Tanshinone: A Comprehensive Reference
1. Identity, Nomenclature, and Natural Sources
Tanshinones are a class of abietane diterpene compounds isolated from Salvia miltiorrhiza (Danshen or Tanshen in Chinese), a well-known herb in Traditional Chinese Medicine (TCM). The term "tanshinone" does not refer to a single molecule but to a family of chemically related compounds. Since they were first identified in the 1930s, more than 40 lipophilic tanshinones and structurally related compounds have been isolated from Danshen.
The roots of Salvia miltiorrhiza are the source of the traditional Chinese medicine Danshen and the class of tanshinones — particular quinoid nor-diterpenoids of the abietane type. Salvia miltiorrhiza Bunge, a member of the Lamiaceae family, is valued in traditional Chinese Medicine. The plant is commonly known in English as red sage or Chinese red sage.
Principal Tanshinone Compounds
The lipophilic diterpenoid components are generally known as tanshinones, including structurally related tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone I. Of these:
- Tanshinone IIA (Tan IIA) — the most extensively studied and pharmacologically prominent member. The structural characterization of Tan IIA (PubChem CID: 164676) was first established by Kakisawa in the 1960s, marking the commencement of extensive research into its synthesis and structural analogs.
- Cryptotanshinone (CPT) — also abundant and studied for distinct activities including transcriptional signal suppression.
- Tanshinone I and Dihydrotanshinone I (DHT) — structurally related congeners with complementary activities. Cryptotanshinone, dihydrotanshinone I, tanshinone I, and tanshinone IIA have been extensively studied for their anticancer potential, not only but also because of their high abundance in S. miltiorrhiza and their thus easy availability.
Other Plant Sources
Additional Salvia species are known to contain tanshinones, mainly such of the subgenus Glutinaria, of which S. glutinosa is the only species widely occurring in Europe. Tanshinones are also mainly detected in the roots of Salvia przewalskii, Salvia trijuga, Salvia castanea, and Salvia yunnanensis.
Phytochemical Classification
The active components of Salvia miltiorrhiza mainly include water-soluble phenolic acids and liposoluble tanshinones, and there are significant differences in their pharmacokinetic characteristics. The tanshinones are the liposoluble (fat-soluble) fraction, in contrast to the hydrophilic salvianolic acids (including rosmarinic acid and salvianolic acid B). The hydrophilic phenolic acids include rosmarinic acid, salvianolic acid B, lithospermic acid, and dihydroxyphenyllactic acid or Danshensu, and they may function as antibacterial, anti-oxidative and antiviral reagents.
2. Traditional and Historical Use
Origins and Earliest Records
Salvia miltiorrhiza Bunge was first recorded in the Shenlong Bencao Jing (200–300 AD, Han Dynasty), the oldest medicine monograph in China. Danshen as a traditional Chinese medicine was first published in "Shennong's Herbal Classic of the Materia Medica" and is the dried root and rhizome of Salvia miltiorrhizae Bunge of the Labiatae family, with a surface that is reddish-brown or dark reddish-brown with longitudinal wrinkles.
Traditional Indications
Its dried root (named Danshen) has been used for hundreds of years, primarily for the treatment of cardiovascular and cerebrovascular diseases. Salviae miltiorrhizae Radix et Rhizoma, the dry roots of Danshen, has been widely applied in the clinical treatment of cardiovascular diseases, dysmenorrhea, amenorrhea, hypertension, hepatocirrhosis, chronic renal failure, and other diseases.
Danshen is bitter in taste and slightly cold in nature and belongs to the heart and liver meridians. According to traditional Chinese medicine, Danshen is effective in clearing the heart and removing vexation, activating blood circulation, eliminating blood stasis, cooling the blood, eliminating carbuncles, and clearing menstruation and relieving pain.
According to the 2020 edition of the Pharmacopoeia of the People's Republic of China, Salvia miltiorrhiza is used to treat chest stupor and pain, abdominal and hypoflank pain, dysentery accumulation, heat stupor and pain, restlessness, irregular menstruation, dysmenorrhea, sores, and swelling.
