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Danshen

Scientific Name(s): Salvia miltiorrhiza Bunge
Common Name(s): Dan shen, Danshen, Tan-shen, Tanshen

Medically reviewed by Drugs.com. Last updated on Jul 13, 2022.

Clinical Overview

Use

Danshen has been used extensively in traditional Chinese medicine as a single herb and in multiherb formulations. Limited clinical studies have shown efficacy in coronary artery disease and acute ischemic stroke, but the quality of methodology limits the validity and extrapolation of these findings.

Dosing

Active components in commercially available preparations of danshen vary greatly. Doses include danshen 20 mg/kg capsules. Dosages of danshen root extract 5 g twice daily for 60 days have been used in diabetic patients with coronary heart disease.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

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

Interactions

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

Adverse Reactions

Adverse reactions include allergy, dizziness, headache, mild GI symptoms, and reversible thrombocytopenia.

Toxicology

No data.

Scientific Family

Botany

Danshen is a perennial herb found mainly on sunny hillsides and stream edges in China. It has violet-blue flowers that bloom in the summer, with oval, finely serrated leaves. The fruit is an oval brown nut. Danshen's vivid scarlet red roots, from which many of the common names derive, are the primary medicinal part of the plant. Danshen is related to common sage, the culinary herb.Wu 2007, Zhou 2005 A study of samples sold in Chinese markets identified 18 related Salvia species collected, used, and sold as danshen, and evaluated their folk uses, traditional functions, and chemistry.Li 2008 Although only S. miltiorrhiza is recorded as the official species of danshen in the Pharmacopoeia of the People's Republic of China, Salvia przewalskii Maxim is widely used in southern China. Genetic diversity and population structure of S. miltiorrhiza have been studied.Song 2010 Danshen is related to other Salvia species such as Salvia hispanica L. (chia) and Salvia officinalis (sage).

History

Danshen is considered one of the most important traditional Chinese medicines and has widespread use in Asian countries.Fang 2010 The "dripping pill" is made by thermally blending the extract with excipients and then dripping the mixture into an insoluble cooling liquid until solidified droplets are formed.Zhou 2005 As a single herbal supplement, S. miltiorrhiza has been investigated in clinical trials for its effect on cardiovascular risk factors in patients with hyperlipidemia, hypertension, and diabetes.Qian 2012, Qian 2012, van Poppel 2015

Traditionally, danshen has been used to improve body function (eg, promote circulation, blood flow), as well as to treat hemorrhage, dysmenorrhea, miscarriage, swelling, insomnia, and hepatitis. More recent primary uses include treatment of cardiovascular and cerebrovascular conditions.Wang 2007, Zhou 2005

Chemistry

More than 50 compounds have been identified in danshen, the majority being lipophilic diterpenes, known as tanshinones, and polar phenolic compounds.Wang 2007 Antibacterial, antioxidant, and antineoplastic effects are attributed to the lipophilic compounds, of which more than 30 have been described; tanshinone I, tanshinone IIA, and cryptotanshinone are the major constituents. Hydrophilic compounds from danshen consist of phenolic acids, including caffeic acid and its derivatives, such as danshensu, salvianolic acids A and B, rosmarinic acid, and prolithospermic acid.Jiang 2005, Wang 2007 Antioxidant and anticoagulant effects may derive from these hydrophilic compounds. Other compounds include baicalin, beta-sitosterol, daucosterol, flavanones, vitamin E, and tannins.Jiang 2005, Wang 2007, Zhou 2005

A study of chemical variations of 13 constituents in 74 samples of danshen collected in China has been conducted using high-performance liquid chromatography (HPLC) analysis.Zhong 2009 Seasonal and cultivar variation in danshen grown in Australia has also been analyzed.Li 2009, Li 2009, Sheng 2009 A metabonomic nuclear magnetic resonance study examined primary metabolites of 3 phenotypically distinct cultivars of danshen.Dai 2010 Analytical procedures for determination of important constituents in crude danshen have proliferated, with HPLC/diode array/mass spectral techniques the most prominent.Chen 2011, Park 2008 Measurements of danshen compounds in body fluids have been achievedLu 2008 and several pharmacokinetic and distribution studies have been conducted on isolated constituents and their interactions with each other.Bi 2008, Chang 2010, Pan 2008, Xiaohui 2007

