Danshen

Scientific Name(s): Salvia miltiorrhiza Bunge Family: Lamiaceae (mints)

Common Name(s): Danshen , Dan Shen , Tanshen , Tan-Shen , Radix Salviae miltiorrhiza , Fufang Danshen

Clinical Overview

Uses of Danshen

Danshen has been extensively used in Chinese medicine for many years. Limited studies have shown efficacy in coronary artery disease and acute ischemic stroke, but the quality of methodology limits the validity of some findings.

Danshen Dosing

Active components in commercially available preparations vary greatly. Commonly cited dosages include the following: 10 “dripping pills” taken 3 times a day (oral or sublingual), 3 Fufang Danshen tablets taken orally 3 times a day, danshen 20 mg/kg capsules. Doses of 100 mg/kg as a bolus injection have been used in children.

Contraindications

Data are lacking.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Avoid use.

Danshen Interactions

Danshen may interfere with laboratory digoxin plasma levels and may increase the anticoagulant effect of warfarin.

Danshen Adverse Reactions

Adverse reactions appear to be limited to allergy, dizziness, headache, mild GI symptoms, and reversible thrombocytopenia.

Toxicology

Information is limited.

Botany

Danshen is a perennial herb found mainly on sunny hillsides and stream edges. Violet-blue flowers bloom in the summer. The leaves are oval, with finely serrated edges. The fruit is an oval brown nut. Danshen's roots, from which many of the common names are derived, are a vivid scarlet red. Danshen is related to common sage, the culinary herb. 1 , 2

History

Danshen is considered one of the most important traditional Chinese medicines and has widespread use in Asian countries. Fufang Danshen is registered as a drug in several countries including Vietnam, Russia, Cuba, Korea, and Saudi Arabia. In 1997, danshen was the first traditional Chinese medicine used in US phase 2 and 3 clinical trials. In addition to standard dosage forms, danshen is available as an injection, as well as in rapid-soluble, liposomal, and solid dispersion forms. The “dripping pill” is made by a process of thermally blending the extract with the excipients and then dripping the mixture into an insoluble cooling liquid until solidified droplets are achieved.

Traditionally, danshen has been used to improve bodily functioning, as well as to treat hemorrhage, dysmenorrhea, miscarriage, swelling, insomnia, and hepatitis. More recent uses include treatment of cardiovascular and cerebrovascular conditions. 2 , 3

Chemistry

More than 50 compounds have been identified in danshen. Antibacterial, antioxidant, and antineoplastic effects are attributed to the lipophilic compounds, which include more than 30 diterpenes such as tanshinone Ι, ΙΙA, ΙΙB, and cryptotanshinone. Hydrophilic compounds from danshen largely contain phenolic acids including various caffeic and salvianolic acids and related compounds (eg, danshensu, procatechuic aldehyde, acid). Antioxidant and anticoagulant effects may derive from the hydrophilic compounds. Other compounds identified include baicalin, beta-sitosterol, daucosterol, flavanones, vitamin E, and tannins. 2 , 3 , 4

Danshen Uses and Pharmacology

Experiments show that danshen inhibits angiogenesis, possibly caused by the chemicals cryptotanshinone and tanoshinone IIa. 5 Danshen inhibits cell growth and induces apoptosis in human hepatoma cells. 6 Several studies have evaluated the immunomodulatory effects of danshen combined with yunzhi ( Coriolus versicolor ) in nasopharyngeal and breast cancer. Enhanced cellular immunity was demonstrated as well as improvements in quality of life indicators. 6 , 7 , 8

In rats, danshen was cardioprotective for infarct size and mortality, and in another experiment was comparable to captopril. 9

A meta-analysis of trials conducted among patients with angina found that compound salvia pellets (a mixed preparation containing danshen) improved angina symptoms and electrocardiogram parameters compared with nitrates. However, the trials were of poor methodological quality. 2 , 9 , 10 A review of trials using danshen to treat angina reported that danshen may be more suitable than isosorbide dinitrate for long-term management of angina. Danshen also appears to be effective in relieving angina caused by coronary artery spasm, possibly because of its calcium antagonistic properties. 2 , 9

Apparent efficacy in treatment of myocardial infarction may be caused by sedative, antioxidant, and antiplatelet effects as well as by improved coronary microcirculation. 9 Danshen also decreases myocardial reperfusion injury in patients with acute myocardial infarction following percutaneous intervention. 9