Salvia miltiorrhiza has been used in China to treat neurasthenic insomnia, because of its tranquilizing effect.
Salvia miltiorrhiza is traditionally used to treat liver disease in Asia.
Traditional Preparations
In Chinese traditional medicine there were two primary types of S. miltiorrhiza preparations used by patients: directly prepared herbal raw materials (decoctions, extracts, tinctures) and Chinese patent medicines (water pills, honey pills). The use of other products such as injection and ultrafine granular powder has been increasing significantly.
Danshen has been known for the function of improving body functions such as activating blood circulation and removing blood stasis according to the theory of traditional Chinese medicine. Danshen and its various formula products have been long-time widely used in oriental countries, especially China, to treat various inflammatory and cardiovascular diseases for its pharmacological actions, including vasodilatation, anticoagulation, anti-inflammation, and free radical scavenging, with negligible adverse effects observed.
Modern Dosage Forms
With the development of science and technology, the dosage forms containing Danshen have been gradually diversified. Tablet, injection solution, dripping pill, oral liquid, capsule, slow-release formulation, and soft gel are all dosage forms that have been prepared into medicines. Among these diverse preparations, composite Danshen droplet pills, used to treat angina pectoris and coronary heart disease, represent a star drug and a demonstration of traditional Chinese medicine entering the international market. Fufang Danshen, a composite multi-herbal TCM formula containing Danshen as the major ingredient, is officially listed in the Chinese Pharmacopoeia for many indications.
It has been officially recorded in the Chinese pharmacopoeia since 1963 and is used for the treatment of various diseases, such as Alzheimer's disease, diabetes, cerebrovascular disease, coronary heart disease, cancer, hepatocirrhosis, and Parkinson's disease.
3. Key Active Constituents and Mechanisms of Action
General Pharmacological Profile
Tanshinones are the main active ingredients in S. miltiorrhiza and exhibit significant pharmacological activities, such as antioxidant activity, anti-inflammatory activity, cardiovascular effects, and antitumor activity. Studies have shown that Tanshinone IIA modulates numerous physiological processes, with reported activities including anti-inflammatory, antioxidant, metabolic regulatory (glucose and lipid metabolism), anti-fibrotic, antithrombotic, and cardioprotective effects.
Multi-Target Molecular Signaling
Tan IIA modulates multi-targets referring to Nrf2, AMPK, GSK-3β, EGFR, CD36, HO-1, NOX4, Beclin-1, TLR4, TNF-α, STAT3, Caspase-3, and bcl-2 proteins and multi-pathways including NF-κB, SIRT1/PGC1α, MAPK, SREBP-2/Pcsk9, Wnt, PI3K/Akt/mTOR pathways, TGF-β/Smad, and Hippo/YAP pathways, which directly or indirectly influence disease course.
Anti-Inflammatory Mechanisms
Numerous proposed mechanisms have been reported on the role of Tan IIA in cardiovascular protection, including apoptosis and autophagy, anti-inflammatory and antioxidant actions, antithrombotic and anti-proliferative effects on vascular smooth muscle cells, inhibition of expression of vascular endothelium and leukocyte adhesion molecules, and improved acute myocardial ischemia. Tan IIA is involved in both the innate and the acquired immune response which facilitates all stages of inflammatory pathways. It can regulate signal transduction pathways, i.e., TLR/NF-κB pathway and MAPKs/NF-κB pathway, thereby exhibiting anti-inflammatory, anticoagulant, antithrombotic, and neuroprotective roles.
Aside from its antioxidative activity, TanIIA inhibits inflammatory signaling like the TLR4-NF-κB axis and the MAPK pathway. TanIIA also blocks profibrotic components like TGF-βR1 and AT1R and the Wnt, Notch, and ET-1 signaling pathways.