Uses and Pharmacology

Alcoholism

Animal data

Cryptotanshinone and danshen extract were protective against ethanol injury to rat hepatocytes.(Yin 2009) Studies suggest tanshinone IIA may inhibit voluntary intake of alcohol in rats with induced alcoholism.(Cheng 2007, Xu 2005) Danshen limited the effects of experimental pancreatitis or obstructive jaundice in rats.(Xiping 2009, Xiping 2009) It also protected against ischemia reperfusion injury in experimental liver transplantation in rats.(Liang 2009) In a mouse model, danshen was protective against damage associated with alcoholic liver disease.(Ding 2017)

Antithrombotic effects

Animal data

Antithrombotic actions of danshen have been reported in animal experiments.(Chang 1985, Dong 1996, Yu 1994, Zou 1993)

Antiosteoclastogenic activity

In vitro data

In a study to examine the effects of S. miltiorrhiza on osteoclastogenesis and osteoblast differentiation, the S. miltiorrhiza fraction (methanol and ethanol isolated) with a low concentration of tanshinone IIA inhibited osteoclastogenesis.(Kim 2008)

Antioxidant effects

Clinical data

The effect of S. miltiorrhiza root extract on biomarkers of oxidative stress in diabetic patients with coronary heart disease was investigated in a randomized, placebo-controlled trial (N=62). Only serum malonaldehyde levels were significantly decreased after 30 days of treatment (5 g twice daily) compared with baseline (P<0.05), with further reductions after 60 days (P<0.005). No other oxidative stress biomarkers changed significantly. Similarly, no lipid parameters were affected by S. miltiorrhiza root extract supplementation.(Qian 2012)

Cancer

In vitro data

Danshen and its constituents inhibit the growth of several types of cancer cell lines, including breast,(Yang 2010) prostate,(Gong 2011, Won 2010) liver,(Lee 2010) and colon.(Lin 2017) The effects appear to be primarily due to tanshinones. The effect in hepatocellular cancer may be mediated through TGF-beta/SMAD signaling,(Liu 2010) while the effect in prostate cancer cells has been attributed to the PI3-kinase/AKT pathway.(Won 2010) Experiments show that danshen inhibits angiogenesis, possibly due to cryptotanshinone and tanoshinone IIa.(Fan 2006)

Animal data

Tanshinone I has been observed to inhibit prostate cancer xenografts in mice.(Gong 2011)

Clinical data

A retrospective cohort analysis found that survival time was slightly increased in colon cancer patients using danshen at greater dosages and for longer durations.(Lin 2017)

Cognitive impairment

Animal data

In a study of mice, crytotanshinone attenuated beta-amyloid deposition in the brain,(Mei 2009) and another study showed cholinesterase inhibition, suggesting potential for use in Alzheimer disease.(Wong 2010)

Coronary artery disease

In vitro data

In one study, a standardized extract of danshen protected rat cardiac myocytes from tumor necrosis factor–induced apoptosis. In cultured cardiac fibroblasts, the extract reduced collagen synthesis.(Ling 2009) The isolated constituent 15,16-dihydrotansinone I inhibited collagen-induced platelet aggregation, blocking intracellular calcium mobilization and liberation of arachidonic acid.(Park 2008) Several tanshinones inhibited prostaglandin and nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells, further supporting anti-inflammatory mechanisms for danshen.(Jeon 2008) Tanshinone IIA inhibited migration of human aortic smooth muscle cells through an AKT and matrix metalloprotease-9 pathway.(Jin 2008)

Animal data

In a study in rats, danshen was cardioprotective for infarct size and mortality, and in another experiment, danshen demonstrated comparable effects to captopril.(Cheng 2007) A similar rat coronary artery ligation experiment found that tanshinone IIA reduced monocyte chemoattractant protein 1 expression, thereby blocking inflammation. Macrophage infiltration and transforming growth factor (TGF)–beta secretion were also blocked.(Ren 2010) The effect of the phenolic danshen constituent danshensu on the homocysteine pathway was studied in a rat model, with the compound lowering elevated plasma total homocysteine levels after 3 weeks of treatment, which may result in activation of the transsulfuration pathway.(Cao 2009)

