Dihydrotanshinone I

278.3

278.30

DTXSID20236187

Red powder

29329990

43.4

3.93 (est)

red

1.3±0.1 g/cm3

201-203 °C @ Solvent: Methanol

479.2±45.0 °C at 760 mmHg

214.9±28.8 °C

1.671

ethanol: soluble1mg/mL, clear, orange to red

2-8°C

3.5X10-9 mm Hg at 25 deg C (est)

Henry's Law constant = 1.3X10-10 atm-cu m/mol at 25 °C (est)

UN 3077 9 / PGIII

3

22-50

61

SF8282630

Xn,N

Stable under recommended storage conditions.

P273

H302-H400

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.

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P273, P301+P312, P330, P391, and P501|Aggregated GHS information provided by 194 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.

Not flammable or combustible.

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

Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.|Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.

...When HeLa cells were grown as xenografts in nude mice, combination treatment with /dihydrotanshinone I/ (DI) and /irradiation/ (IR )induced a significant decrease in tumor growth, and without signs of general or organ toxicity...|Tanshinones are a group of diterpenoids found in the roots of Salvia miltiorrhiza Bunge which has been used to treat cardiac disease. In the present study, /the authors/ investigated the effect of the tanshinone congeners, tanshinone I, tanshinone IIA, cryptotanshinone, and 15, 16-dihydrotanshinone I, on learning and memory impairments induced by scopolamine (1 mg/kg, ip), a muscarinic antagonist, using passive avoidance tasks in mice. Tacrine was used as a positive control. Tanshinone I (2 or 4 mg/kg, po), tanshinone IIA (10 or 20 mg/kg, po), cryptotanshinone (10 mg/kg, po), and 15, 16-dihydrotanshinone I (2 or 4 mg/kg, po) significantly reversed scopolamine-induced cognitive impairments (P<0.05). Tanshinone I (2 mg/kg, po) and tanshinone IIA (10 or 20 mg/kg, po) were also reversed diazepam-induced cognitive dysfunctions (P<0.05). In addition, cryptotanshinone and 15, 16-dihydrotanshinone I were found to have an inhibitory effect on acetylcholinesterase in vitro with IC(50) values 82 and 25 uM, respectively. Furthermore, cryptotanshinone inhibited acetylcholinesterase activity for 3 hr and 15, 16-dihydrotanshinone I for 6 hr in an ex-vivo study. These results suggest that tanshinone congeners may be useful for the treatment of cognitive impairment and that their beneficial effects are mediated, in part, by cholinergic signaling enhancement.

Dihydrotanshinone I is an extract from Danshen root (Salvia miltiorrhiza)(1).

Dihydrotanshinone I's production and use in traditional Chinese medicine to tumor treatment(1) and as an antibacterial/antifungal agent(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 1.1X10+4(SRC), determined from a structure estimation method(2), indicates that dihydrotanshinone I is expected to be immobile in soil(SRC). Volatilization of dihydrotanshinone I from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.3X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Dihydrotanshinone I is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.5X10-9 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 1.1X10+4(SRC), determined from a structure estimation method(2), indicates that dihydrotanshinone I 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 1.3X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 26(SRC), from an estimated log Kow of 3.93(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(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), dihydrotanshinone I, which has an estimated vapor pressure of 3.5X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase dihydrotanshinone I may be removed from the air by wet or dry deposition(SRC). Dihydrotanshinone I contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

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

An estimated BCF of 26 was calculated in fish for dihydrotanshinone I(SRC), using an estimated log Kow of 3.93(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of dihydrotanshinone I can be estimated to be 1.1X10+4(SRC). According to a classification scheme(2), this estimated Koc value suggests that dihydrotanshinone I is expected to be immobile in soil.

The Henry's Law constant for dihydrotanshinone I is estimated as 1.3X10-10 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that dihydrotanshinone I is expected to be essentially nonvolatile from moist soil and water surfaces(2). Dihydrotanshinone I is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.5X10-9 mm Hg(SRC), determined from a fragment constant method(3).

