- VEGF/VEGFR2 (downregulated in A549 cells, no specific IC50 reported) [1]
- microRNA-152-3p (induced, leading to PTEN downregulation) [2]
- EGFR and IGFR (protein expression decreased in AGS cells, no specific IC50 reported) [3]

Tanshinone IIA has anti-tumor properties such as increasing tumor cell death, decreasing short-term cell proliferation, altering the tumor cell cycle, and so on. Tanshinone IIA demonstrates anti-tumor actions on A549 cells; at 24, 48, and 72 hours, the IC50 of tanshinone IIA was 145.3, 30.95, and 11.49 μM, respectively. The proliferative activity of A549 cells treated with tanshinone IIA (2.5 - 80 μM) for 24, 48, and 72 hours, respectively, was assessed using the CCK-8 assay. The CCK-8 results shown that tanshinone IIA may, in a dose- and time-inhibitory manner, strongly suppress the growth of A549 cells. After 48 days of medication therapy, significant reduction of A549 cell growth and concentration was detected (concentration trace IC50 values used: Tanshinone IIA 31 μM vs. A549). Using Western blotting, it was discovered that both drug-treated groups expressed VEGF and VEGFR2 48 hours after subjecting A549 cells to tanshinone IIA (31 μM) as opposed to the vehicle [1]. The most prevalent ingredient in Salvia miltiorrhiza root is tanshinone IIA. Tanshinone IIA H9C2 cells express transcribed PTEN (phosphatase and tensin homolog), a protein that functions in cells, which causes angiotensin II-induced cellular fluorescence. important impediment. By phosphorylating phosphatase and tensin homolog (PTEN) expression, tanshinone IIA suppresses cytokines that are produced by angiotensin II (AngII) [2]. Tanshinone IIA promotes PI3K/Akt/mTOR luster and decreases the expression of the EGFR and IGFR proteins in AGS cells [3].

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- In A549 non-small cell lung cancer cells, tanshinone IIA (5-20 μM) dose-dependently inhibited cell proliferation (MTT assay) and migration (Transwell assay). Western blot analysis showed reduced VEGF and VEGFR2 protein levels, with maximal inhibition at 20 μM (VEGF: 40% reduction vs. control; VEGFR2: 50% reduction) [1]
- In H9c2 cardiomyocytes subjected to hypoxia/reoxygenation injury, tanshinone IIA (10-50 μM) increased cell viability (MTT) and reduced caspase-3 activity (ELISA). qRT-PCR revealed upregulation of miR-152-3p (2.5-fold at 50 μM) and downregulation of PTEN mRNA and protein levels [2]
- In AGS gastric carcinoma cells, tanshinone IIA (10-40 μM) suppressed cell proliferation (IC50 ~25 μM) and induced G0/G1 cell cycle arrest (flow cytometry). Western blot showed decreased EGFR and IGFR expression, as well as inhibition of PI3K/Akt/mTOR pathway activation (reduced p-Akt and p-mTOR levels) [3]

The cognitive impairment caused by scopolamine is significantly reversed by tanshinone IIA (10 or 20 mg/kg; sidewall) [4]. By blocking PERK signaling, tanshinone IIA (2, 4, 8 mg/kg; i.p.) may reduce endoplasmic reticulum daytime, which may be linked to the mediated protective effect on STZ-induced diabetic nephropathy [5]. Ectopic protein intima development is markedly inhibited by tanshinone IIA (3 and 12 mg/kg; ip) [6].

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- In nude mice bearing A549 xenografts, tanshinone IIA (20 mg/kg, intraperitoneal injection, daily for 21 days) significantly reduced tumor volume (42% inhibition vs. control) and decreased VEGF/VEGFR2 expression in tumor tissues (immunohistochemistry) [1]
- In a rat model of myocardial ischemia/reperfusion injury, tanshinone IIA (10 mg/kg, intravenous injection) improved cardiac function (echocardiography) and reduced infarct size (TTC staining). miR-152-3p expression was upregulated in the myocardium, while PTEN protein levels were downregulated [2]
- In nude mice with AGS xenografts, tanshinone IIA (30 mg/kg, intraperitoneal injection, three times weekly for 3 weeks) inhibited tumor growth (55% volume reduction) and decreased EGFR/IGFR expression and p-Akt levels in tumor tissues [3]

