT1R activation can cause arterial vasoconstriction, smooth muscle
cell proliferation and strengthen myocardial contraction, which can
O lead to hypertension, vascular remodeling and cardiac hypertrophy.54
Several studies have demonstrated that Xiaxi oral liquid lowers BP and
Figure 2 Chemical structure of isoliensinine. the content of myocardial AT1Rs by downregulating the expression
of AT1 mRNA in spontaneously hypertensive rats (SHR).55
Furthermore, the antihypertensive effect of Niuhuangjiangya pill,
CH3
another traditional Chinese patent medicine, is related to directly
blocking AT1R and indirectly activating angiotensin II type 2
N OCH3
receptor.56,57
ACE2 is a zinc-dependent metalloproteinase that has a strong
O homology with ACE. In addition, ACE2 is similar to the endogenous
N
ACEI that can degrade ACE substrates and decompose ACE products
O OCH3
H such as Ang II (1–7), thereby resulting in lowered BP and inhibited
Figure 3 Chemical structure of rhynchophylline. myocardial hypertrophy. Much research has shown that Banxia
Baizhu Tianma Tang (a decoction of Pinellia ternata, Atractylodes
macrocephala and Gastrodia elata) can improve the expression of
factors in cardiac RAAS via a dynamic long-term process. The
expression of ACE2 mRNA gradually increases with the extension
N O of delivery time. Importantly, the effect was similar with captopril.58
H
Puerarin, also called 40 –7-dihydroxy-8-beta-D-glucose isoflavones, is
the major active ingredient extracted from the roots of the kudzuvine,
O which induces anti-platelet aggregation, activates blood vessels and
N HO O lowers BP (as shown in Figure 5). Study has demonstrated that low
H
dose of puerarin decreases the mRNA expression of AT1 and ACE2
Figure 4 Chemical structure of isorhynchophylline. mRNA in the heart, whereas high doses increase these expression
levels in the kidney. A feedback correlation might exist between AT1
and ACE2.59
directly inhibiting the vasomotor center and blocking the sympathetic
nerves or ganglions (as shown in Figures 3 and 4).50 Niuhuangjiangya Improving endothelial function
pill can suppress sympathetic activity and enhance vagal activity, Vascular endothelial factors also have a crucial role in the regulation
thereby significantly lowering plasma rennin activity and epinephrine of BP. Under the stimulation of hypertension, vessel endothelial cells
after a grip-strength test to stabilize BP under stress and effectively (VEC) release a series of endothelial growth factors that can result in
control 24-h BP levels.51 the proliferation and hypertrophy of VSMC, increase intimal collagen,
thicken vascular walls and increase peripheral vascular resistance.
Blocking the renin–angiotensin system Finally, all these actions contribute to a vicious circle.60,61 The
For the past three decades, the renin–angiotensin system has been a research concerning VEC, an initiating factor and carrier of the
major focus in high BP research. RAAS has an important role in the ‘endothelium-hypertension-cardiovascular event’ chain, has become a
acute and chronic regulation of BP. Excessive RAAS activation not hot issue in the field of hypertension. Thus, early endothelial
only causes sustained increases in BP but also leads to arterial dysfunction interventions can delay and control the development of
vasoconstriction, fibrosis and cardiac remodeling. Ang II, a crucial cardiovascular and cerebrovascular events.
vasoactive peptide, which is one of the strongest hormones among VEC-stimulated synthesis releases a variety of vasoactive substances
the endogenesis active peptides used to reduce BP, is involved in through paracrine, autocrine and endocrine systems to regulate

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X Xiong et al
575

vascular tone, stimulate smooth muscle cell growth and proliferation, to kidney disease; qi and blood deficiencies leading to liver-yang rising
promote blood/endothelial cell adhesion, reverse vascular remodeling patterns were related to HD and kidney disease; and kidney yin/yang
and participate in blood coagulation, fibrinolysis and immune deficiency patterns were related to cerebrovascular and eye disease
system.62 The endothelium-dependent contraction factors produced and HD.
