Notoginsenoside R1

933.13

933.13

Z62692362Z

White to off-white powder

29389090

298

log Kow = -0.66 (est)

white to off-white

1.4±0.1 g/cm3

215～217℃

1010.5°C at 760 mmHg

564.9±34.3 °C

1.614

H2O: soluble1mg/mL, clear, colorless

2-8°C

6.7X10-38 mm Hg at 25 °C (est)

Henry's Law constant = 1.5X10-31 atm-cu m/mol at 25 °C (est)

NONH for all modes of transport

3

22

24/25

Xn

Stable under recommended storage conditions.

H302

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.

Wear self contained breathing apparatus for fire fighting if necessary.|Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

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.|Provide appropriate exhaust ventilation at places where dust is formed.|Avoid dust formation. Avoid breathing vapors, mist or gas.

Notoginsenoside R1 is isolated from the roots of various Panax species(1-3).

Notoginsenoside R1's productiuon and use as an antioxidant, antiproliferative and pro-apoptotic(1) 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 0.16(SRC), determined from an estimated log Kow of -0.66(2) and a regression-derived equation(2), indicates that notoginsenoside R1 is expected to have very high mobility in soil(SRC). Volatilization of notoginsenoside R1 from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.5X10-31 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Notoginsenoside R1 is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.7X10-38 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2013).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 0.16(SRC), determined from an estimated log Kow of -0.66(2) and a regression-derived equation(2), indicates that notoginsenoside R1 is not 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 1.5X10-31 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Notoginsenoside R1 is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(6). 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), notoginsenoside R1, which has an estimated vapor pressure of 6.7X10-38 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 notoginsenoside R1 may be removed from the air by wet or dry deposition(SRC). Notoginsenoside R1 does not contain chromophores that absorb at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

Notoginsenoside R1 is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Notoginsenoside R1 does not contain chromophores that absorb at wavelengths >290 nm(1) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for notoginsenoside R1(SRC), using an estimated log Kow of -0.66(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).

The Koc of notoginsenoside R1 is estimated as 0.16(SRC), using an estimated log Kow of -0.66(1) and a regression-derived equation(1). According to a classification scheme(2), this estimated Koc value suggests that notoginsenoside R1 is expected to have very high mobility in soil.

The Henry's Law constant for notoginsenoside R1 is estimated as 1.5X10-31 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that notoginsenoside R1 is expected to be essentially nonvolatile from water and moist soil surfaces(2). Notoginsenoside R1 is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.7X10-38 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to notoginsenoside R1 may occur through dermal contact with this compound at workplaces where notoginsenoside R1 is extracted or used. Use data indicate that the general population may be exposed to notoginsenoside R1 via ingestion as a medication and dietary supplement. (SRC)

*Ginsenosides

Zebrafish, a common model organism for studies of vertebrate development and gene function, has been used in pharmaceutical research as a new and powerful tool in recent years. In the present study, /the researchers/ applied zebrafish ...in a metabolic study of notoginsenoside (R1), ginsenoside (Rg1) and ginsenoside (Rb1), which are saponins isolated from Panax notoginseng. Metabolites of these three saponin compounds in zebrafish after exposure for 24 hr were identified by high performance liquid chromatography - electrospray mass spectrometry (HPLC-ESI-MS) with a Zorbax C-18 column for separation using a binary gradient elution of 0.05% formic acid acetonitrile - 0.05% formic acid water. The quasi-molecular ions of compounds were detected in negative mode. Step-wise deglycosylation metabolites and hydroxylation metabolites of the three saponins were found, which were /consistant/ with regular methods for metabolic analysis...