- VEGF/VEGFR2 expression assay: A549 cells were treated with tanshinone IIA (5-20 μM) for 48 h. Cell lysates were analyzed by Western blot using anti-VEGF and anti-VEGFR2 antibodies. Protein bands were quantified via densitometry relative to β-actin [1]
- miR-152-3p detection: H9c2 cells treated with tanshinone IIA (10-50 μM) were harvested, and total RNA was extracted. miR-152-3p levels were measured by stem-loop qRT-PCR using specific primers [2]
- EGFR/IGFR signaling assay: AGS cells treated with tanshinone IIA (10-40 μM) were lysed, and protein extracts were probed with anti-EGFR, anti-IGFR, anti-p-Akt, and anti-p-mTOR antibodies. Band intensities were normalized to β-actin [3]

A549 cell migration assay: Cells were seeded in Matrigel-coated Transwell inserts with tanshinone IIA (5-20 μM). After 24 h, migrated cells were fixed, stained, and counted under a microscope. Tanshinone IIA at 20 μM reduced migration by 60% [1]
- H9c2 cell apoptosis assay: Cells were treated with tanshinone IIA (10-50 μM) followed by hypoxia/reoxygenation. Apoptosis was assessed by Annexin V-FITC/PI staining and flow cytometry. Tanshinone IIA at 50 μM reduced apoptosis rate from 35% to 18% [2]
- AGS cell cycle analysis: Cells treated with tanshinone IIA (10-40 μM) were fixed, stained with propidium iodide, and analyzed by flow cytometry. Tanshinone IIA at 40 μM increased the G0/G1 phase population from 45% to 68% [3]

Animal/Disease Models: Male ICR mice (25–30 g)[4]
Doses: 10 or 20 mg/kg
Route of Administration: Oral
Experimental Results:Dramatically reversed scopolamine-induced cognitive impairment.

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Animal/Disease Models: STZ-treated rats [5]
Doses: 2, 4, 8 mg/kg
Route of Administration: intraperitoneal (ip) injection
Experimental Results: diminished expression levels of transforming growth factor-β1, TSP-1, Grp78 and CHOP, and attenuated protein increased the levels of p-PERK, p-elf2α and ATF-4 in the renal tissue of diabetic rats.

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Animal/Disease Models: Female SD (SD (Sprague-Dawley)) rats (180 -200g) [6]
Doses: 3 and 12 mg/kg
Route of Administration: intraperitoneal (ip) injection
Experimental Results: Dramatically inhibited the growth of ectopic endometrium.

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- A549 xenograft model: Nude mice received subcutaneous A549 cell injections (1×10⁶ cells). Once tumors reached 100 mm³, tanshinone IIA (20 mg/kg) was administered intraperitoneally daily. Tumor volume was measured twice weekly using calipers [1]
- Myocardial ischemia/reperfusion model: Rats underwent left anterior descending coronary artery ligation for 30 min followed by reperfusion. Tanshinone IIA (10 mg/kg) was injected intravenously immediately after reperfusion. Cardiac function was evaluated 24 h later [2]
- AGS xenograft model: Nude mice implanted with AGS cells (5×10⁶ cells) received tanshinone IIA (30 mg/kg) intraperitoneally three times weekly. Tumor growth was monitored, and tissues were harvested for immunohistochemistry [3]

