SALVIA

and the History of Microcirculation Research in China

by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon

Salvia refers to the root of Salvia miltiorrhiza (see Figure 1), sometimes
described as Chinese sage or red sage root. Any herb of the Salvia genus may be
called sage, but most people are familiar with the common garden plant-and the
common Western kitchen herb-obtained from Salvia officinalis. There are
significant differences in medicinal components of the tops and roots of
the Salvia plants that influence their uses. The Western sage leaves are used
medicinally to treat dyspepsia and excessive perspiration (1). The tops of Salvia
plebia (lichicao) and the whole plant of Salvia chinensis (shijianchuan) are used
medicinally by the Chinese, but infrequently; the former is said to treat bleeding and
turbid urine, the latter treats swellings and infections (2). Salvia root (danshen), as
employed in Chinese medicine and the subject of the rest of this article, is different
in nature from the other sage herbs, despite the botanical relationship.

Danshen was used infrequently in ancient Chinese medicine, yet it has become
an important herb in modern Chinese clinical practice. The transformation of salvia
from a rarely used and minor component of formulas to a key herb is a story that
sheds light on the evolution of the Chinese medical tradition.

A review of herb formula guides shows that salvia appears in very few
traditional formulas that are studied by modern practitioners. The only frequently
mentioned traditional formula that includes this herb is Tianwang Buxin Dan (the
Heavenly Emperor's Heart Nourishing Pill; Ginseng and Zizyphus Formula). The
prescription has been made into a popular patent remedy, mainly used for insomnia,
poor memory, and mental agitation (see: Tianwang Buxin Dan). The formula has 16
ingredients, with only a small amount of salvia, which has been included for its heart
nourishing and spirit pacifying actions.

In modern Chinese clinical practice, salvia is one of the most commonly used
Chinese herbs: it appears in numerous formulations, sometimes as the key
ingredient. In addition, salvia is sometimes given as a single herb remedy, and is
even prepared in injection form for IV administration. The elevation of salvia to a
key herb took place in two steps: recognition of salvia as a valuable blood-vitalizing
agent leading to incorporation of the herb in modern formulas for angina pectoris;
and then, investigations of its effectiveness in treating microcirculation disorders,
leading to its use in treating liver fibrosis and cirrhosis.

STATUS OF SALVIA IN ANCIENT CHINESE MEDICINE

The Chinese name for salvia, danshen, carries much meaning. Here, dan is the term
used to describe cinnabar (dansha; sha = sand, depicting the small crystals of the
mineral); in this context dan refers, in part, to the deep red color of salvia roots,
which are likened to the color of cinnabar. Beyond the color, however, using this
name for salvia may have been intended to convey the high value of the herb, since
cinnabar has long been regarded as the premier substance of Chinese medicine. Red
colors in Chinese herbs are usually described by the term hong (as in honghua:
carthamus), or by chi (as in chishao: red peony); purple might also apply (zi; salvia
is sometimes called zidanshen); so using dan is a rather unique
designation. Shen refers to ginseng (renshen; ren = man, alluding to the man-shaped
roots), long regarded as the most highly respected herb in China (see: The meaning
of shen in renshen). Only about a dozen herbs, most of them deemed suitable as
substitutes for ginseng, have been given the name shen.

Salvia first appeared in the Shennong Bencao Jing (ca. 100 A.D.); in that text,
the highest position for all medicinal materials was held by cinnabar and the highest
position for all herbs was ginseng (and the mushroom ganoderma). Here are the
descriptions of properties of cinnabar, ginseng, and salvia (3):
Cinnabar is sweet and slightly cold. It treats hundreds of diseases
of the five viscera and the body. It nurtures the essence spirit,
quiets the ethereal and corporeal souls, boosts the qi, brightens
the eyes, and kills spirit demons and evil ghosts. Protracted taking
may enable one to communicate with the spirit light and prevent
senility.
Ginseng is sweet and a little cold. It mainly supplements the five
viscera. It quiets the essence spirit, settles the ethereal and
corporeal souls, checks fright palpitations, eliminates evil qi,
brightens the eyes, opens the heart, and sharpens the wits.
Protracted taking may make the body light and prolong life
Salvia is bitter and slightly cold. It is nontoxic, treating mainly
evil qi in the heart and abdomen, continual gurgling of the
intestines like water running, cold and heat, and gatherings and
accumulations. It breaks concretions and eliminates
conglomerations, relieves vexatious fullness, and boosts the qi.

