Figure 1: Salvia miltiorrhiza
Figure 2: Images of nail bed capillaries before and after treatment with salvia.
SALVIA
and the History of Microcirculation Research in China
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.
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]."
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.
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 yingqi carries 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).
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).
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.
Figure 1: Salvia miltiorrhiza
Figure 2: Images of nail bed capillaries before and after treatment with salvia.
