- 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]

丹参酮 IIA 具有抗肿瘤特性，例如增加肿瘤细胞死亡、减少短期细胞增殖、改变肿瘤细胞周期等。丹参酮 IIA 对 A549 细胞具有抗肿瘤作用； 24、48和72小时，丹参酮IIA的IC50分别为145.3、30.95和11.49 μM。使用 CCK-8 测定法评估分别用丹参酮 IIA (2.5 - 80 μM) 处理 24、48 和 72 小时的 A549 细胞的增殖活性。 CCK-8结果表明，丹参酮IIA可以以剂量和时间抑制的方式强烈抑制A549细胞的生长。药物治疗 48 天后，检测到 A549 细胞生长和浓度显着降低（使用浓度微量 IC50 值：丹参酮 IIA 31 μM 与 A549 相比）。使用蛋白质印迹法发现，与媒介物相比，将 A549 细胞置于丹参酮 IIA (31 μM) 48 小时后，两个药物治疗组均表达 VEGF 和 VEGFR2 [1]。丹参根中最常见的成分是丹参酮 IIA。丹参酮 IIA H9C2 细胞表达转录的 PTEN（磷酸酶和张力蛋白同源物），这是一种在细胞中发挥作用的蛋白质，可引起血管紧张素 II 诱导的细胞荧光。重要的障碍。通过磷酸化磷酸酶和张力蛋白同源物 (PTEN) 的表达，丹参酮 IIA 抑制血管紧张素 II (AngII) 产生的细胞因子 [2]。 Tanshinone IIA 促进 PI3K/Akt/mTOR 光泽并降低 AGS 细胞中 EGFR 和 IGFR 蛋白的表达 [3]。

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- 在A549非小细胞肺癌细胞中，丹参酮IIA（5-20 μM）剂量依赖性抑制细胞增殖（MTT法）和迁移（Transwell实验）。Western blot显示VEGF和VEGFR2蛋白水平降低，20 μM时抑制率最高（VEGF减少40%，VEGFR2减少50%）[1]
- 在缺氧/复氧损伤的H9c2心肌细胞中，丹参酮IIA（10-50 μM）提高细胞存活率（MTT法）并降低caspase-3活性（ELISA）。qRT-PCR显示miR-152-3p上调（50 μM时达2.5倍），PTEN mRNA和蛋白水平下调[2]
- 在AGS胃癌细胞中，丹参酮IIA（10-40 μM）抑制细胞增殖（IC50约25 μM）并诱导G0/G1期细胞周期阻滞（流式细胞术）。Western blot显示EGFR和IGFR表达减少，PI3K/Akt/mTOR通路活性受抑制（p-Akt和p-mTOR水平降低）[3]

东莨菪碱引起的认知障碍可被丹参酮 IIA（10 或 20 mg/kg；侧壁）显着逆转[4]。通过阻断 PERK 信号传导，丹参酮 IIA（2、4、8 mg/kg；腹腔注射）可能会减少白天的内质网，这可能与对 STZ 诱导的糖尿病肾病的介导保护作用有关 [5]。丹参酮 IIA（3 和 12 mg/kg；腹腔注射）可显着抑制异位蛋白内膜发育 [6]。

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- 在荷A549异种移植瘤的裸鼠中，丹参酮IIA（20 mg/kg，腹腔注射，每日1次，连续21天）显著缩小肿瘤体积（较对照组抑制42%），并降低肿瘤组织中VEGF/VEGFR2表达（免疫组化）[1]
- 在大鼠心肌缺血/再灌注模型中，丹参酮IIA（10 mg/kg，静脉注射）改善心脏功能（超声心动图）并减少梗死面积（TTC染色）。心肌组织中miR-152-3p上调，PTEN蛋白水平下调[2]
- 在荷AGS异种移植瘤的裸鼠中，丹参酮IIA（30 mg/kg，腹腔注射，每周3次，连续3周）抑制肿瘤生长（体积减少55%），并降低肿瘤组织中EGFR/IGFR表达及p-Akt水平[3]

- VEGF/VEGFR2表达检测：A549细胞经丹参酮IIA（5-20 μM）处理48小时后，提取细胞裂解液进行Western blot，使用抗VEGF和抗VEGFR2抗体。蛋白条带通过密度分析定量，以β-actin为内参[1]
- miR-152-3p检测：H9c2细胞经丹参酮IIA（10-50 μM）处理后提取总RNA，通过茎环qRT-PCR检测miR-152-3p水平，使用特异性引物[2]
- EGFR/IGFR信号通路检测：AGS细胞经丹参酮IIA（10-40 μM）处理后裂解，蛋白提取物与抗EGFR、抗IGFR、抗p-Akt和抗p-mTOR抗体孵育。条带强度以β-actin标准化[3]

