아피제닌

/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.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ... While in alloxan-treated diabetic animals, a significant decrease in the concentrations of serum insulin, thyroxine (T4) and triiodothyronine (T3), with a parallel increase in serum glucose and hepatic glucose-6-phospatase (G-6-Pase) activity, was observed, administration of 0.78 mg/kg of apigenin for 10 consecutive days increased the levels of serum insulin and thyroid hormones with a parallel decrease in glucose concentration and hepatic G-6-Pase activity. Alloxan-induced elevation in serum cholesterol was also reduced by the compound. With respect to LPO, while in alloxan-treated animals an increase in hepatic lipid peroxidation (LPO) and a decrease in the activity of cellular antioxidants, such as catalase (CAT) and superoxide dismutase (SOD), and in glutathione (GSH) content was observed, administration of apigenin to alloxan-treated mice reversed all these changes, suggesting its hepatoprotective potential. Similar effects of apigenin were also observed in most of the parameters in normoglycaemic animals.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... The effects of apigenin ... on prostate carcinogenesis in TRAMP mice /were investigated/ ... Oral intake of apigenin by gavage at doses of 20 and 50 ug/mouse/day, 6 days per week for 20 weeks, significantly decreased tumor volumes of the prostate as well as completely abolished distant-site metastases to lymph nodes, lungs, and liver in TRAMP mice. Apigenin-treated mice had significantly diminished weights of their genitourinary apparatuses and dorsolateral and ventral prostate lobes, compared with the control group, and showed reduced proliferation and increased apoptosis in the dorsolateral prostates, which correlated with elevated plasma apigenin levels. Continuous intake of apigenin up to 50 weeks by TRAMP mice significantly improved their overall survival ... /Oral/ administration of apigenin further resulted in increased levels of E-cadherin and decreased levels of nuclear beta-catenin, c-Myc, and cyclin D1 in the dorsolateral prostates of TRAMP mice. Similar effects were noted in TRAMP mice with established tumors ...

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ This investigation studied the effect of topical application of apigenin on skin tumorigenesis initiated by 7,12-dimethylbenz(a)anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA) in SENCAR mice. Apigenin was a potent inhibitor of epidermal ornithine decarboxylase induction by TPA in a dose-dependent manner from 1 to 20 umol. Two tumorigenesis studies were conducted. In the first study, 20 umol of apigenin was applied topically and no effect on body weight was observed. By week 33 after DMBA initiation, 48% of DMBA/TPA-treated mice developed carcinomas, while none occurred in DMBA/apigenin/TPA-treated groups. In the second study, doses of 5 and 20 umol of apigenin were used. The papilloma incidence for 0, 5, and 20 umol apigenin at 26 weeks after DMBA was 93.3, 58, and 39.3%, and papilloma numbers per mouse were 7.5, 2.5, and 1.8, respectively. Apigenin prolonged by 3 weeks the latency period of tumor appearance. In addition, apigenin significantly inhibited the incidence of carcinoma and the numbers of carcinomas. The incidence of carcinomas per tumor-bearing animal and the ratio of carcinomas/papillomas in two apigenin-treated groups decreased although there were no significant differences between the three groups. These data indicate that apigenin inhibited skin papillomas and showed the tendency to decrease conversion of papillomas to carcinomas.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Apigenin showed dose-dependent and significant antiimplantation activity when administered to rats from days 1 to 4 of pregnancy. In immature ovariectomized rats, oral administration of apigenin caused a significant increase in uterine weight and diameter, as well as thickness of the endometrium and its epithelial height, thus exhibiting estrogenic properties ...

For more Non-Human Toxicity Excerpts (Complete) data for APIGENIN (15 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/

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.

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.