Apigenin

270.23700

270.24

926-224-7

7V515PI7F6

83244

DTXSID6022391

Yellow needles from aqueous pyridine

2942000000

90.90000

1.7

Solid

1.548 g/cm3

347.5 °C

555.5ºC at 760 mmHg

217ºC

1.732

DMSO: 27 mg/mL;In water, 183 mg/L at 25 deg C (est)

-20ºC

1.01X10-10 mm Hg at 25 deg C (est)

Henry's Law constant = 5.12X10-17 atm-cu m/mol at 25 °C (est)

pKa1 = 7.12 (phenol); pKa2 = 8.10 (phenol) (est)

156 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Hydroxyl radical reaction rate constant = 2.31X10-10 cu cm/molec-sec at 25 °C (est)|Ozone reaction rate constant = 1.05X10-16 cu cm/molec sec at 25 °C (est)

NONH for all modes of transport

3

R36/37/38

S26-S36

LK9276000

Xi

P261-P305 + P351 + P338

H315-H319-H335

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

H412 (100%): Harmful to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]|P273, and P501|Aggregated GHS information provided by 29 companies from 2 notifications to the ECHA C&L Inventory.| |Warning|H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 79 companies from 9 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H315 (28.57%): Causes skin irritation [Warning Skin corrosion/irritation]|P264, P273, P280, P302+P352, P321, P332+P313, P362, and P501|Aggregated GHS information provided by 231 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Despite widescale use, chamomile has not been convincingly linked to instances of clinically apparent liver injury.

... This study ... investigated the anti-genotoxic effects of apigenin against a known genotoxicant, benzo(a)pyrene (B(a)P) (125 mg/g orally) toxicity in Swiss albino mice. B(a)P administration led to induction of cytochrome P-450 (CYP), aryl hydrocarbon hydroxylase (AHH) and DNA strand breaks (P < 0.001), which was suppressed by apigenin (2.5 and 5 mg/kg orally) dose dependently (P < 0.001). B(a)P-induced depletion in the level of reduced glutathione (GSH), quinone reductase (QR) and glutathione-S-transferase (GST) was also shown to be restored by apigenin pre-treatment (P < 0.001). A simultaneous significant and dose-dependent reduction was noted in DNA strand breaks and in-vivo DNA damage (P < 0.001), which gives some insight into restoration of DNA integrity in modulator groups. These results strongly support the protective nature of apigenin against B(a)P-induced toxicity.|Apigenin (0.01 uM) significantly increased the growth of MC3T3-E1 cells and caused a significant elevation of alkaline phosphatase (ALP) activity and collagen content in the cells (P < 0.05). The effect of apigenin in increasing ALP activity and collagen content was completely prevented by the presence of 10-6 M cycloheximide and 10-6 M tamoxifen, suggesting that apigenin's effect results from a newly synthesized protein component and might be partly involved in estrogen action.|The effect of ... apigenin on the development of bombesin-enhanced peritoneal metastasis from intestinal adenocarcinomas induced by azoxymethane was investigated in male Wistar rats. From the start of the experiment, rats were given weekly sc injections of azoxymethane (7.4 mg/kg body weight) for 10 weeks and sc injection of bombesin (40 ug/kg body weight) every other day, and from week 16, sc injections of apigenin (0.75 or 1.5 mg/kg body weight) every other day until the end of the experiment in week 45. Bombesin significantly increased the incidence of intestinal tumors and cancer metastasis to the peritoneum in week 45. It also significantly increased the labeling index of intestinal cancers. Although administration of apigenin at either dose with bombesin had little or no effect on the enhancement of intestinal carcinogenesis by bombesin, the location, histologic type, depth of involvement, infiltrating growth patterns and labeling index, it was found to decrease significantly the incidence of cancer metastasis. Apigenin significantly decreased the incidence of lymphatic vessel invasion of adenocarcinomas, which was enhanced by bombesin. In vitro experiments revealed that apigenin inhibited bombesin-enhanced phosphorylation of mitogen-activated protein kinase (MAPK), but not matrix metalloprotease (MMP)-9 expression.

Apigenin is a major constituent of chamomile ...

