Tanshinone IIA

294.34400

294.34

686519

DTXSID60205352

Red powder

29321900

47.28000

4.3

Cherry crystal.

1.209 g/cm3

205-207 °C @ Solvent: Ethyl acetate

480.7ºC at 760 mmHg

236.4ºC

1.603

5 mg/mL methanol

Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: 2 - 8 deg C Keep in a dry place.

2.54X10-8 mm Hg at 25 deg C (est)

Henry's Law constant = 4.95X10-9 atm-cu m/mole at 25 °C (est)

164 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Red powder; MW: 276.29; MF: C18H12O3; soluble at 5 mg/mL methanol/Tanshinone I (568-73-0)/

NONH for all modes of transport

3

24/25

Stable under recommended storage conditions.

SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Strong oxidizing agents

Not flammable or combustible.

Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Sweep up and shovel. Keep in suitable, closed containers for disposal.

Avoid dust formation. Avoid breathing vapors, mist or gas.

Protective effects of sodium tanshinone IIA sulphonate against adriamycin-induced lipid peroxidation were investigated. Data showed that treatment with sodium tanshinone IIA sulphonate could prevent mice from decrease in body weight caused by adriamycin. It was found that myocardial lipid peroxidation in sodium tanshinone IIA sulphonate-treated mice was lower compared with that in adriamycin-treated ones. The activities of some endogenous antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase and catalase, were higher in the sodium tanshinone IIA sulphonate group than that in the adriamycin group. In vitro experiments showed that sodium tanshinone IIA sulphonate could inhibit adriamycin-induced mitochondrial lipid peroxidation and swelling. Sodium tanshinone IIA sulphonate could scavenge adriamycin semiquinone free radical in heart homogenate dose-dependently. Thus, protective effects of sodium tanshinone IIA sulphonate may not only be related to its antioxidant activity but also to its regulation of antioxidant enzyme activities in the heart.|Although doxorubicin (DXR) is an effective antineoplastic agent; the serious cardiotoxicity mediated by the production of reactive oxygen species has remained a considerable clinical problem. /The/ hypothesis is that tanshinone IIA sodium sulfonate (TSNIIA-SS), which holds significant affects on cardioprotection in clinic, protects against DXR-induced cardiotoxicity. In vitro investigation on H9c2 cell line, as well as in vivo study in animal model of DXR-induced chronic cardiomyopathy were performed. TSNIIA-SS significantly increased cell viability and ameliorated apoptosis of DXR-injured H9c2 cells using CCK-8 assay and Hoechst 33342 stain respectively. Furthermore, the cardio-protective effects of TSNIIA-SS were confirmed with decreasing ST-interval and QRS interval by electrocardiography (ECG); improving appearance of myocardium with haematoxylin and eosin (H&E) stain; increasing myocardial tensile strength using tension to rupture (TTR) assay and decreasing fibrosis through picric-sirius red staining comparing with those receiving DXR alone. These data have provided the considerable evidences that TSNIIA-SS is a protective agent against DXR-induced cardiac injury.|Although doxorubicin (DXR) is an important antineoplastic agent, the serious toxicity mediated by the production of reactive oxygen species has remained a considerable clinical problem. Our hypothesis is that tanshinone II A sodium sulfonate (TSNIIA-SS), which holds significant effects against oxidative stress, protects against DXR-induced nephropathy. Firstly, the antioxidative effects of TSNIIA-SS were confirmed using oxygen radicals absorbance capacities (ORAC) assay in vitro. Then, DXR nephropathy was induced by repeated DXR treatment and verified by kidney index (20.76 +/- 3.04 mg/mm versus 14.76 +/- 3.04 mg/mm, p < 0.001) and histochemical stain. The mice were randomized into three groups: Control group, DXR group and DXR-TSNIIA-SS group. TSNIIA-SS treatment not only improved DXR lesion identified by histochemical stain, but also regulated the expression of several proteins related with the cytoskeleton, oxidative stress and protein synthesis or degradation detected by two-dimensional electrophoresis (2-DE). These data have provided the evidence that TSNIIA-SS is a protective agent against DXR-induced nephropathy.

Tanshinone II is present in Danshen root (Salvia miltiorrhiza)(1).