/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 object of this study was to explore the effects of Panax notoginosides (PNS) on proliferation and differentiation of human CD34(+) stem/progenitor cells. CD34(+) cells were isolated from human bone marrow by using immune beads of Dynal M- 450 system. The cells were exposed to PNS at different concentrations in both liquid and semi-solid culture for 14 days. The cells were marked with monoclonal antibodies and analyzed by flow cytometry after culture. The CFU-Mix colony formation from CD34(+) cells was assayed. The results showed that: (1) The yield of CD34(+) cells after being selected by immune beads were (1.03 +/- 0.74)% out of bone marrow nuclear cells with purity of 86% - 93%. (2) PNS (10 - 25 mg/L) stimulated the proliferation of CD34(+) cells, and raised the colony numbers of CFU-Mix obviously in vitro. PNS 25 mg/L was the optimal concentration to promote proliferation of CD34(+) cells, the increasing rate of CFU-Mix colony was (34.7 +/- 16.0)%. (3) The differentiation of CD34(+) cells was induced by exposure to PNS (25, 50 and 100 mg/L) in liquid culture for 14 days. The percentages of CD33(+) and CD15(+) cells were increased after PNS exposure, which were significantly higher than those of control (P < 0.01), however CD71(+) and G-A(+) cells were no obviously difference after PNS treatment. In conclusion, Panax notoginosides not only promote the proliferation of CD34(+) cells, but also induce the differentiation committed to granulocytes.|/ALTERNATIVE and IN VITRO TESTS/ Among other Chinese herb drugs, Panax notoginseng is used to treat cardiovascular diseases. To elucidate any possible effects of this drug on the hemostatic system in vitro, /the researchers/ analyzed the influence of one of its major active constituents on fibrinolytic parameters of cultured human umbilical vein endothelial cells (HUVECs). When confluent cultures of HUVECs (passages 2 to 3) were conditioned with purified notoginsenoside R1 (NR1), a dose- (0.01 to 100 ug NR1/mL) and time-dependent increase in tissue-type plasminogen activator (TPA) synthesis was observed, which was significant from 0.1 ug NR1/mL and from 6 hours of incubation with 100 ug NR1/mL on. TPA antigen increased from 3.9 +/- 0.2 ng per 10(5) cells per 24 hours to 8.0 +/- 0.5 ng per 10+5 cells per 24 hours on addition of 100 ug NR1/mL. In contrast, no change in urokinase-type plasminogen activator and plasminogen activator inhibitor-1 (PAI-1) antigen synthesis was seen. There was also no effect of NR1 on PAI-1 deposition in the extracellular matrix. As judged from fibrin autography and reverse fibrin autography, TPA activity and TPA-PAI-1 complexes reached a maximal stimulation of more than threefold and twofold, respectively, at a concentration of 100 micrograms NR1/mL in conditioned media. On the contrary, NR1 induced a more than fivefold decrease in PAI-1 activity at the same concentration of NR1 in conditioned media. On Northern blot analysis of RNA obtained from NR1-stimulated and control HUVECs, NR1 induced a significant increase in TPA mRNA (192% of control value at 100 ug NR1/mL) while PAI-1 mRNA remained unchanged.|/ALTERNATIVE and IN VITRO TESTS/ ...this study ... investigated a possible counteracting activity notoginsenoside R1 (NG-R1) on lipopolysaccharide (LPS)-induced effects in vitro... The upregulation of plasminogen activator inhibitor-1 (PAI-1) antigen due to LPS (1 ug/mL for 12 hours) in human umbilical vein endothelial cells (HUVECs) was prevented when the cells were incubated simultaneously with 100 ug/mL NG-R1 (PAI-1 antigen: LPS-treated cells, 969 +/- 54 ng/10+5 cells; control cells, 370 +/- 15 ng/10+5 cells; LPS + NG-R1-treated cells, 469 +/- 29 ng/10+5 cells; n = 6). The 2.5- and 3.4-fold (2.2- and 3.2-kb) increases in PAI-1 mRNA levels induced by LPS (1 ug/mL for 6 hours) were reduced to 1.4- and 2.6-fold increases in the presence of both LPS and 100 ug/mL NG-R1. LPS-induced tissue factor (TF) activity in HUVECs was also counteracted when the cells were coincubated with both LPS and 100 ug/mL NG-R1 for 6 hours (TF activity: LPS-treated cells, 88.6 +/- 6.5 mU/10+6 cells; control cells, 0.7 +/- 0.01 mU/10+6 cells; LPS + NG-R1-treated cells, 56.0 +/- 1.9 mU/10+6 cells). The 26-fold increase in TF mRNA levels induced by LPS (1 ug/mL for 2 hours) was reduced to a 13-fold increase in the presence of both LPS and 100 ug/mL NG-R1. PAI activity levels in the plasma of mice 4 hours after injection of LPS (10 ng/g body wt) increased 2.3-fold compared with a control group. ...The production of TNF-alpha induced by 1 ug/mL LPS by cultured human whole-blood cells was inhibited by 46% when the cells were incubated together with 100 ug/mL NG-R1. ...To extend this study to inflammatory cells, the effect of NG-R1 on LPS stimulation of the monocytic cell line THP-1 was investigated. NG-R1 inhibited the LPS-induced degradation of I kappa B-alpha and superinduced LPS-induced I kappa B-alpha mRNA, indicating that the effect of NG-R1 is not restricted to endothelial cells and is at least in part mediated by interference with the NF-kappa B/I kappa B-alpha pathway.|/ALTERNATIVE and IN VITRO TESTS/ To observe the effects of Panax Notoginosides (PNS) on up-regulation of AP-1 family transcription factors NF-E2, c-jun and c-fos for exploring intracellular signal pathway of PNS in hematopoietic cells, four human hematopoietic cells lines including myeloid HL-60, erythroid K562, megakaryoid CHRF-288 and Meg-01 were incubated in the presence of PNS for 14 days. The nuclear protein of cells were extracted and analyzed by Western blot with antibodies against NF-E2, c-fos and c-jun. Electrophoretic mobility shift assay (EMSA) was performed by using (32)P labeled AP-1 consensus oligonucleotide which contains binding site for NF-E2, c-jun and c-fos. The results showed that the transcription factors NF-E2, c-jun and c-fos of AP-1 family could be induced by PNS. Western blot demonstrated that the nuclear protein of both NF-E2 and c-jun in four cell lines treated by PNS were increased by 1.5-2.5- and 2.0-3.0-fold over untreated cells respectively. The c-fos protein in three cell lines of K562, CHRF-288 and Meg-01 was also elevated by 2.0-3.0-fold respectively, while c-fos protein in HL-60 cells was no detectable difference after PNS treatment. EMSA results in four cell lines indicated that AP-1 binding activity initiated by PNS was apparently elevated to form higher density band of AP-1-DNA complex. In conclusion, the intracellular transcription regulation initiated by PNS was involved in transcription factors NF-E2, c-jun and c-fos of AP-1 family members, which could play an important role in the up-regulation of genes expression related to proliferation and differentiation of hematopoietic cells.

notoginsenoside R 1