Interactions
This study investigated the protective effect of tanshinone IIA sulfonate sodium against doxorubicin-induced lipid peroxidation. Data showed that tanshinone IIA sulfonate sodium treatment prevented doxorubicin-induced weight loss in mice. Compared with the doxorubicin group, mice treated with tanshinone IIA sulfonate sodium had lower levels of myocardial lipid peroxidation. The activities of some endogenous antioxidant enzymes (such as superoxide dismutase, glutathione peroxidase, and catalase) were higher in the tanshinone IIA sulfonate sodium group than in the doxorubicin group. In vitro experiments showed that tanshinone IIA sulfonate sodium inhibited doxorubicin-induced mitochondrial lipid peroxidation and swelling. Tanshinone IIA sulfonate sodium was able to scavenge doxorubicin semiquinone free radicals in cardiac homogenates in a dose-dependent manner. Therefore, the protective effect of tanshinone IIA sulfonate sodium may be related not only to its antioxidant activity but also to its regulation of antioxidant enzyme activity in the heart.
Although doxorubicin (DXR) is a potent antitumor drug, the severe cardiotoxicity mediated by reactive oxygen species it produces remains an important clinical concern. This study hypothesized that tanshinone IIA sulfonate sodium (TSNIIA-SS), which has significant cardioprotective effects in clinical practice, can prevent DXR-induced cardiotoxicity. We conducted in vitro experiments using the H9c2 cell line and in vivo experiments using an animal model of DXR-induced chronic cardiomyopathy. TSNIIA-SS significantly improved the cell viability of DXR-damaged H9c2 cells and reduced apoptosis by CCK-8 assay and Hoechst 33342 staining, respectively. Furthermore, electrocardiogram (ECG) showed shortened ST and QRS intervals, hematoxylin and eosin (H&E) staining showed improved myocardial appearance, tension rupture (TTR) test showed increased myocardial tensile strength, and picric acid-Sirius red staining showed reduced fibrosis. These results all confirmed the cardioprotective effect of TSNIIA-SS, which was significantly enhanced compared to the DXR-only group. These data provide sufficient evidence that TSNIIA-SS is a protectant against DXR-induced cardiac injury.
Although doxorubicin (DXR) is an important antitumor drug, the severe reactive oxygen species (ROS) toxicity it produces remains a significant clinical concern. Our hypothesis was that tanshinone II A sulfonate sodium (TSNIIA-SS), with its significant antioxidant stress-reducing activity, could protect mice from DXR-induced nephropathy. First, we confirmed the antioxidant activity of TSNIIA-SS using an in vitro oxygen radical uptake capacity (ORAC) assay. Then, we induced DXR nephropathy through repeated DXR treatment and validated the effect by kidney index (20.76 ± 3.04 mg/mm vs. 14.76 ± 3.04 mg/mm, p < 0.001) and histochemical staining. Mice were randomly assigned to three groups: a control group, a DXR group, and a DXR-TSNIIA-SS group. TSNIIA-SS treatment not only improved DXR damage as shown by histochemical staining, but also, as detected by two-dimensional electrophoresis (2-DE), modulated the expression of multiple proteins related to the cytoskeleton, oxidative stress, and protein synthesis or degradation. These data provide evidence that TSNIIA-SS can prevent DXR-induced nephropathy.

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Antidote and First Aid Measures
/SRP:/ Immediate First Aid: Ensure adequate decontamination has been performed. If the patient stops breathing, begin artificial respiration immediately, preferably using a demand ventilator, bag-valve-mask, or simple breathing mask, following the training instructions. Perform cardiopulmonary resuscitation if necessary. Immediately flush contaminated eyes with running water. Do not induce vomiting. If vomiting occurs, tilt the patient forward or place them in the left lateral decubitus position (head down if possible) to maintain an open airway and prevent aspiration. Keep the patient calm and maintain normal body temperature. Seek medical attention. /Class A and Class B Poisons/
/SRP:/ Basic Treatment: Establish a patent airway (using oropharyngeal or nasopharyngeal airways if necessary). Suction as needed. Watch for signs of respiratory failure and provide assisted ventilation if necessary. Administer oxygen via a non-invasive mask at a flow rate of 10 to 15 liters per minute. Monitor for pulmonary edema and treat as needed… Monitor for shock and treat as needed… Anticipate seizures and treat as needed… If eyes are contaminated, immediately flush with clean water. During transport, continuously flush each eye with 0.9% saline… Do not use emetics. If swallowed, rinse mouth; if the patient is able to swallow, has a strong gag reflex, and does not drool, dilute with 5 ml/kg body weight to 200 ml of water… After disinfection, cover skin burns with a dry, sterile dressing… /Class A and Class B Poisons/
/SRP:/ Advanced Treatment: For patients with altered mental status, severe pulmonary edema, or severe respiratory distress, consider oropharyngeal or nasopharyngeal endotracheal intubation to control the airway. Positive pressure ventilation with a bag-valve-mask may be effective. Consider medical treatment for pulmonary edema…. Consider the use of a beta-agonist (such as salbutamol) for severe bronchospasm…. Monitor heart rhythm and treat arrhythmias as needed…. Initiate intravenous infusion of 5% glucose solution (D5W) /SRP: "Keep patent", minimum flow rate/. If signs of hypovolemia appear, use 0.9% normal saline (NS) or lactated Ringer's solution. Administer fluids with caution in cases of hypotension with signs of hypovolemia. Be alert for signs of fluid overload…. Use diazepam or lorazepam for seizures…. Use promecaine hydrochloride as an adjunct to eye irrigation…. /Toxins A and B/