and released by VEC include ET-1, thromboxane A2 (TXA2), Ang II, Left ventricular hypertrophy is often assumed to be a serious TOD
asymmetric dimethyl arginine, O2  (superoxide anion (O2 )), for hypertension. In fact, left ventricular hypertrophy is an indepen-
urotensin and coupling factor 6. The endothelium-dependent dent risk factor for sudden death, coronary HD, congestive heart
relaxing factors produced and released by the VEC include NO, failure, arrhythmia and other cardiovascular events. Because of the
prostacyclin (PGI2), calcitonin gene-related peptide (CGRP), increased long-term pressure load, catecholamine, Ang II and other
endothelium-derived hyperpolarizing factor and C-type natriuretic growth factors can stimulate myocardial hypertrophy and interstitial
peptide. fibrosis. Therefore, simply lowering BP might not solve the problem
NO, which is synthesized by endothelial nitric oxide synthase, of TOD. Furthermore, reversing left ventricular hypertrophy, improv-
maintains vasodilatation and contraction as well as a balance between ing cardiac function and protecting target organs have become the
anticoagulants and procoagulants.63 ET is a strong vasoconstrictor primary goals of hypertension treatment.76–78 Gadol (Sedum rhodiola
that can produce long-lasting concentration-dependent vaso- medicinal plants) and Ganoderma spore (the dissemination of spores
constriction and cause vascular spasms.64 It can also stimulate during the maturation of the medicinal fungus Ganoderma lucidum
VSMC proliferation, thicken the vascular wall in atherosclerosis and fruiting bodies) might treat a variety of CVDs. Gadol and Ganoderma
eventually lead to high BP and vascular structural changes. Therefore, spore medications, either alone or in combination, might significantly
the imbalance between the synthesis and release of NO and ET-1 is reduce systolic BP, diastolic BP and the myocardial hypertrophy index
one of the most important mechanisms in the occurrence and as well as elevate the mRNA expression of carnitine palmitoyl
development of hypertension. In addition, this balance is a transferase in the heart by improving the hemodynamic index in
characteristic of VEC damage. Several studies have demonstrated SHR, thereby enhancing the level of adiponectin and the expression of
that certain classic prescriptions lower the level of ET while increasing its related signal transduction molecules.79 In addition, liver fire/liver-
the level of NO and improve the balance of ET and NO, prevent yang hyperactivity syndrome is strongly related to HD in TOD.
endothelial injury and improve the peroxidation pathological Chinese herbal medicine such as Banxia Baizhu Tianma Tang,
hyperactivity state in the cardiovascular system of patients with Jiangyatongmai decoction and Tianma Gouteng Yin, which are used
hypertension. These types of classic prescriptions include Huanglian to treat liver fire/liver-yang hyperactivity syndrome, all have potential
Jie Du Tang (Arcane Essentials from the Imperial Library written by effects on HD. Banxia Baizhu Tianma Tang might significantly
Wang Tao in Tang dynasty),65 Xiaxi oral liquid,66 Tongxinluo capsule,67 decrease the cardiac hypertrophy of 18-week and 24-week-old SHR
Zhengejiangya decoction,68 Yinianjiangya decoction69,70 and Jiangya by regulating the mRNA expression of the RAS factor. The
capsule.71–73 therapeutic effect of this herbal medicine is similar to that of
CGRP is the strongest vasodilator, and it has a crucial role in the captopril.58 Jiangyatongmai decoction, a Chinese medicine for
systolic and diastolic functions of the cardiovascular system. CGRP invigorating blood circulation and eliminating blood stasis, is a
fights against the vascular effects of ET and Ang II, enhances the left historical prescription dispensed by the famous TCM doctor Guo
ventricular systolic function and reduces myocardial ischemia. Both Shikui. This herb might reduce BP, reverse left ventricular remodeling
Qingxin capsule and Jiangzhitiaoya granule74 could lower levels of and enhance left ventricular function by inhibiting the AKT protein,
plasma ET and the ET/CGRP ratio and elevate the plasma levels of decreasing the levels of ET and Ang II and increasing the level of
CGRP. CGRP.80,81 In addition to substantial myocardium reconstruction,
PGI2 is the strongest in vivo platelet depolymerization and myocardial collagen remodeling is common in hypertension. Much
vasodilator. 6-keto-prostaglandin F1a (6-K-PGF1a) is a metabolite of research has demonstrated that Tianma Gouteng Yin (a decoction of
PGI2 that may indicate the content of PGI2 because of its stable Gastrodia and Uncaria),82–84 Astragalus injection,85 Erigeron injection86
nature. TXA2 is a strong platelet aggregation substance and vasocon- and Shexiangbaoxin pill87 can reverse myocardial and interstitial
strictor. Therefore, PGI2 and TXA2 are important vasoactive sub- remodeling and significantly reduce perivascular collagen area, the
stances in the regulation of vascular wall tension. The balance between levels of left ventricular mass index, left ventricular wall thickness and
these elements has an important role in maintaining hemodynamics interventricular septum thickness, the content of Type I and Type III
and vasoconstriction. Studies have shown that Huanglian Jie Du Tang collagen, the diameter of myocardial cells, myocardial collagen
can increase the levels of 6-keto-prostaglandin (6-K-PG) and 6-K-PG/ synthesis and extracellular matrix deposition. This mechanism
TXA2 while lowering TXA2 in SHR. These findings indicate that PGI2 might be related to the reduction in myocardial transforming
and TXA2 improve hemodynamics and maintain the balance between growth factor-b1 expression.
