Bioactive acridone alkaloids from Swinglea glutinosa

A new prenylated acridone alkaloid, 1,3,5-trihydroxy-2,8-bis(3-methylbut-2-enyl)-10-methyl-9-acridone (1), was isolated from the stembark of Swinglea glutinosa, along with three known acridone alkaloids, 5-hydroxynoracronycine (2), 1,3,5-trihydroxy-4-methoxy-2-(3-methylbut-2-enyl)-10-methyl-9-acridone (3), and 1,3,5-trihydroxy-4-methoxy-10-methylacridone (4). The isolated alkaloids were assessed in vitro against chloroquine-sensitive and -resistant Plasmodium falciparum strains and for cytotoxicity using HeLa cells.     

Conduct Disorder Symptoms and Illicit Drug Use in Juvenile Justice Involved Youth: The Reciprocal Relationship Between Positive Illicit Drug-Use Attitudes and Illicit Drug Use

Conduct disorder (CD) symptoms cooccur at high rates with illicit drug use in juvenile justice involved youth, which results in poorer outcomes; however, research has not identified where best to intervene in this relationship, limiting the identification of modifiable risk factors to reduce negative effects of CD symptoms. Two mediation models were examined to investigate the potential for CD symptoms to influence a reciprocal relationship between illicit drug use and positive drug attitudes, controlling for age, gender, and race. Data were examined for 245 juvenile justice involved youth (mean age = 15.46, SD = 1.30, range 12–18, 64.9% Black, 80.4% male) who completed court-ordered psychological assessments. Findings indicate: (1) Positive attitudes toward illicit drug use significantly mediated the relationship between CD symptoms and illicit drug use (β = 0.16, CI 0.09–0.27; test for indirect effect z = 4.17, p < .001) and (2) illicit drug use significantly mediated the relationship between CD symptoms and positive attitudes toward illicit drug use (β = 0.20, CI 0.12–0.32; test for indirect effect z = 4.87, p < .001). Overall, the present study suggests that CD symptoms impart risk for illicit drug use both indirectly, through more positive attitudes toward illicit drug use, and directly, which further strengthens positive attitudes toward illicit drug use.     

Curcumin attenuates adhesion molecules and matrix metalloproteinase expression in hypercholesterolemic rabbits

Curcumin, the yellow substance found in turmeric, possesses antioxidant, anti-inflammation, anticancer, and lipid-lowering properties. Because we hypothesized that curcumin could ameliorate the development of atherosclerosis, the present study focused on the effects and potential mechanisms of curcumin consumption on high-cholesterol diet–induced atherosclerosis in rabbits. During our study, New Zealand white rabbits were fed 1 of 3 experimental diets: a normal diet, a normal diet enriched with 1% cholesterol (HCD), or an HCD supplemented with 0.2% curcumin. At the end of 8 weeks, blood samples were collected to determine the levels of serum lipids, cytokines, and soluble adhesion molecule levels. Gene expression of adhesion molecules and matrix metalloproteinases (MMPs) in aortas were measured by quantitative real-time polymerase chain reaction and Western blot. Compared with the HCD group, rabbits fed an HCD supplemented with 0.2% curcumin had significantly less aortic lesion areas and neointima thickening. Curcumin reduced the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and oxidized low-density lipoprotein cholesterol in serum by 30.7%, 41.3%, 30.4%, and 66.9% (all P < .05), respectively, but did not affect high-density lipoprotein cholesterol levels. In addition, curcumin attenuated HCD-induced CD36 expression, circulating inflammatory cytokines, and soluble adhesive molecule levels. Curcumin reduced the mRNA and protein expression of intracellular adhesion molecule-1, vascular cell adhesion molecule-1, P-selectin, and monocyte chemotactic protein-1, and it inhibited HCD-induced up-regulation of MMP-1, MMP-2, and MMP-9. Our results demonstrate that curcumin exerts an antiatherosclerotic effect, which is mediated by multiple mechanisms that include lowering serum lipids and oxidized low-density lipoprotein, thus modulating the proinflammatory cytokine levels and altering adhesion molecules and MMP gene expression.     

Improved glucose tolerance in acyl CoA:diacylglycerol acyltransferase 1-null mice is dependent on diet

Background  

Mice that lack acyl CoA:diacylglycerol acyltransferase (Dgat1 ^-/- mice) are reported to have a reduced body fat content and improved glucose tolerance and insulin sensitivity. Studies so far have focussed on male null mice fed a high fat diet and there are few data on heterozygotes. We compared male and female Dgat1 ^-/-, Dgat1 ^+/- and Dgat1 ^+/+ C57Bl/6 mice fed on either standard chow or a high fat diet.     

Involvement of DNA-dependent protein kinase in regulation of the mitochondrial heat shock proteins

Since DNA-dependent protein kinase (DNA-PK) has been known to play a protective role against drug-induced apoptosis, the role of DNA-PK in the regulation of mitochondrial heat shock proteins by anticancer drugs was examined. The levels of basal and drug-induced mitochondrial heat shock proteins of drug-sensitive parental cells were higher than those of multidrug-resistant (MDR) cells. We also demonstrated that the development of MDR might be correlated with the increased expression of Ku-subunit of DNA-PK and concurrent down-regulation of mitochondrial heat shock proteins. The basal mtHsp70 and Hsp60 levels of Ku70(-/-) cells, which were known to be sensitive to anticancer drugs, were higher than those of parental MEF cells, but conversely these mitochondrial heat shock proteins of R7080-6 cells over-expressing both Ku70 and Ku80 were lower than those of parental Rat-1 cells. Also, the mtHsp70 and Hsp60 levels of DNA-PKcs-deficient SCID cells were higher than those of parental CB-17 cells. Our results suggest the possibility that mitochondrial heat shock protein may be one of determinants of drug sensitivity and could be regulated by DNA-PK activity.