Pharmacological Effects of Danshen (Salvia miltiorrhiza)
1. Overview
Danshen, the dried root and rhizome of the plant Salvia miltiorrhiza, is slightly cold in nature and bitter in taste. It has the effects of invigorating blood circulation, removing blood stasis, nourishing blood and calming the mind, regulating menstruation and alleviating pain, as well as cooling blood and relieving pain. It is classified as a superior herb in the Shennong Bencao Jing and has been widely used in ancient times for cardiovascular and blood-related diseases.
2. Chemical Composition of Danshen
The active components of Danshen can be divided into two categories: lipophilic and hydrophilic. In terms of lipophilic components, over 40 compounds have been identified, which can be categorized into two types: tanshinones and rosmarinic acid derivatives. Most tanshinones are diterpenoid compounds, including Tanshinone I, Tanshinone II-A, Tanshinone II-B, Tanshinone III, Isotanshinone, Isodanshinone, Hydroxytanshinone II-A, and Dihydrotanshinone I. The hydrophilic components of Danshen all possess phenolic acid structures, with the earliest discovered being Danshensu, followed by a series of phenolic acids such as Danshen phenolic acid A, B, C, D, E, F, H, I, J, and Tetramethyl Danshen phenolic acid C, as well as rosmarinic acid and lithospermic acid. Both the lipophilic and hydrophilic components of Danshen are effective. The lipophilic tanshinones primarily improve blood circulation, exhibit antibacterial and anti-inflammatory properties, while the hydrophilic phenolic acids are notable for their antioxidant, anticoagulant, anti-thrombotic, lipid-regulating, and cell-protective effects.
3. Pharmacological Effects of Danshen
(1) Pharmacological Effects on the Cardiovascular System
1. Anti-myocardial Ischemia
Danshen can increase coronary blood flow, improve microcirculation, promote the opening of collateral circulation, enhance blood rheology, increase hypoxia tolerance, inhibit lipid peroxidation, scavenge harmful free radicals, and regulate blood distribution in ischemic myocardium. Through these comprehensive actions, it protects ischemic myocardium. Danshen phenolic acid B exhibits a relaxing effect in isolated coronary artery ring contraction models stimulated by high potassium, high calcium, and histamine, which is achieved by blocking calcium channels. Danshen phenolic acid B can increase coronary nitric oxide (NO) production through multiple pathways, dilating coronary blood vessels.
2. Anti-arrhythmic Effects
Imbalances of intracellular sodium and potassium ions and calcium overload are important factors causing arrhythmias. Tanshinone II-A reduces calcium ions in normal myocardium, significantly inhibiting intracellular calcium overload and exhibiting calcium channel blocking effects.
3. Reducing Myocardial Oxygen Consumption
Clinical practice shows that reducing myocardial oxygen consumption is beneficial for treating ischemic coronary heart disease. After blocking blood flow in canine coronary arteries, intravenous injection of saline resulted in an increase in left ventricular end-diastolic pressure, while the experimental group receiving intravenous infusion of Tanshinone II-A showed a significant decrease, indicating that Tanshinone II-A may reduce myocardial oxygen consumption by lowering left ventricular wall tension and myocardial volume.
4. Anti-platelet Effects
The anti-platelet aggregation effect of Danshen was reported as early as 1982. In vitro experiments showed that Danshen phenolic acid A significantly inhibited platelet aggregation induced by arachidonic acid, thrombin, and ADP, with the potency in the order of ADP > thrombin > arachidonic acid.
5. Anti-hyperlipidemic Effects
Abnormal elevation of blood lipids is one of the main causes of atherosclerosis, coronary heart disease, and myocardial infarction. Elevated plasma homocysteine (Hcy) levels are a major risk factor for hyperlipidemia. Danshensu does not affect Hcy levels in normal rats but can significantly reduce Hcy levels in model rats with elevated Hcy by activating transsulfuration pathways, increasing cysteine and GSH levels. Methylation of Danshensu can elevate Hcy levels, but the reduction in Hcy levels due to transsulfuration is stronger than the elevation caused by Danshensu methylation, thus Danshensu overall can lower Hcy levels.
6. Anti-free Radical Effects
When there is a dynamic imbalance of oxygen free radicals in the body, lipid peroxidation can cause endothelial cell damage. Scavenging harmful free radicals and preventing or alleviating lipid peroxidation reactions is one of the mechanisms by which Danshen prevents and treats cardiovascular, cerebrovascular diseases, liver diseases, and kidney diseases. Water extracts of Danshen, Danshen injections, Danshensu, and sodium sulfonate of Tanshinone II-A have the ability to scavenge superoxide anions and hydroxyl radicals.