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

/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/ The IC50 of the most active compound, 15,16-dihydrotanshinone I, on human /recombinant monoamine oxidase A/ (MAO A) was at 23 uM...|/ALTERNATIVE and IN VITRO TESTS/ The aim of this study was to investigate the effect of dihydrotanshinone I (DI) in inhibiting the growth of human cervical cancer cells both in vitro and in vivo, and molecular targets in HeLa cells when treated by DI or irradiation with or without being combined. In this study, MTT, clonogenic assay, flow cytometry, and Western blotting were performed to assess the effect of treatment on cells. After treatment with IR, DI, and DI + IR, the apoptosis was 5.8, 13.3 and 22.5% (P < 0.05 vs. control), respectively. Clonogenic assay revealed that the survival of irradiated HeLa cell was significantly reduced by DI treatment. Combination treatment with IR and DI could down-regulate HPV E6 gene expression. Effect of DI on up-regulation of p21 expression and down-regulation of cyclin B1, p34(cdc2) expression in irradiated HeLa cell was concomitant with cell cycle arrest in G(2) phase. The significant increase in caspase-3 activity was also observed in the combination treatment...|/ALTERNATIVE and IN VITRO TESTS/ /The investigators/ studied the effects of multi- and single-target liposomal drugs on human gastric cancer cell AGS both in vitro and in vivo. The cytotoxic effect of dihydrotanshinone I was significantly enhanced by treatment with octreotide-polyethylene glycol(PEG)-liposome, Arg-Gly-Asp(RGD)-PEG-liposome, and RGD/octreotide-PEG-liposome encapsulated with 0.5 ug/mL of dihydrotanshinone I to AGS cell for 24 hr, compared to control. Furthermore, the AGS cell survival rate for multi-target versus single target liposomal drugs was significantly suppressed. Microscopic examination revealed that significant cell death occurred in the multi- and single-target liposomal encapsulated drug groups...|/ALTERNATIVE and IN VITRO TESTS/ Dihydrotanshinone I (DI), a naturally occurring compound extracted from Salvia miltiorrhiza Bunge, has been reported to have cytotoxicity to a variety of tumor cells. /This study/ investigated its anti-angiogenic capacity in human umbilical vein endothelial cells. DI induced a potent cytotoxicity to human umbilical vein endothelial cells, with an IC(50) value of approximately 1.28 ug/mL. At 0.25-1 ug/mL, DI dose-dependently suppressed human umbilical vein endothelial cell migration, invasion, and tube formation detected by wound healing, Transwell invasion and Matrigel tube formation assays, respectively...|/ALTERNATIVE and IN VITRO TESTS/ ... Evaluation of inhibition potential of danshen's major ingredients towards UDP-glucuronosyltransferases (UGTs) will be helpful for understanding detailed mechanisms for danshen-drugs interaction. Therefore, the aim of the present study is to investigate the inhibitory situation of cryptotanshinone and dihydrotanshinone I towards UGT enzyme-catalyzed propofol glucuronidation. In vitro human liver microsome (HLM) incubation system was used, and the results showed that cryptotanshinone and dihydrotanshinone I exhibited dose-dependent inhibition towards HLM-catalyzed propofol glucuronidation. Dixon plot and Lineweaver-Burk plot showed that the inhibition type was best fit to competitive inhibition type for both cryptotanshinone and dihydrotanshinone I. The second plot using the slopes from the Lineweaver-Burk plot versus the concentrations of cryptotanshinone or dihydrotanshinone I was employed to calculate the inhibition parameters (Ki) to be 0.4 and 1.7 uM, respectively. Using the reported maximum plasma concentration (Cmax), the altered in vivo exposure of propofol increased by 10% and 8.2% for the co-administration of dihydrotanshinone I and cryptotanshinone, respectively. All these results indicated the possible danshen-propofol interaction due to the inhibition of dihydrotanshinone I and cryptotanshinone towards the glucuronidation reaction of propofol.

(-)-dihydrotanshinone I

Tanshinone extracted from a herb, Salvia miltiorrhiza