It is evident that salvia does not have the same level of desirable properties nor
broad uses as do cinnabar and ginseng. Like ginseng, it is said to treat evil qi, and
like cinnabar, it boosts the normal qi (an effect noted for ginseng in all later texts).
The original Tianwang Buxin Dan formulation includes all three: ginseng, cinnabar,
and salvia; the "dan" in the formula name refers to pills containing cinnabar (modern
versions of the formula often delete cinnabar because of concerns about mercury, its
main active component). Each of these three herbs were traditionally considered
important for treating disorders of the heart, as applies to mental functions, and for
treating hot swellings (all have a slightly cold nature). Thus, salvia was described in
the Rihuazi Bencao (713 A.D.) this way: "Salvia nourishes the heart (mind),
reinforces the will power, unblocks the guan pulse, and cures goiter and pyrogenic
infections [fire toxins]."

MODERN DEVELOPMENTS PRIOR TO MICROCIRCULATION THEORY

It was only during the 20th Century that salvia became known for its blood-vitalizing
properties; until then, salvia was more commonly reputed to treat bleeding disorders
(e.g., menstrual bleeding) than blood stasis (4). Wang Qingren (1763-1831), who
turned attention of the Chinese medical community to the importance of blood-
vitalizing therapies, did not rely on this herb. His famous formulas, such as Xuefu
Zhuyu Tang (Decoction for Removing Blood Stasis from the Chest; Persica and
Achyranthes Combination), depended on other herbs to treat blood stasis, as did
most herb formulas of that time. The herbs used then, and still relied on today by
many physicians, were the combination of persica and carthamus with the
ingredients of Si Wu Tang (Tang-kuei Four Combination: tang-kuei, peony,
cnidium, and rehmannia; sometimes one or two of these ingredients would be
deleted); the group of six herbs used alone is known as Tao Hong Siwu Tang. Thus,
in the book Heart Transmission of Medicine by Liu Yiren (who lived in the 19th
Century just after Wang Qingren), the author suggested these same ingredients for
treating blood stasis, but he makes no reference to salvia.

Formal acknowledgement of the value of salvia for vitalizing blood circulation

finally appeared in the 1930s. For example, in the book published around
1935, Yixue Zhongzhong Canxi Lu by Zhang Xichu, there was one formula with
salvia: Huoluo Xiaoling Dan (Open the Luo Vessels and Reduce Inflammation
Pills), comprised of tang-kuei, salvia, myrrh, and frankincense (to be coated in
cinnabar). This prescription was indicated for blood stasis with pain due to trauma,
inflammatory disorders, and abscesses. In subsequent decades, salvia became a
common ingredient in formulas for blood stasis syndromes, particularly for the
cardiac disorders that were increasingly affecting the elderly, marked by angina
pectoris as the main symptom. Still, the herb was not singled out as being particularly
important or has having unique properties in relation to other herbs for blood stasis,
pain, or abscesses.

Qin Bowei, a famous physician born at the turn of the 20th Century who was
instrumental in the spread of TCM in modern China (after the revolution in 1949),
included salvia in some of the formulas he used. He described the herb this way (5):
Salvia is bitter and slightly cold and enters the channels of the
heart and liver. It quickens the blood, moves the blood, and
regulates transportation of blood fluid. The Da Ming [Mingyi
Bielu ca. 500 A.D.] and Ri Hua [Rihuazi Bencao, 713 A.D.,
mentioned above] refer to this as "eliminating stasis and
engendering the new," with the implication of freeing and
supplementing. Salvia is most often used in the treatment of
longstanding costal pain and hard obstruction in the early stage.
 Formulas mentioned by Qin Bowei that include salvia were recommended for
heart pain in a series of case reports from his practice (5). The syndromes described
for these patients correspond closely to angina pectoris. Research into the
cardiovascular effects of salvia were initiated, and resulted in confirmation that the
herb was suitable for treating such disorders, including stroke (6, 7, 8). Similar
research efforts were undertaken with crataegus (shanzha), pueraria (gegen),
ginseng, and notoginseng (sanqi), which also provided positive results. A patent
remedy with salvia as the main ingredient was developed and is still widely used in
China for treating angina: Fufang Danshen Pian, mainly comprised of salvia extract,
notoginseng, and borneol (a heart stimulant, classified in the traditional herb system
as a substance that eliminates phlegm obstructing the orifices of the heart).