Antioxidant Mechanisms
In addition to its anti-inflammatory effects, Tanshinone IIA demonstrates robust antioxidant potential. In AMI models, Tanshinone IIA enhances the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and reduces the production of oxidative stress marker malondialdehyde (MDA), thereby alleviating oxidative stress-induced myocardial damage.
Cardiovascular Mechanisms
Tan IIA can dilate coronary artery, lower blood pressure and lipid, inhibit left ventricular hypertrophy, inhibit smooth muscle cell proliferation and intimal hyperplasia, reverse myocardial hypertrophy, reduce infarct size, and protect from ischemia-reperfusion injury, and it also has anti-atherosclerotic, anti-inflammatory, and antioxidant properties.
The therapeutic efficacy is mediated through multiple mechanisms, including but not limited to anti-atherosclerotic effects, lipid homeostasis regulation, anti-arrhythmic properties, myocardial functional enhancement, and hemodynamic stabilization.
Anticancer Mechanisms
The mechanisms of tanshinones in anticancer activity include the inhibition of tumor cell growth, metastasis, invasion, and angiogenesis, apoptosis induction, cell autophagy, and antitumor immunity. More specifically, Tanshinone IIA inhibits cancer cell proliferation, induces differentiation and apoptosis through MAPK, AMPK/Skp2/Parkin, ER stress and mitochondrial pathways, inhibits invasion and migration through Notch1/NF-κB signaling, induces autophagy in cancer cells through the PI3K/Akt/mTOR signaling pathway, and inhibits angiogenesis by inhibiting the activity of VEGF.
Distinct Properties of Individual Tanshinones
Tanshinone I and dihydrotanshinone I, which share the abietane skeleton but differ in saturation and substituents, display distinct strengths in regulating mitochondrial function, ROS homeostasis, and MAPK/NF-κB signaling; in selected models, they show greater potency in anti-inflammatory, antimicrobial, or anti-angiogenic outcomes. Overall, Tanshinone IIA emphasizes cardiovascular and multi-organ protection, cryptotanshinone (CPT) favors transcriptional-signal suppression and tumor microenvironment modulation, and Tanshinone I/DHT provides complementary control of inflammation and stress responses.
4. Scientific Evidence by Area of Use
4.1 Cardiovascular Disease
Background: The dried root of the rhizome of Salvia miltiorrhiza has been widely used in traditional medicine in China and other oriental regions, especially for treating cardiovascular diseases like coronary heart disease, myocardial infarction (MI), angina pectoris, and atherosclerosis. Tanshinone IIA has been approved to treat cardiovascular diseases by the China State Food and Drug Administration.
Regulatory approval in China: Due to poor intestinal absorption and slow action onset of Tan IIA, sodium Tan IIA sulfonate (STS) was developed to improve the bioavailability of Tan IIA. STS has been researched in a variety of experiments and clinical studies thereafter.
Clinical evidence — inflammatory markers in CAD: A published randomized controlled trial enrolled patients with confirmed coronary artery disease (CAD). The study demonstrates that, on the basis of standard medical therapy, STS further reduces elevated hs-CRP and other circulating inflammation markers in CAD patients (ChiCTR-TRC-12002361). At 30 days after treatment completion, MCP-1 levels remained lower in the experimental group than in the control group (313.88 vs 337.91 pg/mL, p = 0.0078). No serious adverse events occurred.
RCT protocol — STS + simvastatin: Seventy-two inpatients with confirmed CHD and elevated serum hs-CRP were enrolled and randomized. All subjects received standard Western therapy including 20 mg simvastatin orally once per evening. Patients in the experimental group additionally received a daily 80 mg dose of sodium tanshinone IIA sulfate intravenously, diluted into 250 mL 0.9% NaCl solution, for 14 days.
Meta-analysis of STS in atherosclerosis: In numerous experiments based on animal and cellular models, STS injection has been found to reduce levels of pro-inflammatory cytokines, adhesion molecules, and chemokines in patients with atherosclerosis (AS) and atherosclerotic cardiovascular disease (ASCVD), exerting an anti-inflammatory effect. A meta-analysis was undertaken to quantify these effects in RCTs, searching eight literature databases from inception to January 2024.