Clinical data

A review of trials using danshen to treat angina reported that it may be better 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.(Cheng 2007, Zhou 2005) A trial of danshen/Pueraria lobata found modest improvements in cardiovascular parameters over 1 year of treatment.(Tam 2009) The effect of S. miltiorrhiza root extract on biomarkers of coronary heart disease (CHD) (von Willebrand factor [vWF] and serum vascular cell adhesion molecule-1 [sVCAM-1]) was studied in a randomized, placebo-controlled trial (N=62). Diabetic patients with CHD who received S. miltiorrhiza root extract (5 g twice daily for 60 days) experienced significant decreases in sVCAM-1, vWF, and oxidized low-density lipoprotein (LDL) cholesterol (P<0.05, P<0.05, and P<0.01, respectively). Treatment was well tolerated with no adverse events reported.(Qian 2012)

Apparent efficacy in treatment of myocardial infarction (MI) may be due to sedative, antioxidant, and antiplatelet effects, as well as by improved coronary microcirculation. Danshen also decreases myocardial reperfusion injury in patients with acute MI following percutaneous intervention.(Cheng 2007)

Diabetes

In vitro data

Tanshinones enhanced insulin activity in Chinese hamster ovary cells and in adipocytes.(Jung 2009) Pathways through which dihydrotanshinone might affect blood glucose were examined in cellular experiments.(Liu 2010) Inhibition of advanced glycation end products through alpha-glucosidase blockade by danshen was reported.(Ma 2011)

Clinical data

In a double-blind, randomized, placebo-controlled crossover trial in patients with hyperlipidemia and hypertension (N=20), a dose of S. miltiorrhiza root extract 1 g 3 times daily administered for 28 days did not affect metabolic parameters. Changes in fasting plasma glucose, glycosylated hemoglobin (HbA1c), fasting insulin, HOMA-IR, and HOMA-B were not observed.(van Poppel 2015)

Hepatoprotection

Clinical data

Earlier studies suggest danshen may be useful in relieving nausea, malaise, liver pain, and abdominal distention in patients with chronic hepatitis.(Bai 1984, Chang 1985)

A systematic review of clinical data on nutraceuticals used for non-alcoholic fatty liver disease (NAFLD) identified one meta-analysis of 8 controlled clinical trials conducted in 800 Asian patients. Supplementation with the dry extract of S. miltiorrhiza was found to reduce transaminases that reflected a reduction in hepatosteatosis.(Cicero 2018)

Hyperlipidemia

In vitro data

A mixture of danshen and P. lobata decreased total cholesterol while increasing intracellular adhesion molecule (ICAM-1) expression and cellular adhesion in human monocyte–derived macrophages.(Sieveking 2005) Two constituents of danshen, salvianolic acid A and magnesium tanshinoate B, inhibited LDL oxidation. A functional proteomics study of danshen extract in rat smooth muscle cells found effects on oxidative stress pathways.(Hung 2010)

Animal data

ICAM-1 was validated as a hyperlipidemic target of danshen in an apolipoprotein E(-/-) mouse model. While lipid levels were not altered, increased expression of ICAM-1 in circulating leukocytes driven by an atherogenic diet was abolished by danshen treatment. Atherosclerotic plaque was also attenuated in this experiment.(Ling 2008) In a rabbit model, serum triglycerides were lower in the danshen-fed group compared with the control group. A rat model of hyperlipidemia treated with danshen extract showed decreases in total cholesterol, LDL, and triglycerides, with elevation of high-density lipoprotein (HDL).(Ji 2008) Molecular analysis implicated a mechanism operating through farnesoid X receptor/liver X receptor coagonism.(Ji 2008)