Chamomile is an aromatic oil extracted from the flowers or leaves of the daisy-like plants including German chamomile (Matricaria recutita) and Roman or English chamomile (Chamaemelum nobile). Extracts, oils and teas made from chamomile are used for its soothing qualities as a sedative, mild analgesic and sleep medication. Chamomile has not been implicated in causing serum enzyme elevations or clinically apparent liver injury.

Herbal and Dietary Supplements

/EXPL THER/ ... This report ... shows ... that apigenin markedly induces the expression of death receptor 5 (DR5) and synergistically acts with exogenous soluble recombinant human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to induce apoptosis in malignant tumor cells. TRAIL is a promising candidate for cancer therapeutics due to its ability to selectively induce apoptosis in cancer cells. The combined use of apigenin and TRAIL at suboptimal concentrations induces Bcl-2-interacting domain cleavage and the activation of caspases-8, -10, -9, and -3. Furthermore, human recombinant DR5/Fc chimera protein and caspase inhibitors dramatically inhibit apoptosis induced by the combination of apigenin and TRAIL. On the other hand, apigenin-mediated induction of DR5 expression is not observed in normal human peripheral blood mononuclear cells. Moreover, apigenin does not sensitize normal human peripheral blood mononuclear cells to TRAIL-induced apoptosis. These results suggest that this combined treatment with apigenin and TRAIL might be promising as a new therapy against malignant tumors.|/EXPL THER/ ... The protective role of apigenin was examined against the oxidative stress caused by N-nitrosodiethylamine (NDEA) and phenobarbital (PB) in Wistar albino rats. Oxidative stress was measured in terms of lipid peroxidation (LPO) and protein carbonyl formation. Oxidative stress-induced DNA damage was measured by single cell gel electrophoresis (comet assay). Apigenin exhibited its antioxidant defense against NDEA-induced oxidative stress ... Minimal levels of LPO and DNA damage in apigenin-treated hepatoma bearing animals /were observed/.

Four hours after administration of a flavonoid glycoside extract (corresponding to 0.942 mg aglycones) by gavage, the aglycone of apigenin was observed in the lumen and the wall of the stomach, in the lumen of the small intestine and in the lumen and wall of the cecum in Wistar rats. The evidence of glycosides in the stomach wall suggested that the absorption of flavonoids did not require the presence of their aglycones. Under the study conditions, no renal excretion of apigenin was detected ...|Apigenin appears to be absorbable by humans after intake of parsley (Petroselinum crispum). In a randomized crossover study with two one-week intervention periods in succession, fourteen volunteers consumed a diet that included 20 g parsley. The urinary excretion of apigenin was significantly higher (P < 0.05) during the intervention with parsley (20.7 to 5727.3 g/24 hr) than during the basic diet (0 to 1571.7 g/24 hr). The half-life for apigenin was calculated to be on the order of 12 hr. Significant individual variation in the bioavailability and excretion of apigenin was observed ...|... Eleven healthy subjects (5 women, 6 men) in the age range of 23 to 41 years and with an average body mass index of 23.9 + or - 4.1 kg/sq m took part in this study. After an apigenin- and luteolin-free diet, a single oral bolus of 2 g blanched parsley (corresponding to 65.8 + or - 15.5 umol apigenin) per kilogram body weight was consumed. Blood samples were taken at 0, 4, 6, 7, 8, 9, 10, 11 and 28 hr after parsley consumption and 24-hour urine samples were collected ... On average, a maximum apigenin plasma concentration of 127 + or - 81 nmol/L was reached after 7.2 + or - 1.3 hr with a high range of variation between subjects. For all participants, plasma apigenin concentration rose after bolus ingestion and fell within 28 hr under the detection limit (2.3 nmol/L). The average apigenin content in 24-hour urine was 144 + or - 110 nmol/24 hr corresponding to 0.22 + or - 0.16% of the ingested dose. The flavone could be detected in red blood cells without showing dose-response characteristics.|... The present paper shows the study of the absorption and excretion of luteolin and apigenin in rats after a single oral dose of Chrysanthemum morifolium extract (CME) (200 mg/kg). The levels of luteolin and apigenin in plasma, urine, feces, and bile were measured by HPLC after deconjugation with hydrochloric acid or beta-glucuronidase/sulfatase. The results showed that the plasma concentrations of luteolin and apigenin reached the highest peak level at 1.1 and 3.9 hr after dosing, respectively. The area under the concentration-time curves (AUC) for luteolin and apigenin were 23.03 and 237.6 ug h/mL, respectively. The total recovery of the dose was 37.9% (6.6% in urine; 31.3% in feces) for luteolin and 45.2% (16.6% in urine; 28.6% in feces) for apigenin. The cumulative luteolin and apigenin excreted in the bile was 2.05% and 6.34% of the dose, respectively. All of the results suggest apigenin may be absorbed more efficiently than luteolin in CME in rats, and both luteolin and apigenin have a slow elimination phase, with a quick absorption, so a possible accumulation of the two flavonoids in the body can be hypothesized.|After a single oral administration of radiolabeled apigenin /to rats/, 51.0% of radioactivity was recovered in urine, 12.0% in feces, 1.2% in the blood, 0.4% in the kidneys, 9.4% in the intestine, 1.2% in the liver, and 24.8% in the rest of the body within 10 days. Sex differences appear with regard to the nature of compounds eliminated via the urinary route: immature male and female rats, like mature female rats, excreted a higher percentage of the mono-glucuronoconjugate of apigenin than the mono-sulfoconjugate of apigenin (10.0 to 31.6% versus 2.0 to 3.6%, respectively). Mature male rats excreted the same compounds in an inverse ratio (4.9% and 13.9%, respectively). Radioactivity appeared in the blood only 24 hr after oral administration. Blood kinetics showed a high elimination half-time (91.8 hr), a distribution volume of 259 mL, and a plasmatic clearance of 1.95 mL/hr. All of the parameters calculated from these experiments suggested a slow metabolism of apigenin, with a slow absorption and a slow elimination phase. Thus, a possible accumulation of this flavonoid in the body can be hypothesized.