the coagulation and anticoagulation.65 Hypertensive renal injury is another major TOD. Long-term
hypertension can cause renal sclerosis and gradually progress to
Preventing TOD chronic renal failure. Positive control of hypertension is the key to
Given the progress of research on hypertension, the structure and preventing hypertensive renal damage. According to recent studies,
function of target organs such as the heart, brain, kidneys and blood hypertensive renal injury is strongly related to fluid, phlegm and
vessels have been reconsidered to certain extent. Consequently, much dampness retention syndrome and liver-yang hyperactivity syndrome,
attention should be paid to preventing and treating TOD while which are caused by deficiency syndrome. Chinese medicines such as
lowering BP.75 Recent research showed that a strong association exists Zexietang jiawei decoction (a modified decoction of Alisma), Jian-
between TCM syndromes and the clinical symptoms of TOD.35 That gyamaijing liquid and Qingxuanjiangya decoction, which are used to
is, a liver-fire blazing upward pattern was related to cerebrovascular treat fluid, phlegm and dampness retention syndrome, deficiency
and eye disease and heart disease (HD); the obstruction of phlegm syndrome and liver-yang hyperactivity syndrome, respectively, have
and the dampness of the heart/liver/gallbladder pattern were related certain advantages with regard to treating hypertensive renal injury.

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Clinical research indicates that prescriptions such as Zexietang jiawei calcium, relaxing arteriolar smooth muscle and decreasing peripheral
decoction,88 Jiangyamaijing liquid89 and Qingxuanjiangya decoction90 resistance.102 In addition, Xue ling, the primary component of
might control increased systolic BP, inhibit the glomerular and angelica, has a similar effect on verapamil, which indicates that
tubular hyperplasia caused by high BP in SHR and significantly antihypertensive activity is also associated with calcium channel
reduce urinary albumin and b2-microglobulin by increasing the blocking.103
activity of renal rennin and the level of Ang II. Chinese herbal formulas might also improve blood rheological
Vascular remodeling is a series of adaptive structural and functional conditions, such as blood flow, viscosity, deformability and coagula-
changes in the blood vessels caused by hemodynamics and humoral tion, in patients with hypertension. Because of the enhancement of
factors. In addition, it primarily manifests as VSMC hypertrophy and platelet adhesion, aggregation, releasing reaction and the erythrocyte
hyperplasia, increased perivascular collagen, decreased vascular com- deformability dysfunction in patients with hypertension, red blood
pliance and changes in its reactivity to vasoactive substances. cell deformability improvement and platelet activation inhibition
Furthermore, the structure and functional changes of large vessels might help in treating patients with hypertension. Studies show that
might lead to atherosclerosis. Recent studies have shown that the Songlingxuemaikang capsule improves the hemorheology of patients
active ingredients of Chinese medicine might improve vascular with hypertension, especially high shear blood viscosity, plasma
remodeling by regulating RAAS and inhibiting a variety of cytokines viscosity and whole-blood-reduced viscosity.104 Tongxinluo capsule
(inflammatory factors).91,92 Erigeron injection86 and Tongmaining inhibits the platelet activation and vascular inflammation of essential
granule93 might reduce perivascular Type I collagen, improve hypertension patients with comorbid diabetes and reduces the levels
vascular compliance and reverse vascular remodeling through the of serum high-sensitivity C-reactive protein (Hs-CRP), plasma
inhibition of PKC activity in addition to lowering BP. Other studies fibrinogen C (FIB-C), CD62p and glycoprotein b/a (GP b/a).67
have found that Wendantang jiawei decoction (a modified decoction Niuhuangjiangya pill significantly inhibits platelet adhesion and
for clearing away gallbladder heat and a classic TCM prescription for aggregation in normal rats by inhibiting the release of the TXA2
treating phlegm turbid retention syndrome) might significantly lower platelets induced by adenosine diphosphate, which might block
intima-media thickness scores and carotid plaque areas as well as platelet activation and aggregation as well as regulate the positive
improve the endothelium-dependent dilation of the brachial artery.94 feedback between the release of adenosine diphosphate and TXA2.105
The important role of inflammation in the incidence and compli-
Improving insulin resistance as well as glucose and lipid cations of CVD has received much attention. Inflammation, which
metabolism most likely acts as a trigger and may be associated with CRP to a large
Hypertension is often associated with lipid and glucose metabolism extent, tumor necrosis factor-a and other related inflammatory
disorders. The interaction between these disorders might continue to factors most likely have vital roles in the process of remodeling of
diminish arterial elasticity, increase peripheral resistance and change the vessels, myocardium and renal interstitial cells in patients with
hemorheology, thereby leading to microcirculation disturbance and hypertension. For instance, Qingxuanjiangya decoction not only lowers
high rates of CVD. Therefore, intervening and treating risk factors Hs-CRP and inhibits the inflammatory response but also regulates