- A549细胞迁移实验：细胞接种于Matrigel包被的Transwell上室，含丹参酮IIA（5-20 μM）的无血清培养基培养24小时。固定染色后显微镜下计数迁移细胞，20 μM时迁移率降低60%[1]
- H9c2细胞凋亡实验：细胞经丹参酮IIA（10-50 μM）预处理后进行缺氧/复氧，Annexin V-FITC/PI染色结合流式细胞术检测凋亡。50 μM时凋亡率从35%降至18%[2]
- AGS细胞周期分析：细胞经丹参酮IIA（10-40 μM）处理后固定，碘化丙啶染色，流式细胞术检测。40 μM时G0/G1期细胞比例从45%升至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
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.

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Antidote and Emergency Treatment
/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/

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Human Toxicity Excerpts
/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. PMID:16797899

/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. PMID:22226873

/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. PMID:21262253

/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. PMID:17892911

/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. PMID:21853384

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Non-Human Toxicity Excerpts
/LABORATORY ANIMALS: Acute Exposure/ To explore the protective effect of tanshinone II A on lipopolysaccharide (LPS)-induced lung injury in rats, and possible mechanism. LPS (O(111): B4) was used to produce a rat model of acute lung injury. Sprague-Dawley rats were randomly divided into 3 groups (8 in each group): the control group, the model group (ALI group), and the tanshinone II A treatment group. Expression of adhesion molecule CD18 on the surface of polymorphonuclear neutrophil (PMNCD18) in venous white blood cells (WBC), and changes in coagulation-anticoagulant indexes were measured 6 hr after injection of LPS or normal saline. Changes in malondialdehyde (MDA) content, wet and dry weight (W/D) ratio and morphometry of pulmonary tissue as well as PMN sequestration in the lung were also measured. When compared with the control group, expression of PMNCD18 and MDA content were enhanced in the ALI group with a hypercoagulable state (all P<0.01) and an increased W/D ratio (P<0.05). Histopathological morphometry in the lung tissue showed higher PMN sequestration, wider alveolar septa; and lower alveolar volume density (V(V)) and alveolar surface density (S(V)), showing significant difference (P<0.01). When compared with the ALI group, the expression of PMN-CD18, MDA content, and W/D ratio were all lower in Tanshinone II A treatment group (P<0.05) with ameliorated coagulation abnormality (P<0.01). Histopathological morphometry in the lung tissue showed a decrease in the PMN sequestration and the width of alveolar septa (both P<0.01), and an increase in the V(V) and S(V) (P<0.05, P<0.01). Tan II A plays a protective role in LPS-induced lung injury in rats through improving hypercoagulating state, decreasing PMN-CD18 expression and alleviating migration, reducing lipid peroxidation and alleviating pathological changes. PMID:17609914

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Tanshinone IIA (Tan IIA) is a diterpene quinone extracted from the root of Salvia miltiorrhiza, a Chinese traditional herb. Although previous studies have reported the anti-tumor effects of Tan IIA on various human cancer cells, the underlying mechanisms are not clear. The current study was undertaken to investigate the molecular mechanisms of Tan IIA's apoptotic effects on leukemia cells in vitro. The cytotoxicity of Tan IIA on different types of leukemia cell lines was evaluated by the 3-[4,5-dimethylthiazol-2,5]-diphenyl tetrazolium bromide (MTT) assay on cells treated without or with Tan IIA at different concentrations for different time periods. Cellular apoptosis progression with and without Tan IIA treatment was analyzed by Annexin V and Caspase 3 assays. Gene expression profiling was used to identify the genes regulated after Tan IIA treatment and those differentially expressed among the five cell lines. Confirmation of these expression regulations was carried out using real-time quantitative PCR and ELISA. The antagonizing effect of a PXR inhibitor L-SFN on Tan IIA treatment was tested using Colony Forming Unit Assay. Our results revealed that Tan IIA had different cytotoxic activities on five types of leukemia cells, with the highest toxicity on U-937 cells. Tan IIA inhibited the growth of U-937 cells in a time- and dose-dependent manner. Annexin V and Caspase-3 assays showed that Tan IIA induced apoptosis in U-937 cells. Using gene expression profiling, 366 genes were found to be significantly regulated after Tan IIA treatment and differentially expressed among the five cell lines. Among these genes, CCL2 was highly expressed in untreated U-937 cells and down-regulated significantly after Tan IIA treatment in a dose-dependent manner. RT-qPCR analyses validated the expression regulation of 80% of genes. Addition of L-sulforaphane (L-SFN), an inhibitor of Pregnanexreceptor (PXR) significantly attenuated Tan IIA's effects using colony forming assays.Tan IIA has significant growth inhibition effects on U-937 cells through the induction of apoptosis. And Tan IIA-induced apoptosis might result from the activation of PXR, which suppresses the activity of NF-kappaB and lead to the down-regulation of CCL2 expression. PMID:22248096

