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Shengmai San:

An Ancient Formula now Used in Chinese Hospitals

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

Shengmai San is a widely used formula in modern China, often given as a prepared liquid (Shengmai Yin), a decoction (Shengmai Tang), or as an intravenous drip (Shengmai Zhusheye). The formula is administered to patients who have suffered a serious illness, especially heart attack, congestive heart failure, or severe bronchitis, and to treat a sudden drop in blood pressure associated with cardiogenic or septic shock. The name of the formula includes a description of its action: shengmai means "to generate the pulse," indicating that the prescription is given to persons who have a very weak pulse, with the expectation that the pulse strength will improve markedly. The original form of the prescription was a powder (san), but the form of administration is not deemed critical other than to assure that the patient is able to utilize it.

Shengmai San was described by the famous physician Li Gao (aka Li Dongyuan; 1180-1251), in his book Neiwai Shangbian Huoluo (Clarification about Internal and External Disease Causation), published in 1247 during the Jin-Yuan medical reformation. Li Gao was one of the founders of the "Spleen/Stomach" school that was greatly concerned with treating qi-deficiency syndromes, an objective of Shengmai San. The formula is a simple one, comprised of three ingredients; the original specification for a single dose was (1):

Ginseng 1.5 grams
Ophiopogon 1.5 grams
Schizandra 7 fruits

The 7 fruits of schizandra have a weight of about 1 gram, so this ingredient comprises roughly 25% of the formula. The powder would be boiled for a short time in water and the resulting tea consumed; the powder could also be consumed directly (its volume is about that of a heaping teaspoon) and swallowed with water. The dose could be repeated two to three times per day if necessary.

According to the original presentation about the use of this formula, the person requiring it would usually have suffered from a consumptive type of disease involving profuse sweating; the individual becomes deficient in qi and yin as a result. If the disease could be halted by effective therapy or spontaneous remission, the patient would usually remain quite weak and susceptible to deterioration: failing to regain an appetite, becoming sick again with another illness, or having irregularities in the heart that could lead to sudden death. Therefore, Shengmai San was to be administered in order to regain health. Ginseng invigorates the qi, ophiopogon nourishes the yin, and schizandra astringes sweating, generates fluids, and aids ophiopogon in nourishing yin; together they fill the deficiency and prevent further losses.

Tonification therapy, such as administration of qi and yin tonics, is provided after the pathogenic force that produced the original disease had been greatly weakened or eliminated. It was thought that administering such tonics while the pathogen is present simply entices the pathogen to remain in the body (1). Thus, Shengmai San was administered during the recovery phase of the disease process; a different formulation would be used prior to that. Since the patient would often become quite weak during the time when the disease pathogen was considered still present, the formula aimed at alleviating the pathogenic influence might still contain tonics: their presence would not be contraindicated so long as they did not make up the main part of the formula.

Examples of formulas (2) used to treat the active phase of the consumptive disease are Qinjiao Fulei Tang (Decoction with Chin-chiu to Support the Lungs), Qinjiao Biejia San (Powder of Chin-chiu and Turtle Shell), and Huangqi Biejia San (Powder of Astragalus and Turtle Shell). These formulas all include bupleurum, lycium bark, and turtle shell to clear heat and alleviate the "bone-steaming fever" that was characteristic of the disease and accompanied by heavy perspiration. Huangqi Biejia San includes ginseng and ophiopogon in common with Shengmai San, illustrating the inclusion of tonics as secondary components of the therapy. An important ingredient in the first two formulas mentioned, qinjiao (chin-chiu) is obtained from Gentiana macrophylla, and is traditionally used for treating fevers, especially those that occur in the afternoon.

Generally, the consumptive diseases involved a lung disorder, such as pulmonary tuberculosis, in which the person suffered from chronic cough. Even without such a respiratory system ailment at its base, the disease would usually leave the person with shortness of breath due to severe weakness of the diaphragm muscles. The three herbs of Shengmai San tonify the lungs. The formula can be used treat weakness of the lungs associated with chronic persistent coughing, even in the absence of a feverish wasting disease.