Pulmonary hypertension: Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA isolated from Salvia miltiorrhiza that has been studied in a clinical trial (NCT01637675) to evaluate whether it exhibits beneficial effects on pulmonary hypertension.
Blood pressure: Sanghuang–Danshen, a mixture of drugs containing TanIIA, reduced blood pressure and arterial stiffness in healthy smokers. A recent meta-analysis revealed that TanIIA reduces blood pressure in patients with hypertensive nephropathy and improves renal function due to cardiac-renal crosstalk.
Evidence strength — cardiovascular: The cardiovascular evidence is the strongest among all areas studied. Clinical trials and a meta-analysis of RCTs support anti-inflammatory effects of the injectable STS derivative in patients with atherosclerosis and CAD. The China State Food and Drug Administration has approved a formulation for cardiovascular indications. Nevertheless, although numerous clinical trials have demonstrated that certain Danshen products in China are effective and safe for the treatment of cardiovascular diseases, most of these lack sufficient quality and large randomization.
4.2 Anticancer Activity
Scope of preclinical investigation: Tanshinone has been proven to be highly effective in combating tumors in various parts of the body in preclinical settings, including liver carcinoma, gastric cancer, ovarian cancer, cervix carcinoma, breast cancer, colon cancer, and prostate cancer.
Cell and animal studies: Tanshinone IIA possesses anticancer activities through inducing the apoptosis of tumor cells. The purpose of multiple studies has been to analyze the ability of Tan IIA to induce apoptosis of human cancer cells in vitro and in vivo. In nasopharyngeal carcinoma cell lines, tanshinone IIA inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cells via activation of PARP, p53, cyclin B1/CDC2, and caspase-3-mediated signaling.
TRAIL sensitization: Research has focused on the TRAIL-sensitizing effect of tanshinones, the anticancer ingredients of Salvia miltiorrhiza. Research has revealed the synergy of a tanshinones-TRAIL combination in diverse types of cancer cells through up-regulation of DR5 and/or down-regulation of anti-apoptotic proteins such as survivin.
Clinical evidence — limitations: Whereas previous studies have suggested anti-cancer potential of tanshinones affecting multiple cellular processes and molecular targets in cell culture models, data from in vivo potency assessment experiments in preclinical models vary greatly due to lack of uniformity of solvent vehicles and routes of administration. Chemical modifications and novel formulations have been made to address the poor oral bioavailability of tanshinones. So far, human clinical trials have been far from ideal in their design and execution for the purpose of supporting an anti-cancer indication of tanshinones.
Evidence strength — anticancer: Evidence is predominantly in vitro and animal-based. Few reported clinical trials have shown promising results in different cancer patients. Nevertheless, it has been found in several studies that tanshinones may have a limited bioavailability when administered orally, and thus efforts are being channelized to improve their pharmacokinetic parameters through developing novel formulations. Anti-cancer claims in humans currently lack robust, well-designed clinical trial support.
4.3 Neuroprotection and Alzheimer's Disease
Mechanism — neuroinflammation: Tanshinone IIA has been shown to suppress neuroinflammation, which plays a crucial role in AD pathogenesis. It inhibited the activation of the receptor for advanced glycation end products (RAGE)/nuclear factor-κB (NF-κB) signaling pathway.
Mechanism — amyloid processing: Cryptotanshinone was found to upregulate α-secretase activity, which promotes the non-amyloidogenic processing of amyloid precursor protein (APP). This leads to increased release of the neuroprotective secreted fragment of APP (sAPP) and decreased generation of Aβ. In APP/PS1 transgenic mice, cryptotanshinone treatment reduced Aβ plaque deposition in the brain and improved spatial learning and memory abilities.
Mechanism — synaptogenesis: Tan IIA can promote synaptogenesis and enhance neuronal plasticity by upregulating synaptic proteins SYN and PSD-95 and activating BDNF. Moreover, it demonstrates neuroprotective properties by rescuing long-term potentiation defects, which is associated with the activation of the CREB-BDNF-TrkB pathway.
