Calycosin

284.26

284.26

09N3E8P7TA

DTXSID70174580

White to off-white powder

2914509090

76

2.4

white to light yellow

1.4±0.1 g/cm3

250-251 °C

536.8°C at 760 mmHg

205.7±23.6 °C

1.669

methanol: soluble1mg/mL, clear, colorless

2-8°C

3.9E-12mmHg at 25°C

Henry's Law constant = 2.3X10-17 atm-cu m/mol at 25 °C (est)

pKa1 = 9.65; pKa2 = 7.31; pKa3 = 7.25; pKa4 = 9.86 (est)

UN 3462 6.1 / PGIII

3

25

45

T

Stable under recommended storage conditions.

P301 + P310

H301

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.|Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.

Strong oxidizing agents

Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.

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.

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.

Radix Astragali is the dried root of Astragalus membranaceus (Fisch.) Bunge and Astragalus mongholicus Bunge (Fabaceae). Fabaceae are also known as Leguminosae(1).

Danggui Buxue Tang (DBT), a herbal decoction contains Astragali Radix (AR) and Angelicae Sinensis Radix (ASR), has been used as a health food supplement in treating menopausal irregularity in women for more than 800 years in China. Several lines of evidence indicate that the synergistic actions of AR and ASR in this herbal decoction leading to a better pharmacological effect of DBT. Here, the role of different herbs in directing the transport of active ingredients of DBT was determined. A validated RRLC-QQQ-MS/MS method was applied to determinate the permeability of ingredients across the Caco-2 cell monolayer. AR-derived chemicals, including astragaloside IV, calycosin and formononetin, as well as ASR-derived chemicals, including ferulic acid and ligustilide, were determined by RRLC-QQQ-MS/MS. The pharmacokinetic results showed that the membrane permeabilities of calycosin and formononetin, two of the major flavonoids in AR, could be markedly increased in the presence of ASR extract: this induction effect could be mediated by ferulic acid deriving from ASR. In contrast, the extract of AR showed no effect on the chemical permeability. The current results suggested that the ingredients of ASR (such as ferulic acid) could enhance the membrane permeability of AR-derived formononetin and calycosin in cultured Caco-2 cells. The possibility of herb-drug synergy within DBT was proposed here.

Calycosin is found in Trifolium pratense L. (cowgrass, peavine clover, purple clover, red clover)(1), Astragalus membranaceus(2) and was isolated from sprouted chickpea seeds(3).

Calycosin's extraction and use as an herbal medication(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 1500(SRC), determined from a structure estimation method(2), indicates that calycosin is expected to have low mobility in soil(SRC). The estimated pKa of calycosin is 7.25(3), indicating that this compound will exist almost entirely in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the acid exists as an anion and anions do not volatilize. Calycosin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.4X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Biodegradation data in soil were not available(SRC, 2013).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1500(SRC), determined from a structure estimation method(2), indicates that calycosin is expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 7.25(3) indicates calycosin will exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 4(SRC), from an estimated log Kow of 2.37(5) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Calycosin is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(7). 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), calycosin, which has an estimated vapor pressure of 2.4X10-10 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 calycosin may be removed from the air by wet or dry deposition(SRC). Calycosin contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

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

An estimated BCF of 4 was calculated in fish for calycosin(SRC), using an estimated log Kow of 2.37(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 calycosin can be estimated to be 1500(SRC). According to a classification scheme(2), this estimated Koc value suggests that calycosin is expected to have low mobility in soil. The pKa of calycosin is estimated as 7.25(3), indicating that this compound will exist almost entirely in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

An estimated pKa of 7.25(1) indicates calycosin will exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water and moist soil surfaces is not expected to be an important fate process(SRC). Calycosin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.4X10-10 mm Hg(SRC), determined from a fragment constant method(2).