Adaptation of Shengmai San to other applications (mainly, treating patients who have suffered from cardiovascular diseases) came about by considering the symptom picture and the therapeutic actions of the formula. Many people who suffer from cardiac diseases describe symptoms of fatigue, shortness of breath, and thirst (which may come from mouth breathing to get more air). In the case of post heart attack, the patient may be virtually unable to move for some time due to weakness and heart irregularities. For the severely debilitated patient who is in a Chinese hospital, the formula may be administered by intravenous drip. One of the main sources of this special preparation is the Shanghai Number One Herb Factory, which has specialized in herbs for hospital administration and provides the IV form to hospitals all around China. The same factory also produces a granule form that is used to make a convenient instant tea for oral dosing.

MODERN APPLICATIONS OF SHENGMAI SAN

The Pharmacopoeia of the PRC (3) specifies the liquid form, Shengmai Yin, as the official product. It is to be made with 25% each of ginseng and schizandra, and 50% ophiopogon. The herbs are first extracted with alcohol (60%), which is then concentrated and the resulting liquid is diluted with water and sugar syrup to make the final product, usually packed in vials containing 10 ml (typical dosage: one vial each time, three times daily or two vials each time, two times daily). Its official indications are: "Deficiency of qi and yin marked by cardiac palpitation, shortness of breath, scarcely perceptible pulse, and spontaneous sweating."

A small clinical trial involving patients with dilated cardiomyopathy treated with Shengmai yin (20 ml each time, twice per day), revealed an increased tolerance to treadmill exercise and improved left ventricular contractility (4). In a review of cardiovascular actions and applications of Shengmai yin, (5), it was confirmed that the formula increases myocardial contractility and enhances myocardial energy metabolism, with applications to treatment of shock, arrhythmia, and cardiac glycoside poisoning. Other applications of Shengmai preparations mentioned in the literature include viral myocarditis, reaction to high altitude (mountain sickness), congestive heart failure, and symptoms remaining after a heart attack.

In a more recent review (6), Shengmai San was reported to be effective in pharmacology experiments testing its protective actions against myocardial anoxia (a condition that arises during a heart attack) and adriamycin-induced cardiac damage (a problem that arises with breast cancer treatments). Included in the review were mention of recent clinical studies on treatment of post-heart attack conditions (reported in 1994) and viral myocarditis (reported in 1996). It was shown that Shengmai San exerts an antioxidant activity that may be a contributor to the positive outcomes observed in heart attack patients, suggesting a potential role in preventive therapy for future heart attacks in patients with coronary heart disease (21).

Shengmai intravenous drip was developed about 25 years ago, originally for emergency treatment of heart attack and shock (15, 16, 17). The formula was shown to improve left ventricular performance in cases of coronary heart disease (18), thus expanding its use into treatment of congestive heart failure, characterized by weakness of the left ventricular ejection of blood (19). For these purposes, it is sometimes prepared without schizandra, called shenmai injection (here, shen = renshen; ginseng; mai = maimendong; ophiopogon). The original shengmai injection has also been employed to treat arrhythmias (20).

Shengmai intravenous drip was used recently to treat chronic obstructive pulmonary disease (COPD), a common cause of death due to progressive suffocation (7, 13; two publications of the same report). The drip solution included 100 ml of the shengmai herb preparation (100 ml contained the extracts of 10.0 grams red ginseng, 31.2 grams ophiopogon, and 15.6 grams of schizandra) dissolved in 500 ml of glucose solution. This drip was administered each day for 14 consecutive days. Patients also received drugs that are normally given for COPD, such as antitussives, antiinflammatories, and antispasmodics. The authors of the study explained the observed effects of shengmai intravenous drip:

COPD patients often show reduction in pulmonary function, strength, and endurance of respiratory muscles due to airflow blockage and progressive development of the disease. The pulmonary function deficit was often related to the respiratory muscles' strength, especially the function of the diaphragmatic muscle....Animal experiments have confirmed that shengmai injection could improve energy metabolism of the muscle cells, increase the diaphragm's cross sectional area, and enhance its contraction, so as to enhance respiratory function. Results of the current study have shown that respiratory function and clinical symptoms were obviously improved after COPD patients received shengmai injection [IV drip] therapy, which was in accord with the results of the animal experiments....For COPD patients who suffered from irreversible changes in both airway and lung, shengmai injection could improve their diaphragm function but could not change their airway resistance, resulting in limited lung function improvements.

The authors indicated that shengmai intravenous drip specifically increases the strength of the diaphragm in weakened patients; this action can be seen as consistent with the strengthening effect of the formula on cardiac muscle when administered to patients suffering from heart disease.