Cognitive function in animal models — systematic review: Tanshinone can improve learning and memory ability, reduce the inflammatory response of brain tissue, regulate apoptosis-related proteins (Bcl-2, Bax, and caspase-3), and inhibit the apoptosis of hippocampal cells in AD rats.
Tanshinone I in Aβ aggregation: Tanshinone I can reduce the formation of Aβ42 fibers and break down Aβ42 aggregates. Tanshinone I can also upregulate antioxidant enzymes such as Mn superoxide dismutase, glutathione peroxidase, and the catalytic and modified subunit of γ-glutamate cysteine ligase.
Evidence strength — neurology: Recent years have seen reports of clinical trials examining the effects of tanshinones on cognitive impairment among individuals with AD, as well as the publication of pertinent basic research. Tanshinones are not yet commonly utilized in the therapeutic treatment of AD, and the effectiveness of tanshinones as a treatment program for AD is not yet adequately supported by evidence. The bulk of existing evidence derives from animal models and in vitro experiments. Human clinical data are sparse.
4.4 Hepatoprotection
The ability of tanshinone I, tanshinone IIA, and cryptotanshinone to protect against acute and subacute liver damage induced by carbon tetrachloride has been tested by measuring serum transaminase levels, reduced glutathione (GSH), antioxidant enzyme activities, and lipid peroxidation levels in the liver, as well as their ability to protect primary cultured rat hepatocytes from tertiary-butylhydroperoxide (tBH) or d-galactosamine (GalN).
Tanshinone I, tanshinone IIA, and cryptotanshinone (at 40 µM) inhibited lactate dehydrogenase leakage, GSH depletion, lipid peroxidation, and free radical generation in vitro. A purified extract of S. miltiorrhiza and its major constituents can protect against liver toxicity in vivo and in vitro due to antioxidant effects. Protective doses were reported as 50–200 mg/kg per day in acute liver injury and 25–100 mg/kg per day in subacute liver injury (animal study; doses are not directly translatable to humans).
Evidence strength — liver: Evidence is primarily from cell culture and animal studies. No robust human clinical trials specifically evaluating tanshinone for hepatic indications have been identified in the indexed literature reviewed here.
4.5 Bone Metabolism
Tanshinone IIA has a dual role in regulating bone formation and bone resorption, making it a potential drug for the treatment of osteoporosis. Studies have shown that Tan IIA can promote osteoblast differentiation and inhibit osteoclast activity, targeting key signaling pathways such as NF-κB, PI3K/Akt, and Wnt/β-catenin.
Evidence strength — bone: Evidence is preclinical (cell and animal studies). No published human clinical trials evaluating tanshinone specifically for bone metabolism outcomes were identified.
4.6 Immune Modulation
Studies have found that Tan IIA has a significant contribution to the activation, development, and proper functioning of immune cells. Tan IIA is involved in both the innate and the acquired immune response which facilitates all stages of inflammatory pathways (from initiation to progression).
Evidence strength — immune: Preclinical and mechanistic evidence only. Human immunological outcomes have not been established in well-designed trials.
5. Body Systems Associated with Tanshinone Research
Tan IIA shows multiple pharmacological effects, including anticarcinogenic, cardiovascular, nervous, respiratory, urinary, digestive, and motor systems activities. The systems most supported by evidence (in decreasing order of clinical evidence strength) include:
- Cardiovascular system: Atherosclerosis, angina pectoris, coronary heart disease, myocardial infarction, arrhythmia, hypertension, and pulmonary hypertension.
- Central nervous system: Alzheimer's disease, ischemic stroke, neuroprotection against Aβ-related toxicity.
- Oncology: Multiple cancer cell types studied in vitro and in rodent models.
- Hepatic system: Liver fibrosis, hepatocellular protection from toxin-induced damage.