Two constituents of danshen, salvianolic acid A and magnesium tanshinoate B, inhibit low-density lipoprotein (LDL) oxidation. In a rabbit model, serum triglycerides were lower in the danshen-fed group compared with the control group. A study among elderly patients with hyperlipidemia (N = 96) showed decreased total cholesterol and LDL with danshen. 9 In other human experiments, a reduction in cholesterol, triglyceride, and LDL levels was seen with administration of the Fufang Danshen dripping pill, but the component responsible for the effect was not identified. 2

Danshen is used for the management of hypertension in China, Korea, and Japan, and is thought to act via inhibition of angiotension-converting enzymes. Experiments in rats suggest that the chemicals lithospermic acid B and salvianolic acid B are responsible for this activity. Reductions in blood pressure were achieved in pregnant women given intravenous danshen infusions for 10 days. 9

Animal and human experiments suggest that danshen exerts an effect on glomerular filtration rate and renal blood flow. 9 , 11 Experiments with danshen injections given daily for 10 days in renal transplant patients resulted in an increase in urinary volume and endogenous creatinine clearance rates over control. 9 Danshen has been used as add-on therapy to conventional steroid treatment in children with primary nephrotic syndrome. 9

Many studies reflect danshen's extensive use as a standard treatment for acute ischemic stroke in China. Animal experiments with extracts of danshen demonstrate increased cerebral microcirculation. Two meta-analyses have been conducted on human trials meeting inclusion criteria for analysis. One meta-analysis includes 11 trials in which danshen is compared with other medicines, 12 and the other includes 6 trials in which danshen is compared with placebo. 1 Although improvement in neurological deficit was reported for danshen, 1 , 13 quality of life was not assessed and deaths (of any cause) were not reported. No long-term follow up was reported, and few trials reported adverse reactions. Both meta-analyses question the quality of trials, and ultimately neither can make definitive statements about the role of danshen in therapy. 1 , 2 , 12 , 13

Studies suggested tanshinone ΙΙa may act to inhibit voluntary intake of alcohol in rats with induced alcoholism. 9 , 14

Antithrombotic actions of danshen were reported in animal experiments, 15 , 16 , 17 , 18 but human trials are lacking.

Earlier studies suggest danshen affects chronic hepatitis patients in relieving nausea, malaise, liver pain, and abdominal distention. 18 , 19

Dosage

Active components in commercially available preparations vary greatly. 2 The Pharmacopoeia of the People's Republic of China describes standards for the Fufang Danshen dripping pill (no less than 0.08 mg/pill of danshensu) and the Fufang Danshen tablet (no less than tanshinone 0.20 mg and salvianolic acid B 5 mg per tablet). 2 Commonly cited dosages include 10 dripping pills taken 3 times a day orally or sublingually, 3 Fufang Danshen tablets taken orally 3 times a day, 2 danshen 20 mg/kg capsules, 6 , 8 and danshen 100 to 200 mg/kg injection. 9 , 20 Danshen has been used in children with pulmonary hypertension (2 to 15 years of age) at a total dosage of 400 mg/kg (100 mg/kg bolus followed by 100 mg/kg continuous infusion repeated twice) 20 and in pregnant women with hypertension. Deaths, however, were not reported in either study. 9

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Avoid use.

Interactions

Danshen may interfere with laboratory values for digoxin plasma levels. Monitoring free digoxin concentrations can circumvent the positive and negative interference caused by danshen. 9 , 21

Three case reports of overcoagulation exist for coadministration of warfarin and danshen. Pharmacokinetic and dynamic factors are suggested for this effect. In rats, danshen appears to increase the absorption rate and area under the curve and to decrease clearance and volume of distribution. 2 , 22 , 23 , 24

Danshen and salicylate may compete for protein binding sites. 2 , 22 Danshen induces CYP-450 in rats but not in mice. 2 Experiments suggest that danshen may exhibit a protective effect against the nephrotoxic and ototoxic effects of gentamicin. 9

Adverse Reactions

Few trials report adverse reactions related to danshen usage in detail; therefore, any comments regarding safety are difficult to qualify. 1 Allergy, dizziness, headache, mild GI symptoms, and reversible thrombocytopenia have been reported. 1 , 2 , 9 , 10

Toxicology

Research reveals little information regarding toxicology with the use of danshen. Oral danshen (2,500 mg/kg body weight) given to rats for 90 days at a dosage 400 times that of the recommended human dosage was reported to be nontoxic. 2 The median lethal dose of the water-soluble extract of danshen is reported to be 25 g/kg body weight in mice. 2

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