The concept of eliminating stasis to generate new blood, as mentioned by Qin

Bowei, has been described frequently in modern Chinese literature. In order for new
blood to be generated, as this theory goes, old blood that is not vital must be
removed. Therefore, when examining cases of blood deficiency, one must determine
if blood stasis is a root problem; if it is, then there will be little effect from merely
providing blood nourishing herbs, but a substantial effect obtained from using herbs
that treat blood stasis. In this sense, salvia is often compared to Tang-kuei Four
Combination (Si Wu Tang), because salvia has the effect (in these blood stasis cases)
of both vitalizing blood and nourishing blood, just like the four ingredient formula
(the only significant difference is that salvia has a cold nature, while Si Wu Tang is
warming). The theory of vitalizing blood to generate new blood has been applied to
the treatment of bone marrow deficiencies, where millettia (jixueteng) has been a
prominent ingredient in the formulas (see: Millettia; and Counteracting side effects
of modern medical therapies with Chinese herbs), sometimes combined with salvia.

A relatively new area of concern for blood stasis is in relation to aging. In the
theoretical framework of ancient Chinese medicine, aging was understood to be
related to a degradation of the essence (jing) that is stored in the kidney and which
helps nourish the liver yin and blood and also helps stimulate the nutritive functions
associated with the spleen. Decline in essence results in drying of the blood,
contraction of the ligaments, withering of the flesh, and overall reduction in vitality,
mental function, and health. During the 20th Century, possibly due to changes in the
environment, diet, and lifestyle (as well as progress in medical research into aging),
it was generally agreed that disorders associated with aging additionally involve
blood stasis This was an idea that was first presented by Xu Lingtai, a famous
physician of the Qing Dynasty who wrote during the mid-18th Century. He argued
that: "Since the qi and blood of the elderly do not flow very well, how can they bear
supplementation which keeps the evils, thus making difficulties with the qi and
blood?" This follows the theory, developed strongly during the Qing Dynasty period,
that administering formulas comprised only of tonics retains pathological influences
(evils) within the body, rather than helping them to leave the body. One must rectify
all imbalances in order to assure departure of the adverse influences, in this case
improving the circulation of qi and blood. However, Xu's concept did not get much
attention for another 200 years.

Yan Dexin, a physician who learned traditional style medicine prior to the
Chinese revolution and incorporated some of the new concepts developed through
modern research, published works on the subject of gerontology that have been
translated to English under the title: Aging and Blood Stasis (23). He mainly refers
to traditional formulas from earlier centuries, modified slightly, and only
occasionally refers to the newer uses of salvia. For example, the first modified
formula mentioned in his book is Wang Qingren's Xuefu Zhuyu Tang to which salvia
(15 grams/day in decoction) has been added. This formula is used for the general
purpose of treating poor circulation of qi and blood in the elderly. Applying the
theory of Xu Lingtai, in treating acute ailments such as common cold, he
recommends adding salvia (9 grams/day in decoction) to the standard formulas that
dispel wind-cold or wind-heat. Even so, like most doctors trained prior to the
introduction of microcirculation research, he mainly relies on blood vitalizing herbs
other than salvia.

MICROCIRCULATION RESEARCH
One of the important steps leading to more widespread use of salvia was the
development of a concept new to the Chinese system: microcirculation. Since
ancient times, Chinese doctors have known the importance of blood circulation.
Indeed, the whole system of meridians (jingluo; major and branch vessels) was based
on an attempt to map the blood vessels (see: Drawing a concept: jing), and to
influence the circulation within them by using acupuncture, moxibustion, and herb
therapies. A well-known saying regarding the circulation is: "The qi moves the
blood; the blood carries the qi." Put another way, the qi and blood flow together
through the vessels, including the major vessels (jing, mainly arteries) and the minor
vessels (luo, mainly veins). Within this flow of qi and blood, one can distinguish two
types of qi: the nutritive qi (yingqi) and the defensive qi (weiqi). The nutritive qi is
said to flow within the vessels intermingled with the blood, while the defensive qi is
said to flow at the surface of the vessels. The concept of microcirculation merely
adds yet another dimension to the description, and refers primarily to the flow of
blood through tiny vessels invisible to the naked eye, such as the capillaries. Since
these tiny vessels could not be visualized by examiners in the past, they were only
described as part of modern scientific investigations into human physiology.
Western research into the dynamics of capillary bed flow was undertaken during the
1960s; Chinese investigations began about a decade later.

