Abstract. We investigated the cell death effects of eight xanthones on PC12 rat pheochromocytoma cells. Among these compounds, a -mangostin, from the fruit hull of Garcinia mangostana L., had the most potent effect with the EC 50 value of 4 mM. a -Mangostin-treated PC12 cells demonstrated typical apoptotic DNA fragmentation and caspase-3 cleavage (equivalent to activation). The flow cytometric analysis indicated that this compound induced apoptosis in time-and concentration-dependent manners. a-Mangostin showed the features of the mitochondrial apoptotic pathway such as mitochondrial membrane depolarization and cytochrome c release. Furthermore, a -mangostin inhibited the sarco(endo)plasmic reticulum Ca 2+ -ATPase markedly. There was a correlation between the Ca
2+-ATPase inhibitory effects and the apoptotic effects of the xanthone derivatives. On the other hand, c-Jun NH 2 -terminal kinase (JNK/ SAPK), one of the signaling molecules of endoplasmic reticulum (ER) stress, was activated with a -mangostin treatment. These results suggest that a-mangostin inhibits Ca
2+-ATPase to cause apoptosis through the mitochondorial pathway.
We discovered a phenomenon in which the blood flow in vein microcirculation markedly decreases in response to hen-egg white lysozyme (HEL)-sensitization without any change in blood pressure. Using this blood flow decrease as a guide, we developed an in vivo assay method to search for substances, which can prevent allergies. Antagonists of histamine, serotonin and platelet activating factor (PAF) did not affect the blood flow decrease in response to HEL-sensitization. On the other hand, cyclooxygenase (COX)-1, COX-2, thromboxane (TX) A 2 , endothelin-1 (ET-1), prostacyclin (PGI 2 ) and granulocytic elastase (GE) as well as nitric oxide (NO) from inducible NO synthase (iNOS) were involved in the blood flow decrease. Thus, these substances might injure vascular endothelial cells, and cause a decrease in blood flow in vein microcirculation. Our method can be used to search for preventive agents against allergies involving NO, COX-1, 2 and PGI 2 . This is the first report to applying to an assay method the specific blood flow decrease to occur in the promotion stage of allergy.
Three new acetylenic compounds, compounds I, II and III were isolated from the cultured cells of Asparagus officinalis L. (Liliaceae) and their structures identified as 1-methoxy-4-[5-(4-methoxyphenoxy)-3-penten-1-ynyl]-benzene, 4-[5-(4-methoxyphenoxy)-3-penten-1-ynyl]phenol and 4-[5-(4-hydroxyphenoxy)-3-penten-1-ynyl]phenol, respectively, from chemical and spectral analysis.
We examined the effects of a 35% ethanol extract (IB) from the petals of Impatiens balsamina L. and the principal active compounds from IB on chronic and serious pruritus and the development of dermatitis using NC mice, a model of atopic dermatitis. IB at 100 mg/kg significantly inhibited serious scratching behaviour in the NC mouse with established dermatitis when administered i.v. 1 h before, or p.o. 24 h before the measurement. A 10 microg/kg dose of kaempferol 3-rutinoside and 2-hydroxy-1,4-naphthoquinone (lawsone) isolated from IB also inhibited scratching behaviour in the NC mouse with established dermatitis. When 4-week-old NC mice with no symptoms were administered orally 100 mg/kg/day of IB until 13 weeks of age, protection was also noted against scratching behaviour during the development of dermatitis. IB was effective for the prevention and treatment of atopic dermatitis.
Dinaphthofuran-7,12-dione derivatives named balsaminones A (1) and B (2) were isolated from the pericarp of Impatiens balsamina L. together with the known compound 2-methoxy-1,4-naphthoquinone (3). Their structures were elucidated by spectral techniques. These compounds have significant antipruritic activity.
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