Piceatannol (trans-3,3',4,5'-tetrahydroxystilbene), a natural analogue of resveratrol, has multiple biological functions. Nevertheless, piceatannol's biological fate is yet to be determined. In this study, we evaluated the absorption and metabolism of piceatannol in rats. Furthermore, the area under the plasma concentration curves (AUC) and metabolic pathway of piceatannol were compared with those of resveratrol. We determined the plasma concentrations of piceatannol, resveratrol, and their respective metabolites following their intragastric administration. Resveratrol metabolites were only conjugates, whereas piceatannol metabolites were piceatannol conjugates, O-methyl piceatannol, and its conjugates. The AUC for piceatannol, resveratrol, and their metabolites increased in a dose-dependent manner (90-360 μmol/kg). The AUC for total piceatannol was less than that for total resveratrol, whereas the AUC for piceatannol (8.6 μmol·h/L) after piceatannol and resveratrol coadministration was 2.1 times greater than that for resveratrol (4.1 μmol·h/L). The greater AUC for piceatannol was a result of its higher metabolic stability.

No abstract

Chemical communication plays an important role in the social lives of various mammalian species. Some of these chemicals are called pheromones. Rats release a specific odor into the air when stressed. This stress-related odor increases the anxiety levels of other rats; therefore, it is possible that the anxiety-causing molecules are present in the stress-related odorants. Here, we have tried to identify the responsible molecules by using the acoustic startle reflex as a bioassay system to detect anxiogenic activity. After successive fractionation of the stress-related odor, we detected 4-methylpentanal and hexanal in the final fraction that still possessed anxiogenic properties. Using synthetic molecules, we found that minute amounts of the binary mixture, but not either molecule separately, increased anxiety in rats. Furthermore, we determined that the mixture increased a specific type of anxiety and evoked anxiety-related behavioral responses in an experimental model that was different from the acoustic startle reflex. Analyses of neural mechanisms proposed that the neural circuit related to anxiety was only activated when the two molecules were simultaneously perceived by two olfactory systems. We concluded that the mixture is a pheromone that increases anxiety in rats. To our knowledge, this is the first study identifying a rat pheromone. Our results could aid further research on rat pheromones, which would enhance our understanding of chemical communication in mammals.stress-related odor | alarm pheromone | acoustic startle reflex | anxiety | rat C hemical communication plays an important role in the social lives of various mammalian species. Some of these chemicals are called "pheromones." Because the term pheromone was coined and defined based on findings in insects (1), there is still a debate as to whether the original definition can be applied to mammals (2). Researchers have proposed revised definitions by modifying the original definition and/or specifying additional requirements (3-6). On the basis of the original and revised definitions, we set a working definition of pheromone within this study as (i) substances that are secreted to the outside by an individual and received by a second individual of the same species, in which they cause a specific reaction; (ii) substances that are effective in minute amounts; (iii) substances that are released from living individuals; and (iv) substances that mediate communication for an evolutionarily adaptive function.Rats release a specific odor into the air when stressed (7). This stress-related odor increases anxiety levels (8, 9) and induces a variety of anxiety-related responses depending on their situation with other rats (9-18). Rats respond to their own stressrelated odor in a similar manner to odor released from the other rats, suggesting that the odor has general effects (10,19). In addition, the stress-related odor appears to be effective in minute amounts (20,21). Therefore, the molecules responsible for increasing anxiety levels should exist in the...

Shortening and removal of the polyadenylate [poly(A)] tail of mRNA, a process called deadenylation, is a key step in mRNA decay that is mediated through the CCR4-NOT (carbon catabolite repression 4-negative on TATA-less) complex. In our investigation of the regulation of mRNA deadenylation in the heart, we found that this complex was required to prevent cell death. Conditional deletion of the CCR4-NOT complex components Cnot1 or Cnot3 resulted in the formation of autophagic vacuoles and cardiomyocyte death, leading to lethal heart failure accompanied by long QT intervals. Cnot3 bound to and shortened the poly(A) tail of the mRNA encoding the key autophagy regulator Atg7. In -depleted hearts, expression was posttranscriptionally increased. Genetic ablation of , but not, increased survival and partially restored cardiac function of or knockout mice. We further showed that in -depleted hearts, Atg7 interacted with p53 and modulated p53 activity to induce the expression of genes encoding cell death-promoting factors in cardiomyocytes, indicating that defects in deadenylation in the heart aberrantly activated Atg7 and p53 to promote cell death. Thus, mRNA deadenylation mediated by the CCR4-NOT complex is crucial to prevent Atg7-induced cell death and heart failure, suggesting a role for mRNA deadenylation in targeting autophagy genes to maintain normal cardiac homeostasis.

We previously found that passion fruit (Passiflora edulis) seeds contained a high amount of piceatannol (3,5,3′,4′-trans-tetrahydroxystilbene), a natural analog of resveratrol (3,5,4′-trans-trihydroxystilbene). Resveratrol has been proposed as a potential anti-metabolic disorder compound, by its activation of sirtuin and AMP-activated protein kinase. Many reports show that resveratrol ameliorates diet-induced obesity and insulin resistance. However, it is not known whether piceatannol also affects diet-induced obesity. We explored the effect of piceatannol on high fat diet-fed mice. The results showed that piceatannol did not affect high fat diet-induced body weight gain or visceral fat gain in mice. However, piceatannol did reduce fasting blood glucose levels. Furthermore, to explore the potential of passion fruit seed extract containing piceatannol as a functional food, passion fruit seed extract was administered in a genetic diabetic mouse model (db/db mice). Single administration of passion fruit seed extract, as well as piceatannol reduced the blood glucose levels of these db/db mice. These results suggest that piceatannol and passion fruit seed extract may have potential application in the prevention of diabetes.Key words piceatannol; passion fruit seed; antidiabetic activity; high fat diet; db/dbThe incidence of metabolic syndrome is increasing worldwide due to aging and changes in lifestyle. In particular, this increase is largely attributed to the rise in the prevalence of obesity, and this common metabolic disorder is associated with increased risk of cardiovascular diseases and type II diabetes, and the latter substantially decreases quality of life and increases health care costs. It is difficult to strictly control blood glucose levels over the long term, even though many anti-diabetic medications are clinically available. Therefore, the development of functional foods that can prevent or improve type II diabetes is an urgent matter.Resveratrol is a natural component of several plants, including grapes, berries, and peanuts. Resveratrol displays widespread functions and has several health-promoting effects owing to its anti-cancer, anti-inflammation, and antioxidant activity.1) Recently, resveratrol has been proposed as a potential anti-metabolic syndrome compound because of its role in activating sirtuin and AMP-activated protein kinase (AMPK).2-5) Indeed, several studies have shown that resveratrol protects mice against diet-induced obesity.6-8) Resveratrol has also been shown to have a favorable effect on glucose metabolism in humans.9,10) However, it should be noted that no weight loss has been reported after resveratrol treatment in any human study. 11)Piceatannol is a hydroxylated analog of resveratrol and is also found in various plants, including grapes and rhubarb. Although piceatannol shows activities similar to resveratrol, its levels in plants are significantly lower than those of resveratrol, 12) and it has therefore received far less research attention. We previously found that passion...