7. Anti-atherosclerotic Effects
Tanshinone can inhibit the oxidation of low-density lipoprotein, suppress lipid metabolic enzyme activity, and improve lipid metabolism processes. Danshensu inhibits cholesterol synthesis, reducing the content of malondialdehyde in oxidized lipoproteins, significantly decreasing the toxicity of oxidized lipoproteins to cells. Numerous studies have shown that Danshensu primarily exerts anti-atherosclerotic effects by inhibiting monocyte activation and foam cell formation, reducing the release of pro-inflammatory factors, and inhibiting the proliferation of vascular smooth muscle cells.
8. Anti-myocardial Hypertrophy
Left ventricular hypertrophy is a complication of hypertension. Danshensu intervention can promote the proliferation of peripheral endothelial progenitor cells and significantly improve the adhesion, migration, and proliferation capabilities of peripheral blood EPCs. Tanshinone II-A has no significant effect on the number and function of endothelial progenitor cells.
(2) Effects on the Digestive System
Danshen has effective components that combat ulcers, particularly against indomethacin and acetic acid-induced gastric ulcers. Danshen can increase gastric mucosal blood flow and potential difference, reduce the reverse diffusion of hydrogen ions, protect the integrity of the mucosal barrier, and enhance its defensive function. In pathological conditions where gastric mucosa is damaged by aspirin, it can delay the progression of lesions but cannot reverse the damage.
(3) Protective Effects on the Liver
Danshen has protective effects against liver damage and promotes liver cell regeneration. Experiments show that intramuscular injection of Danshen can significantly increase liver blood flow in normal rats and mice, while liver blood flow is significantly reduced in mice and rats with acute and chronic carbon tetrachloride poisoning. Using Danshen can restore the reduced liver blood flow to normal levels, thus protecting the damaged liver.
(4) Anti-tumor Effects
Tanshinone II-A (Tan IIA) can inhibit the growth of various tumor cell lines, including breast cancer, lung cancer, liver cancer, leukemia, and gastric cancer cell lines. The effective component of Danshen, Tanshinone, exerts its anti-tumor effects through mechanisms such as killing various tumor cells, inducing differentiation, and inducing apoptosis. Dihydrotanshinone I has strong cytotoxic effects on human liver cancer and lung cancer cell lines and can enhance the sensitivity of tumor cells to X-rays.
(5) Antibacterial and Anti-inflammatory Effects
Numerous studies have shown that Danshen has definite anti-infection effects, with its antibacterial components including Isotanshinone, Tanshinone II-A, and Tanshinone II-B. Danshen exhibits strong inhibitory effects against Gram-positive bacteria, especially Staphylococcus aureus, with the effective antibacterial component being total tanshinones, particularly the effect of Tanshinone I being the strongest. Tanshinone II-A can inhibit the synthesis of the gene promoter of nuclear factor kappa B (NF-κB) activated by lipopolysaccharides in RAW264.7 cells and inhibit the production of inflammatory mediators and the occurrence of inflammatory responses. Methanol extracts of Danshen show strong antibacterial activity against 10 common bacteria, with Staphylococcus epidermidis being the most sensitive, indicating that Danshen extracts have broad-spectrum antibacterial effects as a natural antibacterial substance.
(6) Effects on the Central Nervous System
1. Neuroprotective Effects
The components of Danshen that protect brain cells mainly include Tanshinone, Tanshinone II-A, and Danshen phenolic acids. The mechanisms of their anti-damage effects may involve two aspects: reducing free radical damage and decreasing the release of glutamate, thereby inhibiting glutamate excitotoxicity.
2. Repair of Nervous Tissue
Danshensu can significantly improve mitochondrial oxidative phosphorylation dysfunction caused by hypoxia and hypoglycemia, regulating cellular energy metabolism, alleviating ischemic damage to brain tissue, and participating in the repair of nervous tissue.
3. Anti-thrombotic Effects
Hydrophilic phenolic acids from Danshen significantly inhibit platelet aggregation induced by various factors, and at the same time, they also significantly inhibit the release of serotonin from platelets induced by collagen. Danshen polyphenolic acids have significant anti-platelet aggregation effects, thus helping to maintain blood flow and prevent thrombosis.