Clinical data

A study among elderly patients with hyperlipidemia (N=96) showed decreased total cholesterol and LDL with danshen.(Cheng 2007) A double-blind, randomized, controlled crossover study (N=20) investigated S. miltiorrhiza root extract administered as 1 g 3 times daily for 28 days in patients with risk factors for cardiovascular disease (ie, hyperlipidemia, hypertension). After correcting for baseline values and changes observed with placebo, danshen root extract caused a significant increase in LDL cholesterol compared with baseline and placebo (P<0.01 each). No other lipid parameters or blood pressure, vascular response, metabolic, antioxidant, inflammatory, or coagulation measurements changed significantly. Peripheral facial nerve paralysis was the one serious adverse event that occurred during danshen treatment.(van Poppel 2015)

Hypertension

In vitro data

Dihydrotanshinone relaxed isolated rat coronary arteries stimulated with 5-hydroxytryptamine (5-HT). The effect was blocked by the guanylate cyclase inhibitor ODQ, indicating a mechanism involving inhibition of calcium influx in smooth muscle cells of the vasculature.(Lam 2008) A novel phenolic compound from danshen, isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxylpropanoate (IDHP), also had a vasorelaxant effect on rat mesenteric artery contracted with 5-HT or epinephrine. The authors posited a direct effect on vascular smooth muscle cells through intracellular calcium release and inhibition of calcium influx. Potassium channels may also be involved.(Wang 2008) In contrast, the phenolic danshen constituent danshensu had a biphasic effect on isolated rat aortic rings, with high doses producing vasodilation.(Zhang 2010) In vitro experiments with isolated arteries implicated ATP-sensitive calcium channels in the mechanism.(Chan 2011)

Animal data

In a study investigating the effects of danshen on blood pressure and its possible mechanisms, danshen constituent tanshinone IIA given intraperitoneally at 10 mg/kg lowered systolic blood pressure in spontaneously hypertensive rats but had no effect on blood pressure in normotensive rats. Oral administration had the same effects.(Chan 2011) In another study, rats treated with phenylephrine followed by either danshen extract or magnesium tanshinoate B displayed lower blood pressure values.(Leung 2010)

Clinical data

Danshen is used for the management of hypertension in China, Korea, and Japan, and is thought to act via inhibition of angiotensin-converting enzymes.(Cheng 2007) However, in a double-blind, randomized, placebo-controlled crossover study (N=20), blood pressure and vascular response did not change in patients with hypertension and hyperlipidemia following treatment with S. miltiorrhiza root extract 1 g 3 times daily for 28 days.(van Poppel 2015)

Immunomodulation

Animal data

Tanshinones inhibited cutaneous anaphylaxis in a study in mice.(Trinh 2010)

Ototoxicity

Animal data

In a study in guinea pigs, S. miltiorrhiza demonstrated protection against cisplatin-induced ototoxicity.(Xu 2011)

Renal

Animal data

Animal experiments suggest that danshen affects glomerular filtration rate and renal blood flow.(Cheng 2007, Wojcikowski 2004) Tanshinone IIA given to rats with experimental renal insufficiency improved many end points.(Ahn 2010) Pretreatment with danshen before experimental kidney transplantation in rats reduced ischemia reperfusion injury.(Guan 2009)

Stroke

Many studies reflect danshen's extensive use in China as a standard treatment in acute ischemic stroke. The injury to the vasculature following ischemia and reperfusion may be ameliorated by danshen treatment.(Han 2008, Lin 2010)

In vitro data

In one study, rat basilar artery rings precontracted with the prostaglandin analog U46619 were relaxed by a formulation containing danshen and Pueraria lobata. This effect was not dependent on voltage-sensitive or inwardly rectifying potassium channels, but could be blocked by glibenclamide, an inhibitor of adenosine triphosphate (ATP)–sensitive potassium channels. The authors concluded that danshen's vasorelaxant effect is independent of the arterial endothelium.(Lam 2010) In another study, tanshinone IIA inhibited vascular smooth muscle cell proliferation and reduced intimal hyperplasia through a mitogen-activated protein kinase and c-fos mechanism.(Li 2010)

Animal data

Animal experiments with extracts of danshen have demonstrated increased cerebral microcirculation. A study of balloon-induced vascular injury in rats showed that oxidative damage was limited by treatment with magnesium lithospermate, a danshen constituent.(Hur 2008) Two reviews summarize the pharmacologic effects of polar and lipophilic danshen constituents in models of cerebral infarction, with emphasis on antioxidant pathways.(Han 2008, Lin 2010)