- Musculoskeletal system: Bone remodeling, osteoporosis models.
- Renal system: The main active ingredients—tanshinones—possess the ability to improve renal function.
- Reproductive/gynecological system: Dysmenorrhea and menstrual irregularities (traditional indication).
6. Dosage Forms and Reported Dosages
Because tanshinones are typically used as components of Salvia miltiorrhiza extracts or as pharmaceutical derivatives (particularly STS), dosages vary widely across formulations and study designs.
- Intravenous STS (clinical study): Patients in the experimental group received a daily 80 mg dose of sodium tanshinone IIA sulfate intravenously, diluted into 250 mL 0.9% NaCl solution.
- Purified oral extract — hepatoprotection (animal): PF2401-SF (a standardized fraction of S. miltiorrhiza) was protective at 50–200 mg/kg per day in acute liver injury and 25–100 mg/kg per day in subacute liver injury.
- In vitro hepatocyte protection: Tanshinone I, tanshinone IIA, and cryptotanshinone at 40 µM inhibited lactate dehydrogenase leakage, GSH depletion, lipid peroxidation, and free radical generation in vitro.
- Nanotechnology formulations (research-stage): Encapsulating tanshinone IIA in lipid nanocapsules via a phase inversion method significantly increased oral absorption and prolonged retention time in vivo. The LNCs had a particle size of ~70 nm, PDI < 0.2, zeta potential ~−13.5 mV, extremely high encapsulation efficiency (~98%), and good drug loading (2.6 mg/g).
No universally established or regulatory-approved oral supplemental dosage for isolated tanshinone compounds exists in Western markets. The absence of standardized human dosing guidance reflects, in part, the severe pharmacokinetic challenges posed by low oral bioavailability (see Section 7).
7. Pharmacokinetics
Extensive pharmacokinetic studies indicate that the systemic oral bioavailability of Tanshinone IIA is extremely low. Its extremely low oral bioavailability (<2%) and significant first-pass effect indicate that Tanshinone IIA is not suitable as a conventional oral formulation. It likely requires injectable formulations or advanced delivery technologies to improve its pharmacokinetic behavior and clinical prospects.
Pharmacokinetic studies have identified two primary contributing factors to its limited oral bioavailability: P-glycoprotein-mediated intestinal efflux and extensive first-pass hepatic metabolism.
Tan IIA is insoluble in water, and its oral preparation has poor intestinal absorption and low bioavailability. Its absorption mechanism in the stomach may be passive transport, while its absorption mechanism in the intestine may be active diffusion, and the colon is the best site for absorption. It has been reported that there are a variety of bacteria and bioconvertases in the colon which also promote the absorption of Tan IIA.
Tanshinone IIA rapidly partitions into the heart, liver, kidneys, and lungs, with the highest levels in the heart and liver, consistent with its principal pharmacological sites of action; it can also cross the blood–brain barrier, suggesting potential neuroprotective activity. Its tissue distribution is time-dependent. Metabolism occurs predominantly in the liver and involves cytochrome P450 isoforms — particularly CYP3A4, CYP2C9, and CYP1A2 — which generate multiple metabolites via hydroxylation, demethylation, and related transformations.
Tan IIA can be hydroxylated by CYP2A6 in liver microsomes, followed by glucuronidation and excretion via bile.
Micronization has been proven to improve the bioavailability of some drugs, and research has been conducted to investigate whether micronized granular powder of S. miltiorrhiza could improve the bioavailability of tanshinones compared with traditional decoction. To improve absorption, nano-formulations such as nanoparticles and liposomes have been developed with encouraging progress.
8. Safety Considerations and Drug Interactions
General Observed Safety
The adverse effects of the therapeutic components of Salvia miltiorrhiza are often mild. Although dried roots have been used as herbal medicine for more than a thousand years, the study of therapeutic content in the plant did not start until the early 20th century. No adverse reactions were observed in a pharmacokinetic study in healthy volunteers, which may be due to the wide safety of S. miltiorrhiza, but toxicities need further observation in clinical applications.