Ether extracts of the urine of male Wistar rats administered apigenin (200 mg) orally contained the phenolic acid metabolites phydroxyphenylpropionic acid, p-hydroxycinnamic acid, and p-hydroxybenzoic acid. Unreacted apigenin, partially characterized apigenin glucuronides, and ethereal sulfates were also identified. With the exception of p-hydroxybenzoic acid and the apigenin conjugates, all of the metabolites detected in the urine after oral administration were also formed in vitro by rat intestinal microorganisms under anaerobic conditions ... In contrast, these metabolites were not detected in SENCAR mice treated topically with apigenin. Furthermore, no evidence of metabolites were observed from the HPLC profiles of epidermal extracts from apigenin-treated mice ...|The main in vitro metabolite of apigenin in rat liver Aroclor 1254-induced microsomes has been identified tentatively as the corresponding 3'-hydroxylated compound, luteolin. Apigenin itself is the 3'-hydroxylated metabolite of chrysin ...|Apigenin has known human metabolites that include (2S,3S,4S,5R)-3,4,5-Trihydroxy-6-[5-hydroxy-2-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyoxane-2-carboxylic acid.

... The half-life for apigenin was calculated to be on the order of 12 hr ...

The dietary flavonoid apigenin (Api) has been demonstrated to exert multiple beneficial effects upon the vascular endothelium. The aim of this study was to examine whether Ca(2+)-activated K(+) channels (K(Ca)) are involved in endothelial nitric oxide (NO) production and antiangiogenic effects ... Endothelial NO generation was monitored using a cyclic guanosine monophosphate radioimmunoassay. K(Ca) activity and changes of the intracellular Ca(2+) concentration [Ca(2+)](i) were analyzed using the fluorescent dyes bis-barbituric acid oxonol, potassium-binding benzofuran isophthalate, and fluo-3. The endothelial angiogenic parameters measured were cell proliferation, [(3)H]-thymidine incorporation, and cell migration (scratch assay). Akt phosphorylation was examined using immunohistochemistry ... Api caused a concentration-dependent increase in cyclic guanosine monophosphate levels, with a maximum effect at a concentration of 1 uM. Api-induced hyperpolarization was blocked by the small and large conductance K(Ca) inhibitors apamin and iberiotoxin, respectively. Furthermore, apamin and iberiotoxin blocked the late, long-lasting plateau phase of the Api-induced biphasic increase of [Ca(2+)](i). Inhibition of Ca(2+) signaling and the K(Ca) blockade both blocked NO production. Prevention of all three (NO, Ca(2+), and K(Ca) signaling) reversed the antiangiogenic effects of Api under both basal and basic fibroblast growth factor-induced culture conditions. Basic fibroblast growth factor-induced Akt phosphorylation was also reduced by Api ... Based on ... /the/ experimental results ... /the authors/ propose the following signaling cascade for the effects of Api on endothelial cell signaling. Api activates small and large conductance K(Ca), leading to a hyperpolarization that is followed by a Ca(2+) influx. The increase of [Ca(2+)](i) is responsible for an increased NO production that mediates the antiangiogenic effects of Api via Akt dephosphorylation.