ルパ-20(29)-エン-3β-オール

/ALTERNATIVE and IN VITRO TESTS/ ... Human pancreatic adenocarcinoma cells AsPC-1 were used to investigate the effect of Lupeol on cell growth and its effects on the modulation of multiple Ras-induced signaling pathways. Lupeol caused a dose-dependent inhibition of cell growth as assessed by MTT assay and induction of apoptosis as assessed by flow cytometry, fluorescence microscopy and western blotting. Lupeol treatment to cells was found to significantly reduce the expression of Ras oncoprotein and modulate the protein expression of various signaling molecules involved in PKCalpha/ODC, PI3K/Akt and MAPKs pathways along with a significant reduction in the activation of NFkappaB signaling pathway. ...

/OTHER TOXICITY INFORMATION/ DNA topoisomerases (Topos) are enzymes that play a crucial role in DNA metabolism events such as replication, transcription, recombination, and chromosome segregation at mitosis. Thus, Topo inhibitors could be expected to have antitumor effects. Naturally occurring lupane- and oleanane-type triterpenoids isolated from the bark of Phyllanthus flexuosus were screened for human Topos I and II inhibitory activities. Olean-12-en-3 beta,15 alpha-diol (1), olean-12-en-3 beta,15 alpha,24-triol (3), lupeol (4), and betulin (6) were found to be selective catalytic inhibitors of human Topo II activity with IC(50) values in the range of 10-39 uM.

/LABORATORY ANIMALS: Acute Exposure/ The oral LD(0) in mice was more than 2 g/kg body weight.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ...Chemopreventive properties of lupeol and mango pulp extract (MPE) were evaluated against 7,12-dimethylbenz(a)anthracene (DMBA) induced alteration in liver of Swiss albino mice. Lupeol (25 mg/kg body weight, bw) or 1 mL of 20% w/v aqueous MPE/mouse were daily given once for 1 wk after a single dose of DMBA (50 mg/kg bw). Lupeol/MPE supplementation effectively influenced the DMBA induced oxidative stress, characterized by restored antioxidant enzyme activities and decrease in lipid peroxidation. A reduction of apoptotic cell population in the hypodiploid region was observed in lupeol and MPE supplemented animals. The inhibition of apoptosis was preceded by decrease in reactive oxygen species (ROS) level and restoration of mitochondrial transmembrane potential followed by decreased DNA fragmentation. In DMBA treated animals, downregulation of antiapoptotic Bcl-2 and upregulation of proapoptotic Bax and Caspase 3 in mouse liver was observed. These alterations were restored by lupeol/MPE, indicating inhibition of apoptosis. Thus, lupeol/MPE was found to be effective in combating oxidative stress induced cellular injury of mouse liver by modulating cell-growth regulators.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... Topical application of lupeol (1-2 mg/mouse) 30 min prior to 12-O-tetradecanoyl-phorbol-13-acetate (TPA) (3.2 nmol/mouse) application onto the skin of CD-1 mice afforded significant inhibition, in a time- and dose-dependent manner, against TPA-mediated increase in (i) skin edema and hyperplasia, (ii) epidermal ornithine decarboxylase (ODC) activity, and (iii) protein expression of ODC, cyclo-oxygenase-2 and nitric oxide synthase. As of the role of nuclear factor kappa B (NF-kappaB) and phosphatidyl inositol 3-kinase (PI3K)/Akt signaling in tumor promotion, /it was/ next determined the effect of topical application of lupeol to mouse skin against these signaling pathways. ... Lupeol treatment to mouse skin resulted in the inhibition of TPA-induced (i) activation of PI3K, (ii) phosphorylation of Akt at Thr(308), (iii) activation of NF-kappaB and IKKalpha, and (iv) degradation and phosphorylation of IkappaBalpha. The animals pretreated with Lupeol showed significantly reduced tumor incidence, lower tumor body burden and a significant delay in the latency period for tumor appearance. At the termination of the experiment at 28 weeks, 100% of the animals in TPA-treated group exhibited seven to eight tumors/mouse, whereas only 53% of the mice receiving Lupeol prior to TPA treatment exhibited one to three tumors/mouse.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The present study was undertaken to evaluate the antifertility activity of the active principle, ie lupeol acetate, isolated from benzene extract of Alstonia scholaris in male albino rats. The treatment with lupeol acetate at the dose level of 10 mg/rat/day did not cause any significant change in the body weights, but significant reduction in the weight of reproductive organs, i.e. testes, epididymides, seminal vesicle and ventral prostate, was observed. Testicular sperm count, epididymal sperm count and motility were found significantly declined when compared with controls, which resulted in reduction of male fertility by 100%. Arrest of spermatogenesis was noted at various stages with production of primary spermatocytes (preleptotene and pachytene), secondary spermatocytes and step-19 spermatids were decreased by 52.36, 54.91, 55.67 and 69.65%, respectively. The seminiferous tubules appeared reduced in size by 24.62%. Cross-sectional surface area of Sertoli cells as well as their counts were found to be significantly depleted. Leydig cell nuclear area and number of mature Leydig cells were decreased by 27.65 and 35.47%. Biochemical parameters of tissues i.e. protein, sialic acid, glycogen and cholesterol content of testes and seminal vesicular fructose also showed significant reduction. /Lupeol acetate/.

For more Non-Human Toxicity Excerpts (Complete) data for LUPEOL (7 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/

LD50 Rat oral >2 g/kg /from table/

LD50 Mouse oral >2 g/kg /from table/