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ This was the ... study to determine the effect of tanshinone IIA (an active ingredient in herb Danshen) on fetuses in utero under unstressed condition. Tanshinone IIA or 0.9% NaCl as control was intravenously (i.v.) administrated into pregnant ewes. Both maternal and fetal blood were analyzed for PO(2), PCO(2), SO(2)%, hemoglobin, hemotecrit, glucose, lactic acid, Na(+), K(+), and Cl(-) concentrations. Maternal and fetal heart functions were assessed by examining cardiac enzymes and cardiovascular responses. The results showed that tanshinone IIA did not alter the blood values in ewes and fetuses. Cardiac enzyme activities related to the heart remained unchanged. In cardiovascular experiments, no alternation in maternal blood pressure by tanshinone IIA was observed. However, fetal systolic pressure was slightly and significantly increased following iv tanshinone IIA into the mothers, while fetal diastolic pressure, mean arterial pressure, and heart rate were not changed. The results demonstrated that tanshinone IIA used during the last third of gestation did not cause the biochemical changes related to cardiac functions in both maternal and fetal sheep. ... PMID:19938214

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ This was the ... study in determination of the effects of the herbal medicine, danshen, on fetal hepatic and renal functions in utero. Tanshinone IIA, an active ingredient of danshen, was tested in the experimental /ovine/ fetal model. Three doses (20, 40, or 80 mg) of tanshinone IIA and 0.9% NaCl (as the control) were intravenously (i.v.) administrated into pregnant ewes. Both maternal and fetal blood samples were collected and analyzed for renal and liver functions by examining the enzymes and renal excretion. The results showed that tanshinone IIA did not alter fetal urine volume, urine electrolytes, and osmolality. Enzyme activities related to the hepatic and renal functions were not changed. In addition, maternal application of tanshinone IIA had no effect of maternal and fetal lipid profile. The results demonstrated that tanshinone IIA used during the last third of gestation did not cause the biochemical changes related to renal and liver functions in both the mother and fetus. This provides new information to guide the use of herbal medicine during pregnancy. PMID:19793029

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Ecological Information
Environmental Fate / Exposure Summary
Tanshinone II's production and use as a dietary supplement and in cancer research may result in its release to the environment through various waste streams. The compound is extracted from Danshen root (Salvia miltiorrhiza). If released to air, an estimated vapor pressure of 2.5X10-8 mm Hg at 25 °C indicates tanshinone II will exist solely in the particulate phase in the atmosphere. Particulate-phase tanshinone II will be removed from the atmosphere by wet or dry deposition. Tanshinone II contains chromophores that absorb at wavelengths >290 nm and, therefore, may be susceptible to direct photolysis by sunlight. If released to soil, tanshinone II is expected to have low mobility based upon an estimated Koc of 660. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 5.0X10-9 atm-cu m/mole. Tanshinone II is not expected to volatilize from dry soil surfaces based upon its estimated vapor pressure. If released into water, tanshinone II is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. An estimated BCF of 6800 suggests the potential for bioconcentration in aquatic organisms is very high, provided the compound is not metabolized by the organism. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. 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. (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 abietane diterpenoid.
Tanshinone IIA has been reported in Salvia miltiorrhiza, Salvia glutinosa, and other organisms with data available.
See also: Salvia Miltiorrhiza Root (part of).

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Mechanism of Action
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.

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- Tanshinone IIA is a lipophilic diterpenoid isolated from Salvia miltiorrhiza (Danshen), traditionally used in Chinese medicine for cardiovascular and anti-inflammatory effects [1][2][3]
- Its antitumor mechanism involves multi-target inhibition, including VEGF/VEGFR2 signaling in lung cancer, miR-152-3p/PTEN axis regulation in cardiomyocytes, and EGFR/IGFR/PI3K/Akt/mTOR pathway suppression in gastric cancer [1][2][3]
- The drug shows tissue-specific effects, such as cardioprotection via miRNA modulation and tumor inhibition via tyrosine kinase receptor downregulation [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

47.28

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

注意： 该产品在溶液状态不稳定，请现配现用。

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

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。