|... Apigenin inhibits the production of proinflammatory cytokines IL-1beta, IL-8, and TNF in LPS-stimulated human monocytes and mouse macrophages. The inhibitory effect on proinflammatory cytokine production persists even when apigenin is administered after LPS stimulation. Transient transfection experiments using NF-kappaB reporter constructs indicated that apigenin inhibits the transcriptional activity of NF-kappaB in LPS-stimulated mouse macrophages. The classical proteasome-dependent degradation of the NF-kappaB inhibitor IkappaBalpha was observed in apigenin LPS-stimulated human monocytes. Using EMSA ... apigenin does not alter NF-kappaB-DNA binding activity in human monocytes. Instead ... apigenin, as part of a non-canonical pathway, regulates NF-kappaB activity through hypophosphorylation of Ser536 in the p65 subunit and the inactivation of the IKK complex stimulated by LPS. The decreased phosphorylation on Ser536 observed in LPS-stimulated mouse macrophages treated with apigenin was overcome by the over-expression of IKKbeta. In addition ... /the/ studies indicate that apigenin inhibits in vivo LPS-induced TNF and the mortality induced by lethal doses of LPS. Collectively, these findings suggest a molecular mechanism by which apigenin suppresses inflammation and modulates the immune response in vivo.|Treatment of /human prostate cancer/ LNCaP and PC-3 cells with apigenin causes G0-G1 phase arrest, decrease in total Rb protein and its phosphorylation at Ser780 and Ser807/811 in dose- and time-dependent fashion. Apigenin treatment caused increased phosphorylation of ERK1/2 and JNK1/2 and this sustained activation resulted in decreased ELK-1 phosphorylation and c-FOS expression thereby inhibiting cell survival. Use of kinase inhibitors induced ERK1/2 phosphorylation, albeit at different levels, and did not contribute to cell cycle arrest in comparison to apigenin treatment. Despite activation of MAPK pathway, apigenin caused a significant decrease in cyclin D1 expression that occurred simultaneously with the loss of Rb phosphorylation and inhibition of cell cycle progression. The reduced expression of cyclin D1 protein correlated with decrease in expression and phosphorylation of p38 and PI3K-Akt, which are regulators of cyclin D1 protein. Interestingly, apigenin caused a marked reduction in cyclin D1, D2 and E and their regulatory partners CDK 2, 4 and 6, operative in G0-G1 phase of the cell cycle. This was accompanied by a loss of RNA polymerase II phosphorylation, suggesting the effectiveness of apigenin in inhibiting transcription of these proteins. This study provides an insight into the molecular mechanism of apigenin in modulating various tyrosine kinases and perturbs cell cycle progression, suggesting its future development and use as anticancer agent in humans.|The aim of this study was to clarify the anti-inflammatory mechanism of apigenin. Apigenin inhibited the collagenase activity involved in rheumatoid arthritis (RA) and suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production in a dose dependent manner in RAW 264.7 macrophage cells. Pretreatment with apigenin also attenuated LPS-induced cyclooxygenase-2 (COX-2) expression. In addition, apigenin profoundly reduced the tumor necrosis factor-alpha (TNF-alpha)-induced adhesion of monocytes to HUVEC monolayer. Apigenin significantly suppressed the TNF-alpha-stimulated upregulation of vascular cellular adhesion molecule-1 (VCAM-1)-, intracellular adhesion molecule-1 (ICAM-1)-, and E-selectin-mRNA to the basal levels. Taken together, these results suggest that apigenin has significant anti-inflammatory activity that involves blocking NO-mediated COX-2 expression and monocyte adherence ...|For more Mechanism of Action (Complete) data for APIGENIN (16 total), please visit the HSDB record page.