Adverse Effects of the Sodium Tanshinone IIA Sulfonate (STS) Injection
The main adverse reaction of STS is anaphylaxis (about 30%), which mainly involves the skin and its appendages. Although the adverse effects of STS are mostly mild, some life-threatening conditions can occur, such as anaphylactic shock.
Developmental Toxicity Signal
In zebrafish embryo at high concentrations, Tan IIA shows potential developmental deformity and cardiac toxicity. This is a preclinical signal from a non-mammalian model; its relevance to human exposure is unknown.
Interaction with Warfarin
The interaction between Danshen/tanshinones and warfarin is among the most documented and clinically significant herb-drug interactions associated with this plant. Single-dose and steady-state studies in rats indicated that Danshen increased the absorption rate constants, AUCs, maximum concentrations, and elimination half-lives, but decreased the clearances and apparent volume of distribution of both R- and S-warfarin. Consequently, the anticoagulant response to warfarin was exaggerated. Three cases have previously been published reporting gross overanticoagulation and bleeding complications when patients receiving chronic warfarin therapy also took Danshen. Because of both pharmacokinetic and pharmacodynamic interactions, Danshen should be avoided in patients taking warfarin.
The mechanism involves multiple pathways: in vitro studies have found that tanshinones in Danshen inhibit CYP1A1, 2C6, and 2C11-mediated warfarin metabolism, and that sodium tanshinone IIA sulfonate replaces warfarin from the binding site on human serum albumin-warfarin complex, increasing free warfarin concentration in blood.
At the CYP level, tanshinone I, tanshinone IIA, and cryptotanshinone strongly inhibited CYP1A2, moderately inhibited CYP2C9, while dihydrotanshinone competitively inhibited CYP1A2 and CYP2C9 but had no effect on CYP3A4 (in one study).
Enhanced anticoagulation and/or even bleeding are often observed when patients on long-term warfarin therapy consumed Danshen, a well-known medicinal herb in traditional Chinese medicine.
Interactions with Other Anticoagulants
Lipid-soluble components of Danshen, such as tanshinone I, tanshinone IIA, dihydrotanshinone, and cryptotanshinone, possess pharmacological properties such as promoting blood circulation, and their active components can affect the expression level and activity of CYP enzymes. Research has also examined potential interactions with rivaroxaban, a newer anticoagulant, given that Danshen and rivaroxaban are sometimes simultaneously used in patients with heart disease. However, the interaction between Danshen and rivaroxaban remains under investigation. From the perspective of patient safety, attention to herb-drug interaction is needed to formulate a reasonable treatment plan and avoid adverse reactions.
Interaction with Antiplatelet Drugs
Danshen is often co-administered with other drugs in order to improve therapeutic efficacies; thus, the possible herb-drug interactions must be taken as a precaution to avoid severe damage in the clinic. Numbers of herb-drug interactions leading to adverse outcomes have been reported to involve Danshen when co-administered with therapeutic agents, including gross anticoagulation and bleeding complications when combined with warfarin.
CYP Enzyme Inhibition and UDP-Glucuronosyltransferase (UGT)
Efforts have been made to explain Danshen–clinical drug interactions; major components of Danshen — tanshinones — are regarded as the substance basis for Danshen–drug interaction. Influence of P-glycoprotein (P-gp) and cytochrome P450 (CYP) by these tanshinones is considered to be a potential reason for Danshen–drug interaction. It can be concluded that precautions should be taken when using Danshen preparations rich in tanshinones for CYP-related herb-drug interactions.
Quality and Standardization Concerns
Only six of the final products surveyed by European regulators had significant salvianolic acid B and tanshinone IIA — the chemical standards for Salviae miltiorrhiza. The authors concluded that results illustrate the variable composition of Danshen-labeled products sold on the market. This variability in product quality is a critical practical consideration for anyone consuming commercial tanshinone-containing supplements, as the actual content of active tanshinone compounds may differ substantially from labeling.
References
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