To sum up, the English-Chinese Encyclopedia of Practical Traditional Chinese Medicine (8) describes the formula this way:

This medicine can regulate the heart rate and the functions of the internal organs, increase heart output and the ability of the body to protect against diseases, strengthen cardiac contractility, reduce oxygen consumption in the heart muscles, adjust blood pressure, exert actions against shock, expand the coronary arteries and increase coronary arterial blood flow. It can be used clinically to treat coronary heart disease, pulmonary disease, rheumatic heart disease, arrhythmia, heart neurosis, hypotension, sunstroke, chronic bronchitis, and tuberculosis.

ORIGINS: BAKED LICORICE COMBINATION

The origins of Shengmai San may be traced to the Shanghan Lun formula Zhi Gancao Tang (Baked Licorice Combination), which has similar applications. The formula is indicated for a qi and yin deficiency syndrome that manifests as an irregular and weak pulse. Zhi Gancao Tang has six more ingredients than Shengmai San, but mainly uses multiple herbs that reinforce one another to get the same basic effects rather than adding other therapeutic actions. The formula, prepared as a decoction, is (9):

Baked licorice 12 grams
Ophiopogon 10 grams
Rehmannia, raw 30 grams
Cannabis seed 10 grams
Gelatin 6 grams
Ginseng 6 grams
Cinnamon 9 grams
Ginger, fresh 9 grams
Jujube 10 pieces

Zhi Guizhi Tang is most easily compared to Shengmai San by grouping the herb ingredients into the key categories of qi tonics (ginseng, baked licorice, and jujube) and yin-nourishing and moistening herbs (ophiopogon, rehmannia, gelatin, and cannabis seed). To this is added a characteristic herb of the Shanghan Lun, cinnamon twig, which unblocks the circulation of qi, particularly the heart qi that regulates sweating. Thus, the most significant difference between Zhi Gancao Tang and Shengmai San is that the former includes cinnamon twig as an opening agent and the latter includes schizandra as a restraining agent. Otherwise, they have the same basic actions (though Zhi Gancao Tang has some blood-nourishing effects absent in Shengmai San) and both have the essential qi and yin tonics ginseng and ophiopogon.

In modern practice, especially in Japan, Zhi Gancao Tang is usually selected for irregularities of the pulse as felt at the radial artery of the wrist or noted in the actual heartbeat. Such applications arise from the original indication from the Shanghan Lun. Thus, mitrial valve disorders and various arrhythmias are treated by Zhi Gancao Tang (in Japan, the common form is the dried decoction). However, there is no reason to believe that Zhi Gancao Tang would be more or less effective than Shengmai San for this purpose.

The combination of ginseng, ophiopogon, and schizandra is found in several large formulations used to treat heart disorders. For example, Pingbu Zhenxin Dan from the Hejiju Fang (1110 A.D.) includes these herbs with 12 others as a therapy for heart palpitations due to heart-qi deficiency, and Tianwang Buxin Dan from the Shesheng Mi Pao (1638 A.D.) includes these three in a formula with 10 other herbs, used for deficiency of heart yin and blood leading to heart palpitations.

ACTIVE COMPONENTS

Preliminary pharmacological studies have been reported for each of the three herbs of Shengmai San, for which the main active components are already known (10). Both ginseng and ophiopogon contain saponins, that are likely responsible for most, if not all of the cardiac effects noted (11). These two herbs administered together were also shown to protect against adriamycin cardiac damage in laboratory animal tests (14). Schizandra contains lignans, which may be responsible for some vascular effects. Pharmacology studies have demonstrated an antiarrhythmic effect for ophiopogon (10). The animal models had cardiac arrhythmia induced by a variety of chemical agents, including epinephrine (adrenalin, a potent heart stimulant), barium chloride (used in diagnostic procedures, with potential cardiac side effects), aconitine (active ingredient in raw aconite, a toxic herb that can cause cardiac irregularities and failure), and ouabain (chemical that opens cell membranes to calcium transport commonly used in pharmacology experiments). These same models have been used to demonstrate an anti-arrhythmia effect for various types of ginseng (11), including Panax ginseng, Panax quinquefolium (American ginseng), and Panax notoginseng (sanqi or tienchi ginseng). Ginseng has been shown to have a corrective effect on shock if given in high enough doses; it is almost always administered by IV, alone or as a component of the shengmai formula, for this indication. Schizandra has been credited with a normalizing effect on blood pressure.