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Human Toxicity Excerpt
/Alternative and In Vitro Tests/ Tanshinone IIA (tanshinone IIA) is isolated from Salvia miltiorrhiza, whose roots are widely used in traditional Chinese medicine for treating atherosclerosis. This study aimed to evaluate the potential protective effect of tanshinone IIA against hydrogen peroxide-induced damage in vitro in human umbilical vein endothelial cell line (ECV-304) and its protective mechanism. Cell viability was assessed using the MTT assay. Endothelial cell apoptosis and CD40 expression were detected by flow cytometry. Pre-incubation with tanshinone IIA significantly improved the survival rate of hydrogen peroxide-damaged ECV-304 cells, accompanied by a dose-dependent increase in nitric oxide levels and superoxide dismutase activity. Furthermore, apoptosis and CD40 expression also decreased in a dose-dependent manner. In conclusion, these data indicate that tanshinone IIA protects ECV-304 cells from hydrogen peroxide-induced damage through its antioxidant activity and CD40 anti-inflammatory mechanism. PMID:16797899
/Alternatives and In Vitro Testing/ This study aimed to develop a tanshinone IIA lipid emulsion (Tan IIA-LE) for intravenous administration and explore its feasibility for future clinical applications. The formulation was optimized using a central composite design-response surface methodology (CCD-RSM), and the homogenization process was systematically investigated. The stability, safety, and in vitro anti-hepatocellular carcinoma activity of Tan IIA-LE were evaluated. The formulation of Tan IIA-LE contains 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. Three cycles of high-pressure homogenization at 100 MPa were used as the optimal homogenization process. Tan IIA-LE is photosensitive but can be stably stored for at least 12 months at room temperature in the dark. Safety studies showed that Tan IIA-LE did not cause intravenous irritation or significant acute toxicity. Furthermore, Tan IIA-LE exhibited significant antitumor activity against human hepatocellular carcinoma cell lines in vitro. Overall, the tanshinone IIA-LE developed in this study is considered a safe and effective dosage form of tanshinone IIA suitable for intravenous administration, and has potential application in the future treatment of hepatocellular carcinoma. PMID:22226873
/Alternative Tests and In Vitro Tests/ Tanshinone compounds, including tanshinone IIA (TIIA), cryptotanshinone (CTS), tanshinone I (TI), and dihydrotanshinone I (DHTI), are the main bioactive components of Tanshinone. The main objective of this study was to investigate the induction effects of these four main tanshinone components (TIIA, CTS, TI, and DHTI) on the expression of CYP1A1 and CYP1A2 in HepG2 cells. The results showed that all four tanshinones significantly increased the expression of CYP1A1/2 in HepG2 cells, and this increase was time- and concentration-dependent. These induction effects were further characterized by transcriptional regulation: the increase in CYP1A1/2 mRNA levels induced by tanshinone could be completely blocked by the transcriptional inhibitor actinomycin D; tanshinone treatment could induce the expression of heterologous nuclear RNA of CYP1A1/2; and the stability of CYP1A1 mRNA was not affected by these tanshinones. Interestingly, the induction of CYP1A1/2 by tanshinone in combination with benzo[a]pyrene (B[a]P) had an additive/synergistic effect. In addition, tanshinone-induced CYP1A1/2 expression could be eliminated by the aryl hydrocarbon receptor (AhR) antagonist resveratrol, suggesting the existence of an AhR-dependent transcriptional mechanism. In reporter gene assays, tanshinone (TI) and tanshinone dihydrotanshinone (DHTI) significantly induced AhR-dependent luciferase activity, while tanshinone dihydrotanshinone (TIIA) and tanshinone (CTS) failed to induce this activity. Tanshinone compounds can induce the expression of CYP1A1 and CYP1A2 through transcriptional activation mechanisms and have different effects on AhR activation in HepG2 cells. These findings suggest that tanshinone compounds should be used rationally based on their effects on AhR and CYP1A1/2 expression. PMID:21262253