Tanshinone II's production and use as a dietary supplement(1) and in cancer research(2) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 660(SRC), determined from a structure estimation method(2), indicates that tanshinone II is expected to have low mobility in soil(SRC). Volatilization of tanshinone II from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.0X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Tanshinone II is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.5X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradation data in soil were not available(SRC, 2013).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 660(SRC), determined from a structure estimation method(2), indicates that tanshinone II is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 5.0X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 6800(SRC), from an estimated log Kow of 6.31(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is very high(SRC), provided the compound is not metabolized by the organism(SRC). Biodegradation data in water were not available(SRC, 2013).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), tanshinone II, which has an estimated vapor pressure of 2.5X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist solely in the particulate phase in the ambient atmosphere. Particulate-phase tanshinone may be removed from the air by wet or dry deposition(SRC). Tanshinone II contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Tanshinone II is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Tanshinone II contains chromophores that absorb at wavelengths >290 nm(1) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 6800 was calculated in fish for tanshinone II(SRC), using an estimated log Kow of 6.31(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is very high(SRC), provided the compound is not metabolized by the organism(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of tanshinone II can be estimated to be 660(SRC). According to a classification scheme(2), this estimated Koc value suggests that tanshinone II is expected to have low mobility in soil.

The Henry's Law constant for tanshinone II is estimated as 5.0X10-9 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that tanshinone II is expected to be essentially nonvolatile from water and moist soil surfaces(2). Tanshinone II is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.5X10-8 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to tanshinone II may occur through inhalation and dermal contact with this compound at workplaces where tanshinone II is extracted or used. Use data indicate that the general population may be exposed to tanshinone II via ingestion as a dietary supplement or medication. (SRC)

Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. (See all compounds classified as Anti-Infective Agents.)|Agents that prevent BLOOD CLOTTING. (See all compounds classified as Anticoagulants.)|Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. (See all compounds classified as Anti-Inflammatory Agents, Non-Steroidal.)|Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity. (See all compounds classified as Antineoplastic Agents, Phytogenic.)|Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. (See all compounds classified as Immunosuppressive Agents.)

