Terpenoids: natural inhibitors of NF-κB signaling with anti-inflammatory and anticancer potential

Traditional medicine has been a fertile source for revealing novel lead molecules for modern drug discovery. In plants, terpenoids represent a chemical defense against environmental stress and provide a repair mechanism for wounds and injuries. Interestingly, effective ingredients in several plant-derived medicinal extracts are also terpenoid compounds of monoterpenoid, sesquiterpenoid, diterpenoid, triterpenoid and carotenoid groups. Inflammatory diseases and cancer are typical therapeutic indications of traditional medicines. Thus folk medicine supports the studies which have demonstrated that plant-derived terpenoid ingredients can suppress nuclear factor-κB (NF-κB) signaling, the major regulator in the pathogenesis of inflammatory diseases and cancer.We review the extensive literature on the different types of terpenoid molecules, totalling 43, which have been verified both inhibiting the NF-κB signaling and suppressing the process of inflammation and cancer. It seems that during evolution, plants have established a terpene-based host defense which also represents a cornucopia of effective therapeutic compounds for common human diseases. Received 11 March 2008; received after revision 28 April 2008; accepted 29 April 2008     

Penetration barrier to sodium fluorescein and fluorescein-labelled dextrans of various molecular sizes in brain capillaries

Summary The permeability of the blood-brain barrier to sodium fluorescein, or fluorescein-labelled dextrans of various molecular weights, was investigated. Unlike the capillaries in both the area postrema and the eminentia mediana, the capillaries of the cerebral cortex were impermeable to all the intravenous tracer substances used.Part of the experimental work was carried out when F.J. worked at the Department of Anatomy, University of Helsinki on a fellowship from the Finnish-Hungarian Exchange Programme. The authors are grateful to Miss Irma Hiltunen for excellent technical assistance.     

Increased susceptibility to lipid peroxidation in skeletal muscles of dystrophic hamsters

The results showed that the total content of lipids, which could be peroxidized with Fe(2 +)/ascorbate stimulation in vitro, was 45.4% and 53.7% higher than normal in the dystrophic hamster muscle at the age of 1 and 3 months, respectively. Correspondingly, the susceptibility to lipid peroxidation (stimulated by ADP-chelated iron at 37 degrees C) was 38.6-74.3% higher in dystrophic muscles. The increases were not related to necrotic lesions and inflammation observed. The activities of glucose-6-phosphate dehydrogenase, glutathione reductase, thioredoxin reductase and catalase were increased in dystrophic muscles but those of superoxide dismutases and glutathione peroxidase were unaffected.     

Endurance training and antioxidants of lung

Mice and rats were adjusted to daily treadmill training programs, which were heavy enough to increase the oxidative capacity of skeletal muscles. Endurance training did not affect the activities of catalase and glutathione peroxidase and the concentration of vitamin E in the lungs of mice and rats. Thus increased ventilation and oxygen utilization induced by exercise training do not modify lung antioxidants, in contrast to hyperoxia and hypoxia.     

Chronic hydrogen peroxide intake and peroxide metabolizing enzyme activities in some tissues of mice and rats

Chronic daily intake of 0.5% H2O2 in drinking water decreased Se-dependent glutathione peroxidase (Se-GSHPx) activity in rat skeletal muscle, kidney and liver. Non-Se GSHPx activity decreased in kidney. Deprivation of drinking water decreased Se-GSHPx activity in kidney and non-Se GSHPx activity in kidney and liver. H2O2 intake decreased activity of catalase in rat skeletal muscle. H2O2 intake or water deprivation caused no changes in these enzyme activities in mice.     

Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL; MIM 221770), also known as Nasu-Hakola disease, is a recessively inherited disease characterized by a combination of psychotic symptoms rapidly progressing to presenile dementia and bone cysts restricted to wrists and ankles. PLOSL has a global distribution, although most of the patients have been diagnosed in Finland and Japan, with an estimated population prevalence of 2x10-6 (ref. 2) in the Finns. We have previously identified a shared 153-kb ancestor haplotype in all Finnish disease alleles between markers D19S1175 and D19S608 on chromosome 19q13.1 (refs 5,6). Here we characterize the molecular defect in PLOSL by identifying one large deletion in all Finnish PLOSL alleles and another mutation in a Japanese patient, both representing loss-of-function mutations, in the gene encoding TYRO protein tyrosine kinase binding protein (TYROBP; formerly DAP12). TYROBP is a transmembrane protein that has been recognized as a key activating signal transduction element in natural killer (NK) cells. On the plasma membrane of NK cells, TYROBP associates with activating receptors recognizing major histocompatibility complex (MHC) class I molecules. No abnormalities in NK cell function were detected in PLOSL patients homozygous for a null allele of TYROBP.