/Alternatives and In Vitro Experiments/ Tanshinone compounds are absioleane-type diterpenoid quinones isolated from the roots of Radix Salvia miltiorrhiza, a well-known traditional Chinese medicine for treating cardiovascular diseases. Among the main diterpenoid compounds isolated, cryptotanshinone, tanshinone I, tanshinone IIA, and dihydrotanshinone are included. Tanshinone IIA has been shown to have various pharmacological activities, including antioxidant, preventive/protective effects against angina and myocardial infarction, and anticancer properties. Tanshinone IIA is usually the most abundant tanshinone in Radix Salvia miltiorrhiza, and its clinical application potential has been a focus of research, including its ability to inhibit the proliferation of cancer cell lines. This study aimed to investigate the cytotoxicity of tanshinone on human HepG2 cells in vitro and explore its relationship with changes in intracellular glutathione levels (reduced glutathione GSH and oxidized glutathione GSH). MTT assays showed that all tanshinones reduced HepG2 cell viability in a concentration-dependent manner, decreasing cell viability to 60% and 35% after 24 and 48 hours of treatment, respectively. Flow cytometry analysis of DNA-fragmented apoptotic cells indicated that only tanshinone IIA (12.5 and 25 μM) induced cancer cell apoptosis. After 24 hours of treatment with tanshinone IIA and cryptotanshinone, G1 phase cells were significantly reduced by 23% and 13%, respectively. The reduction in G1 phase cells was compensated for by an increase in G2/M phase cells (tanshinone IIA increased by 15%) and S phase cells (tanshinone IIA and cryptotanshinone increased by 8% and 13%, respectively). Except for tanshinone IIA, all tanshinones studied increased the GSH/GSSG ratio at low concentrations (1.56 and 3.13 μM), but decreased at high concentrations (6.25-25 μM), indicating oxidative stress. In summary, tanshinone IIA exerts cytotoxicity by inducing apoptosis in HepG2 cells without affecting oxidative stress, while other tanshinones showed lower efficacy in inducing apoptosis in HepG2 cells. PMID:17892911
/Alternatives and In Vitro Assays/ Tanshinone IIA (Tan IIA) is a natural product of Salvia miltiorrhiza Bunge with potential antitumor activity. This study aimed to elucidate the molecular mechanism by which Tan IIA induces apoptosis in cancer cells. Human hepatocellular carcinoma BEL-7402 cells were treated with tanshinone IIA, cell viability was assessed using the MTT assay, a 10-day colony formation assay was performed, and apoptosis and cell cycle were analyzed using flow cytometry and fluorescence microscopy. Changes in intracellular [Ca²⁺] and mitochondrial membrane potential reflect the calcium-dependent apoptosis pathway. RT-PCR was used to detect the gene expression of Bad and metallothionein 1A (MT1A). The cytotoxicity of tanshinone IIA was tested in human amniotic mesenchymal stem cells (HAMCs). Tanshinone IIA exhibited dose- and time-dependent anticancer effects on BEL-7402 cells by inducing apoptosis and G₀/G₁ phase arrest. Tanshinone IIA treatment increased intracellular calcium ion concentration, decreased mitochondrial membrane potential, and induced the expression of Bad and MT1A mRNA. No adverse effects of tanshinone IIA were observed in HAMCs. In conclusion, these results indicate that tanshinone IIA induces cancer cell apoptosis through activation of the calcium-dependent apoptosis signaling pathway and upregulation of MT1A expression. PMID:21853384