Doxorubicin, one of the original anthracyclines, remains among the most effective anticancer drugs ever developed. Clinical use of doxorubicin is, however, greatly limited by its serious adverse cardiac effects that may ultimately lead to cardiomyopathy and heart failure. Tanshinone IIA is the main effective component of Salvia miltiorrhiza known as 'Danshen' in traditional Chinese medicine for treating cardiovascular disorders. The objective of this study was set to evaluate the protective effect of tanshinone IIA on doxorubicin-induced cardiomyocyte apoptosis, and to explore its intracellular mechanism(s). Primary cultured neonatal rat cardiomyocytes were treated with the vehicle, doxorubicin (1 uM), tanshinone IIA (0.1, 0.3, 1 and 3 uM), or tanshinone IIA plus doxorubicin. /The authors/ found that tanshinone IIA (1 and 3 uM) inhibited doxorubicin-induced reactive oxygen species generation, reduced the quantity of cleaved caspase-3 and cytosol cytochrome c, and increased BcL-x(L) expression, resulting in protecting cardiomyocytes from doxorubicin-induced apoptosis. In addition, Akt phosphorylation was enhanced by tanshinone IIA treatment in cardiomyocytes. The wortmannin (100 nM), LY294002 (10 nM), and siRNA transfection for Akt significantly reduced tanshinone IIA-induced protective effect. These findings suggest that tanshinone IIA protects cardiomyocytes from doxorubicin-induced apoptosis in part through Akt-signaling pathways, which may potentially protect the heart from the severe toxicity of doxorubicin.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/ALTERNATIVE and IN VITRO TESTS/ Tanshinone IIA (Tan IIA) is isolated from Salvia miltiorrhiza, the root of which is widely used as a traditional Chinese medicine to treat atherosclerosis. The aim of the present study was to evaluate the putative protective effect of Tan IIA in a human umbilical vein endothelial cell line (ECV-304) injured by hydrogen peroxide in vitro and the mechanism of its protection. The percentage of cell viability was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The endothelial cell apoptosis and expression of cluster of differentiation 40 (CD40) were detected by flow cytometric analysis. Preincubation with Tan IIA significantly increased the viability of ECV-304 cell injured by hydrogen peroxide, which was accompanied with the increased nitric oxide level and superoxide dismutase activity in a dose-dependent manner. Moreover, cell apoptosis and CD40 expression were decreased in a dose-dependent manner. In conclusion, /these/ data suggests that Tan IIA protects ECV-304 cell damage induced by hydrogen peroxide through its anti-oxidant effect and CD40 anti-inflammatory approach.|/ALTERNATIVE and IN VITRO TESTS/ The purpose of this study was to develop a lipid emulsion of tanshinone IIA (Tan IIA-LE) for intravenous administration and to investigate its feasibility for future clinical practice. The formulation was optimized using central composite design-response surface methodology (CCD-RSM), and the homogenization process was investigated systematically. The Tan IIA-LE was evaluated in terms of stability, safety and in vitro anti-hepatoma activity. The formulation of Tan IIA-LE is composed of 0.05% (w/v) Tan IIA, 20% (w/v) soybean oil-MCT mixture (1:1, w/w), 1.2% (w/v) soybean lecithin, 0.3% (w/v) F68 and 2.2% (w/v) glycerol, a high pressure homogenization at 100 MPa for 3 cycles was selected as the optimal homogenization process. The Tan IIA-LE was light-sensitive but stable for at least 12 months at room temperature in dark. The safety study demonstrated that the Tan IIA-LE did not cause venous irritation or obvious acute toxicity. Furthermore, the Tan IIA-LE displayed significant anti-tumor activity against human hepatoma cell lines in vitro. Overall, the Tan IIA-LE developed in this study was suggested to be a suitable and safe dosage form of Tan IIA for intravenous administration and has potential in liver cancer therapy in future.|/ALTERNATIVE and IN VITRO TESTS/ Diterpenoid tanshinones including tanshinone IIA (TIIA), cryptotanshinone (CTS), tanshinone I (TI) and dihydrotanshinone I (DHTI) are the major bioactive components from Danshen. The major aim of ...present study was to investigate the induction potential of these four main components of tanshinones (TIIA, CTS, TI, and DHTI) on the expression of CYP1A1 and CYP1A2 in HepG2 cells. /The/ results showed that all of these four tanshinones caused a significant time- and concentration-dependent increase in the amount of CYP1A1/2 expression in HepG2 cells. These induction effects were further characterized through transcriptional regulation: the induction of CYP1A1/2 mRNA level by tanshinones was completely blocked by the transcription inhibitor actinomycin D; the expression of CYP1A1/2 heterogeneous nuclear RNA was induced by tanshinone treatment; and CYP1A1 mRNA stability was not influenced by these tanshinones. Interestingly, tanshinones plus B[a]P produced additive/synergistic effect on CYP1A1/2 induction. In addition, the tanshinone-induced CYP1A1/2 expression was abolished by the aryl hydrocarbon receptor (AhR) antagonist resveratrol, suggesting an AhR dependent transcription mechanism. In the reporter gene assay, while TI and DHTI significantly induced AhR-dependent luciferase activity, TIIA and CTS failed to induce this activity. Collectively, the tanshinones could induce CYP1A1 and CYP1A2 expression through transcriptional activation mechanism and exert differential effects on activating AhR in HepG2 cells. /These/ findings suggest that rational administration of tanshinones should be considered with respect to their effect on AhR and CYP1A1/2 expression.|/ALTERNATIVE and IN VITRO TESTS/ Tanshinones are abietane type-diterpene quinones isolated from the roots of Radix Salvia miltiorrhiza (Danshen), a well-known traditional Chinese medicine in the treatment of cardiovascular diseases. Among the major diterpenes isolated, including cryptotanshinone, tanshinone I, tanshinone IIA and dihydrotanshinone, tanshinone IIA had been shown to posses various pharmacological activities including antioxidant, protection/prevention from angina pectoris and myocardial infarction, and anticancer properties. Tanshinone IIA, usually the most abundant tanshinone present in the herb, has been the focus of studies in its clinical potential, among which its ability to inhibit the proliferation of cancer cell lines. The aim of this study was to study the cytotoxicity of the tanshinones on human HepG2 cells in vitro in relation to intracellular glutathione perturbation (reduced glutathione, GSH and oxidized glutathione, GSSG). Studies using MTT assay showed that all tanshinones decreased cell viability of HepG2 cells in a concentration-dependent manner, with the cell viability decreased to 60% and 35% after 24 hr and 48 hr treatment, respectively. Assessment of apoptotic cells with fragmented DNA by flow cytometry indicated that only tanshinone IIA (12.5 and 25 uM) induced apoptosis in the cancer cells. Tanshinone IIA and cryptotanshinone caused significant decreases in G(1) cells by 23% and 13%, respectively, after 24 hr treatment. The declines in G(1) cells were compensated by increases in G(2)/M (15% for tanshinone IIA) and S cells (8% and 13% for tanshinone IIA and cryptotanshinone, respectively). All the tanshinones studied, except tanshinone IIA, elevated GSH/GSSG ratio at low concentrations (1.56 and 3.13 uM), but the ratio decreased, indicating oxidative stress at high concentrations (6.25-25 uM). Taken together, tanshinone IIA caused HepG2 cytotoxicity through apoptosis without influencing oxidative stress, while the other tanshinones showed lower efficacy in inducing apoptosis in the HepG2 cells.|/ALTERNATIVE and IN VITRO TESTS/ Tanshinone IIA (Tan IIA), a natural product from herb Salvia miltiorrhiza Bunge, has potential anti-tumor activity. The aim of this study was to pinpoint the molecular mechanisms underlying Tan IIA-induced cancer cell apoptosis. Human hepatoma BEL-7402 cells treated with Tan IIA underwent assessment with MTT assay for cell viability, 10-day culture for colony formation, flow cytometry and fluorescence microscopy for apoptosis and cell cycle analysis. Changes in intracellular [Ca(2+)] and mitochondrial membrane potential reflected the calcium-dependent apoptosis pathway. RT-PCR was used to detect gene expression of Bad and metallothionein 1A (MT 1A). Cytotoxicity of Tan IIA was tested in human amniotic mesenchymal stem cells (HAMCs). Tan IIA exhibited dose-dependent and time-dependent anticancer effects on BEL-7402 cells through apoptosis and G(0)/G(1) arrest. Cells treated with Tan IIA increased their intracellular calcium, decreased their mitochondrial membrane potential and induced Bad and MT 1A mRNA expression. No adverse effects of Tan IIA were found in HAMCs. In conclusion, these results indicate that Tan IIA-induced cancer cell apoptosis acts via activation of calcium-dependent apoptosis signaling pathways and upregulation of MT 1A expression.