MODIFICATIONS OF SHENGMAI SAN

Shengmai San is viewed by Chinese herbalists as providing a valuable formulation principle; but the details of the formula can be adjusted slightly to make it more suited to a particular case or as part of a general effort to enhance its effects. A modification of Shengmai San was developed by Zhang Jingyue, who was famous for his emphasis on yin-nourishing prescriptions, in his book Jingyue Quanshu (1624 A.D.). The formula is Wuweizi Tang (Schizandra Combination), comprised of equal parts of ginseng, ophiopogon, schizandra, astragalus, and licorice. The formula is indicated for deficiency of heart qi manifesting as palpitations, shortness of breath, dizziness, lassitude, and spontaneous sweating that is aggravated by exertion (9). The incorporation of astragalus and licorice reinforces the qi tonification therapy provided by ginseng, and the combination of astragalus and schizandra aids treatment of spontaneous perspiration. The formula is used in high dosage, with 12 grams of each ingredient in decoction.

American ginseng (xiyangshen), introduced to China long after Shengmai San was first described, has sometimes been used as a substitute for the standard Chinese ginseng in preparing the formula. It has the reputation of treating the combined syndrome of qi and yin deficiency, thus fitting the overall formula approach. Sometimes other herbs for tonifying qi and nourishing yin are added. One example is yu-chu (yuzhu), which is classified along with ophiopogon as a yin-nourishing agent, but it also is thought to have some qi-tonification properties (a related herb, polygonatum, huangjing, is classified with the qi tonics); another example is pseudostellaria (taizishen), classified as a qi tonic with secondary yin-nourishing qualities.

In modern China, it has become customary to replace ginseng by the more affordable and readily available herb codonopsis. This does not necessarily improve the formula's effect; in fact, it is recommended that this substitution not be made when the patient has a severe deficiency of qi. But, it is an entirely reasonable substitute when the formula is to be used over an extended period for cases of qi and yin deficiency that are not very severe. Some practitioners would prefer codonopsis for this role, since ginseng could be viewed as an unnecessarily strong qi-tonification agent; others prefer ginseng, as it may be used in smaller quantities to get the desired effect. In a pharmacology study of the protective effect of Shengmai San on the cardiac muscle in rats exposed to elevated temperatures, the formula using codonopsis in place of ginseng was tested (10). It was suggested by the authors that the formula was able to stabilize the myocardial energy reserve, which is one of the claimed benefits of the original formula with ginseng.

Finally, aside from adjusting the dosage form (e.g., to liquid or injection), Shengmai San may be reformulated by adjusting the amounts of each of the three basic ingredients according to the therapeutic principle to be addressed. Some formulations have relatively larger amounts of ginseng to invigorate the qi, while others emphasize ophiopogon to nourish the yin. As an example, shengmai granules from Shanghai Number One Pharmaceutical Factory are made with 1 gram ginseng, 1.5 grams schizandra, and 3 grams ophiopogon per packet (dose is 1 packet each time, three times daily). This preparation emphasizes the yin-nourishing action of ophiopogon and schizandra. By contrast, the shengmai liquid described in the Pharmacopoeia of the PRC has equal parts ginseng and schizandra, and only twice as much ophiopogon as ginseng; giving more emphasis to the qi-tonic aspects.

MODERNIZING TRADITIONAL MEDICINE

The story of Shengmai San illustrates how the efforts of the physicians living many centuries ago inspire modern clinical work. Li Gao established a firm reputation in the history of Chinese medicine. Several of his formulas have been studied carefully by subsequent generations, continuing to the present day. The tradition, as a whole, is given credence by many modern clinicians, which leads them to apply ancient formulas for new diseases that have similar symptom patterns even though the underlying causes are different. Thus, Shengmai San has largely been retained in its original form: a prescription for tonifying qi and nourishing yin. Modern circumstances and new technologies also lead to innovations for herb administration. In the case of Shengmai San, an intravenous injection form of the prescription has been developed by pharmaceutical manufacturers and is in use in modern Chinese hospitals. The oral preparations are now available as ready-to-consume liquid in vials and in granules that are used to prepare instant teas. As a result, the benefits embedded within the traditional medical system become available to many people who might otherwise find its therapeutic agents cumbersome or irrelevant. The combined and coordinated efforts of herbalists, scholars, researchers, and manufacturers provide a means for successfully carrying the tradition into the future.

November 2001

REFERENCES

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