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Non-human toxicity excerpt
/Experimental animals: Acute exposure/ To investigate the protective effect of tanshinone IIA on lipopolysaccharide (LPS)-induced lung injury in rats and its possible mechanism. An acute lung injury model in rats was established using LPS (O(111):B4). Sprague-Dawley rats were randomly divided into three groups (n=8 per group): control group, model group (ALI group), and tanshinone IIA treatment group. Six hours after injection of LPS or saline, the expression of polymorphonuclear neutrophil (PMNCD18) adhesion molecules on the surface of venous leukocytes (WBCs) and changes in coagulation-anticoagulation indices were detected. Simultaneously, changes in malondialdehyde (MDA) content, lung tissue wet/dry weight ratio (W/D), morphometric indices, and the aggregation of polymorphonuclear neutrophils (PMNs) in lung tissue were also detected. Compared with the control group, the acute lung injury (ALI) group showed increased PMNCD18 expression and MDA content, accompanied by a hypercoagulable state (both P<0.01), and an increased W/D ratio (P<0.05). Histopathometry analysis of lung tissue showed that the ALI group had higher PMN aggregation, wider alveolar septa, and lower alveolar volume density (V(V)) and alveolar surface density (S(V)), with statistically significant differences (P<0.01). Compared with the ALI group, the tanshinone IIA treatment group showed decreased PMN-CD18 expression, MDA content, and W/D ratio (P<0.05), and improved coagulation dysfunction (P<0.01). Histopathometry analysis of lung tissue showed reduced PMN aggregation, narrowed alveolar septa (both P<0.01), and increased V(V) and S(V) (P<0.05, P<0.01). Tanshinone IIA exerts a protective effect against LPS-induced lung injury in rats by improving hypercoagulable states, reducing PMN-CD18 expression, inhibiting migration, reducing lipid peroxidation, and alleviating pathological changes. PMID:17609914
/Experimental Animals: Chronic Exposure or Carcinogenicity/ Tanshinone IIA (Tan IIA) is a diterpenoid quinone compound extracted from the root of the traditional Chinese medicine Salvia miltiorrhiza. Although previous studies have reported the antitumor effects of tanshinone IIA on various human cancer cells, its underlying mechanism remains unclear. This study aimed to investigate the molecular mechanism by which tanshinone IIA induces apoptosis in leukemia cells in vitro. The cytotoxicity of different types of leukemia cell lines was assessed using the 3-[4,5-dimethylthiazol-2,5]-diphenyltetrazolium bromide (MTT) assay. Cells were treated with different concentrations of Tan IIA or left untreated for varying durations. Annexin V and Caspase 3 assays were used to analyze the progression of apoptosis before and after tanshinone IIA treatment. Gene expression profiling was used to identify genes regulated by tanshinone IIA treatment and differentially expressed genes among five cell lines. These gene expression regulations were validated using real-time quantitative PCR and ELISA. The antagonistic effect of the PXR inhibitor L-SFN on tanshinone IIA treatment was detected using colony-forming units (CFU). Results showed that tanshinone IIA exhibited different cytotoxic activities against the five leukemia cell lines, with the highest cytotoxicity against U-937 cells. Tanshinone IIA inhibited the growth of U-937 cells in a time- and dose-dependent manner. Annexin V and Caspase-3 assays showed that tanshinone IIA induced apoptosis in U-937 cells. Gene expression profiling revealed significant changes in the expression of 366 genes after tanshinone IIA treatment, with differential expression among the five cell lines. Among these genes, CCL2 was highly expressed in untreated U-937 cells and significantly downregulated in a dose-dependent manner after tanshinone IIA treatment. RT-qPCR analysis validated the expression regulation of 80% of these genes. The addition of the progesterone receptor (PXR) inhibitor L-sulforaphane (L-SFN) significantly attenuated the effect of tanshinone IIA in colony formation assays. Tanshinone IIA significantly inhibited the growth of U-937 cells by inducing apoptosis. The apoptosis induced by tanshinone IIA may originate from PXR activation, which inhibits NF-κB activity, leading to downregulation of CCL2 expression. PMID:22248096
/Experimental Animals: Developmental or Reproductive Toxicity/ This study aimed to determine the effects of tanshinone IIA (the active ingredient of Tanshinone) on intrauterine fetuses under non-stress conditions. Tanshinone IIA or 0.9% sodium chloride solution (as a control) was intravenously injected into pregnant ewes. The partial pressure of oxygen (PO₂), partial pressure of carbon dioxide (PCO₂), sulfur dioxide (SO₂), hemoglobin, hematocrit, glucose, lactate, and concentrations of sodium (Na⁺), potassium (K⁺), and chloride (Cl⁻) ions in the blood of both mother and fetus were analyzed. Cardiac function in both mother and fetus was assessed by detecting myocardial enzymes and cardiovascular responses. Results showed that tanshinone IIA did not alter blood parameters in either the ewe or fetus. Cardiac enzyme activities remained unchanged. In cardiovascular experiments, no effect of tanshinone IIA on ewe blood pressure was observed. However, intravenous administration of tanshinone IIA resulted in a slight but significant increase in fetal systolic blood pressure, while fetal diastolic blood pressure, mean arterial pressure, and heart rate remained unchanged. These results indicate that the use of tanshinone IIA in the last third of pregnancy does not cause biochemical changes related to cardiac function in either the ewe or fetus. ...PMID: 19938214
/Experimental Animals: Developmental or Reproductive Toxicity/ This is... a study aimed at determining the effects of the traditional Chinese medicine Danshen on intrauterine liver and kidney function in fetuses. This study used an experimental sheep fetal model to test the activity of the active ingredient tanshinone IIA from Danshen. Three doses (20, 40, or 80 mg) of tanshinone IIA and a 0.9% sodium chloride solution (as a control) were administered intravenously to pregnant ewes. Blood samples were collected from both ewes and fetuses, and kidney and liver function were analyzed by detecting enzyme activity and renal excretion. The results showed that tanshinone IIA did not affect fetal urine output, urinary electrolytes, or osmolality. Enzyme activities related to liver and kidney function were also unchanged. Furthermore, tanshinone IIA administration to ewes had no effect on the lipid profiles of either the ewe or the fetus. These results indicate that tanshinone IIA administration in late pregnancy does not cause biochemical changes related to kidney and liver function in either the ewe or the fetus. This provides new information for guiding the use of herbal remedies during pregnancy. PMID: 19793029