tanshinone

Phenanthrenequinone consitutent of Chinese medicinal herb Danshen (Salvia miltiorrhiza) /Tanshinone I (568-73-0)/

The TLC separation technique was applied to investigate the Chinese medicine samples of danshen, gegen (DG), the reference herb of dashen, as well as the two batches of DG. The two markers tanshinone IIA and puerarin were used in the TLC study for quality control. Visible light was utilized to detect these two markers in the developed TLC plates. These markers were found in all the samples concerned. The HPLC provides better separation power of chemical components than TLC, and the markers considered in the TLC work were further investigated by HPLC-DAD and LC-MS. Again the respective markers of danshen and gegen (tanshinone IIA and puerarin) were identified in the single herb samples. These component herbs were also found in the DG products based on these two markers and the other target compounds. In doing so, /the authors/ compared both their retention times obtained and the observed UV spectra at the same times in different chromatograms. The stability of the DG product using both the marker and the pattern approach was then evaluated. Stability is very important to assure the consistency of the quality of encapsulated herbs such as the DG capsules used in the clinical trial... Here, /the authors/ scrutinized the variation in the chemical compositions of the DG samples before and after 3 months of "accelerated aging" treatment, which is commonly used to establish the shelf life of a product. All samples were analyzed by HPLC-DAD with the sample preparation and experimental procedures all exactly the same. Results showed that the marker contents at time 0 and after 3 months were 0.42 and 0.45 mg/g, respectively, for puerarin and 0.07 and 0.03 mg/g, respectively, for tanshinone IIA. This indicates the product was stable.