such as impaired glucose tolerance, dyslipidemia, abdominal obesity lipid metabolism and increases the level of endogenous estrogen in
and hyperhomocysteinemia are equally important in hypertension perimenopausal women. Furthermore, Qingxuanjiangya decoction can
treatment.95,96 In addition, several recent studies have shown that the reduce the occurrence of cardiovascular events in addition to lowering
fasting insulin levels in patients with hypertension were significantly BP. Songlingxuemaikang capsule has a better therapeutic effect than
higher than normal. Moreover, insulin resistance is one of the most Qingxuanjiangya decoction for inflammatory and carotid atherosclero-
important aspects of the pathological basis of hypertension. Clinical sis, which reduces the content of Hs-CRP and the atherosclerotic
studies have also shown that Chinese herbal formulas for treating plaque index in patients with hypertension.106 Niuhuangjiangya pill
hypertension, such as Puerarin, Banxia baizhu tianma Tang and also has a role in anti-atherosclerosis. The tumor necrosis factor
Bushenyixin pill, might reverse the risk factors of hypertension, among patients with atherosclerosis was significantly lower after
regulate glucose and lipid metabolisms, lower insulin levels and taking this medicine.107
enhance insulin sensitivity.97–101 Furthermore, Puerarin has a crucial
role in eliminating free radicals.98 Banxia baizhu tianma Tang might DISCUSSION AND PERSPECTIVES
improve salt sensitivity and lower cholesterol, low-density lipoprotein TCM has a long history and abundant experience with regard to
cholesterol, triglycerides and the body mass index of patients with treating the clinical manifestations frequently reported by patients
hypertension and abundant phlegm-dampness syndrome.99,100 with hypertension and probable TOD.108,109 With the increasing
Bushenyixin pill might reduce the serum uric acid level in patients popularity of complementary and alternative medicines among
with essential hypertension and insulin resistance.101 patients with hypertension,110–112 TCM is being more frequently
used in China and the West.113,114 TCM also has a unique way of
Other mechanisms diagnosing and treating this disease. Furthermore, a variety of TCM
In addition to the above mechanisms, calcium ions have a vital role practices, including Chinese herbal formulas, acupuncture,
in the development of hypertension. The activation of potential- moxibustion, cupping, qigong, Tai Chi (a shadow-boxing exercise),
dependent calcium channel and receptor regulation of calcium diet and exercise therapy, originated in China.115–121 Among these
channel might cause an extracellular calcium influx, release of practices, Chinese herbal formulas are a key research area. Great
intracellular calcium and lead to a higher concentration of intracel- amount of effective Chinese herb and formulas including classical
lular free Ca2 þ . Chinese herbal formulas also have calcium channel prescriptions originated from a ‘classic’ textbook, experienced
antagonists and lower BP. Tetrandrine, a well-known extract of Fangji prescriptions dispensed by famous TCM physicians, traditional
(Radix stephaniae tetrandrae), is both a natural, non-selective calcium Chinese patent medicines and others have been widely used in
channel blocker and a calmodulin antagonist; moreover, it lowers BP clinical practice by TCM practitioners for thousands of years.
by blocking calcium channels, thereby reducing total intracellular Under the guidance of holistic concept and treatment based on

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syndrome differentiation and formula syndrome differentiation,122 hypertension within the ‘concept of holism’ and the ‘syndrome
TCM practitioners diagnose certain syndromes and prescribe certain differentiation’ in TCM.124,125 Furthermore, the experiments on
formulas according to the clinical manifestations of patients with classic and experienced prescriptions should also be strengthened.
hypertension. Thus, corresponding Chinese herbal formulas are By providing intensive research on the antihypertensive effects of
prescribed based on a TCM diagnosis. In most cases, selected Chinese herbal formulas, we can develop many new antihypertensive
classical prescriptions should be modified (either added or deleted) drugs that possess definite curative effects that target clear
based on individual symptoms. Current research demonstrates that mechanisms to significantly advance the research on hypertensive
Chinese herbal formulas possess the advantage of whole body treatment.
regulation in many ways for many targets. Recently, the continued
study of the anti-hypertensive mechanisms of Chinese herbal CONFLICT OF INTEREST
formulas for hypertension has made great progress with regard to The authors declare no conflict of interest.
the etiology and pathogenesis of this disease. In addition, progress has
been made with regard to treatment regulations and the principles of ACKNOWLEDGEMENTS
antihypertensive drugs as well as concerning active ingredients, The National Basic Research Program of China (973 Program, No.
traditional Chinese patent medicine and Chinese herbs and 2003CB517103) and the National Natural Science Foundation Project of China
formulas. Chinese herbal formulas not only stabilize BP but also (No. 90209011) partially supported the current work.
improve clinical symptoms and quality of life, reverse hypertension-
related risk factors and protect targeted organs to improve the chances
of long-term survival. Thus, therapeutic advantages exist for overall
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