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

Calycosin and calycosin-7-O-beta-d-glucoside are two main bioactive isoflavonoids in Astragali Radix. To profile the metabolites of calycosin in rat hepatic 9000 g supernatant incubation system and the metabolites of calycosin-7-O-beta-d-glucoside in rat urine, high performance liquid chromatography with diode array detector and combined with electrospray ionization ion trap time-of-flight multistage mass spectrometry (HPLC-DAD-ESI-IT-TOF-MSn) technique was used. Totally, 24 new in vitro metabolites of calycosin and 33 new in vivo metabolites of calycosin-7-O-beta-d-glucoside were identified. Monoglucosylation, monopentosylation, demethylation, dehydroxylation, dimerization, and trimerization were found to be new in vitro metabolic reactions of calycosin; hydroxylation and hydrogenation were new metabolic reactions of calycosin-7-O-beta-d-glucoside in vivo. The major metabolic reactions of calycosin in rat hepatic 9000 g supernatant incubation system were monohydroxylation on A-ring, dimerization (CO coupling), dimerization (CC coupling) and dehydroxylation; the major phase I metabolic reactions of calycosin-7-O-beta-d-glucoside in rats were deglycosylation, hydroxylation, demethylation and dehydroxylation. Hydroxylation, dehydroxylation, and demethylation were common metabolic pathways to calycosin and calycosin-7-O-beta-d-glucoside, and some of their metabolites formed through these reactions, such as 8-hydroxycalycosin (S10, M10), pratensein (5-hydroxycalycosin, S19, M27) and formononetin (S22, M28), daidzein (M22), 7,3',4'-trihydroxyisoflavone (S13, aglycon of M3 and M8), equol (aglycon of M19 and M20) had been reported to have many bioactivities related to the pharmacological effects of calycosin and calycosin-7-O-beta-d-glucoside. These findings would enhance understanding of the metabolism and real active forms of calycosin and calycosin-7-O-beta-d-glucoside.|In vivo and in vitro metabolites of calycosin-7-O-beta-D-glucopyranoside in rats were identified using a specific and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS(n)) method. The parent compound and twelve metabolites were found in rat urine after oral administration of calycosin-7-O-beta-D-glucopyranoside. The parent compound and six metabolites were detected in rat plasma. In heart, liver, spleen, lung and kidney samples, respectively, six, eight, seven, nine and nine metabolites were identified, in addition to the parent compound. Three metabolites, but no trace of parent drug, were found in the rat intestinal flora incubation mixture and feces, which demonstrated cleavage of the glycosidic bond of the parent compound in intestines. The main phase I metabolic pathways of calycosin-7-O-beta-D-glucopyranoside in rats were deglycosylation, dehydroxylation and demethylation reactions; phase II metabolism included sulfation, methylation, glucuronidation and glycosylation (probably). Furthermore, two metabolites commonly found in rat urine, plasma and tissues were isolated from feces and characterized by NMR. The antiviral activities of the metabolite calycosin against coxsackie virus B3 (CVB3) and human immunodeficiency virus (HIV) were remarkably stronger than those of calycosin-7-O-beta-D-glucopyranoside.

... The present study was designed to explore the therapeutic effect of calycosin, an active component from A. radix, on AGEs-induced macrophages infiltration in HUVECs. ...Transwell HUVEC-macrophage co-culture system was established to evaluate macrophage migration and adhesion. Immunocytochemistry was applied to examine TGF-beta1, ICAM-1 and RAGE protein expressions; real-time PCR was carried out to determine mRNA expression of TGF-beta1, ICAM-1 and RAGE. Immunofluorescence was carried out to observe estrogen receptor-alpha, ICAM-1, RAGE expression and the phosphorylation status of ERK1/2 and NF-kappaB. Calycosin significantly reduced AGEs-induced macrophage migration and adhesion to HUVEC. Pre-treatment with calycosin strikingly down-regulated HUVEC TGF-beta1, ICAM-1 and RAGE expressions in both protein and mRNA levels. Furthermore, calycosin incubation significantly increased estrogen receptor expression and reversed AGEs-induced ERK1/2 and NF-kappaB phosphorylation and nuclear translocation in HUVEC, and this effect of calycosin could be inhibited by estrogen receptor inhibitor, ICI182780. These findings suggest that calycosin can reduce AGEs-induced macrophage migration and adhesion to endothelial cells and relieve the local inflammation; furthermore, this effect was via estrogen receptor-ERK1/2-NF-kappaB pathway.