Capillaries are the part of the vascular system that distributes blood carried
within the large vessels (arteries) to the tissues of the body. The capillaries are so
fine that they generally permit no more than one blood cell through at a time, and
are linked to the large vessels through intermediaries, called arterioles. The capillary
walls, unlike those of arteries and veins, are permeable: nutrients, oxygen, and other
blood constituents are able to leave the capillaries and enter the surrounding cells,
while waste materials (including carbon dioxide) are able to enter the capillaries and
be flushed away from the surrounding cells. A capillary can only provide these
services to a depth of a few cells, so the body is completely enmeshed in a system
of capillaries. The characteristics of fluid flow through these capillaries are different
than through the major vessels due to their small size and their permeability.

At a Chinese herb conference held in Hong Kong in 1984, there was a special
session devoted to microcirculation, following up on the new research on the subject
in China. A collaborating team of Dr. R.J. Xiu of the Research Center for
Microcirculation (Chinese Academy of Medical Science, Beijing) and M. Intaglietta,
of the Department of Applied Mechanics, Engineering Sciences, and Bioengineering
(University of California, San Diego), provided an overview (9). They introduced
the subject by describing the capillary bed system and arterioles without mentioning
them by name:
The microcirculation is the principal avenue for the delivery and
exit of the substances involved in the metabolism of every cell of
the tissues. In normal physiological conditions, the optimal
regulation of this process is accomplished through the control of
the state of tension of the smooth muscle cells present in the
vascular wall, which ultimately determines the maintenance of
three different homeostatic processes, namely the maintenance of
fluid balance, the delivery of blood to each microscopic domain
of the tissues, and the maintenance of the systemic blood pressure.
In normal conditions, the controls of the homeostatic processes
act in concert, causing the simultaneous adjustment of all
variables in such a fashion that local blood pressure, flow, and
fluid balance are, on the average, kept within the narrow range
characteristic and necessary for the successful long-term survival
of the organism.
The control of the state of smooth muscle constriction, or tone, is
provided by three fundamentally different mechanisms, namely
the numerous chemicals present in the blood stream, the
regulatory activity of the nervous system, and the special
characteristic of these [smooth muscle] cells to react to changes
in pressure, termed myogenic property. It is important to note that
when the smooth muscle ceases to be active-as a consequence of
diseases, or because it has reached an extreme limiting condition
of constriction and dilation-flow, pressure, and exchange become
regulated solely by the fluid mechanical characteristics of the
microvasculature.

This somewhat obtuse description focuses on the concern that the

microvasculature (i.e., capillaries) can become constricted and unresponsive to
vasodilation signals, thus limiting their ability to regulate blood flow. In the absence
of regulation, especially when there are constricted vessels that do not allow the
optimal flow of blood, the surrounding tissues can become damaged. From the
traditional Chinese perspective, the authors are describing a syndrome of blood stasis
that is secondary to a disorder of the qi circulation, particularly of the weiqi, which
is responsible for regulating the vessel walls (the yingqicarries the substances that
can induce changes in the vascular walls, such as the vasodilation signals these
authors mentioned).

One of the therapeutic substances of great interest in relation to microcirculation

was an alkaloid that had been recently isolated: anisodamine (from Anisodus
tanguticus, an herb found primarily in the Tibetan region). This compound was
introduced into clinical use in China as a synthetic drug in 1965, initially for
treatment of epidemic meningitis, a problem that was causing widespread disability
and deaths. Later, anisodamine was shown to produce favorable results in treatment
of numerous serious ailments, including shock, glomerular nephritis, rheumatoid
arthritis, hemorrhagic necrotic enteritis, eclampsia, and lung edema. The mechanism
of its actions were sought and traced to a vasodilating action that affected the
microcirculation (9, 10).