Clinical data

Three meta-analyses of clinical trials evaluating use of danshen for ischemic stroke have been conducted. One meta-analysis included 11 trials in which danshen was compared with other medicines(Sze 2005) and another included 6 trials in which danshen was compared with placebo.(Wu 2007) A third meta-analysis included trials that examined use of many traditional Chinese medicines, including danshen.(Wu 2007) Although improvement in neurological deficit was reported with danshen use,(Wu 2007, Wu 2007) quality of life was not assessed and deaths (from any cause) were not reported. Long-term follow-up was not reported, and few trials reported adverse reactions. The authors of all 3 meta-analyses question the quality of trials, and ultimately were not able to make definitive statements about the role of danshen in therapy.(Sze 2005, Wu 2007, Wu 2007, Zhou 2005)

Dosing

Active components in commercially available preparations of danshen vary greatly.Zhou 2005 The Pharmacopoeia of the People's Republic of China recommends an S. miltiorrhiza dosage of 9 to 15 g/day of the root.van Poppel 2015 Commonly cited dosages include danshen 20 mg/kg capsules.Fang 2010, Jiang 2005

A dosage of S. miltiorrhiza hydrophilic root extract 5 g (as a tablet) twice daily for 60 days has been used in diabetic patients with coronary heart disease.Qian 2012, Qian 2012

Pregnancy / Lactation

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

Interactions

Danshen and salicylate may compete for protein-binding sites.(Hu 2005, Zhou 2005) Danshen induces CYP-450 in rats but not in mice.(Zhou 2005) Danshen aqueous extract has been shown to competitively inhibit CYP1A2 metabolism of caffeine in human and rat liver microsomes, and decrease caffeine clearance in rats. Tanshinones were responsible for the inhibition.(Wang 2009, Wang 2010) Different modes of inhibition (competitive, uncompetitive, and noncompetitive) were posited for tanshinones on 4 human CYP isoforms.(Wang 2010) Danshen decreased CYP3A in rats, increasing the effect of midazolam.(Wang 2010) In a study of 12 healthy men, pretreatment with danshen extract 4 g 3 times daily increased midazolam oral clearance by approximately 35% and reduced the maximum plasma concentration and AUC by approximately 31% and 27%, respectively.(Qiu 2010) However, in healthy volunteers, no effect was seen on theophylline metabolism.(Qiu 2008) In rats, no effect on the metabolism of metoprolol by salvianolic acid B was detected.(Wan 2010)

Experiments suggest that danshen may protect against the nephrotoxic and ototoxic effects of gentamicin.(Cheng 2007)

Digoxin: Danshen may interfere with laboratory values for digoxin plasma levels. Monitoring free digoxin concentrations can circumvent the positive and negative interference caused by danshen.(Cheng 2007, Wahed 2001)

Warfarin: Danshen interacts with warfarin; avoid use in patients with heart failure.(Page 2016) Three case reports of overcoagulation with coadministration of warfarin and danshen exist. Pharmacokinetic and dynamic factors have been suggested for this effect. In rats, danshen appears to increase warfarin absorption rate and area under the curve (AUC) and decrease clearance and volume of distribution.(Holbrook 2005, Hu 2005, Izzo 2005, Zhou 2005)

Adverse Reactions

Few trials report adverse reactions related to danshen use; therefore, any statements regarding safety are difficult to qualify. Allergy, dizziness, headache, mild GI symptoms, and reversible thrombocytopenia have been reported.Cheng 2007, Wu 2007, Zhou 2005

In a 2016 scientific statement by the American Heart Association regarding drugs that may cause or exacerbate heart failure, danshen was recognized as a product with antiplatelet activity that may increase bleeding risk when used with anticoagulants. The guidance noted that natural medicines are not recommended for the management of heart failure symptoms, nor for secondary prevention of cardiovascular events, and that nutritional supplements are not recommended for the treatment of heart failure.Page 2016

Toxicology

Research reveals limited information regarding toxicity 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. The median lethal dose of the water-soluble extract of danshen is reported to be 25 g/kg body weight in mice.Zhou 2005

Index Terms

References

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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