/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/ Radix Astragali (RA) is commonly used as a health food supplement to reinforce the body vital energy. Flavonoids, including formononetin, ononin, calycosin, and calycosin-7-O-beta-d-glucoside, are considered to be the major active ingredients within RA. Here, we provided different lines of evidence that the RA flavonoids stimulated the expression of erythropoietin (EPO), the central regulator of red blood cell mass, in cultured human embryonic kidney fibroblasts (HEK293T). A plasmid containing hypoxia response element (HRE), a critical regulator for EPO transcription, was tagged upstream of a firefly luciferase gene, namely, pHRE-Luc, which was being transfected into fibroblasts. The application of RA flavonoids onto the transfected cells induced the transcriptional activity of HRE. To account for the transcriptional activation after the treatment of flavonoids, the expression of hypoxia-inducible factor-1a (HIF-1a) was markedly increased: The increase was in both mRNA and protein levels. In addition, the degradation of HIF-1a was reduced under the effect of flavonoids. The regulation of HIF-1a therefore could account for the activation of EPO expression mediated by the RA flavonoids. The current results therefore reveal the function of this herb in enhancing hematopoietic functions.|/ALTERNATIVE and IN VITRO TESTS/ Flavonoids are found in most parts of plants and have been shown to have multiple biological activities such as anticancer, anti-inflammation, antibacteria, antivirus, and immune-stimulation. Existing data showed that the total flavonoids of Astragalus (TFA) can provide biological system with resistance to injury and can possess antimutagenic, atherosclerotic inhibition, and other biological effects. This study investigated the effects of TFA and calycosin (a compound isolated from TFA), on apoptosis induction, and cell cycle of human erythroleukemia cell line K562 by an array of techniques, including proliferation (MTT), PI staining, Annexin V/PI double staining, and RT-PCR. The experimental data showed that TFA and calycosin could inhibit the proliferation of K562 cells. The 50% inhibiting concentrations of TFA and calycosin were 98.63 ug/mL and 130.32 ug/mL, respectively. However, TFA and calycosin could not induce apoptosis in K562 cells, but could increase the number of the cells in the G(0)/G(1) phase. The level of cyclin D1 mRNA in K562 cells decreased after the treatment with TFA and calycosin. This study provides new insights into the functional mechanism of total flavonoids of Astragalus and calycosin on human erythroleukemia cells.|/ALTERNATIVE and IN VITRO TESTS/ Calycosin is one of main components in the herb radix astragali and is considered a typical phytoestrogen. It has either estrogenic or antiestrogenic effects that mainly depend on estrogen levels in vivo. This study investigated the effects and mechanisms of calycosin on estrogen receptor (ER)-positive human breast cancer (MCF-7) cells in vitro. ER-positive MCF-7 cells were treated with different concentrations of calycosin. Effects of calycosin on the proliferation of ER-positive MCF-7 cells were determined by the MTT assay. Apoptosis in these treated cells was examined by flow cytometry. The mRNA and protein levels of Bcl-2 and Bax in these treated cells were also determined by reverse-transcription polymerase chain reaction and immunohistochemical staining, respectively. Compared with the vehicle control, calycosin stimulated proliferation of ER-positive MCF-7 cells at low concentrations (2, 4, and 8 umol/L). Furthermore, at these concentrations, calycosin decreased the percentage of early apoptosis in MCF-7 cells, downregulated mRNA and protein levels of Bax, and upregulated those of Bcl-2 at low concentrations. On the other hand, calycosin at higher concentrations (16 and 32 umol/L) inhibited cell proliferation. At relatively low concentrations, calycosin has stimulatory effects on the proliferation of MCF-7 cells, with the estrogenic effect the mechanism.|/ALTERNATIVE and IN VITRO TESTS/ Danggui Buxue Tang (DBT), a herbal decoction contains Astragali Radix (AR) and Angelicae Sinensis Radix (ASR), has been used as a health food supplement in treating menopausal irregularity in women for more than 800 years in China. Several lines of evidence indicate that the synergistic actions of AR and ASR in this herbal decoction leading to a better pharmacological effect of DBT. Here, the role of different herbs in directing the transport of active ingredients of DBT was determined. A validated RRLC-QQQ-MS/MS method was applied to determinate the permeability of ingredients across the Caco-2 cell monolayer. AR-derived chemicals, including astragaloside IV, calycosin and formononetin, as well as ASR-derived chemicals, including ferulic acid and ligustilide, were determined by RRLC-QQQ-MS/MS. The pharmacokinetic results showed that the membrane permeabilities of calycosin and formononetin, two of the major flavonoids in AR, could be markedly increased in the presence of ASR extract: this induction effect could be mediated by ferulic acid deriving from ASR. In contrast, the extract of AR showed no effect on the chemical permeability. The current results suggested that the ingredients of ASR (such as ferulic acid) could enhance the membrane permeability of AR-derived formononetin and calycosin in cultured Caco-2 cells. The possibility of herb-drug synergy within DBT was proposed here.|For more Human Toxicity Excerpts (Complete) data for Calycosin (6 total), please visit the HSDB record page.

7,3'-dihydroxy-4'-methoxyisoflavone

Isoflavone and phytoestrogen isolated from traditional Chinese medicinal herb

Polyketides [PK] -> Flavonoids [PK12] -> Isoflavonoids [PK1205]