Unfortunately, potent alkaloid drugs can be dangerous, and anisodamine fell

into the category of a drug therapy requiring careful monitoring (the whole herb also
contains the alkaloids hyoscyamine, anisodine, scopalamine, and cuscohygrine, all
potentially toxic). Adverse effects of the whole herb include dry mouth, dizziness,
headache, blurred vision, lassitude, drowsiness, palpitation, and dysuria; the isolated
anisodamine has fewer side effects, but may still cause these symptoms (11). The
main method of administration of anisodamine in Chinese hospitals was by injection,
using just 50 mg or less, a relatively tiny amount.

The interest in microcirculation that was spurred by the use of anisodamine

turned out to have positive implications for salvia. At the same conference, Dr. A.
Koo, from the Department of Physiology at the Chinese University of Hong Kong,
described widely used Chinese herbs that had good potential for treating
microcirculation disorders by their vasodilation activity: salvia, ilex (maodongqing),
and capillaris (yinchenhao). Dr. Koo described the nature and importance of
microcirculation, reflecting the description by Xiu and Intaglietta, but mentioning
the specific vessels explicitly (12):
Microcirculation has been demonstrated as occupying a key
position in the cardiovascular system. Thus, in classical
description, structural components of a microvascular bed include
a network of microvessels and terminal capillaries. Among
several types of microvessels, terminal arterioles (20-50
micrometers in diameter) are distinctly different from others by
the presence of a profusely reactive circumferential layer of
vascular smooth muscle cells. The function of arterioles in the
 circulatory system is indeed the myogenic reactivity of these
vascular smooth muscle cells. Hence, active changes in
dimension of arterioles not only regulate local blood flow to
downstream capillaries supplying organs and tissues, but also
alter total peripheral resistance to flow as well as control systemic
arterial pressure. Usually, two types of myogenic activities of
arterioles are observed: sustained constriction or dilation, and
rhythmic alterations of contraction and relaxation (vasomotion).
Such sustained or rhythmic myogenic activities are either
responses of vascular smooth muscle to endogenous neural and
humoral effects, or induced by exogenously administered drugs,
including vasoactive agents from Chinese medicinal herbs.

The implications for medical research and application seemed very promising,
so a search through the range of Chinese herbs for active constituents that are
vasoactive-and that specifically effect microcirculation-was undertaken. This time,
the emphasis was on herbs of low toxicity that would allow widespread and regular
use.

To observe the effects of herb components on the small vessels, Koo developed
a video microscope (first reported by him in 1977), which he used in laboratory
animal studies to view internal tissues (exposed by surgery). The development of
laser technology around that time permitted improved observation of blood pulsing
through the microvessels, by utilizing on a doppler flowmetric technique (in essence,
observing light reflected from a moving object to determine its speed). This
procedure worked well for laboratory animal studies, but in order to move on to
clinical evaluations, it was necessary to examine the blood flow non-surgically.

A clinical microscopic viewing technique was developed in mainland China,

first reported in 1979, in which circulation in burned skin was evaluated so as to
monitor the healing effects of herbal therapies (13). It was found that blood clots
(thrombosis) within the capillaries in the area of burn damage led to necrosis of the
underlying skin; vasoconstriction and slow blood flow were the key conditions
leading to thrombosis. Therefore, if a substance could counter vasoconstriction and,
thereby, free up the blood flow, the level of necrosis could be lower, so long as it
was administered (internally or topically) very soon after the burn. A traditional burn
remedy, huzhang (Polygonum cuspidatum), was confirmed by this method to be a
useful agent that prevents thrombosis. It is still relied on for this purpose today.