/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/ Treatment of asynchronous human diploid fibroblasts with 10 to 50 mM apigenin produced both the G2/M and G0/G1 cell cycle arrest. The latter appeared to be mediated by the apigenin-induced inhibition of the Cdk2 kinase activity and the phosphorylation of retinoblastoma (Rb) protein, as well as via the induction of the Cdk inhibitor p21/WAF1, a downstream effector of the p53 tumor suppressor protein ...|/ALTERNATIVE and IN VITRO TESTS/ In the human anaplastic thyroid carcinoma cell line (ARO), apigenin treatment resulted in a decrease in the level of phosphorylated EGF receptor tyrosine kinase, as well as MAP kinases and their nuclear substrate, c-Myc, ultimately triggering apoptosis ...|/ALTERNATIVE and IN VITRO TESTS/ Apigenin was shown to induce a dose-dependent reduction in viability of human promyelocytic leukemia HL-60 cells (IC50 = 50 mM) through a rapid induction of caspase-3 activity, proteolytic cleavage of poly-(ADP-ribose) polymerase (PARP), loss of mitochondrial transmembrane potential, elevation of reactive oxygen species (ROS) production, release of mitochondrial cytochrome c into the cytosol, and subsequent induction of procaspase-9 processing ...|/ALTERNATIVE and IN VITRO TESTS/ This research assessed the importance of the adenomatous polyposis coli (APC) tumor suppressor mutation in the ability of apigenin to induce cell cycle arrest using HT29-APC cells, which contain inducible wild-type APC under the metallothionein promoter ... Treatment with apigenin (0, 20, 40, 60, and 80 uM) for 48 hr resulted in reduction in the cell number (P < 0.05) concurrent with flow cytometry results showing a dose-dependent accumulation of cells in the G2/M phase in ... HT29-APC ... cells without ZnCl(2) treatment. Flow cytometric analysis showed an increase (P < 0.05) in the percentage of cells in G2/M when HT29-APC cells were treated with 80 uM apigenin for 120 hr. This increase was not present in HT29-APC cells when treated with both 80 uM apigenin and 100 uM ZnCl(2) for 120 hr. Western blot analysis verified the induction of APC protein expression in ZnCl(2)-treated HT29-APC cells ... Apigenin plus ZnCl(2) treatment increased the expression of APC protein in HT29-APC cells by 50 fold above expression observed with ZnCl(2) alone. Upon induction of the APC gene with ZnCl(2) in HT29-APC cells, the percentage of apoptotic cells increased significantly (P < 0.05) after 120-hr treatment. Additionally, apigenin treatment (80 uM) further increased the percentage of apopototic HT29-APC following ZnCl(2) treatment to induce wild-type APC expression. These results suggest that APC dysfunction may be critical for apigenin to induce cell cycle arrest in human colon cancer cell lines and furthermore, apigenin enhances APC expression and apoptosis in cells with wild-type APC.|For more Human Toxicity Excerpts (Complete) data for APIGENIN (11 total), please visit the HSDB record page.

Apigenin

Oils, chamomile, German: ACTIVE

Analyte: apigenin or luteolin; matrix: rat plasma; procedure: liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS); limit of detection: 2.5 ng/mL in 0.1mL of rat plasma|Analyte: apigenin; matrix: tissue (epidermal cell); procedure: high-performance liquid chromatography with ultraviolet detection at 337 nm; limit of detection: 1.15 ng

Polyketides [PK] -> Flavonoids [PK12] -> Flavones and Flavonols [PK1211]|Cosmetics -> Masking; Tonic