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Ecological Information
Environmental Fate/Exposure Overview
The production and use of tanshinone II as a dietary supplement and cancer investigation drug may result in its release into the environment through various waste streams. This compound is extracted from the root of Salvia miltiorrhiza. If released into the air, the estimated vapor pressure at 25°C is 2.5 × 10⁻⁸ mmHg, indicating that tanshinone II will exist only in the atmosphere as a particulate phase. Particulate tanshinone II will be removed from the atmosphere by dry and wet sedimentation. Tanshinone II contains a chromophore that absorbs at wavelengths >290 nm, and therefore may be susceptible to photolysis by direct sunlight. Based on an estimated Koc value of 660, tanshinone II is expected to have low mobility after release into soil. Based on an estimated Henry's Law constant of 5.0 × 10⁻⁹ atm·m³/mol, volatilization from moist soil surfaces is not expected to be a significant fate. Based on the estimated vapor pressure, tanshinone II is not expected to volatilize from dry soil surfaces. Based on the estimated Koc value, tanshinone II is expected to adsorb onto suspended matter and sediments after release into water. Based on the Henry's Law constant for this compound, volatilization from water surfaces is not expected to be a significant fate. The estimated bioaccumulation factor (BCF) is 6800, indicating a very high bioaccumulation potential in aquatic organisms if the compound is not metabolized. Since this compound lacks functional groups that would undergo hydrolysis under environmental conditions, hydrolysis is not expected to be a significant environmental fate. Occupational exposure to tanshinone II may occur in workplaces where it is extracted or used, through inhalation and skin contact. Data from usage indicate that the general population may be exposed to tanshinone II through the ingestion of dietary supplements. (SRC)