The same basic observation technique was applied to examination of capillaries

in the finger nail beds (see Figure 2). The nail bed is easy to view and is richly
endowed with capillaries very close to the skin surface beneath the nail. It was
theorized that the condition of the capillaries at this site would reflect the condition
of the capillaries elsewhere in the body. One of the first applications of the nail bed
measurements was reported at the Hong Kong conference (14). A group of
researchers at the Huashan Hospital of the Shanghai First Medical College reported
that nail bed circulation in patients with chronic viral hepatitis was abnormal, and
that as treatment of hepatitis with Chinese herbs progressed, with reduction of
symptoms and liver inflammation, the nail bed circulation improved. Salvia was a
featured herb in the treatment for hepatitis in these studies. The authors concluded
their presentation thus:
Salvia has been tried clinically in our hospital. The results suggest
that promoting blood circulation will be beneficial to
microcirculatory perfusion, hasten the development of collateral
circulation, and lower the lactic acid content within the
microcirculation. With the improvement in microcirculation,
deficiency of blood and anoxia in liver tissues could be relieved,
these in turn will be beneficial to the recovery and regeneration of
liver cells. Repeated liver biopsies had been done in 5 patients, 3
of them were treated with medicines activating blood circulation
and eliminating blood stasis. Pathologic findings were improved,
but not completely recovered in 2 cases. Their microcirculation
was also improved. Thus, the use of blood activating and sludge
eliminating medicines is worth studying.

These findings led to widespread use of microscopic studies of nail bed

circulation and intensive use of salvia for treatment of conditions thought to be
associated with microcirculation disorders, especially hepatitis, a disease that affects
many millions of Chinese. In the same year as the Hong Kong conference, the
Journal of Traditional Chinese Medicine (English language version) offered its first
report on microcirculation: it involved use of salvia for the prevention and treatment
of experimental cirrhosis (15). The authors, working at the Laboratory of Hepatic
Diseases at the Shanxi Medical College, pointed out that salvia was already being
widely used in China for treatment of chronic liver disease. Some of the substances
used for treating hepatitis (e.g., glycyrrhizin from licorice and oleanolic acid from
ligustrum) previously tested by the authors, showed good results in inhibiting liver
damage due to fibrosis, but did not have an effect on existing fibrosis. The findings
with salvia indicated that, after three weeks treatment of laboratory animals with
induced liver damage, the fibrous septa were thinner or disappeared. The authors
wrote:
Cirrhosis is characterized by connective tissue septa and
hyperplastic liver nodules. The excess fibrous tissue between the
hepatic nodules result from the collapse of the existing fibrous
frame after necrosis of the liver cells. Fibrosis is therefore the
consequence of liver cell necrosis....In our experiments, we
observed that the disturbances of hepatic microcirculation
affected metabolic exchange between the blood and the liver cells
resulting in degeneration [necrosis] of the liver cells. The vicious
cycle of necrosis-fibrosis-necrosis thus aggravated cirrhosis of
 the liver. Salvia treatment reduces these pathological changes,
speeds blood circulation, and opens up a larger capillary network.
Microcirculation of the liver is thus improved by salvia, breaking
the vicious cycle and preventing occurrence of cirrhosis.

Nearly 20 years later, salvia has become the main herb recommended for
prevention and treatment of liver damage due to viral hepatitis (see: Hepatitis C:
update 2001). The mechanism of action of salvia on preventing fibrosis in the liver
has been tentatively elucidated. Fibrous collagens are released by hepatic stellate
cells (fat storage cells) that have been activated and transformed into myofibroblasts
rich in alpha-actin. This transformation occurs when the cells are exposed to
activators such as hepatic viral infection, excess iron or alcohol, liver-damaging
drugs, tumor invasion of the liver, or excess bile due to cholestasis. The
myofibroblasts are then responsible for excess collagen deposition resulting in
fibrosis and cirrhosis of the liver. As described in one laboratory animal study (26):
"The extract of Salvia miltiorrhiza markedly reduced protein expression of alpha-
smooth muscle cell-like actin, which indicates that hepatic stellate cell activation
was inhibited during liver fibrosis." The inhibition of hepatic stellate cell activation
was also suggested to be the mechanism of salvia action found in an in vitro study
(27). The vasodilating activity of salvia may relax the stellate cells (actin is one of
the components that contracts the stellate cells) and aid bile flow and hepatic blood
circulation.

Spontaneous resolution of liver fibrosis occurs mainly as the result of the action
of collagenases, known as matrix metalloproteinases (enzymes incorporating heavy
metals; these are partly induced by zinc), that breakdown the accumulated collagen.
When new liver fibrosis is inhibited by salvia, it is possible that natural processes
slowly reverse the existing fibrosis. Although not yet studied, it is also possible that
salvia helps induce collagenase or reduces collagenase inhibitors so that fibrosis
recovery is speeded up. It has been proposed that liver regeneration is promoted by
salvia through general mechanisms of improving hepatic microcirculation, reducing
lipid peroxidation, elevating plasma levels of fibronectin (an antifibrotic agent), and
regulating immune responses (28).

While treatment of angina and hepatitis remain the most common clinical
applications of salvia in modern Chinese clinical practice, the herb has been shown
to have other valuable applications, based on its effects on microcirculation. For
example, laboratory experiments with bone fracture healing at the Shanghai Institute
of Traumatology and Orthopedics have indicated that salvia helps mobilize calcium
and aid deposition of calcium to the fracture zone (16).

ACTIVE CONSTITUENTS
The main active constituents of salvia are diterpene quinones, known as tanshinones
(the Wade-Giles transliteration of danshen is tan-shen, hence the quinones were
called tanshinones). Most of these compounds are colored, providing the reddish
appearance of the roots. The group of components, labeled tanshinone I, tanshinone
II, cryptotanshinone, etc. (see Figure 3), were first described by Japanese researchers
in 1968 (17), though investigations had been underway since the pigments were
isolated from salvia in 1934 (18). More recently, nearly 40 variants of the basic
tanshinone structures have been found in the roots. The tanshinones are unique
chemical constituents, and similar compounds are not found in other Chinese herbs.
The total tanshinone content of the roots is about 1%, with tanshinone I and II and
cryptotanshinone being present in the largest amount (19). In one recent study, the
extraction of salvia yielded tanshinone II 0.29%; cryptotanshinone 0.23%;
tanshinone I: 0.11% (24). The isolated tanshinones have been shown to inhibit
bacteria, reduce fever and inflammation, inhibit platelet aggregation, dilate the blood
vessels, and aid urinary excretion of toxins (22).

DOSAGE, TOXICITY, AND ADVERSE EFFECTS

The Pharmacopoeia of the People's Republic of China (20) indicates a
recommended dosage of 9-15 grams per daily dose in decoction form. In a few
instances, higher doses are administered, up to 20 grams per day, in the treatment of
inflammatory diseases, including viral hepatitis. According to English-Chinese
Rare Chinese Materia Medica, up to 30-60 grams can be used in cases of angina
and heat-type arthritis (21). The relatively high dosage of salvia, compared to most
other Chinese herbs (typical dosage recommendations are 3-9 grams for many herbs)
may be attributed to the relatively low level of active constituents and their poor
solubility in water.

At the higher dosage levels, salvia may on rare occasions cause dry mouth,
dizziness, lassitude, numbness, shortness of breath, and other symptoms that will
usually disappear spontaneously without interrupting the treatment. Rare Chinese
Materia Medica notes that salvia is not suitable for patients who have deficiency
but not stasis, or deficiency accompanied by cold, or with tendency to bleed.
However, most materia medica guides do not present these cautions. Salvia has very
low acute toxicity, with an LD50 by injection of 40-80 g/kg (19).

It is recommended that salvia, or its preparations used for treatment of poor

blood circulation, not be combined with coumadin (Warfarin), as there is a
possibility of increasing the anticoagulant effects (see: The interactions of herbs and
drugs). In a literature survey conducted through October 2000, three cases of
increased anticoagulant activity were reported in the literature in persons taking
salvia along with Warfarin (25). Such effects may be rare and are likely to be dose
dependent, as the mechanism appears to be a simple additive effect of anticoagulant
activity of salvia along with that produced by Warfarin. Therefore, persons using
coumadin should either avoid using salvia, or use it in relatively low dosage (not
more than the equivalent of 6-9 grams per day in decoction) while paying attention
to blood coagulation tests that are routinely performed for persons taking the drug.

REFERENCES
1. Blumenthal M, Goldberg A, and Brinckmann J, Herbal Medicine:
Expanded Commission E Monographs, 2000 American
Botanical Council, Austin, TX.
2. Hong-Yen Hsu, et al., Oriental Materia Medica: A Concise
Guide, 1986 Oriental Healing Arts Institute, Long Beach, CA.
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Figure 1: Salvia miltiorrhiza

Figure 2: Images of nail bed capillaries before and after treatment with salvia.

Figure 3: The primary active constituents of salvia.