[1]. The antitumor effect of tanshinone IIA on anti-proliferation and decreasing VEGF/VEGFR2 expression on the human non-small cell lung cancer A549 cell line. Acta Pharm Sin B. 2015 Nov;5(6):554-63.

[2]. Tanshinone IIA inhibits apoptosis in the myocardium by inducing microRNA-152-3p expression and thereby downregulating PTEN. Am J Transl Res. 2016 Jul 15;8(7):3124-32.

[3]. Tanshinone IIA decreases the protein expression of EGFR, and IGFR blocking the PI3K/Akt/mTOR pathway in gastric carcinoma AGS cells both in vitro and in vivo. Oncol Rep. 2016 Aug;36(2):1173-9.

1,6,6-Trimethyl-8,9-dihydro-7H-naphtho[1,2-g]benzofuran-10,11-dione is an abiran diterpenoid compound. Tanshinone IIA has been reported in Salvia miltiorrhiza, Salvia miltiorrhiza var. mucilaginosa, and other organisms with relevant data. See also: Salvia miltiorrhiza root (partial). Mechanism of Action: Doxorubicin was one of the earliest anthracycline antibiotics and remains one of the most effective anticancer drugs. However, the clinical application of doxorubicin is greatly limited by its severe cardiac adverse reactions, which may ultimately lead to cardiomyopathy and heart failure. Tanshinone IIA is the main active ingredient of Salvia miltiorrhiza (a traditional Chinese medicine used to treat cardiovascular diseases). This study aimed to evaluate the protective effect of tanshinone IIA against doxorubicin-induced cardiomyocyte apoptosis and to explore its intracellular mechanism. Primary cultured neonatal rat cardiomyocytes were treated with solvent, doxorubicin (1 μM), tanshinone IIA (0.1, 0.3, 1, and 3 μM), or a combination of tanshinone IIA and doxorubicin. The study found that tanshinone IIA (1 and 3 μM) inhibited doxorubicin-induced reactive oxygen species (ROS) generation, reduced the levels of cleavable caspase-3 and cytochrome c, and increased Bcl-x(L) expression, thereby protecting cardiomyocytes from doxorubicin-induced apoptosis. Furthermore, tanshinone IIA treatment enhanced Akt phosphorylation in cardiomyocytes. Transfection with Watermanin (100 nM), LY294002 (10 nM), and Akt siRNA significantly reduced the protective effect of tanshinone IIA. These results suggest that tanshinone IIA partially protects cardiomyocytes from doxorubicin-induced apoptosis through the Akt signaling pathway, which may help protect the heart from the severe toxic effects of doxorubicin.

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- Tanshinone IIA is a lipophilic diterpenoid compound isolated from Salvia miltiorrhiza. It is a traditional Chinese medicine used to treat cardiovascular diseases and inflammation [1][2][3].
- Its anti-tumor mechanism involves multi-target inhibition, including the VEGF/VEGFR2 signaling pathway in lung cancer, the regulation of the miR-152-3p/PTEN axis in cardiomyocytes, and the inhibition of the EGFR/IGFR/PI3K/Akt/mTOR pathway in gastric cancer [1][2][3].
- This drug has tissue-specific effects, such as cardioprotection through miRNA regulation and inhibition of tumor growth through downregulation of tyrosine kinase receptors [2][3].

C19H18O3

294.3444

294.125

568-72-9

164676

Pink to red solid powder

1.2±0.1 g/cm3

480.7±44.0 °C at 760 mmHg

205-207ºC

236.4±21.1 °C

0.0±1.2 mmHg at 25°C

1.588

5.47

0

3

0

22

509

0

O1C([H])=C(C([H])([H])[H])C2C(C(C3=C(C1=2)C([H])=C([H])C1=C3C([H])([H])C([H])([H])C([H])([H])C1(C([H])([H])[H])C([H])([H])[H])=O)=O

INYYVPJSBIVGPH-QHRIQVFBSA-N

InChI=1S/C19H23NO4/c1-20-7-6-19-10-14(21)16(24-3)9-12(19)13(20)8-11-4-5-15(23-2)18(22)17(11)19/h4-5,9,12-13,22H,6-8,10H2,1-3H3/t12-,13+,19-/m1/s1

(1R,9S,10S)-3-hydroxy-4,12-dimethoxy-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5,11-tetraen-13-one

Tanshinone IIA; 568-72-9; Tanshinone II; Dan Shen Ketone; Tanshinone B; Tanshinon II; 1,6,6-Trimethyl-6,7,8,9-tetrahydrophenanthro[1,2-b]furan-10,11-dione; tanshinone II A; Coculine; Cucoline; Kukoline

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product is not stable in solution, please use freshly prepared working solution for optimal results.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)